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Biomedical subjects

A Liu

Publications and source records attributed to A Liu.

At least 19 recordsLinked to original sources
PubMed2006

Time to pregnancy and multiple births.

BACKGROUND: Mothers of multiples are alleged to be more fecund than mothers of singletons. Some authors have suggested monitoring twinning rates for assessing temporal changes in a population's reproductive health. METHODS: Using a nested case-control design, we estimated the odds of a multiple birth in relation to fecundity in the US Collaborative Perinatal Project inclusive of 8546 pregnant women who reported a known time-to-pregnancy (TTP) upon enrolment in the cohort, 1959-1966. Case mothers comprised 81 women giving birth to twins/triplets; control mothers comprised 243 women giving birth to singletons matched to case mothers on maternal age at a ratio of 3:1. The odds ratio (OR) for a multiple birth within 6 months of trying adjusting for maternal age and prior pregnancies was estimated using logistic regression. Discrete time Cox regression analysis was also utilized to estimate the fecundability OR. RESULTS: Women with a TTP of 6 months [OR=1.95; 95% confidence interval (95% CI)=1.09-3.51]. Excluding pregnancies after 13+ months resulted in a loss of precision (OR=2.14; 95% CI=0.90-5.04). CONCLUSIONS: These data support higher fecundity among mothers of multiples than mothers of singletons.

Adult↗
PubMed2005

Demonstration of intracellular microorganisms (Rickettsia spp., Chlamydia pneumoniae, Bartonella spp.) in pathological human aortic valves by PCR.

OBJECTIVES: Rickettsiae, which causes vasculitis, has not been linked to atherosclerotic cardiovascular disease in contrast to Chlamydia pneumoniae whose association with coronary artery disease and with sclerotic heart valves in patients undergoing aortic valve replacement is well established, even if causality is yet to unproven. In the search for any of these infectious agents, 84 pathological and 15 normal aortic heart valves of patients undergoing forensic autopsy were analysed by PCR and DNA-sequencing. METHODS: Two to four pieces of all valves were examined by semi-nested PCR, with primers specific for 16S rDNA, citrate synthase (gltA) and 17 kDa outer membrane protein (OMP) genes. RESULTS: Genetic material from Rickettsia spp. and C. pneumoniae was found in 17 (20.2%) and 22 (26.2%), respectively, of the 84 pathological aortic valves. In 35 (41.7%) of these 84 valves either C. pneumoniae or Rickettsia spp. were detected by PCR and in six cases (7.1%) these two organisms co-existed. In one case with Lambl's excrescences, previously considered as aseptic, presence of rickettsia-like organisms also was demonstrated by light microscopy, immunohistochemistry and sequencing of the amplified PCR product showing 100% homology with the published sequence for R. helvetica. In three of the 15 control valves, genetic material from only C. pneumoniae was detected compared to Rickettsia spp. that was significantly detected only in the pathological valves (Fisher's Exact test, 1-sided p = 0.046). CONCLUSIONS: The findings suggest that Rickettsia spp. also have a role in the pathogenesis of aortic valve disease.

Adolescent↗
PubMed2005

A new cerebroside from Uvaria tonkinensis var. subglabra.

A new cerebroside, subglain A (1), together with five known compounds (2-6) have been isolated from the stems of Uvaria tonkinensis var. subglabra. The structure of 1 has been determined to be 1-O-beta-D-glucopyranosyl-(2S,3S,4R,8Z,2'R)-2-[N-(2'-hydroxytetracosanyl)-N-(1'',2''-dihydroxyethyl)-amide]-8-tetradecene-1,3,4-triol by spectroscopic evidence. The known compounds were identified as schisandriside (2), erythritol (3), beta-D-glucopyranose (4), kaempferol-3,7-O-alpha-L-dirhamnoside (5), and (+)-lyoniresinol (6).

Cerebrosides↗
PubMed2004

Measurement of a linear free energy relationship one molecule at a time.

