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Biomedical subjects

C Lin

Publications and source records attributed to C Lin.

At least 19 recordsLinked to original sources

Water chemistry and ecotoxicity of an acid mine drainage-affected stream in subtropical China during a major flood event.

Field and laboratory work was carried out to investigate the chemistry and ecotoxicity of stream water affected by acid mine drainage in a tributary catchment of the Pearl River in subtropical China during a major flood that corresponded to a return period of 100 years. The results indicate that stream water was affected by acid mine drainage from the Dabaoshan mine at least to a distance of 25 km downstream of the mine water discharge point. It appears that H(+) generated from sulfide oxidation in the waste rock dumps was readily available for exporting. The amount of H(+) being discharged into the receiving stream depended on the volume of out-flowing waters. However, there was a lag time for the discharges of the metals. This may be attributed to the slower release of metals, relative to H(+), because it might take more time for the dissolution of heavy metal-bearing compounds, particularly the sparsely soluble jarosites. Fe, Zn and Al were the major metals of potential toxicity contained in the AMD-affected stream water, followed by Mn, Cu, Pb, As, Cd and Ni. The concentrations of these metals in the water decreased rapidly down the stream. This corresponds with an increase in the concentrations of reactive heavy metal fractions in benthic mud down the stream, reflecting the precipitation of heavy metal compounds with increasing pH and their subsequent deposition in the streambed. Toxicity tests show that the AMD-affected stream water at 3.5 km downstream of the discharge point was highly toxic to the test organism. At 25 km downstream of the discharge point where stream water pH was as high as 5.75, marked toxic responses of the test organism were still observed.

China↗

Progress in designing nucleic acid structures and fine-tuning their interactions.

The prediction of the structure of biological macromolecules at the atomic level and the design of new meta-stable structures and secondary interactions are critical tests of our understanding of the structures and the inter-atomic forces that underlie molecular biology. The capacity to accurately predict and design new structures and interactions will allow us to create nucleic acid sequences that will fold in new and useful ways. Here, we present some results to demonstrate the progress we have made in designing and assembling new nucleic acid structures that will make an increasingly important contribution to biology and medicine. We call the reaction cycle that exemplifies our approach 'A handshake from a hairpin on the way to a double helix.'

Base Sequence↗

The expression of pituitary gland genes in laying geese.

The purpose of this study was to detect differential expression of genes in the pituitary gland in laying geese by suppression subtractive hybridization (SSH). Pituitary glands from prelaying and laying geese were dissected for mRNA extraction. The cDNA from pituitary glands of prelaying geese was subtracted from the cDNA from the pituitary glands of laying geese (forward subtraction); the reverse subtraction was also performed. We screened 384 clones with possible differentially expressed gene fragments by differential screening. Sixty-five clones from the differential screening results were subjected to gene sequencing and further analysis. We found that at least 19 genes were highly expressed in the pituitary glands of laying geese compared with prelaying geese. Among these, 6 genes (including 4 novel genes) were confirmed by virtual Northern analysis. We found that prolactin and visinin-like protein were highly expressed in the pituitary glands of laying geese compared with prelaying geese (P < 0.05). Further investigation is needed to demonstrate specific functions of the novel genes discovered in the current study.

Animals↗

Antisense c-myc fragments induce normal differentiation cycles in HL-60 cells.

BACKGROUND: We have investigated the potential for using antisense technology as a means of delivering treatment for acute myeloblastic leukaemia (FAB-M2) by gene therapy. MATERIALS AND METHODS: A test recombinant adenovirus vector was constructed containing human c-myc antisense fragments to study the effects of altering c-myc overexpression in the human HL-60 cell line. Control vector contained the human LacZ gene. Transfection efficiency in HL-60 cells was determined using control vector in the presence of protamine sulphate and multiplicity of infection of 100. Morphological and mechanistic changes were assessed using immunohistochemical analysis, flow cytometry and reverse transcription-polymerase chain reaction. RESULTS: Transfection efficiency of control vector was 79.8% and morphological differences were observed after 72 h in culture. The rate of proliferation of HL-60 cells infected with test vector was inhibited by 73% compared with control following 6 days in culture. Normal terminal differentiation leading to apoptosis was only evident in test vector infected cells. Peak apoptosis (34.7%) was detected at day 6 and cell cycle arrest at days 2, 4 and 6. Expression of c-fos protein was significantly increased in test vector treated cells with a noticeable down-regulation of c-myc expression. CONCLUSIONS: These data suggest that transfection of a human HL-60 cell line with vector containing c-myc antisense fragments could inhibit proliferation, but induce differentiation and apoptosis. Thus, we believe that further study of this construct is warranted as a potential gene therapy reagent for treatment of acute myeloblastic leukaemia.

