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Biomedical subjects

Y Yuan

Publications and source records attributed to Y Yuan.

At least 19 recordsLinked to original sources
PubMed2006

Identification of the critical role of Tyr-194 in the catalytic activity of a novel N-acyl-homoserine lactonase from marine Bacillus cereus strain Y2.

Enzymatic disruption of quorum-sensing (QS) pathways in pathogenic organisms is a promising anti-infection therapeutic strategy. AHL-lactonase, a potent tool for biocontrol, can hydrolyze QS signal molecule N-acyl-homoserine lactones (AHLs) into inactive products, thereby blocking the QS systems. A marine bacterial isolate Y2, identified as a Bacillus cereus subsp., was found capable of inactivating AHLs. The aiiA gene encoding the AHL-degrading enzyme from bacterial strain Y2 was cloned and expressed in Escherichia coli. The 28-kDa recombinant Y2-AiiA protein was purified and showed strong AHL-degrading activity. Sequence comparisons of Y2-aiiA with known AHL-lactonases revealed high identities in the deduced amino-acid sequences. Functional determination of a potential catalytic residue Tyr-194 of AHL-lactonases was performed by site-directed mutagenesis. As judged by AHL-degrading bioassay, substitution of Tyr-194 with Ala resulted in a dramatic decrease of activity compared with wild-type (WT) recombinant Y2-AiiA, although the expression level of the mutated Y2-AiiA protein was equivalent to that of WT Y2-AiiA. These results suggested that the conserved residue Tyr-194 is critical for catalytic function of the novel AHL-lactonase.

Amino Acid Sequence↗
PubMed2006

Pregnancy outcomes, infant mortality, and arsenic in drinking water in West Bengal, India.

Between 2001 and 2003, the authors studied pregnancy outcomes and infant mortality among 202 married women in West Bengal, India. Reproductive histories were ascertained using structured interviews. Arsenic exposure during each pregnancy, including all water sources used, was assessed; this involved measurements from 409 wells. Odds ratios for spontaneous abortion, stillbirth, neonatal mortality, and infant mortality were estimated with logistic regression based on the method of generalized estimating equations. Exposure to high concentrations of arsenic (> or =200 microg/liter) during pregnancy was associated with a sixfold increased risk of stillbirth after adjustment for potential confounders (odds ratio (OR) = 6.07, 95% confidence interval (CI): 1.54, 24.0; p = 0.01). Arsenic-related skin lesions were found in 12 women who had a substantially increased risk of stillbirth (OR = 13.1, 95% CI: 3.17, 54.0; p = 0.002). The odds ratio for neonatal death was 2.81 (95% CI: 0.73, 10.8). No association was found between arsenic exposure and spontaneous abortion (OR = 1.01, 95% CI: 0.38, 2.70) or overall infant mortality (OR = 1.33, 95% CI: 0.43, 4.04). This study adds to the limited evidence that exposure to high concentrations of arsenic during pregnancy increases the risk of stillbirth. However, there was no indication of the increased rates of spontaneous abortion and overall infant mortality that have been reported in some studies.

Arsenic Poisoning↗
PubMed2006

Characterization of chitosan films and effects on fibroblast cell attachment and proliferation.

Chitosan has been researched for implant and wound healing applications. However, there are inconsistencies in reports on the tissue and fibroblast responses to chitosan materials. These inconsistencies may be due to variations in chitosan material characteristics. The aim of this study was to correlate fibroblast responses with known chitosan material characteristics. To achieve this aim, chitosan was characterized for degree of deacetylation (DDA), molecular weight (MW), residual protein and ash contents, and then solution cast into films and characterized for hydrophilicity by water contact angle. The films were seeded with normal human dermal fibroblasts and the number of attached cells was evaluated for after 30 min. Cell proliferation was evaluated over 5 days. This study found no relationship between DDA, contact angle, cell attachment, and or proliferation. General trends were observed for increasing proliferation with increasing residual ash content and decreasing residual protein. These data indicate that chitosan characteristics other than DDA may be important to their biological performance.

