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Biomedical subjects

Z Lin

Publications and source records attributed to Z Lin.

At least 19 recordsLinked to original sources
PubMed2006

Potent antitumor efficacy of XAF1 delivered by conditionally replicative adenovirus vector via caspase-independent apoptosis.

XAF1 is a newly identified tumor-suppressor gene that can antagonize XIAP and sensitize cells to other cell death triggers. In this study, we utilized ZD55, a conditionally replicative adenovirus (CRAd) similar to ONYX-015 as the vector to transfer XAF1 into the tumor cells to evaluate its antitumor efficacy in vitro and in vivo. Potent and specific cytopathic effect (CPE) was observed upon infection with ZD55-XAF1 in tumor cell lines. Importantly, ZD55-XAF1 exhibited a superior suppression of tumor growth in an animal model of colorectal carcinoma in nude mice compared with Ad-XAF1 (E1-deleted replication-defective viral) and ONYX-015. Complete eradication of the established tumors was observed in four of eight mice. Our data also showed that infection with ZD55-XAF1 resulted in caspase-independent apoptosis. Although caspase-3, poly(ADP-ribose) polymerase were mildly activated in response to ZD55-XAF1 infection, pretreatment with pan-caspase inhibitor hardly influence its apoptosis-inducing activity. In summary, our study strongly suggested that ZD55-XAF1 could serve as an effective gene-virotherapy strategy and has highly potential against human cancers.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Zinc and cadmium accumulation and tolerance in populations of Sedum alfredii.

To investigate the variation of Zn and Cd accumulation and tolerance of Sedum alfredii (a newly reported Zn/Cd hyperaccumulator), field surveys and hydroponic experiments were conducted among three populations of this species: two originating from old Pb/Zn mines in Zhejiang (ZJ) and Hunan (HN) Provinces and one from a "clean" site in Guangdong (GD) Province, China. Under field conditions, up to 12,524 and 12,253 mg kg(-1) Zn, and 1400 and 97 mg kg(-1) Cd in shoots of ZJ and HN plants were recorded respectively. Under hydroponic conditions, ZJ and HN plants accumulated significantly higher Zn and Cd in their leaves and stems, and possessed significantly higher Zn and Cd tolerance than GD plants. Among the two contaminated populations, ZJ plants showed higher Cd tolerance and accumulation (in leaves) than HN plants. The present results indicate that significant differences in Zn and Cd accumulation and tolerance exist in populations of S. alfredii.

Biomass↗
PubMed2006

Characterization and expression of a cDNA encoding a tubuliform silk protein of the golden web spider Nephila antipodiana.

Spider silks are renowned for their excellent mechanical properties. Although several spider fibroin genes, mainly from dragline and capture silks, have been identified, there are still many members in the spider fibroin gene family remain uncharacterized. In this study, a novel silk cDNA clone from the golden web spider Nephila antipodiana was isolated. It is serine rich and contains two almost identical fragments with one varied gap region and one conserved spider fibroin-like C-terminal domain. Both in situ hybridization and immunoblot analyses have shown that it is specifically expressed in the tubuliform gland. Thus, it likely encodes the silk fibroin from the tubuliform gland, which supplies the main component of the inner egg case. Unlike other silk proteins, the protein encoded by the novel cDNA in water solution exhibits the characteristic of an alpha-helical protein, which implies the distinct property of the egg case silk, though the fiber of tubuliform silk is mainly composed of beta-sheet structure. Its sequence information facilitates elucidation of the evolutionary history of the araneoid fibroin genes.

Amino Acid Sequence↗
PubMed2006

Detection of Hong Kong 97-like H5N1 influenza viruses from eggs of Vietnamese waterfowl.

