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Biomedical subjects

X Han

Publications and source records attributed to X Han.

At least 19 recordsLinked to original sources

99mTc-MIBI myocardial perfusion imaging in myocarditis.

Myocardial perfusion imaging with technetium-99m-labelled methoxyisobutyl isonitrile single photon emission computed tomography (99mTc-MIBI SPECT) has proven to be an important clinical procedure in assessing the severity of myocardial ischaemia. The uptake and clearance of 99mTc-MIBI by the myocardium is affected by cell viability and membrane integrity. Consequently, infectious diseases, such as myocarditis, may also affect myocardial perfusion by inducing local inflammation and necrosis. We compared 99mTc-MIBI myocardial perfusion imaging with other heart monitoring methods in order to assess its value in the diagnosis of children with Coxsackie viral myocarditis. We examined 46 patients (age, 3-12 years) with Coxsackie viral myocarditis using 99mTc-MIBI myocardial perfusion imaging and compared the perfusion data with myocardial enzymes, electrocardiographic findings and echocardiography. Regions of hypoperfusion were found in all 46 patients. Seventeen patients (37%) showed two or more areas of diminished perfusion. Myocardial hypoperfusion was mild-to-moderate (<30%) in 33 (72%) patients and severe (>30%) in 13 (28%) patients. Characteristic creatine-kinase isoenzyme (CK-MB) increases, ST-T segment changes and diminished heart function were significantly correlated with reduced myocardial perfusion (all comparisons P<0.05). The results of this study suggest that the presence of myocardial uptake of 99mTc-MIBI may be a marker of myocardial inflammation and necrosis. All 46 patients with Coxsackie viral myocarditis showed a certain degree of reduced perfusion. When the perfusion findings were compared with other parameters, it was shown that myocardial enzyme levels, ST-T segment changes and left ventricular function correlated well with the 99mTc-MIBI-established perfusion defect severity. 99mTc-MIBI SPECT imaging is therefore helpful in providing additional diagnostic information in patients with Coxsackie viral myocarditis.

Child↗

IGF-1 signaling enhances cell survival in periodontal ligament fibroblasts vs. gingival fibroblasts.

The role of insulin-like growth factors (IGFs) in the regulation of apoptosis has been suggested, yet their impact on specific cells such as periodontal ligament fibroblasts (PDLF) and gingival fibroblasts (GF) remains unknown. The purpose of this study was to test the role of IGF-1 signaling in cell survival in PDLF compared with GF. In periodontal tissue sections, a significantly reduced apoptotic rate was first demonstrated in PDLF compared with GF. In vitro, IGF-1 substantially enhanced cell survival in PDLF compared with GF by the up-regulation of anti-apoptotic molecules and the down-regulation of pro-apoptotic molecules. Furthermore, the differential expression of insulin-like growth factor binding protein 5 (IGFBP-5) was observed in vitro, and its differential distribution was confirmed in vivo. Analysis of the present data suggests an enhanced cell survival in PDLF compared with GF by the up-regulation of IGF-1 signaling pathway.

Animals↗

Folk yoghurt kills Helicobacter pylori.

AIMS: To evaluate a traditional yoghurt used as folk medicine for its ability to kill Helicobacter pylori in vitro. METHODS AND RESULTS: Micro-organisms from the yoghurt were identified and tested in different food substrates for their effects on H. pylori in a co-culture well system. Two yeasts and several strains of lactobacilli were isolated from the yoghurt, and both the yeast and the lactobacilli independently showed cidal activity against H. pylori. The microbes from the original yoghurt also retained their cidal effect when grown in corn meal and soy milk. CONCLUSIONS: The yeast and lactobacilli found in this yoghurt form a hardy symbiotic culture. The organisms secrete soluble factors capable of killing H. pylori, and these factors may include some organic by-products of fermentation. SIGNIFICANCE AND IMPACT OF THE STUDY: These yoghurt-derived food preparations could become simple and inexpensive therapies to suppress H. pylori infections in endemic countries.

Bacteriological Techniques↗

Identification of genes differentially expressed in cultured human periodontal ligament fibroblasts vs. human gingival fibroblasts by DNA microarray analysis.

