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Biomedical subjects

B Lin

Publications and source records attributed to B Lin.

At least 19 recordsLinked to original sources
PubMed2006

Regulation of Nur77 nuclear export by c-Jun N-terminal kinase and Akt.

Proapoptotic nuclear receptor family member Nur77 translocates from the nucleus to the mitochondria, where it interacts with Bcl-2 to trigger apoptosis. Nur77 translocation is induced by certain apoptotic stimuli, including the synthetic retinoid-related 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalenecarboxylic acid (AHPN)/CD437 class. In this study, we investigated the molecular mechanism by which AHPN/CD437 analog (E)-4-[3-(1-adamantyl)-4-hydroxyphenyl]-3-chlorocinnamic acid (3-Cl-AHPC) induces Nur77 nuclear export. Our results demonstrate that 3-Cl-AHPC effectively activated Jun N-terminal kinase (JNK), which phosphorylates Nur77. Inhibition of JNK activation by a JNK inhibitor suppressed 3-Cl-AHPC-induced Nur77 nuclear export and apoptosis. In addition, several JNK upstream activators, including the phorbol ester TPA, anisomycin and MAPK kinase kinase-1 (MEKK1), phosphorylated Nur77 and induced its nuclear export. However, Nur77 phosphorylation by JNK, although essential, was not sufficient for inducing Nur77 nuclear export. Induction of Nur77 nuclear export by MEKK1 required a prolonged MEKK1 activation and was attenuated by Akt activation. Expression of constitutively active Akt prevented MEKK1-induced Nur77 nuclear export. Conversely, transfection of dominant-negative Akt or treatment with a phosphatidylinositol 3-kinase (PI3-K) inhibitor accelerated MEKK1-induced Nur77 nuclear export. Furthermore, mutation of an Akt phosphorylation residue Ser351 in Nur77 abolished the effect of Akt or the PI3-K inhibitor. Together, our results demonstrate that both activation of JNK and inhibition of Akt play a role in translocation of Nur77 from the nucleus to the cytoplasm.

Adamantane↗
PubMed2006

Modelling the fate of faecal indicators in a coastal basin.

The paper describes a modelling study of near-shore coastal waters, undertaken to assess the impact of various bacterial input loads on the receiving waters in a coastal basin in the UK. Total and faecal coliforms, used as the indicators for bathing water quality under the European Union (EU) Bathing Water Directive, were numerically modelled using a 2D depth integrated hydro-environmental model. Details are given of the governing equations and solution methods used in the numerical model, together with a discussion of the recent development in faecal bacterial indicator modelling. Details are also given of a field data collection exercise, which involved initially collecting existing information on effluent input loads and followed by an intensive field survey. Using the water quality model, the mortality rate of the pathogen bacteria was investigated. Three methods were used to represent the relationship between the decay rate and the level of solar radiation including: a constant decay rate, day- and night-time decay rates and a solar radiation related time varying decay rate. Relatively close agreement between model predicted and measured total and faecal coliform concentration distributions were obtained for different day- and night-time decay rates and time varying decay rates. No significant differences were found in the optimum decay rates for total and faecal coliform levels. Finally, the impact of the individual inputs on the bathing water quality of the basin was also statistically and numerically investigated. Results showed that the River Irvine was the most significant input during high river flows, and that under these conditions the bathing waters were likely to fail to comply with the European Union Bathing Water Directive. For base river flow conditions the Meadowhead effluent input was found to be critical for both total and faecal coliform level predictions.

Enterobacteriaceae↗
PubMed2006

A comparative map of macrochromosomes between chicken and Japanese quail based on orthologous genes.

In order to develop a comparative map between chicken and quail, we identified orthologous gene markers based on chicken genomic sequences and localized them on the Japanese quail Kobe-NIBS linkage map, which had previously been constructed with amplified fragment length polymorphisms. After sequencing the intronic regions of 168 genes located on chicken chromosomes 1-8, polymorphisms among Kobe-NIBS quail family parents were detected in 51 genes. These orthologous markers were mapped on eight Japanese quail linkage groups (JQG), and they allowed the comparison of JQG to chicken macrochromosomes. The locations of the genes and their orders were quite similar between the two species except within a previously reported inversion on quail chromosome 2. Therefore, we propose that the respective quail linkage groups are macrochromosomes and designated as quail chromosomes CJA 1-8.