Three H5N1 influenza viruses were isolated from shell washes of duck and goose eggs confiscated from travelers coming from Vietnam. All eight gene segments of these viruses share high sequence identity with the H5N1 avian influenza viruses that caused outbreaks in poultry and humans in Hong Kong in 1997. Animal studies indicate that these isolated viruses are able to replicate in mouse lung and could be found in the organs of ducks without causing any clinical signs or death. However, the viruses are highly pathogenic for chickens. Although the source of these recently isolated Hong Kong 97-like H5N1 viruses is undetermined, their detection in the egg shell of duck and goose suggests that this particular genotype of H5N1 virus may have re-emerged in nature or may have been circulating continuously.

Animals↗
PubMed2006

Human genetics and pharmacology of neurotransmitter transporters.

Biogenic amine neurotransmitters are released from nerve terminals and activate pre- and postsynaptic receptors. Released neurotransmitters are sequestered by transporters into presynaptic neurons, a major mode of their inactivation in the brain. Genetic studies of human biogenic amine transporter genes, including the dopamine transporter (hDAT; SLC6A3), the serotonin transporter (hSERT; SLC6A4), and the norepinephrine transporter (hNET; SLC6A2) have provided insight into how genomic variations in these transporter genes influence pharmacology and brain physiology. Genetic variants can influence transporter function by various mechanisms, including substrate affinities, transport velocity, transporter expression levels (density), extracellular membrane expression, trafficking and turnover, and neurotransmitter release. It is increasingly apparent that genetic variants of monoamine transporters also contribute to individual differences in behavior and neuropsychiatric disorders. This chapter summarizes current knowledge of transporters with a focus on genomic variations, expression variations, pharmacology of protein variants, and known association with human diseases.

Amino Acid Sequence↗
PubMed2006

Conversion of operating theatre from positive to negative pressure environment.

The severe acute respiratory syndrome (SARS) crisis led to the construction of a negative pressure operating theatre at a hospital in Hong Kong. It is currently used for treatment of suspected or confirmed airborne infection cases, and was built in anticipation of a return of SARS, an outbreak of avian influenza or other respiratory epidemics. This article describes the physical conversion of a standard positive pressure operating theatre into a negative pressure environment, problems encountered, airflow design, and evaluation of performance. Since entering regular service, routine measurements and observations have indicated that the airflow performance has been satisfactory. This has also been confirmed by regular air sampling checks. Computational fluid dynamics, a computer modelling technique, was used to compare the distribution of room air before and after the design changes from positive to negative pressure. The simulation results show that the physical environment and the dispersion pattern of bacteria in the negative pressure theatre were as good as, if not better than, those in the original positive pressure design.

Aerosols↗
PubMed2006

Symptom responses, long-term outcomes and adverse events beyond 3 years of high-frequency gastric electrical stimulation for gastroparesis.

The aims were to determine symptom responses and long-term outcomes in gastroparetic patients receiving gastric electrical stimulation (GES) therapy beyond 3 years by presenting per protocol analysis and intention-to-treat (ITT) analysis. Data collected at baseline, 1 year and beyond 3 years in 55 patients included total symptom scores (TSS), nutritional status, weight, hospitalizations, the use of prokinetic and/or antiemetic medications, HbA1c in diabetics and adverse events. Of the 55 patients, 10 died of non-pacemaker-related complications, six had the devices removed and two could not be reached. The remaining 37 patients had the device activated for a mean of 45 months. Both per protocol and ITT analysis demonstrated that TSS, hospitalization days and the use of medications were all significantly reduced at 1 year and were sustained beyond 3 years. Average TSS decreased by 62.5% for the 37 patients completing 3 years of GES. At implantation, 15/37 patients required nutritional support and only five continued beyond 3 years. Mean HbA1c level in diabetics was significantly reduced from 9.5 to 7.9% at 3 years. We conclude that a significant improvement in symptoms and all measures of clinical outcome can be maintained for greater than 3 years with GES in patients with refractory gastroparesis.

Adult↗
PubMed2006

Transvaginal, ultrasound-guided, ovarian, interstitial laser treatment in anovulatory women with clomifene-citrate-resistant polycystic ovary syndrome.