Adenoviridae↗

Evidence for effects of testis and epididymis expressed genes on sperm quality and boar fertility traits.

Retinol-binding protein 4 (RBP4), androgen receptor (AR), relaxin (RLN), acrosin (ACR) and osteopontin (polymorphism in intron 6 named OPNin6; polymorphism in promoter region named OPNprom) were addressed as functional candidate genes for sperm quality and boar fertility and investigated for their association with sperm concentration, motility, semen volume per ejaculate, plasma droplets rate, abnormal spermatozoa rate as well as non-return rate and number of piglets born alive. Therefore 356 AI boars of the purebred Pietrain (PI) and crossbred Pietrain x Hampshire (PI x HA) were genotyped at these loci. Analysis of variance revealed significant associations of RBP4 (p < 0.05), ACR (p < 0.01), and OPNin6 (p < 0.05) with sperm motility. OPNin6 (p < 0.05) was also associated with number of piglets born alive. Moreover, AR (p < 0.05) and OPNprom (p < 0.05) were significantly associated with abnormal spermatozoa rate. For RLN (p < 0.01) there was evidence for effects on sperm volume and ACR significantly affected sperm concentration (p < 0.05) as well as non-return rate (p < 0.05). No significant effects of any locus on plasma droplets rate were observed.

Acrosin↗

Purification and characterization of an extracellular serine protease from the nematode-trapping fungus Dactylella shizishanna.

AIMS: To evaluate the production of an extracellular serine protease by Dactylella shizishanna and its potential as a pathogenesis factor. METHODS AND RESULTS: An extracellular alkaline serine protease (Ds1) was purified and characterized from the nematode-trapping fungus D. shizishanna using cation-exchange chromatography and hydrophobic interaction chromatography. The molecular mass of the protease was approximately 35 kDa estimated by SDS-PAGE. The optimum activity of Ds1 was at pH 10 and 55 degrees C (over 30 min). The purified protease could degrade purified cuticle of Penagrellus redivivus and a broad range of protein substrates. The purified protease was highly sensitive to phenylmethyl sulfonyl fluoride (PMSF) (0.1 mmol l(-1)), indicating it belonged to the serine protease family. The N-terminal amino acid residues of Ds1 are AEQTDSTWGL and showed a high homology with Aozl and PII, two serine proteases purified from the nematode-trapping fungus Arthrobotrys oligospora. CONCLUSIONS: Nematicidal activity of D. shizishanna was partly related to its ability to produce extracellular serine protease. SIGNIFICANCE AND IMPACT OF THE STUDY: In this report, we purified a new serine protease from D. shizishanna and provided a good foundation for future research on infection mechanism.

Amino Acid Sequence↗

Discovery and development of VX-950, a novel, covalent, and reversible inhibitor of hepatitis C virus NS3.4A serine protease.

The hepatitis C virus (HCV) NS3.4A protease, which is essential for viral replication, is considered one of the most attractive targets for developing novel anti-HCV therapies. However, discovery of potent and selective small-molecule inhibitors of HCV NS3.4A protease as oral drug candidates has been hampered by the shallow substrate-binding groove of the protease. Serine trap warheads have been used to covalently anchor inhibitor scaffolds and to increase their affinity to the protease. This review will examine the evolution of covalent inhibitors of the HCV NS3.4A protease from early aldehyde molecules to alpha-ketoamide inhibitors. Kinetic and structural studies of alpha-ketoacid and alpha-ketoamide inhibitors revealed an unusual mechanism of binding in the catalytic site. Optimization of alpha-ketoamide scaffolds by scientists at Vertex and Eli Lilly led to the discovery of VX-950, a novel, potent, selective inhibitor of HCV NS3.4A protease. VX-950 possesses excellent antiviral activity in both HCV replicon cells and human fetal hepatocytes infected with HCV-positive patient sera. In addition, VX-950 exhibits a favorable pharmacokinetic profile in several animal species and demonstrates potent inhibition of the HCV NS3.4A protease activity in a mouse model. In a recent phase 1b clinical trial, VX-950 was able to rapidly reduce the plasma viral load of patients chronically infected with genotype 1 HCV by a mean approximately 3 log(10) in 2 days. The median viral load reduction was 4.4 log(10) for the best dose group after 14 days of dosing. The pre-clinical profile and early clinical data of VX-950 will be discussed in this review.