Animals↗
PubMed2005

Surveillance of transcriptomes in basic military trainees with normal, febrile respiratory illness, and convalescent phenotypes.

Gene expression profiles permit analysis of host immune response at the transcriptome level. We used the Pax gene Blood RNA (PAX) System and Affymetrix microarrays (HG-U133A&B) to survey profiles in basic military trainees and to classify them as healthy, febrile respiratory illness (FRI) without adenovirus, FRI with adenovirus, and convalescent from FRI with adenovirus. We assessed quality metrics of RNA processing for microarrays. Class prediction analysis discovered nested sets of transcripts that could categorize the phenotypes with optimized accuracy of 99% (nonfebrile vs febrile, P<0.0005), 87% (healthy vs convalescent, P=0.001), and 91% (febrile without vs with adenovirus, P<0.0005). The discovered set for classification of nonfebrile vs febrile patients consisted of 40 transcripts with functions related to interferon induced genes, complement cascades, and TNF and IL1 signaling. The set of seven transcripts for distinguishing healthy vs convalescent individuals included those associated with ribosomal structure, humoral immunity, and cell adhesion. The set of 10 transcripts for distinguishing FRI without vs with adenovirus had functions related to interferon induced genes, IL1 receptor accessory protein, and cell interactions. These results are the first in vivo demonstration of classification of infectious diseases via host signature transcripts and move us towards using the transcriptome in bio-surveillance.

Adenovirus Infections, Human↗
PubMed2005

A dominant form of congenital stationary night blindness (adCSNB) in a large Chinese family.

Summary A pedigree of congenital stationary night blindness (CSNB) is described in a large Chinese family. The clinical description, pedigree, dark adaptation and elctroretinogram (ERG) studies indicate that the patients have an autosomal dominant form (ad) of CSNB. The disorder has been transmitted through at least 12 generations with over 40 affected individuals identified. The ERG data reveal that affected persons have severely diminished b-wave responses to dim light, but normal a-wave and subnormal b-wave responses to maximum light stimuli. The dark adaptation curves of three patients show a monophase curve, typical for night blindness. We have excluded the five previously known mutations in the three genes (RHO, PDE6B and GNAT1) associated with adCSNB, and linkage studies have excluded tight linkage between the disease locus and markers associated with these three genes. Thus, this family has adCSNB caused by a different gene from the previously identified RHO, PDE6B, and GNAT1.

Adult↗
PubMed2005

Toxicity, bioavailability and pharmacokinetics of a newly formulated colistin sulfate solution.

We formulated a new colistin sulfate injectable solution and tested its effectiveness, toxicity and pharmacokinetics in vivo on mice, rabbits, and piglets. When intramuscularly injected (i.m.) into rabbits at 0.5 mL per site, the 2.5% colistin sulfate solution caused no reaction at the injection site, but the 5.0% solution caused the muscle circumference to appear erythematic. Tested LD50 in CD-1 mice were 38.72 mg/kg for i.m. and 431.95 mg/kg for oral administration, respectively. At 15.0 mg/kg/day (i.m.) for 5 days, colistin sulfate caused obvious neurotoxicity to piglets with moderate granular degenerations in the epithelial tissues from kidney and liver. These toxic responses were not seen when colistin sulfate was injected at 10.0 mg/kg/day for 5 days. Pharmacokinetic studies revealed Cmax of 3.73 +/- 0.28 and 6.40 +/- 0.18 microg/mL, Tmax of 32 +/- 1.5 and 34 +/- 1.8 min, t(1/2beta) of 256 +/- 14 and 264 +/- 29 min, and absolute bioavailability of 95.94 and 88.45% for colistin sulfate intramuscularly injected to piglets at 2.5 and 5.0 mg/kg, respectively. Serum colistin sulfate concentration followed a two-compartment open model showing first-order absorption. The high bioavailability and the long-lasting serum retention time indicated that the new solution is suitable for i.m. in piglets with a recommended dose of 2.5 mg/kg injected twice daily.

Administration, Oral↗
PubMed2005

Inhibition of hepatitis B virus replication in 2.2.15 cells by expressed shRNA.