Despite their similar spindle-shaped appearance, periodontal ligament fibroblasts (PDLF) and gingival fibroblasts (GF) appear to display distinct functional activities in the maintenance of tissue integrity and during inflammatory/immune responses. We postulated that different characteristics of PDLF and GF are defined by the differential expression of specific genes. To test this, we investigated the possible variance of gene expression profile between cultured PDLF and GF, using DNA microarray technology. One hundred sixty-three genes were found differentially expressed by at least three-fold between PDLF and GF. Genes encoding transmembrane proteins and cytoskeleton-related proteins tended to be up-regulated in PDLF, whereas genes encoding cell-cycle regulation proteins and metabolism-related proteins tended to be up-regulated in GF. We concluded that PDLF and GF appear to display different gene expression patterns that may reflect intrinsic functional differences of the two cell populations and may well coordinate with their tissue-specific activities.

Blotting, Northern↗

Identification of genes differentially expressed in cultured human osteoblasts versus human fibroblasts by DNA microarray analysis.

Little is known about patterns of gene expression from cells populating the connective tissues. This study investigated the possible variance of gene expression profile between human osteoblasts (HO) and human fibroblasts (HF) in vitro, using DNA microarray technology. Clustering identification was used to compare expression patterns between HO and HF for biological significance. Our results showed that genes encoding the extracellular matrix or apoptosis-related proteins tended to be expressed in greater abundance in HO, while more proteolysis-related proteins were expressed in higher level in HF. Significant differences in expression were also noted with genes related to signaling pathways. To confirm the array results, three genes (periostin, MFG-E8, MMP-10) were selected and analyzed independently by RT-PCR and northern blot. The results were found consistent with the array data in HO and HF. The present findings suggest that HO and HF differ not only phenotypically but in the expression level of tissue specific genes to assure the turnover and homeostasis of their respective tissues.

Antigens, Surface↗

Electrochemistry and spectroscopy study on the interaction of microperoxidase-11 with lipid membrane.

The interaction of microperoxidase-11 (MP11) with cationic lipid vesicles of didodecyldimethylammonium bromide (DDAB) induces an alpha-helical conformation from random coil conformations in solution and this change then makes heme macrocycle more distorted. DDAB-induced MP11 conformations were investigated by cyclic votammetry (CV), circular dichroism (CD) and UV-vis spectrometry. All results indicate that the binding of MP11 in solution to DDAB vesicles and the ordered structure formation are driven by mostly electrostatic interaction between negatively charged residues in the undecapeptide and positively charged lipid headgroups on the membrane surface. Upon binding to DDAB, its half-peak potential was also changed. The mechanism of the interaction between MP11 and DDAB was also discussed.

Circular Dichroism↗

TGF-beta1 up-regulates paxillin protein expression in malignant astrocytoma cells: requirement for a fibronectin substrate.

Cytokines can influence the interactions between members of the integrin cell adhesion receptor family and the extracellular matrix thereby potentially affecting cell function and promoting cell adhesion, growth and migration of malignant astrocytoma tumor cells. As malignant astrocytoma cells synthesize TGF-beta1 in vivo, we analysed the effects of TGF-beta1 on signaling events associated with integrin receptor ligation, focusing on the effects on paxillin, a phosphorylated adaptor protein, that acts as a scaffold for signaling molecules recruited to focal adhesions. TGF-beta1-stimulation of primary astrocytes and serum-starved U-251MG malignant astrocytoma cells attached to fibronectin induced a substantial increase in the levels of paxillin protein (fivefold increase at 2.0 ng/ml) in a dose- and time-dependent manner compared to the levels observed on plating onto fibronectin in the absence of stimulation. In the astrocytoma cells, this resulted in an increase in the pool of tyrosine-phosphorylated paxillin, although it did not appear to alter the extent of phosphorylation of the paxillin molecules. In contrast, in primary astrocytes the protein levels were upregulated in the absence of a parallel increase in phosphorylation. The TGF-beta1-stimulated increase in paxillin levels required ligation of the fibronectin receptor, as it was not induced when the cells were plated onto vitronectin, collagen or laminin. The increase in the pool of paxillin on TGF-beta1 stimulation of the fibronectin-plated astrocytoma cells was associated with an increase in translation, but was not associated with an increase in the steady-state levels of paxillin mRNA. Stimulation with TGF-beta1 on a fibronectin substrate increased subsequent attachment and spreading of U-251MG cells onto fibronectin and, to a lesser extent, vitronectin, but not collagen. Our results indicate that physiologic levels of TGF-beta1 stimulate the expression of paxillin protein at the level of translation through a process that requires engagement of the fibronectin receptor, and promotes attachment and spreading of malignant astrocytoma cells on fibronectin.