Acetylation↗
PubMed2006

Determinants of discontinuation of initial highly active antiretroviral therapy regimens in a US HIV-infected patient cohort.

OBJECTIVES: Optimization of initial highly active antiretroviral therapy (HAART) for complete viral suppression and better tolerability is paramount for the prognosis of HIV-infected patients. Observational studies provide a better means than clinical trials of studying the determinants of discontinuation in actual practice. METHODS: A longitudinal cohort of US HIV-positive patients who initiated HAART for the first time from 1996 to 2003 were included in the analysis. Stratified Cox proportional hazards models, considering time-updated viral load and CD4 count data, were developed for analyzing time to first discontinuation. RESULTS: A total of 3414 antiretroviral-naive HAART patients were identified. In a median follow-up period of 211 days (mean 324 days), 628 patients (18.4%) reportedly discontinued the HAART regimen because of drug toxicity, 456 (13.4%) because of non-compliance, and 257 (7.5%) because of treatment failure. In addition to the recorded reasons for discontinuation, black ethnicity [relative risk (RR) 1.28, 95% confidence interval (CI) 1.13-1.45], current smoking (RR 1.33, CI 1.18-1.50), high pill burden (RR 1.44, CI 1.22-1.70), and recent viral control (RR 0.63, CI 0.56-0.70) were all predictive of discontinuation. Only high pill burden (>15 pills/day), which is considered to be a surrogate for treatment regimen complexity, and the most recent poor viral control (HIV RNA) were found to be consistently associated with a higher likelihood of discontinuation. CONCLUSIONS: Risk factors other than physician- or patient-reported reasons play a role in discontinuation of initial HAART regimens. Identification of these risk factors and simplification of treatment regimens in those at high risk for discontinuation appear to be necessary in order to maximize the effectiveness of HAART regimens.

Adult↗
PubMed2005

Identification of human liver cytochrome P450 enzymes involved in the metabolism of SCH 351125, a CCR5 antagonist.

The identification and relative contribution of human cytochrome P450 enzyme(s) involved in the metabolism of SCH 351125 were investigated. In human liver microsomes, O-deethylation was the major metabolic pathway, whereas aromatization of a piperidine ring to pyridine and the reduction of the N-oxide moiety were minor routes. Recombinant human CYP3A4 and CYP2C9 both exhibited catalytic activity with respect to the formation of rotameric O-deethylated metabolites (M12, M13), the metabolites resulting from aromatization (M22/M24) and N-oxide reduction (M31). Using the relative activity factor (RAF) approach, the relative contributions of CYP3A4 and CYP2C9 to M13 formation were estimated to be 76 and 24%, respectively. There was a high correlation (r>0.96) between the rate of formation of M12 and M13 and 6 beta-hydroxylation of testosterone catalysed by CYP3A4/5. Ketoconazole (2microM) and CYP3A4/5-specific inhibitory monoclonal antibody inhibited the formation of M12 and M13 from human liver microsomes by approximately 60 and 71%, respectively. The results demonstrate that the in vitro metabolism of SCH 351125 is mediated primarily via CYP3A4 and that CYP2C9 plays a minor role. Clinical study designs should encompass these enzymology data to address any potential drug interactions.

Biotransformation↗
PubMed2005

Protease inhibitor exposure and increased risk of cardiovascular disease in HIV-infected patients.

OBJECTIVES: To study the relationship between exposure to protease inhibitor (PI) therapy and increased risk of cardiovascular events in HIV-infected patients. METHODS: We estimated the risk of cardiovascular disease (CVD) events with PI exposure in a cohort of HIV-infected patients using a time-dependent Cox proportional hazards model adjusting for the major CVD risk factors. Only the first CVD event for each subject was counted. RESULTS: Of a total of 7542 patients, 77% were exposed to PIs. CVD event rates were 9.8/1000 and 6.5/1000 person-years of follow-up (PYFU) in the PI-exposed and nonexposed groups, respectively (P=0.0008). PI exposure >/=60 days was associated with an increased risk of CVD event [adjusted hazards ratio (HR(adj)) 1.71; 95% confidence interval (CI) 1.08-2.74; P=0.03]. Results from a subgroup of patients aged between 35 and 65 years were similar (HR(adj) 1.90; 95% CI 1.13-3.20; P=0.02). Other significant risk factors included smoking status, age, hypertension, diabetes mellitus and pre-existing CVD. CONCLUSIONS: Patients exposed to PI therapy had an increased risk of CVD events. Clinicians should evaluate the risk of CVD when making treatment decisions for HIV-infected patients.

