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Biomedical subjects

J Yin

Publications and source records attributed to J Yin.

At least 19 recordsLinked to original sources

Induced sputum inflammatory measures correlate with disease severity in children with obstructive sleep apnoea.

OBJECTIVE: To establish the association between airway inflammation and severity of obstructive sleep apnoea (OSA) in children. METHODS: Consecutive children presenting with symptoms suggestive of OSA were recruited. They completed a sleep apnoea symptom questionnaire, underwent physical examination, spirometry, sputum induction and an overnight polysomnography. Adequate sputum contained <50% squamous epithelial cells, and OSA was diagnosed if the obstructive apnoea index was >1. RESULTS: 73 children with a median (interquartile range (IQR)) age of 11.3 (10.0-13.2) years were recruited. There were 21 girls and the median body mass index of the group was 24.0 (18.0-27.0) kg/m2. The most common presenting symptoms were habitual snoring, mouth breathing and prone sleeping position. Sputum induction was successful in 43 (59%) children, of whom 14 were found to have OSA. Children with OSA had significantly greater percentage sputum neutrophil than those without OSA (18.5 (IQR 8.0-42.0) v 4 (IQR 3.0-11.3), p = 0.006). On multiple regression analysis, percentage sputum neutrophil was significantly associated with OSA (odds ratio = 1.1, p = 0.013). CONCLUSION: Children with OSA had airway inflammation characterised by a marked increase in neutrophils. Further studies are needed to confirm these findings and to better define the downstream cellular interactions and molecular pathogenesis in childhood OSA.

Adolescent↗

The activation of lytic replication of Epstein-Barr virus by baculovirus-mediated gene transduction.

A baculoviral mammalian-cell vector was constructed to express Rta, a protein of Epstein-Barr virus (EBV) responsible for the transition from latent infection to lytic replication. EBV lytic replication and cell-growth inhibition was observed in infected D98/HR1 cells. The baculovirus caused little cytotoxicity in the non-targeted HeLa cells, compared to an adenovirus vector. It is concluded that recombinant baculovirus might have the potential as a vector for the therapy of EBV-related cancer.

Baculoviridae↗

Local and regional air pollution in Ireland during an intensive aerosol measurement campaign.

An intensive two month measurement campaign has been performed during a two year study of major component composition of urban PM10 and PM2.5 in Ireland (J. Yin, A. G. Allen, R. M. Harrison, S. G. Jennings, E. Wright, M. Fitzpatrick, T. Healy, E. Barry, D. Ceburnis and D. McCusker, Atmos. Res., 2005, 78(3-4), 149-165). Measurements included size-segregated mass, soluble ions, elemental carbon (EC) distributions, fine and coarse fraction organic carbon (OC) and major gases along with standard meteorological measurements. The study revealed that urban emissions in Ireland had mainly a local character and therefore were confined within a limited area of 20-30 km radius, without significantly affecting regional air quality. Gaseous measurements have shown that urban emissions in Ireland had clear, but fairly limited influence on the regional air quality due to favorable mixing conditions at higher wind speeds, in particular from the western sector. Size-segregated mass and chemical measurements revealed a clear demarcation size between accumulation and coarse modes at about 0.8 microm which was constant at all sites. Carbonaceous compounds at the urban site accounted for up to 90% of the particle mass in a size range of 0.066-0.61 microm. Nss SO4(2-) concentrations in PM2.5 were only slightly higher at the urban site compared to the rural or coastal sites, while NO3- and NH4+ concentrations were similar at the urban and coastal sites, but were a factor of 2 to 3 higher than at the rural site. OC was highly variable between the sites and revealed clear seasonal differences. Natural or biogenic OC component accounted for <10% in winter and up to 30% in summer of the PM2.5 OC at urban sites. A contribution of biogenic OC component to PM2.5 OC mass at rural site was dominant.