A systematic study of the dehydrogenation of substituted thiophenols by controlled charge injection from the tip of a scanning tunneling microscope (STM) reveals a pronounced dependence of the reaction yield on the position and the chemical nature of the substituent. We evaluate the dehydrogenation rate of para-halo-substituted species within a linear free energy relationship, namely the Hammett equation. The resultant rho value of 1.4 can faithfully predict the reaction rates of molecules that are meta-halo-substituted or para-methyl-substituted. The positive sign of rho suggests a negatively charged transition state at the core of the STM-induced process, and the magnitude of the rho value indicates that the presence of the substrate does not preclude substantial substituent effects. The applicability of the Hammett equation to single-molecule chemistry offers facile prediction of the rate of STM-based single-molecule chemistry in a field, which so far has been addressed by focusing on involved quantum-mechanical modeling of its underlying processes.

Benzoic Acid↗
PubMed2004

Halogen-substituted thiophenol molecules on Cu(111).

Para-halosubstituted thiophenols (X-TPs, where X is Br, Cl, or F) form ordered islands and monolayers on Cu(111) at temperatures as low as 81 K. At incomplete coverages, all X-TPs adsorb with the dehydrogenated thiol group attached to the substrate and the substituted ring inclined toward the surface, as verified experimentally and theoretically. The structure of ordered islands has a pronounced dependence on the nature of the halogen substituent: while unsubstituted TP and pentafluoro-TP molecules do not self-assemble into extended ordered patterns at 81 K, X-TP molecules form a range of different structures which depend both on the size and electronegativity of the substituent, as well as on the coverage.

Adsorption↗
PubMed2004

Low-temperature mobility and structure formation of a prochiral aromatic thiol (2,5-dichlorothiophenol) on Cu(111).

We present a low-temperature scanning tunneling microscopy study of increasing coverages of 2,5-dichlorothiophenol, an asymmetrically halo-substituted aromatic thiol, on Cu(111). At low coverage, deprotonation of the thiol occurs spontaneously upon adsorption at 80 K. Albeit the low deposition temperature, we find the formation of adsorbate islands at low coverage, which coalesce into a well-ordered film of horizontally adsorbed molecules at increasing coverage. This behavior indicates (i) significant mobility of the thiols on Cu(111) even at low temperatures and (ii) attractive adsorbate-adsorbate interactions. At higher coverages intermolecular interactions prevent long-range diffusion of adsorbates and thermal activation of the S-H bond becomes necessary. A close analysis of the molecular films reveals chiral recognition between neighboring molecules, which leads to the formation of enantiopure areas on the surface. Upright orientation of individual molecules starts at the boundaries between such phases and can be induced by scanning tunneling microscopy.

Journal Article↗
PubMed2004

Correlation of amplification and overexpression of the c-myc oncogene in high-grade breast cancer: FISH, in situ hybridisation and immunohistochemical analyses.

In this study, we analysed gene amplification, RNA expression and protein expression of the c-myc gene on archival tissue specimens of high-grade human breast cancer, using fluorescent in situ hybridisation (FISH), nonradioactive in situ hybridisation and immunohistochemistry. The specific question that we addressed was whether expression of c-Myc mRNA and protein were correlated with its gene copy amplification, as determined by FISH. Although c-Myc is one of the most commonly amplified oncogenes in human breast cancer, few studies have utilised in situ approaches to directly analyse the gene copy amplification, RNA transcription and protein expression on human breast tumour tissue sections. We now report that by using the sensitive FISH technique, a high proportion (70%) of high-grade breast carcinoma were amplified for the c-myc gene, irrespective of status of the oestrogen receptor. However, the level of amplification was low, ranging between one and four copies of gene gains, and the majority (84%) of the cases with this gene amplification gained only one to two copies. Approximately 92% of the cases were positive for c-myc RNA transcription, and essentially all demonstrated c-myc protein expression. In fact, a wide range of expression levels were detected. Statistically significant correlations were identified among the gene amplification indices, the RNA expression scores and protein expression scores. c-myc gene amplification, as detected by FISH, was significantly associated with expression of its mRNA, as measured by the intensity of in situ hybridisation in invasive cells (P=0.0067), and by the percentage of invasive cells positive for mRNA expression (P=0.0006). c-myc gene amplification was also correlated with the percentage of tumour cells which expressed high levels of its protein, as detected by immunohistochemistry in invasive cells (P=0.0016). Thus, although multiple mechanisms are known to regulate normal and aberrent expression of c-myc, in this study, where in situ methodologies were used to evaluate high-grade human breast cancers, gene amplification of c-myc appears to play a key role in regulating expression of its mRNA and protein.