Animals↗

Direct measurements of Ab and Ac using vertex and kaon charge tags at the SLAC detector.

Exploiting the manipulation of the SLAC Linear Collider electron-beam polarization, we present precise direct measurements of the parity-violation parameters A(c) and A(b) in the Z-boson-c-quark and Z-boson-b-quark coupling. Quark-antiquark discrimination is accomplished via a unique algorithm that takes advantage of the precise SLAC Large Detector charge coupled device vertex detector, employing the net charge of displaced vertices as well as the charge of kaons that emanate from those vertices. From the 1996-1998 sample of 400 000 Z decays, produced with an average beam polarization of 73.4%, we find A(c)=0.673+/-0.029(stat)+/-0.023(syst) and A(b)=0.919+/-0.018(stat)+/-0.017(syst).

Journal Article↗

Alterations in human vitreous humour following cataract extraction.

Cataract extraction is associated with the risk of posterior vitreous detachment, macular edema and retinal detachment possibly as a result of a disturbance to the vitreous body during surgery. While it is common for lens cortical fiber debris to leak into the vitreous humour during cataract extraction, the extent to which the vitreous humour is altered post-surgery is unknown. The current study examines the integrity of the vitreous humour of pseudophakic and phakic human donor eyes by comparing the proteome, the viscosity and the size distribution of macromolecules in different regions of the vitreous humour from human pseudophakic and phakic donor eyes. Major differences between the proteomes of anterior and posterior vitreous humour were observed in phakic and pseudophakic donor eyes. Seventeen spots identified as complete, modified or cleaved forms of alphaA-, alphaB-, betaA4-, betaB2, and gammaS-crystallins were present in the anterior vitreous humour of all pseudophakic eyes studied. Crystallins were not detected in the posterior vitreous humour of the pseudophakic eye or the vitreous humour of the phakic eye. Significant alterations in abundance and/or modification of transthyretin, alpha antitrypsin, and retinoic acid binding protein were observed in all locations of pseudophakic vitreous humour as compared to phakic samples. In addition, a significant decrease in the number and intensity of protein spots was observed for the posterior vitreous humour of pseudophakic eyes when compared to posterior vitreous humour of phakic eyes. Proteins which were affected include antioxidant proteins and enzymes such as carbonic anhydrase and trisephosphate isomerase. A reversal of the viscosity gradient, anterior to posterior, in the vitreous humour of pseudophakic eyes was observed concomitant with alterations in the distribution of 50 nm particles. These particles are likely primarily composed of hyaluronan. While varying degrees of vitreous degradation may have existed prior to surgery and may have contributed to the cataract formation, in no case did the phakic donor eyes exhibit the same alterations in the vitreous humour proteome, viscosity or particle sizes as did the pseudophakic donor eyes. The examination of phakic/pseudophakic donor eye pairs confirmed that the vitreous humour proteome and structural integrity were very similar in the matched phakic donor eye to eyes from donors with no history of cataract. Even though the number of samples for this study was limited, the observed changes support the hypothesis that alterations in the vitreous humour proteome occur in psuedophakic eyes with concurrent alterations in the structure of the vitreous humor. These modifications of the microenvironment of the retina may contribute to the development of retinal complications following cataract surgery.

Adolescent↗

Effects of Bauxsol and biosolids on soil conditions of acid-generating mine spoil for plant growth.

Pot trials were conducted to examine the effects of Bauxsol and biosolids on mine soil conditions for plant growth. Sole application of biosolids did not significantly enhance the growth of the plant because the soils remained highly acidic with soluble concentrations of many metals in excess of toxic levels. Addition of Bauxsol generally resulted in an increase in biomass production by effectively correcting soil acidity and metal toxicity. However, sole application of Bauxsol did not enable meaningful establishment of the grass although the tree grew very well. The combination of Bauxsol and biosolids allowed the establishment of both the grass and the tree and therefore had the better effects on total biomass production, compared to the control and the sole treatments.