Adolescent↗
PubMed2005

Opposing effects of oestradiol and progesterone on intracellular pathways and activation processes in the oxidative stress induced activation of cultured rat hepatic stellate cells.

BACKGROUND: Oxidative stress, including the generation of reactive oxygen species (ROS), is involved in hepatofibrogenesis. The authors' previous studies have shown that oestradiol suppresses hepatic fibrosis in animal models and attenuates the activation of cultured rat hepatic stellate cells (HSCs), which possess oestrogen receptor subtype beta and are also activated by ROS. AIMS: To define the mechanisms by which female sex hormones play an antifibrogenic role in activated HSCs, the effects of oestradiol and progesterone on ROS generation processes and intracellular pathways, leading to the activation of HSCs undergoing oxidative stress, was examined. METHODS: HSCs, isolated from rats, were cultured for 7 days with oestradiol or progesterone for 24 hours as pretreatment, and oxidative stress was then induced by exposure to low doses of hydrogen peroxide for another 24 hours. RESULTS: Oestradiol inhibited ROS generation and antioxidant enzyme loss via the suppression of NADH/NADPH oxidase activity, and attenuated hydrogen peroxide induced transforming growth factor-beta1 (TGF-beta1) expression, HSC proliferation and transformation, and the activation of mitogen activated protein kinase (MAPK) pathways and transcription factors. Progesterone exerted a stimulatory effect through the progesterone receptor on the induction of ROS generation processes and intracellular pathways, resulting in TGF-beta1 expression and HSC activation, and fibrogenic effects were inhibited by oestradiol. CONCLUSION: These findings show for the first time that oestradiol inhibits the activation of transcription factors by suppressing ROS generation processes and the MAPK pathways, and inactivates the downstream transcription processes involved in TGF-beta1 expression and HSC activation, whereas progesterone acts in opposition to the favourable effects of oestradiol and its effects are blocked by oestradiol.

Animals↗
PubMed2005

Effect of accommodating sucking and nosing on the behaviour of artificially reared piglets.

Neonatal piglets are often used in biomedical research applications that require artificial rearing. Social housing can be problematic because the piglets develop belly nosing, navel and ear sucking that can result in injury. Our objective was to determine the effectiveness of using feeding devices that provide various opportunities for sucking and nosing behaviour on reducing piglet-directed behaviour of group-housed laboratory piglets. Fifteen piglets were used in each of four trials. The piglets nursed their dam for approximately 72 h to obtain passive immunity before transfer to a laboratory facility where they were allotted, five per group, to one of three stainless steel isolator units. Each unit featured a different style of feeding system for the delivery of milk replacer: a plastic trough (T), a nipple (N) mounted on a smooth plexiglass wall, or a nipple mounted on a pliant bag of sterile water (artificial udder [AU]). Each system had five feeding spaces so that all piglets fed simultaneously. Milk was provided at 6-h intervals, and behaviour was recorded on alternate days for 12 days post-weaning. Although trough-fed piglets began to eat much sooner than those piglets fed from nipples, time spent nosing, chewing or sucking on pen-mates and belly nosing were markedly higher in T piglets than in either N or AU, overall (mean: P<0.05) and over time (quadratic: P<0.05). Over time, N piglets developed a stereotypic snout rubbing on the wall behind the nipples, while AU piglets massaged and often fell asleep in contact with the udder from day 2 of the trial. Resting patterns were also affected. N and AU piglets settled down to rest more quickly (P<0.01) and spent significantly more time resting in the hour following feeding than T piglets (P<0.05). A feeding device that accommodates both sucking and massage can significantly reduce piglet-directed behaviour and may facilitate social housing of artificially reared piglets.