Animals↗

Palladium(II)-catalyzed asymmetric cyclization of (Z)-4'-acetoxy-2'-butenyl 2-alkynoates. Role of nitrogen-containing ligands in palladium(II)-mediated reactions.

Pd(OAc)(2) combined with nitrogen-containing ligands (e.g., 2,2'-bipyridine) catalyzed the cyclization of (Z)-4'-acetoxy-2'-butenyl 2-alkynoates (1) in acetic acid to afford the alpha-(Z)-acetoxyalkylidene-beta-vinyl-gamma-butyrolactones (2) with high efficiency and high stereoselectivity. The nitrogen-containing ligands, like halides, served to favor beta-heteroatom elimination over beta-hydride elimination in Pd(II)-mediated reactions. The generality of this ligand effect was probed in both stoichiometric and catalytic reactions. With these results in hand, the catalytic asymmetric protocol was achieved with high enantioselectivity (up to 92% ee) when pymox (pyridyl monooxazoline) or bisoxazoline was used. The absolute configuration of the products and the synthetic utility of this asymmetric transformation were established through the convenient synthesis of (3S)-(+)-A-factor.

Journal Article↗

Quantitative analysis and molecular species fingerprinting of triacylglyceride molecular species directly from lipid extracts of biological samples by electrospray ionization tandem mass spectrometry.

Herein we describe a rapid, simple, and reliable method for the quantitative analysis and molecular species fingerprinting of triacylglycerides (TAG) directly from chloroform extracts of biological samples. Previous attempts at direct TAG quantitation by positive-ion electrospray ionization mass spectrometry (ESI/MS) were confounded by the presence of overlapping peaks from choline glycerophospholipids requiring chromatographic separation of lipid extracts prior to ESI/MS analyses. By exploiting the rapid loss of phosphocholine from choline glycerophospholipids, in conjunction with neutral-loss scanning for individual fatty acids, overlapping peaks in the ESI mass spectrum were deconvoluted generating a detailed molecular species fingerprint of individual TAG molecular species directly from chloroform extracts of biological samples. This method readily detects as little as 0.1 pmol of each TAG molecular species from chloroform extracts and is linear over a 1000-fold dynamic range. The sensitivity of individual TAG molecular species to ESI/MS/MS analyses correlated with the unsaturation index and inversely correlated with total aliphatic chain length of TAG. An algorithm was developed which identifies sensitivity factors, thereby allowing the rapid quantitation and molecular species fingerprinting of TAG molecular species directly from chloroform extracts of biological samples.

Animals↗

[Association of 16189 variant (T-->C transition) of mitochondrial DNA with genetic predisposition to type 2 diabetes in Chinese populations].

OBJECTIVE: To assess the prevalence of 16189 variant (T-->C transition) of mitochondrial DNA in Chinese populations and to study the relation between mtDNA 16189 variant and insulin resistance and the role it plays in genetic predisposition to diabetes. METHODS: PCR and RELP techniques were used to examine 383 unrelated type 2 diabetics and 151 non-diabetic controls selected by random sampling. RESULTS: (1) The prevalence of 16189 variant among type 2 diabetics was significantly higher than that among the controls. (2) The prevalence of 16189 variant was significantly higher among type 2 diabetics with maternal family history than among those without maternal family history. (3) In comparison with the type 2 diabetics without 16189 variant, those with 16189 variant showed higher fasting serum insulin level, decreased insulin sensitivity index, and higher Homa insulin resistance index. (4) In the control group, no significant difference in age, gender, body mass index, waist to hip ratio, serum lipid level, fasting plasma glucose level, fasting serum insulin level, insulin sensitivity index, and Homa insulin resistance index was found between those with 16189 variant and those without 16189 variant. CONCLUSION: 16189 variant of mitochondrial DNA is one of the genetic predisposing factors for type 2 diabetes mellitus in Chinese populations. It might interfere with the energy metabolism and the production of ATP, thus causing insulin resistance in peripheral tissues.