OBJECTIVE: To assess the effectiveness of transvaginal, ultrasound-guided, ovarian, interstitial laser coagulation treatment in anovulatory women with polycystic ovary syndrome (PCOS). DESIGN: A pilot study. SETTING: Assisted reproductive technology unit. SAMPLE: Twenty-three anovulatory women with clomifene-citrate-resistant PCOS. METHODS: Ultrasound-guided, transvaginal, ovarian, interstitial yttrium-aluminium-garnet laser treatment. MAIN OUTCOME MEASURES: Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, prolactin and estradiol levels, spontaneous ovulation rate and pregnancy rate were measured over 6 months of follow up. RESULTS: Regular ovulation occurred in 19 out of 22 (86.4%) women in the 6 months following ovarian treatment (one woman was lost to follow up). On the postoperative second, fourth and sixth month, the mean serum LH levels were 4.54 SD 1.21 iu/l, 4.90 SD 2.18 iu/l and 4.42 SD 1.03 iu/l, significantly (P < 0.001, P < 0.001, P < 0.001) lower than the preoperative level of 13.89 +/- 3.62 iu/l; the mean serum testosterone levels were 2.69 SD 1.83 nmol/l, 2.42 SD 1.11 nmol/l and 2.28 SD 1.96 nmol/l and significantly (P < 0.001, P < 0.001, P < 0.001) lower than the preoperative baseline value of 5.37 SD 3.09 nmol/l; the mean LH/FSH ratios of 0.93 SD 0.26, 0.88 SD 0.17 and 0.81 SD 0.14 were also significantly lower than the preoperative value of 2.78 SD 1.21 (P < 0.001). Pregnancy occurred in eight women and there was a cumulative pregnancy rate at 6 months of 36% (8/22) among the subjects. There were no significant operative complications. CONCLUSION: Ultrasound-guided, transvaginal, ovarian, interstitial laser treatment appears effective in improving hormonal profiles and inducing ovulation and successful pregnancy in women with clomifene-resistant PCOS.

Anovulation↗
PubMed2006

Molecular cloning and regulation of porcine SULT2A1: relationship between SULT2A1 expression and sulfoconjugation of androstenone.

Hydroxysteroid sulfotransferase (SULT2A1) is a key enzyme in the testicular and hepatic metabolism of 5alpha-androstenone, which is a major component of the off-odor and off-flavor in pork known as boar taint. The goals of this study were to determine the role of testicular and hepatic SULT2A1 activity on plasma 5alpha-androstenone sulfate levels, the accumulation of 5alpha-androstenone in adipose tissue, and to gain insight into the regulatory control of SULT2A1. Testicular SULT2A1 activity was negatively correlated (r = -0.57; P < 0.01) with 5alpha-androstenone concentrations in fat. The differences observed in SULT2A1 activity warranted investigation into potential genetic variation within porcine SULT2A1. The cDNA sequence of porcine Sult2A1 was determined to be > 82% homologous to the human, mouse, and rat Sult2A1 genes. A single nucleotide polymorphism was detected within the coding region of the Sult2A1 from individual testes and liver samples; however, this did not affect the amino acid sequence of the enzyme. Western blot analysis determined that animals with high concentrations of 5alpha-androstenone in fat and low SULT2A1 activity had corresponding low levels of SULT2A1 protein compared with animals with low levels of 5alpha-androstenone in fat. Real-time PCR analysis indicated that Sult2A1 mRNA was increased 2.8-fold in animals with high levels of the protein relative to animals with low levels of the protein. Furthermore, we demonstrated the positive role of the nuclear receptors constitutive androstane receptor and pregnane X receptor, as well as the possible role of farnesoid X receptor in the regulation of testicular SULT2A1 activity. Together, the results of this study suggest that differences in SULT2A1 expression can influence 5alpha-androstenone accumulation in fat.

Adipose Tissue↗
PubMed2006

Towards a synthesis of data-based and theory-based models of environmental systems.