Breast Neoplasms↗
PubMed2003

Arbuscular mycorrhiza colonization and development at suboptimal root zone temperature.

Temperature has a strong influence on the activity of living organisms. This study, involving two indoor experiments, evaluated the effects of root zone temperature (10, 15 and 23 degrees C) on the formation and development of arbuscular mycorrhizae (AM). In the first trial, greenhouse-grown sorghum [ Sorghum bicolor (L.) Moench] was either colonized by Glomus intraradices Schenck & Smith or left non-mycorrhizal. Root length, root and shoot weight and root colonization were measured after 5, 10 and 15 weeks of plant growth. Although suboptimal root zone temperatures reduced growth in both mycorrhizal and non-mycorrhizal plants, mycorrhizal plants were larger than non-mycorrhizal plants after 15 weeks at 15 and 23 degrees C. At suboptimal root zone temperatures, mycorrhizal inoculation sometimes slightly reduced root development. AM colonization was more affected than root growth at suboptimal root zone temperatures. Colonization was markedly reduced at 15 degrees C compared with 23 degrees C, and almost completely inhibited at 10 degrees C. The second experiment was conducted in vitro using transformed carrot ( Daucus carota L.) roots supporting G. intraradices. Mycelium length and spore number were measured weekly for 15 weeks. Spore metabolic activity (iodonitrotetrazolium reduction), root length and percentage root colonization were measured after 15 weeks. G. intraradices sporulation was reduced at temperatures below 23 degrees C, while spore metabolic activity was significantly reduced only at 10 degrees C. Root length and in particular percentage colonization were decreased at suboptimal temperatures. A negative interaction between AM hyphal growth and root growth resulting in reduced probability of contact at suboptimal root zone temperatures is proposed to explain the greater reduction observed in root colonization than in root and hyphal growth.

Cold Temperature↗
PubMed2003

Keratin 17 mutation in pachyonychia congenita type 2 with early onset sebaceous cysts.

BACKGROUND: Pachyonychia congenita (PC) is a group of autosomal dominant ectodermal dysplasias caused by mutations in four differentiation-specific keratin genes. Two major clinical subtypes of PC have been generally recognized. Symmetrically thickened fingernails and toenails are the defining characteristic of PC type 2 (PC-2) with onset at infancy. Pilosebaceous cysts are the best hallmark of PC-2, but they usually occur at puberty. OBJECTIVES: To report a Chinese pedigree of PC-2 with unusually early onset sebaceous cysts and to explore the genetic mutation and its phenotype. METHODS: Exon 1 of keratin 17 was amplified by polymerase chain reaction (PCR) from genomic DNA from the three patients in the pedigree, the proband, his half-sister and his younger son, two unaffected members in the pedigree and 50 unrelated and unaffected people. PCR products were directly sequenced to detect the mutation. RESULTS: Direct sequencing of the PCR products revealed a heterozygous 275A-->G mutation in all three affected members. This mutation predicts the substitution of asparagine by serine in codon 92 (N92S) located in the 1A domain of keratin 17. CONCLUSIONS: Mutation in the 1A domain of keratin 17 underlies the affected members' phenotype, PC-2 with early onset sebaceous cysts and late-onset thickened fingernails and toenails. The onset of the cysts is very early in some people within this family and the age at onset of thickened fingernails and toenails is variable within the family, implying the existence of modifying factors.

Adolescent↗
PubMed2003

A preliminary study on coastal water quality monitoring and modeling.