Hepatitis B virus (HBV) infection is a worldwide health problem. To determine whether RNA interference (RNAi) could inhibit ongoing HBV replication in 2.2.15 cells, we constructed shRNA-producing vector pU6P based on the mouse U6 RNA promoter and cloned 12 targeted sequences against HBV into the vector, resulting in a series of pU6-siHBV vectors. The recombinant vectors were transfected into 2.2.15 cells, HBsAg and HBeAg in cultured media were assayed using enzyme-linked immunosorbent assay at various days after transfection. The amount of HBV DNA in the culture medium was quantitated by real-time polymerase chain reaction. HBsAg and HBeAg expression were inhibited by 72.8 +/- 5.4% (P = 0.00003) and 55.8 +/- 6.2% (P = 0.000026), respectively, 4 days after transfection with pU6-siHBV5. The greatest inhibition of HBV DNA was decreased by approximately 1.9-fold (P = 0.013) on day 6 post transfection with pU6-siHBV11 compared with that of empty vector. No change was found for HBV protein expression and DNA replication on pU6-siGFP (negative control) transfected cells. Our data demonstrate that the transfection of HBV-targeted shRNA-producing vector in 2.2.15 cells could inhibit the HBV protein expression and HBV DNA replication specifically. RNAi may be considered as a potential antiviral approach for human HBV infection.

Animals↗
PubMed2005

Polymorphism of human leukocyte antigen-DRB1, -DQB1, and -DPB1 genes of Shandong Han population in China.

In the present study, polymerase chain reaction-sequence-based typing (PCR-SBT) was used to analyze human leukocyte antigen (HLA)-DRB1, -DQB1, and -DPB1 alleles of 98 unrelated healthy Shandong Han individuals. A total of 60 alleles, in which 28 in DRB1, 15 in DQB1 and 17 in DPB1 were found. Among the 28 detected DRB1 alleles, DRB1*150101, DRB1*070101, DRB1*090102, DRB1*120201, and DRB1*080302 were commonly observed, with frequencies of 16.3%, 11.2%, 10.2%, 8.2%, and 5.6%, respectively. The most predominant DQB1 allele was DQB1*030101/0309 with the frequency of 20.4%, followed by DQB1*0201/0202 (14.8%), DQB1*0602 (14.3%), DQB1*030302 (12.2%), and DQB1*060101/060103 (10.7%). Of the 17 detected DPB1 alleles, DPB1*0501 was the most frequent allele with the frequency of 37.2%. DPB1*020102 (18.4%), DPB1*040101 (11.2%), DPB1*0402 (7.1%), and DPB1*1701 (6.6%) were also very frequent alleles. A total of 53 estimated DRB1-DQB1 two-locus haplotypes were observed in Shandong Han population, of which DRB1*150101-DQB1*0602 was the most predominant, followed by DRB1*090102-DQB1*030302, DRB1*070101-DQB1*0201/0202 DRB1*120201-DQB1*030101/0309, and DRB1*080302- DQB1*060101/060103. The distribution of the HLA class II alleles and haplotypes frequencies as well as the dendrogram showed that the Shandong Han population belongs to the northern group of Chinese. The data have implications for anthropological studies and disease associations.

Alleles↗
PubMed2005

Phototransformations of advanced glycation end products in the human eye lens due to ultraviolet A light irradiation.

Previous studies from this laboratory have shown that ultraviolet A (UVA) light can bleach the yellow advanced glycation end products (AGEs) of aged and cataractous human lenses. The AGEs OP-lysine and argpyrimidine are two UVA-absorbing posttranslational modifications that are abundant in the eye lens. The purpose of this study was to outline the changes in these two AGEs due to UVA irradiation. The changes of OP-lysine, OP-phenethylamine (a phenethylamine analogue of OP-lysine), and argpyrimidine due to irradiation with UVA light in the presence or absence of air and ascorbic acid were followed by different spectral methods. Aged human lenses were similarly irradiated in artificial aqueous humor. The amounts of OP-lysine in the irradiated lenses and in the corresponding dark controls were determined by HPLC. Both OP-lysine and argpyrimidine decreased 20% when irradiated with UVA light in the absence of ascorbic acid. Under the same conditions, OP-lysine was bleached 80% in the presence of ascorbic acid during irradiation experiments. In contrast, argpyrimidine UVA light bleaching was not affected by the presence of ascorbic acid. Interestingly the major product of OP-phenethylamine after UVA irradiation in the presence of ascorbic acid was phenethylamine, which indicates that the entire heterocycle of this AGE was cleaved and the initial amino group was restored. Some AGEs in the human eye lens can be transformed by UVA light.