A two-pronged approach to interpreting field data through the use of models is presented. This approach builds upon both data- and theory-based models and their associated methods of system identification. It seeks to overcome their respective limitations: that theory-based models are not unambiguously identifiable from the observations, while a well identified data-based model may not be capable of a satisfactory theoretical interpretation. The purpose of the approach is thereby to gain a deeper understanding of complex environmental systems. Recursive methods of time-series analysis are used to identify the data-based models and the modified recursive prediction error algorithm is employed for parameter estimation of the theory-based models. The results of these identification exercises for the two classes of models can be compared in terms of the macro-parameters of the studied system's time constant and steady-state gain. Two case studies are presented to illustrate the overall performance of the two-pronged approach. It is found that: (1) more is to be gained through the joint application of the two classes of models than the exclusive use of either; (2) to some extent, identifying the structure and estimating the parameters of one type of model can be improved by recourse to the corresponding results for the other; and (3) reconciliation of the results from identifying the two classes of model in the parameter space has significant advantages over the more familiar process of evaluating a model's performance in the terms of its (observed) state space features.

Aquaculture↗
PubMed2005

The ratios of individual chemicals in a mixture determine the degree of joint effect: the climax hypothesis.

A new hypothesis, the Climax Hypothesis, is proposed to describe how the ratios of individual chemicals influence the joint effects of chemical mixtures. This hypothesis is derived from a generalized approach using "isobolograms". With this hypothesis, one can predict that for a given mixture, a curvilinear correlation exists between the joint effects and the ratios of individual chemicals and that this curve has a climax at the equitoxic ratio. This prediction is supported by the observed toxicity to Vibrio fischeri of 18 mixtures (12 binary mixtures, 4 ternary mixtures, and 2 quaternary mixtures). With this prediction, the Climax Hypothesis has some promising applications such as controlling the discharge of effluents in environmental science, maximizing detoxifying effects in medicine, and optimizing combined pesticides in agriculture.

Data Interpretation, Statistical↗
PubMed2005

Mining the structural knowledge of high-dimensional medical data using isomap.

The paper describes an application of a new, non-linear dimensionality reduction method, named Isomap, for mining the structural knowledge from high-dimensional medical data. The algorithm was evaluated on two publicly available medical datasets: the pathological dataset of breast cancer (241 malignant samples) and the gene expression dataset from the lung (186 tumours). It was found by Isomap that the approximate intrinsic dimensionalities of these two datasets were as low as three. The spatial structures of both datasets were presented in low-dimensional space. Isomap, as a general tool for dimensionality reduction analysis, is helpful in revealing the nonlinear structural knowledge of high-dimensional medical data.

Algorithms↗
PubMed2004

Development of a fragment constant method for estimating the mixture toxicity.

Based on Group Contribution Theory, a fragment constant model to estimate mixture toxicity is proposed in this paper. The toxicity (EC50M) of 58 mixtures is determined using Photobacterium phosphoreum. Analysis of these EC50M and the mole fraction of the individual chemical fragments (Br, Cl, NO2, OH, NH2) helps work out the fragment toxicity contribution (deltaTi) to EC50M. Thus, a linear regression equation is established between the toxicity contribution deltaTi and the fragment constants of Hansch f(i), and this equation is so significant that it helps provide an approach for calculating EC50M.

Drug Interactions↗
PubMed2004

Chemical-chemical interaction between cyanogenic toxicants and aldehydes: a mechanism-based QSAR approach to assess toxicological joint effects.