The overall objective of this study was to assess the impact of individual rainfall events on Lake Pontchartrain water quality and risk to swimmers. Indicator organisms in lake water under dry weather conditions, in storm water runoff (prior to dilution with lake water), and in the outfall plume within the lake following storm events were monitored and quantified. Results indicated that drainage canals constitute a significant microbial loading to lake waters. Significant reductions of indicator microbes are observed in the water column following two to three days after storm pumping events into the lake. A mathematical model incorporating advection, dispersion, and bacterial die-off gives fairly good prediction on E. coli, enterococcoi, and fecal coliform titers. The somewhat under estimation by model suggests re-suspension of sediment and re-introduction of the indicator organisms that attached to the sediment back into the water column. Future direction of model development should include the mechanism of re-suspension and survival of indicator organisms in sediment.

Enterobacteriaceae↗
PubMed2001

Nerve growth factor uses Ras/ERK and phosphatidylinositol 3-kinase cascades to up-regulate the N-methyl-D-aspartate receptor 1 promoter.

We reported previously that nerve growth factor (NGF) up-regulates activity of the N-methyl-D-aspartate receptor 1 (NR1) promoter. We have explored the pathways and nuclear targets of NGF signaling in regulating the NR1 promoter. PD98059 and wortmannin, but not rapamycin, significantly attenuated NGF-induced transcriptional activity from an NR1 promoter-luciferase construct. Coexpressing constitutively active forms of Ras, Raf, or MAPK/ERK kinase 1 (MEK1) increased promoter activity dramatically. The MEK1-induced increase was largely prevented by mutations of the tandem GC boxes in the promoter. Promoter activity was also increased significantly by coexpressed GC box-binding proteins (Sp1, 3, or 4) in nonstimulated PC12 cells. Either an extracellular signal-regulated kinase-1 (ERK1)- or Sp1-specific antibody coprecipitated Sp1 with ERKs, and the coprecipitation was enhanced significantly by NGF treatment of PC12 cells. ERK2 also incorporated radioactivity of [gamma(32)P]ATP into recombinant Sp1. However, ERK2-treated Sp1 and PC12 nuclear extracts or nuclear extracts from NGF-treated cells exhibited reduced binding to the promoter or a consensus GC box. Our results suggest that NGF utilizes both the Ras/ERK and phosphatidylinositol 3-kinase pathways to up-regulate NR1 promoter activity and that Sp1 is a novel substrate of NGF-activated ERKs. NGF-increased NR1 promoter activity may involve a complicated mechanism of Sp1 phosphorylation and possible transcription factor exchange.

Androstadienes↗
PubMed2001

The LIS1-related protein NUDF of Aspergillus nidulans and its interaction partner NUDE bind directly to specific subunits of dynein and dynactin and to alpha- and gamma-tubulin.

The NUDF protein of Aspergillus nidulans, which is required for nuclear migration through the fungal mycelium, closely resembles the LIS1 protein required for migration of neurons to the cerebral cortex in humans. Genetic experiments suggested that NUDF influences nuclear migration by affecting cytoplasmic dynein. NUDF interacts with another protein, NUDE, which also affects nuclear migration in A. nidulans. Interactions among LIS1, NUDE, dynein, and gamma-tubulin have been demonstrated in animal cells. In this paper we examine the interactions of the A. nidulans NUDF and NUDE proteins with components of dynein, dynactin, and with alpha- and gamma-tubulin. We show that NUDF binds directly to alpha- and gamma-tubulin and to the first P-loop of the cytoplasmic dynein heavy chain, whereas NUDE binds directly to alpha- and gamma-tubulin, to NUDK (actin-related protein 1), and to the NUDG dynein LC8 light chain. The data suggest a direct role for NUDF in regulation of the dynein heavy chain and an effect on other dynein/dynactin subunits via NUDE. The interactions between NUDE, NUDF, and gamma-tubulin suggest that this protein may also be involved in the regulation of dynein function. Additive interactions between NUDE and dynein and dynactin subunits suggest that NUDE acts as a scaffolding factor between components.