Adenosine Triphosphate↗

Potential new antitumor agents from an innovative combination of demethylcantharidin, a modified traditional Chinese medicine, with a platinum moiety.

A combination of demethylcantharidin, a modified component of a traditional Chinese medicine (TCM), with a platinum moiety has produced a series of TCM-based platinum compounds [Pt(C(8)H(8)O(5))(NH(2)R)(2)] 1-5, which demonstrate selective cytotoxicity toward SK-Hep-1 (human liver) cell line, and circumvention of cross-resistance. The inclusion of demethylcantharidin rendered the compounds highly active as protein phosphatase (PP2A) inhibitors. The new TCM-Pt compounds may possess a novel dual mechanism of antitumor action: inhibition of PP2A and platination of DNA.

Animals↗

Prevalence and incidence of hepatitis C virus infection in the US military: a seroepidemiologic survey of 21,000 troops.

Because of a high prevalence of hepatitis C virus (HCV) infection (10-20%) among veterans seeking care in Department of Veterans Affairs (VA) hospitals, current US military forces were evaluated for HCV infection. Banked serum samples were randomly selected from military personnel serving in 1997 and were tested for antibody to HCV (anti-HCV). Overall prevalence of anti-HCV among 10,000 active-duty personnel was 0.48% (5/1,000 troops); prevalence increased with age from 0.1% among military recruits and active-duty personnel aged <30 years to 3.0% among troops aged >/=40 years. Prevalence among 2,000 Reservists and active-duty troops was similar. Based on sequential serum samples from 7,368 active-duty personnel (34,020 person-years of observation), annual incidence of infection was 2/10,000. Of 81 HCV RNA-positive troops for whom genotype was determined, genotypes 1a (63%) and 1b (22%) predominated, as in the civilian population. These data indicate that HCV infection risk among current military forces is lower than in VA studies and the general civilian population aged <40 years. The low level of HCV infection may be attributed to infrequent injection drug use in the military due to mandatory testing for illicit drugs prior to induction and throughout military service.

Adolescent↗

Dual function of troglitazone in ICAM-1 gene expression in human vascular endothelium.

Our previous work has shown that troglitazone (an antidiabetic, thiazolidione drug and a synthetic ligand for peroxisome proliferator-activated receptor gamma, PPARgamma) stimulated basal level of intercellular adhesion molecule-1 (ICAM-1) protein expression in the absence of cytokine stimulation in human vascular endothelial cells. In this study, we examine the molecular mechanism of troglitazone on the basal and TNFalpha-induced ICAM-1 gene expression. Activation of transcription factors, NF-kappaB and AP-1 proteins, known to regulate ICAM-1 gene expression upon external stimulators, was examined. In human vascular endothelial cells (ECV304 cells), troglitazone inhibited TNFalpha-induced ICAM-1 gene expression by suppressing NF-kappaB/DNA binding activity, NF-kappaB transcriptional responses, c-Fos mRNA and protein levels via a ligand-dependent, PPARgamma-activated manner. In contrast, both troglitazone (at 10 microM) and 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2), at 15 microM), a natural ligand for PPARgamma, induce c-Jun phosphorylation by activation of c-Jun N-terminal kinase (JNK) through a posttranslational regulation of c-Jun activity, therefore increasing AP-1/DNA binding activity and transcriptional responses as results of increasing basal ICAM-1 gene expression. These findings suggest dual function of troglitazone in the modulation of both basal and stimulated ICAM-1gene expression in human vascular endothelial cells.