Aerosols↗

Transcriptional profiling suggests that Barrett's metaplasia is an early intermediate stage in esophageal adenocarcinogenesis.

To investigate the relationship between Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), we determined gene expression profiles of discrete pathological stages of esophageal neoplasia using a sequence-verified human cDNA microarray. Fifty one RNAs, comprising 24 normal esophagi (NE), 18 BEs, and nine EACs were hybridized to cDNA microarrays. Five statistical analyses were used for the data analysis. Genes showing significantly different expression levels among the three sample groups were identified. Genes were grouped into functional categories based on the Gene Ontology Consortium. Surprisingly, the expression pattern of BE was significantly more similar to EAC than to NE, notwithstanding the known histopathologic differences between BE and EAC. The pattern of NE was clearly distinct from that of EAC. Thirty-six genes were the most differentially modulated, according to these microarray data, in BE-associated neoplastic progression. Twelve genes were significantly differentially expressed in cancer-associated BE's plus EAC (as a single combined tissue group) vs noncancer-associated BE's. These genes represent potential biomarkers to diagnose EAC at its early stages. Our results demonstrate that molecular events at the transcriptional level in BE are remarkably similar to BE's-associated adenocarcinoma of the esophagus. This finding alarmingly implies that BE is biologically closer to cancer than to normal esophagus, and that the cancer risk of BE is perhaps higher than we had imagined. These findings suggest that changes modulated at the molecular biologic level supervene earlier than histologic changes, and that BE is an early intermediate stage in the process of EAC.

Adenocarcinoma↗

Stability similarities between shells, cells and nano carbon tubes.

The similarity in stability characteristics between multiscale circular cylindrical structures is revealed. Two detailed structures are explored. One is the circular cylindrical shell on an engineering scale, and another is the circular cylindrical lipid bilayer vesicle on a micro- or nanoscale. The critical stability of the vesicle acted on by uniformly distributed radial pressure is analysed. The critical load of the vesicle is derived and compared with that of the thin shell. The astonishing similarity between them is disclosed. The possible applications of such similarity to biophysics, biology and biomedicine are presented.

Animals↗

Evolutionary design on a budget: robustness and optimality of bacteriophage T7.

Exploring how biological systems have been 'designed' by evolution to achieve robust behaviours is now a subject of increasing research effort. Yet, it still remains unclear how environmental factors may contribute to this process. This issue is addressed by employing a detailed computer model for the intracellular growth of phage T7. More than 150 000 in silico T7 mutants were generated and the rates and efficiencies of their growth in two host environments, namely, a realistic environment that offered finite host resources for the synthesis of phage functions and a hypothetical environment where the phage was supplied infinite host resources, were evaluated. Results revealed two key properties of phage T7. First, T7 growth was overall robust with respect to perturbations in its parameters, but fragile with respect to changes in the ordering of its genetic elements. Secondly, the wild-type T7 had close to optimal fitness in the finite environment. Furthermore, a strong correlation was found between fitness and growth efficiency in the finite environment. The results underscore the potential importance of the environment in shaping robust design of a biological system. In particular, the strong correlation between fitness and growth efficiency suggests that T7 may have evolved to maximise its growth rate by minimising waste of finite resources.

Bacteriophage T7↗

Phase I/II study of vaccination with dendritic-like leukaemia cells for the immunotherapy of acute myeloid leukaemia.

Twenty-two patients with acute myeloid leukaemia were recruited into a phase I/II clinical trial investigating the vaccination of patients in complete remission (CR) with autologous dendritic-like leukaemia cells (DLLC). At trial entry, leukaemia cells were harvested and tested for their ability to undergo cytokine-induced dendritic cell differentiation. Patients were then treated with intensive chemotherapy. Five patients achieved both CR and had leukaemia cells that successfully underwent differentiation and therefore proceeded to vaccination. Four escalating doses of DLLC were administered weekly by subcutaneous injection. Vaccination was generally well tolerated although one patient developed extensive eczema and an increased antinuclear factor titre possibly indicating induction of autoimmunity. Development of anti-leukaemic T-cell responses was assessed by enzyme-linked immunospot analysis of gamma-interferon secreting T lymphocytes and by human leucocyte antigen tetramer analysis for WT1-specific T cells. Increases in anti-leukaemic T-cell responses were demonstrated in four patients, but only two of the five remained in remission more than 12 months postvaccination. The study has demonstrated that generation of DLLC is feasible in only a subgroup of patients and is currently neither broadly applicable or clinically effective.