Biomass↗

The relationship between quality of life and psychiatric impairment for a Taiwanese community post-earthquake.

This purpose of this study was to investigate the relationship between quality of life and psychiatric impairment in a Taiwanese community located near the epicenter of the 1999 earthquake, as assessed four to six months after the natural catastrophe. Trained assistants interviewed the 4223 respondents using the disaster-related psychological screening test (DRPST), an instrument specifically designed and validated by senior psychiatrists for assessment of psychiatric impairment after natural catastrophe. Additionally, the 36-Item Short-Form Health Survey (SF-36) was used to evaluate quality of life. The collected results were analyzed using Windows SPSS 10.0 software. Psychiatric impairment rated moderate to severe was assessed for 1448 (34.3%) of the responding residents. The 4223 respondents were divided into 4 psychiatric-impairment groups based on DPRST score: healthy (n = 952); mild impairment (n = 1823); moderate impairment (n = 1126); and, severe impairment (n = 322). The four groups were compared for a number of salient factors, including gender, age, current marital status and psychiatric-impairment score, to determine impact on quality of life. Respondents assessed as psychiatrically impaired tended to be older, female, divorced/widowed, and less educated, and they were more likely to have experienced major familial financial loss as an immediate consequence of the earthquake. Further, the greater the severity of the psychiatric impairment, the lower the scores for quality of life, for both the physical and mental aspects of this important general indicator.

Adolescent↗

The association of a cystatin C gene polymorphism with late-onset Alzheimer's disease and vascular dementia.

A polymorphism in the cystatin C (CST3) gene was suggested to associate with Alzheimer's disease (AD). In the present study we attempted to determine the association between CST3 polymorphism and AD or vascular dementia (VD), and whether such effects are dependent of the APOE4 allele. The polymorphisms of CST3 genotype were determined using polymerase chain reactions (PCR) followed by gel electrophoresis in 124 AD, 70 VD, and 115 control individuals. No statistical difference in CST3B allele frequencies was observed among all three groups. Associations between CST3B/B genotype and AD patients older than 75-year-old, or VD patients younger than 75-year-old were evident. The APOE4 allele alone significantly increased the odds for the developing AD, but not VD. A logistic regression analysis revealed that either CST3 or its interaction with APOE4 were not significant predictors of AD. However, a synergistic association of CST3 and APOE4 alleles was observed in predicting VD patients. These results suggest that CST3 might interact with APOE4 on conferring vascular pathologies.

Aged↗

Improved direct measurement of the parity-violation parameter Ab using a mass tag and momentum-weighted track charge.

We present an improved direct measurement of the parity-violation parameter A(b) in the Z boson-b-quark coupling using a self-calibrating track-charge technique applied to a sample enriched in Z-->bb events via the topological reconstruction of the B hadron mass. Manipulation of the Stanford Linear Collider electron-beam polarization permits the measurement of A(b) to be made independently of other Z-pole coupling parameters. From the 1996-1998 sample of 400,000 hadronic Z decays, produced with an average beam polarization of 73.4%, we find A(b)=0.906+/-0.022(stat)+/-0.023(syst).

Journal Article↗

Brain region-dependent increases in beta-amyloid and apolipoprotein E levels in hypercholesterolemic rabbits.

Recent studies indicate a possible link between serum cholesterol level, beta-amyloid (Abeta) peptide concentrations, and the incidence of Alzheimer's disease (AD). In the present report, the effects of dietary cholesterol on Abeta and apolipoprotein E (APOE) levels in several brain regions were examined using diet-induced hypercholesterolemic rabbits as the animal model. Increased dietary cholesterol levels increased Abeta concentrations in temporal cortex (p = 0.02). A similar trend was observed in the frontal cortex (p = 0.06), yet not in the cerebellum. Interestingly, the regional levels of Abeta in the hypercholesterolemic rabbit paralleled the amyloid pathology observed in AD brain. Elevated APOE levels were also noticed in temporal (p < 0.01) and frontal (p < 0.01) cortices, but not in cerebellum, in the rabbit fed with cholesterol-abundant diet. These results suggest that high serum cholesterol levels could induce the elevation of brain APOE, which may play a role in aggravating the Abeta accumulation.