A QSAR approach was proposed to assess toxicological joint effects based on the mechanism of chemical-chemical interactions between cyanogenic toxicants and aldehydes. It has been observed that the chemical-chemical interaction between cyanogenic toxicants and aldehydes resulted in the formation of carbanion intermediates, and therefore this interaction led to different toxicological joint effects between cyanogenic toxicants and aldehydes. Analysis of this chemical-chemical interaction showed that the formation of carbanion intermediate highly depended on the charge of the carbon atom in the -CHO of aldehydes and this of the carbon atom (C*) in the carbochain of cyanogenic toxicant. By using the Hammett Constant (sigma(p)) to measure the charge of carbon atom in the -CHO of aldehydes, a mechanism-based QSAR approach (M = 0.316 - 4.386sigma(p) with r2 = 0.933, SE = 0.082, F = 55.389, p = 0.002, M = sum of toxic units) was proposed to assess the toxicological joint effects between alpha-hydroxy-isobutyronitrile and individual aliphatic aldehydes. Another one (M = 0.978 - 0.720sigma(p) with r2 = 0.852, SE = 0.152, F = 40.148, p = 0.0001) was also proposed to assess the toxicological joint effects between alpha-hydroxy-isobutyronitrile and individual aromatic aldehydes. Lastly, by using the charge of carbon atom (C*) in the carbochain of cyanogenic toxicant, a mechanism-based QSAR model (M = -0.161 - 7.721C* with r2 = 0.847, SE = 0.227, F = 27.657, p = 0.003) was derived to assess toxicological joint effects between p-nitrobenzaldehyde and cyanogenic toxicants.

Aldehydes↗
PubMed2004

Molecular cloning, expression and functional characterization of the cytochrome P450 2A6 gene in pig liver.

Raising intact male pigs would have a significant economic impact on the pork industry because intact males have improved feed efficiency and a greater lean yield of the carcass compared with barrows. However, the presence of skatole, a major cause of boar taint, in meat from intact male pigs could be highly objectionable to consumers. It has been shown that CYP2A6 is a key enzyme in the hepatic metabolism of skatole and that the activity of CYP2A6 is negatively correlated with skatole accumulation in fat. The aim of this study was to isolate and characterize CYP2A6 from pig liver, as well as identify genetic polymorphisms in the CYP2A6 gene, and examine the association between these polymorphisms and skatole level. We identified a single base deletion in CYP2A6, resulting in a frame shift in the coding region that produces a non-functional enzyme, which was associated with high levels of skatole in fat tissue.

Adipose Tissue↗
PubMed2004

Effect of high-frequency gastric electrical stimulation on gastric myoelectric activity in gastroparetic patients.

The aim of this study was to investigate the effect of gastric electrical stimulation (GES) on gastric myoelectric activity (GMA) and to identify possible mechanisms that could help explain how high-frequency GES is effective in treating nausea and vomiting associated with gastroparesis. Fifteen gastroparetic patients who received high-frequency GES were enrolled. Two pairs of temporary pacing wires were implanted on the serosa of the stomach along the greater curvature during surgery for placement of the permanent stimulation device. Two-channel serosal recordings of GMA before and during GES were measured. A gastric emptying test and severity of nausea and vomiting were assessed at baseline and at 3 months of GES. Power spectral and cross correlation analyses revealed that impaired propagation of slow waves (50%), tachygastria (30%) and abnormal myoelectric responses to a meal (50%) were the main abnormalities observed at baseline. GES with a high frequency significantly enhanced the slow wave amplitude and propagation velocity, and resulted in a significant improvement in nausea and vomiting but did not entrain the gastric slow wave or improve gastric emptying after 3 months of GES.

Adult↗
PubMed2004

Fault detection in a real-time monitoring network for water quality in the lagoon of Venice (Italy).

In the context of monitoring water quality in natural ecosystems in real time, on-line data quality control is a very important issue for effective system surveillance and for optimizing maintenance of the monitoring network. This paper presents some applications of recursive state-parameter estimation algorithms to real-time detection of signal drift in high-frequency observations. Two continuous-discrete recursive estimation schemes, namely the Extended Kalman Filter and the Recursive Prediction Error algorithm, were applied to assuring the quality of the dissolved oxygen (DO) time series, as obtained from the Lagoon of Venice (Italy) during August 2002, through the real-time monitoring network of the Magistrato alle Acque (the Venice Water Authority). Results demonstrate the effectiveness of the methodology in early detection of a probable drift in the DO signal. Comparison of these results with those obtained from the application of a related recursive scheme (a Dynamic Linear Regression procedure) suggests the strong benefits of approaching the problem of on-line data quality control with several (not merely a single) independent such estimation methods.

Algorithms↗