Glycation End Products, Advanced↗
PubMed2004

Decay of intestinal enterococci concentrations in high-energy estuarine and coastal waters: towards real-time T90 values for modelling faecal indicators in recreational waters.

Intestinal enterococci are the principal 'health-evidence-based' parameter recommended by WHO for the assessment of marine recreational water compliance. Understanding the survival characteristics of these organisms in nearshore waters is central to public health protection using robust modelling to effect real-time prediction of water quality at recreation sites as recently suggested by WHO and the Commission of the European Communities Previous models have more often focused on the coliform parameters and assumed two static day-time and night-time T90 values to characterise the decay process. The principal driver for enterococci survival is the received dose of irradiance from sunlight. In the water column, transmission of irradiance is determined by turbidity produced by suspended material. This paper reports the results of irradiated microcosm experiments using simulated sunlight to investigate the decay of intestinal enterococci in relatively turbid estuarine and coastal waters collected from the Severn Estuary and Bristol Channel, UK. High-turbidity estuarine waters produced a T90 value of 39.5 h. Low-turbidity coastal waters produced a much shorter T90 value of 6.6 h. In experiments receiving no irradiation, high-turbidity estuarine waters also produced a longer T90 of 65.1 h compared with corresponding low-turbidity coastal waters, T90 24.8 h. Irradiated T90 values were correlated with salinity, turbidity and suspended solids (r>0.8, p<0.001). The results suggest that enterococci decay in irradiated experiments with turbidity >200 NTU is similar to decay observed under dark conditions. Most significantly, these results suggest that modelling turbidity and or suspended solids offers a potential means of predicting T90 values in 'real-time' for discrete cells of a hydrodynamic model.

Dose-Response Relationship, Radiation↗
PubMed2004

Modelling hydroenvironmental and health risk assessment parameters along the South Wales Coast.

This paper highlights the increasing concerns relating to hydroenvironmetal issues and cites recent examples of the challenges now being regularly faced by hydroenvironmetal scientists and engineers. The limitations and restrictions of both physical (or laboratory) and numerical (or computer based) hydraulic models used in the planning and management of aquatic basins are discussed. General details are given of numerical models used for flow and water quality concentration predictions in estuarine waters, with particular application to the challenges occurring along the South Wales coast. A highly accurate and non-diffusive finite difference scheme that solves the transport equation for predicting water quality indicators and suspended sediment concentration distributions is also discussed. In particular, details are outlined of the extension of the water quality indicators of faecal coliforms, as required to comply with the EU Bathing Water Directive, to predict health risk assessment, in the form of predicting the risk of gastroenteritis. Three example research projects along the South Wales coast are described; the projects involve the application of two-dimensional and three-dimensional hydroenvironmetal models to predict flow patterns and water quality indicator organism distributions in the coastal receiving waters. These studies include: (i) a curvilinear finite difference approach to modelling flows in the Bristol Channel, (ii) coastal health risk predictions in Swansea Bay using combined water quality and epidemiological models, and (iii) combined sewer overflow discharges into Cardiff Bay.

Computer Simulation↗
PubMed2004

The Escherichia coli GTPase CgtAE cofractionates with the 50S ribosomal subunit and interacts with SpoT, a ppGpp synthetase/hydrolase.