Alzheimer Disease↗

Striatal formation of 6-hydroxydopamine in mice treated with pargyline, pyrogallol and methamphetamine.

Formation of 6-hydroxydopamine (6-OHDA) has been posited in the striatum following methamphetamine treatment and plays a critical role in methamphetamine-induced nigrostriatal dopaminergic toxicity. We used high performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) to determine the formation of 6-OHDA by the treatments of methamphetamine combined with pargyline, a monoamine oxidase inhibitor, and pyrogallol, a catechol-O-methyl-transferase inhibitor, in female C57BL/6J mouse striatum. A substantial amount of 6-OHDA (9.9 +/- 0.7 pg/mg wet tissue) was detected in mice treated with pargyline (100 mg/kg) and pyrogallol (25 mg/kg) in combination. Greater striatal 6-OHDA levels were observed in mice treated with combined pargyline, pyrogallol and methamphetamine (50 mg/kg) as compared to mice treated with combined pargyline and pyrogallol. However, mice treated with pargyline and pyragollol in combination followed by one and two doses of methamphetamine exhibited comparable striatal 6-OHDA levels (23.2 +/- 4.3, 27.3 +/- 1.3 pg/mg wet tissue) in our protocol. We conclude that blockade of the primary metabolic pathways of dopamine by inhibiting both monoamine oxidase and catechol-O-methyl-transferase activities is sufficient to induce 6-OHDA formation in the striatum. Acute 6-OHDA accumulation in the striatum can be potentiated by methamphetamine, a potent dopamine releaser, administration following such metabolic inhibitions.

Animals↗

Localized expression of an anti-TNF single-chain antibody prevents development of collagen-induced arthritis.

Although systemic administration of neutralizing anti-TNF antibodies has been used successfully in treating rheumatoid arthritis, there is a potential for side effects. We transduced a collagen reactive T-cell hybridoma with tissue-specific homing properties to assess therapeutic effects of local delivery to inflamed joints of anti-TNF single-chain antibodies (scFv) by adoptive cellular gene therapy. Cell culture medium conditioned with 1 x 10(6) scFv producer cells/ml had TNF neutralizing capacity in vitro equivalent to 50 ng/ml anti-TNF monoclonal antibody. Adding a kappa chain constant domain to the basic scFv (construct TN3-Ckappa) gave increased in vitro stability and in vivo therapeutic effect. TN3-Ckappa blocked development of collagen-induced arthritis in DBA/1LacJ mice for >60 days. Transgene expression was detected in the paws but not the spleen of treated animals for up to 55 days postinjection. No significant variations in cell proliferation or cytokine secretion were found in splenocytes or peripheral lymphocytes. IL-6 expression was blocked in the diseased paws of mice in the scFv treatment groups compared to controls. In conclusion, we have shown that local expression of an anti-inflammatory agent blocks disease development without causing demonstrable systemic immune function changes. This is encouraging for the potential development of safe adoptive cellular therapies to treat autoimmunity.

Animals↗

Spin polarization of the low-density three-dimensional electron gas.

To determine the state of spin polarization of the three-dimensional electron gas at very low densities and zero temperature, we calculate the energy versus spin polarization using diffusion quantum Monte Carlo methods with backflow wave functions and twist averaged boundary conditions. We find a second-order phase transition to a partially polarized phase at r(s) approximately 50+/-2. The magnetic transition temperature is estimated using an effective mean-field method, the Stoner model.

Journal Article↗

Improved direct measurement of A(b) and A(c) at the Z(0) pole using a lepton tag.

The parity violation parameters A(b) and A(c) of the Zb(b) and Zc(c) couplings have been measured directly, using the polar angle dependence of the polarized cross sections at the Z(0) pole. Bottom and charmed hadrons were tagged via their semileptonic decays. Both the electron and muon analyses take advantage of new multivariate techniques to increase the analyzing power. Based on the 1993-1998 SLD sample of 550,000 Z(0) decays produced with highly polarized electron beams, we measure A(b) = 0.919+/-0.030(stat)+/-0.024(syst), and A(c) = 0.583+/-0.055(stat)+/-0.055(syst).

Journal Article↗