Animal Husbandry↗
PubMed2004

A longitudinal study on the ammonia threshold in junior cyclists.

OBJECTIVES: To identify the effect of a one year non-specific training programme on the ammonia threshold of a group of junior cyclists and to correlate ammonia threshold with other common physiological variables. METHODS: The cyclists performed tests at three time points (T1, T2, T3) during the year. Follow up tests were conducted every six months after the original test. Ammonia threshold was obtained from a graded exercise with four minute steps. RESULTS: The relatively non-specific one year training programme was effective in inducing an increase in peak VO(2) (60.6 (5.9), 65.9 (7.4), and 64.6 (6.5) ml/min/kg at T1, T2, and T3 respectively) and endurance time (18.3 (4.5), 20.1 (5.2), and 27.0 (6.1) minutes at T1, T2, and T3 respectively), but was not effective for the sprint related variables. Ammonia threshold, together with lactate threshold and ventilatory threshold, was not significantly different at the three test times. Only endurance time correlated significantly with ammonia threshold (r = 0.915, p = 0.001). CONCLUSIONS: The findings suggest that a relatively non-specific one year training programme does not modify the ammonia threshold of junior cyclists. The significant correlation between ammonia threshold and endurance time further confirms that ammonia threshold is a measure of the ability to sustain exercise at submaximal intensities.

Adolescent↗
PubMed2004

Changes in the multi-joint kinematics and co-ordination after repetitive windsurfing pumping task.

AIM: This study investigated the change in kinematics after repetitive continuous maximal windsurfing pumping on a simulator by utilizing 3-D motion analysis. METHODS: Six competitive windsurfers exercised on a tailor-made simulator. The wind force was simulated by attaching the boom to the power head of a rowing ergometer. The exercise consisted of 3 sets of 3-minute maximum pumping. The motion of wrist, elbow, shoulder (on sagittal and frontal planes), waist, hip, knee and ankle joints were recorded by 2 video cameras. Kinematic analysis included the assessment of the change of the range of motion, movement speed (pulling phase and the whole pumping cycle), as well as the movement pattern of all tested joints. RESULTS: Modified motor strategy was documented by the significant drop of vertical excursion of the body centre of mass. Moreover, the ankle plantar flexors and dorsiflexors, mid-deltoid as well as wrist extensor and flexor, had significant change of movement according to the assessed parameters. Therefore, they may be the muscles that were more influenced than the other assessed muscles after continuous maximal pumping. The change of muscle co-ordination may be a compensation mechanism to maintain work output. CONCLUSIONS: Findings in this study may suggest the importance of implementing specific muscle training program for the competitive windsurfers to increase the pumping capacity.

Adult↗
PubMed2003

Enrichment of gene-coding sequences in maize by genome filtration.

Approximately 80% of the maize genome comprises highly repetitive sequences interspersed with single-copy, gene-rich sequences, and standard genome sequencing strategies are not readily adaptable to this type of genome. Methodologies that enrich for genic sequences might more rapidly generate useful results from complex genomes. Equivalent numbers of clones from maize selected by techniques called methylation filtering and High C0t selection were sequenced to generate approximately 200,000 reads (approximately 132 megabases), which were assembled into contigs. Combination of the two techniques resulted in a sixfold reduction in the effective genome size and a fourfold increase in the gene identification rate in comparison to a nonenriched library.

Chromosomes, Plant↗
PubMed2003

A Controllable and Observable Protein Cystallization Facility.

A Controllable and Observable Protein Crystallization Facility (ACOP) was developed in 1999 for space experiment in the Get Away Special canister of Space Shuttle. To regulate the vapor diffusion rate, in a crystallization chamber, five cells each containing precipitant solution of different concentrations, exposed to one protein cell in turn. Five layers of chambers were overlapped coaxially. The crystallization process was observed and recorded by digital cameras. Structure of facility and result of image sequence were given.