Acute Disease↗

Interleukin-18 affects local cytokine expression but does not impact on the development of kidney allograft rejection.

Interleukin-18 is predominantly a macrophage-derived cytokine with a key role in inflammation and cell-mediated immunity. Having previously demonstrated IL-18 upregulation in a rat model of kidney rejection, here we examined IL-18 in a fully MHC-mismatched murine model of acute kidney rejection using IL-18-deficient recipients (IL-18-/-) and animals administered neutralizing IL-18 binding protein (IL-18BP). Gene expression of IL-18 and its receptor were significantly upregulated in allografts compared to isografts, as was the cellular infiltrate (T cells and macrophages) (p < 0.001). Allografts developed kidney dysfunction (p < 0.05) and tubulitis (p < 0.01) not observed in controls. There was a significant reduction in gene expression of IL-18 downstream pro-inflammatory molecules (iNOS, TNFalpha and IFNgamma) in IL-18-/- recipients (p < 0.01), and IL-18BP-treated animals. The CD4+ infiltrate and IL-4 mRNA expression was greater in the IL-18-/- recipients than wild-type (WT) allografts and IL-18BP-treated animals (p < 0.05), suggesting a Th2-bias which was supported by IFNgamma and IL-4 ELISPOT data and an increased eosinophil accumulation (p < 0.001). Neither IL-18 deficiency nor neutralization prevented renal dysfunction or tubulitis. This study demonstrates increased production of IL-18 in murine kidney allograft rejection and provides evidence that IL-18-induced pathways of inflammation are active. However, neither IL-18 deficiency nor neutralization was protective against the development of allograft rejection.

Animals↗

Measurement and modelling of air pollution and atmospheric chemistry in the U.K. West Midlands conurbation: overview of the PUMA Consortium project.

The PUMA (Pollution of the Urban Midlands Atmosphere) Consortium project involved intensive measurement campaigns in the Summer of 1999 and Winter of 1999/2000, respectively, in which a wide variety of air pollutants were measured in the UK West Midlands conurbation including detailed speciation of VOCs and major component analysis of aerosol. Measurements of the OH and HO2 free radicals by the FAGE technique demonstrated that winter concentrations of OH were approximately half of those measured during the summer despite a factor of 15 reduction in production through the photolysis of ozone. Detailed box modelling of the fast reaction chemistry revealed the decomposition of Criegee intermediates formed from ozone-alkene reactions to be responsible for the majority of the formation of hydroxyl in both the summer and winter campaigns, in contrast to earlier rural measurements in which ozone photolysis was predominant. The main sinks for hydroxyl are reactions with NO2, alkenes and oxygenates. Concentrations of the more stable hydrocarbons were found to be relatively invariant across the conurbation, but the impacts of photochemistry were evident through analyses of formaldehyde which showed the majority to be photochemical in origin as opposed to emitted from road traffic. Measurements on the upwind and downwind boundaries of the conurbation revealed substantial enhancements in NOx as a result of emissions within the conurbation, especially during westerly winds which carried relatively clean air. Using calcium as a tracer for crustal particles, it proved possible to reconstruct aerosol mass from the major chemical components with a fairly high degree of success. The organic to elemental carbon ratios showed a far greater influence of photochemistry in summer than winter, presumably resulting mainly from the greater availability of biogenic precursors during the summer campaign. Two urban airshed models were developed and applied to the conurbation, one Eulerian, the other Lagrangian. Both were able to give a good simulation of concentrations of both primary and secondary pollutants at urban background locations.