Base Sequence↗

Phosphatidic acid-phosphatidylethanolamine interaction and apocytochrome c translocation across model membranes.

The translocation of apocytochrome c (apocyt.c) across large unilamellar vesicles (LUVs) constructed from mixtures of anionic and zwitterionic phospholipids, phosphatidylethanolamine (PE) and phosphatidylcholine (PC), has been studied. It was shown that the import ratio of horse heart apocyt.c in LUVs composed of phosphatidic acid (PA) combined with PE and PC (62+/-10%) was much higher than that in LUVs made of PE and PC plus any other acidic phospholipid species (20+/-5%). This feature was shared by tuna heart and chicken heart apocyt.c. In addition, the greater efficiency of the PA/PE/PC system versus others in facilitating apocyt.c translocation was maintained using synthetic anionic phospholipids with the same acyl chains. Besides, apocyt.c induces more leakage of entrapped fluorescein sulphonate (FS) from the interior of PA/PC/PE vesicles compared with phosphatidylglycerol (PG)/PC/PE ones. By measuring the intrinsic fluorescence emission spectrum and the accessibility of the preprotein to the fluorescence quencher, acrylamide, differences could be detected in the conformational changes of apocyt.c as a consequence of its interaction with PA/PE/PC and PG/PE/PC vesicles, respectively. Particularly notable is that PE is indispensable for the PA/PE/PC system to most efficiently facilitate apocyt.c translocation across the model membranes. With the fraction of PE increasing from 0 to 30 mol%, the translocation efficiency of apocyt.c as well as its ability to induce FS efflux was significantly enhanced in PA-containing LUVs, whereas this was not observed in the case of replacement of PA by PG or phosphatidylserine. It is also interesting to note that in LUVs containing PA, dioleoyl-PE, but not dielaidoyl-PE, can exert such influences, indicative of the role of non-bilayer formation propensity. On the basis of these results it is postulated that PA might increase the bilayer-destabilizing effects of PE, and hence increase the translocation efficiency of apocyt.c and its leakage-induction ability.

Animals↗

An improved synthesis of the saponin, polyphyllin D.

Polyphyllin D, namely diosgenyl alpha-L-rhamnopyranosyl-(1 --> 2)- [(alpha-L-arabinofuranosyl)-(1 --> 4)]-[beta-D-glucopyranoside, was synthesized from diosgenyl-beta-D-glucopyranoside in four steps and in 30% overall yield, taking advantage of regioselective pivaloylation and alpha-L-rhamnopyranosylation reactions.

Carbohydrate Conformation↗

IL-12-dependent vascular cell adhesion molecule-1 expression contributes to airway eosinophilic inflammation in a mouse model of asthma-like reaction.

Bronchial-alveolar eosinophilic inflammation is among the characteristic pathological changes in asthma, which has been shown to be correlated with type 2 cytokine and chemokine production. Exogenous IL-12 has been found to be inhibitory for pulmonary eosinophilia in reported studies. Using a murine asthma-like model induced by OVA, we found in the present study that IL-12 gene knockout (KO) mice showed substantially reduced airway recruitment of eosinophils compared with wild-type control mice following OVA sensitization/challenge, although the levels of circulating eosinophils were comparable in these two groups of mice. Cytokine analysis showed Ag-driven Th1 (IFN-gamma) and Th2 (IL-4, IL-5, IL-10, and IL-13) cytokine production by CD4 T cells from local draining lymph nodes and spleen. Similarly, local eotaxin production was comparable in wild-type and IL-12 KO mice. In contrast, immunohistochemical analysis showed that the expression of VCAM-1 on the lung endothelium of IL-12 KO mice was dramatically less than that in wild-type mice. Furthermore, administration of rIL-12 at the stage of sensitization and challenge with OVA restored airway eosinophilia and VCAM-1 expression in IL-12 KO mice. The results suggest that endogenous IL-12 contributes to the recruitment of eosinophils into airways observed in asthma, possibly via enhancement of the expression of VCAM-1 on local vascular endothelial cells.

Administration, Intranasal↗