Crystallization↗
PubMed2003

Localization of breast sentinel lymph nodes by MR lymphography with a conventional gadolinium contrast agent. Preliminary observations in dogs and humans.

PURPOSE: To test the capability of an indirect MR lymphography (MRLG) using a conventional extracellular gadolinium (Gd)-based contrast agent for localizing breast sentinel lymph node (SLN). METHODS: A total of 1 and 0.5 ml of undiluted gadopentetate dimeglumine were injected subcutaneously into the two periareolar areas overlying each caudal mammary gland in 10 female dogs. Contiguous 2-mm-thick fast gradient echo MR images were acquired through the upper breast and axilla before and for 60 min after gentle massage at the injection sites, yielding 3D displays. The localized SLN was resected from the living animals, followed by post mortem examinations. MRLG (1 ml contrast agent injected) was also attempted in 5 female volunteers. RESULTS: Even with 0.5-ml contrast agent, the MRLG clearly visualized the connection of SLN and lymphatic vessels directly draining from the injection sites, and the remaining distant nodes, with the maximal enhancement peaks within 10 min after massage. The 3D images provided comprehensive anatomy of these lymphatic pathways in each axilla. Of the 20 SLN and 128 distant nodes visualized on the MRLG, all the SLN (100%) and 107 (83.5%) distant nodes could be resected pre- and post mortem, in good correlation with the locations and sizes on the MR images. MRLG also effectively localized SLN in the volunteers, without significant adverse effects. CONCLUSION: An indirect MRLG using small volumes of conventional Gd-based contrast agent may have potential for accurate identification and surgical biopsy of breast SLN.

Animals↗
PubMed2002

Responding to hypoxia: lessons from a model cell line.

Mammalian cells require a constant supply of oxygen to maintain adequate energy production, which is essential for maintaining normal function and for ensuring cell survival. Sustained hypoxia can result in cell death. It is, therefore, not surprising that sophisticated mechanisms have evolved that allow cells to adapt to hypoxia. "Oxygen-sensing" is a special phenotype that functions to detect changes in oxygen tension and to transduce this signal into organ system functions that enhance the delivery of oxygen to tissue in various organisms. Oxygen-sensing cells can be segregated into two distinct cell types: those that functionally depolarize (excitable) and those that do not functionally depolarize (nonexcitable) in response to reduced oxygen. Theoretically, excitable cells have all the same signaling capabilities as the nonexcitable cells, but the nonexcitable cells cannot have all the signaling capabilities as excitable cells. A number of signaling pathways have been identified that regulate gene expression during hypoxia. These include the Ca2+-calmodulin pathway, the 3'-5' adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway, the p42 and p44 mitogen-activated protein kinase [(MAPK); also known as the extracellular signal-related kinase (ERK) for ERK1 and ERK2] pathway, the stress-activated protein kinase (SAPK; also known as p38 kinase) pathway, and the phosphatidylinositol 3-kinase (PI3K)-Akt pathway. In this review, we describe hypoxia-induced signaling in the model O2-sensing rat pheochromocytoma (PC12) cell line, the current level of understanding of the major signaling events that are activated by reduced O2, and how these signaling events lead to altered gene expression in both excitable and nonexcitable oxygen-sensing cells.

Animals↗
PubMed2002

Ammonia threshold--comparison to lactate threshold, correlation to other physiological parameters and response to training.

During standard graded exercise, blood lactate and blood ammonia levels increase in parallel and the two thresholds appear at the same relative intensity. The first part of this study aimed at comparing ammonia threshold to lactate threshold with five different graded exercise protocols. A significant difference between the two thresholds was found only in the continuous protocol with 4-min steps in which ammonia threshold appeared at a higher intensity than lactate threshold. The second part of the study investigated the correlation of ammonia threshold to some common physiological measurements. Correlation was significant with lactate threshold, ventilation threshold and endurance time. No correlation was found the anaerobic power, anaerobic capacity measurement and peak VO2. Ammonia threshold was also studied before and after endurance training and sprint training. The 8-week endurance training program was able to delay the appearance of ammonia threshold, but not the 8-week sprint training program. Findings in this study demonstrate that ammonia threshold is a physiological parameter that should be recognized and has potential to be applied for the evaluation of exercise capacity and the effectiveness of endurance training programs.