Acetone↗

In vivo anti-osteoporotic activity of isotaxiresinol, a lignan from wood of Taxus yunnanensis.

Isotaxiresinol, the main lignan isolated from the water extract of wood of Taxus yunnanensis, was investigated for its effect on bone loss, on serum biochemical markers for bone remodeling and on uterine tissue, using ovariectomized (OVX) rats as the model of postmenopausal osteoporosis. After oral administration of isotaxiresinol (50 and 100mg/kg/d) for 6 weeks, bone mineral content (BMC) and bone mineral density (BMD) in total and cortical bones were increased as compared to those of OVX control rats, and decreases of three bone strength indexes induced by OVX surgery were prevented. Serum biochemical markers for bone remodeling revealed that isotaxiresinol slightly increased bone formation and significantly inhibited bone resorption without side effect on uterine tissue. These results suggest that isotaxiresinol may be useful for treatment of postmenopausal osteoporosis, especially for prevention of bone fracture induced by estrogen deficiency.

Animals↗

Effects of RNA splicing and post-transcriptional regulation on HIV-1 growth: a quantitative and integrated perspective.

Despite major advances over the last two decades in our understanding of RNA splicing and (post-) transcriptional regulation in human immunodeficiency virus type-1 (HIV-1), debate continues on the mechanisms and effects of Rev protein on HIV-1 growth. Moreover, arguments that HIV-1 has been optimised for growth have been largely based on speculation. Here, we begin systematically to address these issues by developing a detailed kinetic model for HIV-1 intracellular development. The model accounts for transcription, successive steps in RNA splicing, nuclear export of mRNAs, translation and shuttling of Rev and Tat, Tat-mediated transactivation of transcription, thresholds on Rev in its effects on nuclear export of mRNA, and inhibitory effects of Rev on splicing. Using the model, we found that inefficient splicing of HIV-1 mRNA was generally beneficial for HIV-1 growth, but that an excessive reduction in the splicing efficiency could be detrimental, suggesting that there exists a splicing efficiency that optimises HIV-1 growth. Further, we identified two key contributors to splicing efficiency, the intrinsic splicing rate and the extent of Rev-mediated splicing inhibition, and we showed how these should be balanced for HIV-1 to optimise its growth. Finally, we found that HIV-1 growth is relatively insensitive to different levels of the Rev export threshold, and we suggest that this mechanism evolved to delay viral growth, perhaps to enable evasion of host defensive responses. In summary, our model provides a quantitative and qualitative framework for probing how constituent mechanisms contribute to the complex, yet logical, process of HIV-1 growth.

Computer Simulation↗

Design and fabrication of ultrafine piezoelectric composites.

Making fine scale (< 20 microm) piezoelectric composites for high frequency (> 50 MHz) ultrasound transducers remains challenging. Interdigital phase bonding (IPhB), described in this paper, presents a new technique developed to make piezoelectric composites at the ultrafine scale using a conventional dicing saw. Using the IPhB technique, a composite structure with a pitch that is less than the dicing saw blade thickness can be created. The approach is flexible enough to make composites of different combination of pitch and volume ratio. Using a conventional dicing saw with a 50 microm thick blade, composite with a 25 microm pitch and a volume ratio of 61 percent are fabricated. Such a composite is suitable for fabrication of ultrasonic transducers and arrays with central frequencies of up to 85 MHz. Single element transducers working at central frequencies of 50-60 MHz were made of these composites as a mean to characterize the acoustic performance. Measurement results of the transducers show that the longitudinal electromechanical coupling coefficient is greater than 0.6 and that there are no noticeable lateral resonances in the frequency range of 55-150 MHz. Design criteria for fine scale elements are also discussed based on theoretical results from finite element analysis (FEA).