Active Transport, Cell Nucleus↗
PubMed2001

Identification and characterization of a new mammalian glutaredoxin (thioltransferase), Grx2.

A thiol/disulfide oxidoreductase component of the GSH system, glutaredoxin (Grx), is involved in the reduction of GSH-based mixed disulfides and participates in a variety of cellular redox pathways. A single cytosolic Grx (Grx1) was previously described in mammals. We now report identification and characterization of a second mammalian Grx, designated Grx2. Grx2 exhibited 36% identity with Grx1 and had a disulfide active center containing the Cys-Ser-Tyr-Cys motif. Grx2 was encoded in the genomes of mammals and birds and expressed in a variety of cell types. The gene for human Grx2 consisted of four exons and three introns, spanned 10 kilobase pairs, and localized to chromosome 1q31.2-31.3. The coding sequence was present in all exons, with the first exon encoding a mitochondrial signal peptide. The mitochondrial leader sequence was also present in mouse and rat Grx2 sequences and was shown to direct either Grx2 or green fluorescent protein to mitochondria. Alternative splicing forms of mammalian Grx2 mRNAs were identified that differed in sequences upstream of exon 2. To functionally characterize the new protein, human and mouse Grx2 proteins were expressed in Escherichia coli, and the purified proteins were shown to reduce mixed disulfides formed between GSH and S-sulfocysteine, hydroxyethyldisulfide, or cystine. Grx1 and Grx2 were sensitive to inactivation by iodoacetamide and H(2)O(2) and exhibited similar pH dependence of catalytic activity. However, H(2)O(2)-inactivated Grx2 could only be reactivated with 5 mm GSH, whereas Grx1 could also be reactivated with dithiothreitol or thioredoxin/thioredoxin reductase. The Grx2 structural model suggested a common reaction mechanism for this class of proteins. The data provide the first example of a mitochondrial Grx and also indicate the occurrence of a second functional Grx in mammals.

3T3 Cells↗
PubMed2001

Resonance Raman studies of the iron(II)--alpha-keto acid chromophore in model and enzyme complexes.

The bidentate coordination of an alpha-keto acid to an iron(II) center via the keto group and the carboxylate gives rise to metal-to-ligand charge-transfer transitions between 400 and 600 nm in model complexes and in alpha-ketoglutarate-dependent dioxygenases. Excitation into these absorption bands of the Fe(II)TauD(alpha-KG) complex (TauD = taurine/alpha-ketoglutarate dioxygenase, alpha-KG = alpha-ketoglutarate) elicits two resonance Raman features at 460 and 1686 cm(-1), both of which are sensitive to (18)O labeling. Corresponding studies of model complexes, the six-coordinate [Fe(II)(6-Me(3)-TPA)(alpha-keto acid)](+) and the five-coordinate [Fe(II)(Tp(Ph2))(alpha-keto acid)] (6-Me(3)-TPA = tris[(6-methyl-2-pyridyl)methyl]amine, Tp(Ph2) = hydrotris(3,5-diphenylpyrazol-1-yl)borate), lead to the assignment of these two features to the Fe(II)(alpha-keto acid) chelate mode and the nu(C==O) of the keto carbonyl group, respectively. Furthermore, the chelate mode is sensitive to the coordination number of the metal center; binding of a sixth ligand to the five-coordinate [Fe(II)(Tp(Ph2))(benzoylformate)] elicits a 9--20 cm(-1) downshift. Thus, the 10 cm(-1) upshift of the chelate mode observed for Fe(II)TauD(alpha-KG) upon the addition of the substrate, taurine, is associated with the conversion of the six-coordinate metal center to a five-coordinate center, as observed for the iron center of clavaminate synthase from X-ray crystallography (Zhang, Z.; et al. Nat. Struct. Biol. 2000, 7, 127-133) and MCD studies (Zhou, J.; et al. J. Am. Chem. Soc. 1998, 120, 13539--13540). These studies provide useful insights into the initial steps of the oxygen activation mechanism of alpha-ketoglutarate-dependent dioxygenases.

Iron↗