CgtA(E)/Obg(E)/YhbZ is an Escherichia coli guanine nucleotide binding protein of the Obg/GTP1 subfamily whose members have been implicated in a number of cellular functions including GTP-GDP sensing, sporulation initiation, and translation. Here we describe a kinetic analysis of CgtA(E) with guanine nucleotides and show that its properties are similar to those of the Caulobacter crescentus homolog CgtA(C). CgtA(E) binds both GTP and GDP with moderate affinity, shows high guanine nucleotide exchange rate constants for both nucleotides, and has a relatively low GTP hydrolysis rate. We show that CgtA(E) is associated predominantly with the 50S ribosomal subunit. Interestingly, CgtA(E) copurifies with SpoT, a ribosome-associated ppGpp hydrolase/synthetase involved in the stress response. The interaction between CgtA(E) and SpoT was confirmed by reciprocal coprecipitation experiments and by two-hybrid assays. These studies raise the possibility that the ribosome-associated CgtA(E) is involved in the SpoT-mediated stress response.

Bacterial Proteins↗
PubMed2003

Immunomodulatory analogs of thalidomide inhibit growth of Hs Sultan cells and angiogenesis in vivo.

We have previously shown that thalidomide and its potent immunomodulatory derivatives (IMiDs) inhibit the in vitro growth of multiple myeloma (MM) cell lines and patient MM cells that are resistant to conventional therapy. In this study, we further characterize the effect of these drugs on growth of B cell malignancies and angiogenesis. We established a beige-nude-xid (BNX) mouse model to allow for simultaneous in vivo measurement of both anti-tumor and anti-angiogenic effects of thalidomide and its analogs. Daily treatment (50 mg/kg/d) with thalidomide or IMiDs was nontoxic. The IMiDs were significantly more potent than thalidomide in vivo in suppressing tumor growth, evidenced by decreased tumor volume and prolonged survival, as well as mediating anti-angiogenic effects, as determined by decreased microvessel density. Our results therefore show that the IMiDs have more potent direct anti-tumor and anti-angiogenic effects than thalidomide in vivo, providing the framework for clinical protocols evaluating these agents in MM and other B cell neoplasms.

Angiogenesis Inhibitors↗
PubMed2003

Predicting near-shore coliform bacteria concentrations using ANNS.

Details are given of the application of Artificial Neural Networks (ANNs) to predicting the compliance of bathing waters along the coastline of the Firth of Clyde, situated in the south west of Scotland, UK. Water quality data collected at 7 locations during 1990-2000 were used to set up the neural networks. In this study faecal coliforms were used as a water quality indicator, i.e. output, and rainfall, river discharge, sunlight and tidal condition were used as input of these networks. In general, river discharge and tidal ranges were found to be the most important parameters that affect the coliform concentration levels. For compliance points close to the meteorological station, the influence of rainfall was found to be relatively significant to the concentration levels.

Enterobacteriaceae↗
PubMed2002

Hydro-environmental modelling for bathing water compliance of an estuarine basin.

In recent years, considerable investment has been committed to sewerage infrastructure and new sewage treatment plants in the catchment surrounding an estuarine basin along the north-west coast of England. Although this capital investment has resulted in a marked reduction in the input of bacterial loads, relatively high counts of faecal indicator organisms are still being encountered in the coastal receiving waters, and the local bathing waters continue to fail on occasions to comply with the European Community (EC) Bathing Water Directive (1976) mandatory standards. Details are given herein of a comprehensive modelling study aimed at quantifying the impact of various bacterial inputs into the estuary and surrounding coastal waters on the bathing water quality. The model domain includes the coastal area and the entire estuary (namely the Ribble) up to the tidal limits of its tributaries. Faecal coliforms have been used as the main water quality indicator organisms. The numerical model developed for this study combines a depth integrated two-dimensional coastal model and a cross-sectionally integrated one-dimensional river model, and is capable of predicting water surface elevations, velocity fields and faecal coliform concentration distributions across the entire model domain. The hydrodynamic model was calibrated using water level and velocity measurements from three surveys and then validated against measured data from three other surveys. In order to predict the faecal coliform concentration distributions, variable faecal coliform decay rates were used, i.e. different values of decay rates were applied to the coastal and riverine waters, for day- and nighttime, and for wet and dry weather conditions. The maximum and minimum decay rates used were 2.32/day and 0.71/day for the dry and wet weather surveys, respectively. The model was then applied to (i) assess the impact of previous discharge strategies and investigate the effectiveness of future capital investment works and (ii) predict the impact of a range of strategic options, including: the effects of adding UV treatment, constructing storm water storage tanks and incorporating various combined sewer overflow (CSO) discharge scenarios for different weather conditions.

Data Collection↗