Ceramics↗

The six-minute walk test in healthy children: reliability and validity.

The aim of this study was to assess the reliability and validity of the 6-min walk test (6MWT) in healthy children. Chinese secondary school students were randomly recruited. They attended the current authors' unit on two occasions, separated by 2 weeks. Physical examination and standardised maximum incremental exercise testing on a treadmill were performed on the first visit. Spirometry and 6MWT were carried out on the second visit. A randomly selected subgroup was invited to return for repeat 6MWT at an interval of 2-4 weeks. Seventy-eight subjects were recruited; however, four failed to achieve maximal effort on exercise test. The final group included 43 young females and the mean+/-sd age of the subjects was 14.2+/-1.2 yrs. Physical examination was unremarkable in all cases. The mean+/-sd per cent predicted forced expiratory volume in one second was 91.4+/-10.2%. Concurrent validity was demonstrated by good correlation between the 6-min walking distance and maximum oxygen uptake determined on the exercise treadmill. Test-retest reliability was undertaken in 52 subjects, and the intraclass correlation coefficient (95% confidence interval) was calculated as 0.94 (0.89-0.96). In addition, Bland and Altman plots demonstrated a high degree of repeatability. In healthy children, the 6-min walk test is a reliable and valid functional test for assessing exercise tolerance and endurance.

Adolescent↗

Concentration and detection of SARS coronavirus in sewage from Xiao Tang Shan Hospital and the 309th Hospital of the Chinese People's Liberation Army.

A worldwide outbreak of severe acute respiratory syndrome (SARS) had been reported. Over 8439 SARS cases and 812 SARS-related deaths were reported to the World Health Organization from 32 countries around the world up to 5 July 2003. The mechanism of transmission of SARS-CoV has been limited only to close contacts with patients. Attention was focused on possible transmission by the sewage system because laboratory studies showed that patients excreted coronavirus RNA in their stools in Amoy Gardens in Hong Kong. To explore whether the stool of SARS patients or the sewage containing the stool of patients would transmit SARS-CoV or not, we used a style of electropositive filter media particle to concentrate the SARS-CoV from the sewage of two hospitals receiving SARS patients in Beijing, as well as cell culture, semi-nested RT-PCR and sequencing of genes to detect and identify the viruses from sewage. There was no live SARS-CoV detected in the sewage in these assays. The nucleic acid of SARS-CoV was found in the sewage before disinfection from both hospitals by PCR. After disinfection, SARS-CoV RNA could be detected from some samples from the 309th Hospital of the Chinese People's Liberation Army, but not from Xiao Tang Shan Hospital after disinfection. In this study, we found that the virus can survive for 14 days in sewage at 4 degrees C, 2 days at 20 degrees C, and its RNA can be detected for 8 days though the virus had been inactivated. In conclusion, this study demonstrates that the RNA of SARS-CoV could be detected from the concentrates of sewage of both hospitals receiving SARS patients before disinfection and occasionally after disinfection though there was no live SARS-CoV; thus much attention should be paid to the treatment of stools of patients and the sewage of hospitals receiving SARS patients.

Bacteriophages↗

Evaluation of heavy metal inhibition of activated sludge by TTC and INT-electron transport system activity tests.

TTC and INT-electron transport system activity tests were compared for assessing heavy metal inhibition of activated sludge. The median inhibitory concentrations (IC50s) of Cu2+, Zn2+, Cd2+, Hg2+, Ni2+, Pb2+ and Ag+ measured via TTC test were lower than those measured via INT test, which indicates that the INT-electron transport system activity test was less sensitive to heavy metal toxicity than the TTC test. Tested heavy metals brought about similar decrease in TTC-electron transport system activity and COD removal rate, but less decrease in INT-electron transport system activity than COD removal rate, which suggests that the TTC-electron transport system activity is a better parameter for reflecting heavy metal inhibition of activated sludge than INT-electron transport system activity. The ranking of tested heavy metals in order of decreasing toxicity based on TTC test was Hg2+, Cd2+, Cu2+, Ag+, Zn2+, Ni2+ and Pb2+, and the ranking based on INT test was Hg2+, Ag+, Cu2+, Cd2+, Zn2+, Ni2+ and Pb2+.