Adult↗
PubMed2002

Energy expenditure and physical activity of obese children: cross-sectional study.

OBJECTIVES: To investigate the total daily energy expenditure and physical activity pattern of a group of obese and non-obese Hong Kong children. DESIGN: Cross-sectional study. SETTINGS: University teaching hospital, Hong Kong. PARTICIPANTS: Eighteen obese children aged 6 to 17 years and 18 age- and sex-matched non-obese children in the local Hong Kong community. MAIN OUTCOME MEASURES: Total daily energy expenditure and physical activity pattern were estimated for 3 days using heart rate monitoring. Body composition was measured by dual-energy X-ray absorptiometry. RESULTS: In obese children, both total fat mass and fat-free mass were greater than in non-obese children. Total daily energy expenditure and its sleep and sedentary components were higher in absolute terms (by 42%, 43%, and 126%, respectively) for obese children. When normalised for body weight, the basal metabolic rate was no different between obese and non-obese children, while the total daily energy expenditure of the obese children was significantly lower (by 22%) than that of non-obese children. When normalised for fat-free mass, the basal metabolic rate and the sedentary component of total daily energy expenditure were significantly higher for obese children. Obese children spent 12% less time asleep, but 51% more time in sedentary activity and 30% less time physically active: a ratio of active-to-sedentary waking time of 0.6 for obese children and 1.9 for non-obese children. CONCLUSIONS: Although the basal metabolic rate may be influenced by body composition, the finding of a normal basal metabolic rate when normalised for body weight suggests that an intrinsic difference of metabolic rate is not a major contributory cause of obesity. The study pointed particularly to the potential benefit of increasing physical exercise time relative to sedentary activities to reduce the prevalence of childhood obesity. Obese and non-obese children had similar basal metabolic rates when adjusted by fat-free mass and fat mass. Obese children spent more time in sedentary activities.

Adolescent↗
PubMed2001

Cholesterol enrichment upregulates intercellular adhesion molecule-1 in human vascular endothelial cells.

Hypercholesterolemia is a major risk factor for atherosclerosis, but the mechanism by which cholesterol activates the endothelium remains undocumented. The present investigation was undertaken to investigate the role of cholesterol, one of the bioactive moieties of the low-density lipoprotein (LDL) particle, in initiating of intracellular signaling in endothelial cells (ECs) and culminating in increased abundance of the intercellular adhesion molecule-1 (ICAM-1). Cholesterol was delivered to human umbilical vein ECs (HUVECs) via cholesterol-enriched liposomes. In HUVECs, the cellular cholesterol:phospholipid ratio increased after 1 h of exposure to cholesterol. The level of ICAM-1 increased in both mRNA and protein after 24 h of cholesterol exposure. ICAM-1 mRNA half-life was not affected by cholesterol exposure. Promoter studies showed greater than two-fold activation of the ICAM-1 gene expression after cholesterol exposure. Electrophoretic mobility shift assay showed that activator protein-1 (AP-1) activity substantially increased after 2 h of exposure to cholesterol. In contrast, cholesterol did not affect nuclear factor-kappaB (NF-kappaB) activity. Results of trans-reporting assay revealed 2.5-fold increased expression of the AP-1-dependent reporter gene after cholesterol exposure whereas NF-kappaB-dependent expression was not affected. The AP-1/Ets (-891 to -908) site, one of the three AP-1-like sites in the ICAM-1 promoter, was most responsive to cholesterol. These data demonstrate for the first time that cholesterol enrichment phenotypically modulates ECs by transcriptionally upregulating ICAM-1 expression.

Cell Membrane↗