Bacteria↗

Hepatic steatosis in obese Chinese children.

OBJECTIVES THE AIMS OF OUR STUDY WERE: (1) to determine the prevalence of asymptomatic hepatic steatosis and presumed nonalcoholic steatohepatitis, in our local population of obese Chinese children referred for medical assessment; and (2) to assess the correlation between severity of ultrasonographic hepatic steatosis and degree of obesity, insulin resistance and serum biochemical abnormalities. DESIGN: Cross-sectional study. METHODS: In total, 84 obese children, 25 girls and 59 boys with median age and body mass index (BMI) of 12.0 years (interquartile range (IR): 9.5-14.0) and 30.3 kg/m(2) (IR: 27.1-33.4), respectively, referred for medical assessment were studied. All subjects underwent physical examination, anthropometric and dual energy X-ray absorptiometry (DEXA) scan measurements and real-time ultrasonographic (US) examination of the liver. Fasting blood samples were collected for the measurement of liver function, hepatitis status, levels of serum glucose and insulin and lipid profile. Degree of fatty infiltration of the liver was graded according to ultrasonic appearance of liver echotexture, liver-diaphragm differentiation in echo amplitude, hepatic echo penetration and clarity of hepatic blood vessels. RESULTS: All recruited subjects had no history of alcohol abuse and tests for Hepatitis B or C virus were negative. Thorough examination showed all of them to be in general good health without signs of chronic liver disease. Hepatic steatosis identified by defined ultrasonic appearances was diagnosed in 65 subjects (77%); 17 girls and 48 boys. The severity of fatty liver was positively related to anthropometric measurements including BMI, waist and hip circumference, subscapular skinfold thickness; insulin resistance markers [QUICKI and homeostasis model assessment (HOMA)], and hypertriglyceridaemia. Multvariate ordinal regression analysis showed that BMI and raised alanine aminotransferase (ALT) were positively associated with fatty liver. Combination of hepatic steatosis with raised ALT (presumptive NASH) was found in 19 subjects (24%). This group of patients had significantly higher waist hip ratio and conicity index compared to those with isolated hepatic steatosis. Boys with presumed NASH were also found to have significantly higher insulin resistance. CONCLUSION: Nonalcoholic fatty liver disease (NAFLD) was common among our cohort of obese children referred for medical assessment. The prevalence of simple steatosis and presumed NASH was 77 and 24%, respectively. The severity of US steatosis was positively correlated with BMI, raised ALT, insulin resistance and hypertryglyceridaemia. Ultrasonography being noninvasive and readily available could be used for the monitoring of the progression of hepatic steatosis. Further longitudinal studies are required to determine the natural disease progression and the role of insulin resistance and other factors in the pathophysiology of NAFLD.

Adolescent↗

Rescue of protein splicing activity from a Magnetospirillum magnetotacticum intein-like element.

The self-catalytic protein splicing mechanism is mediated by the intein plus the first amino acid following the intein C-terminus (termed the +1 residue). Although polymorphisms of conserved residues elsewhere in inteins have been widely reported, no splicing-competent intein has been observed without a Ser, Thr or Cys in this functionally essential +1 position. This residue is the nucleophile in two steps of the protein splicing pathway: ligation of the extein fragments during transesterification and formation of a peptide bond between the exteins by an acyl rearrangement. An intein-like element in a hypothetical protein (gene Magn8951) from Magnetospirillum magnetotacticum has all intein signature sequences except the +1 residue, where it has a Tyr. Although the Tyr side-chain hydroxyl can potentially mediate the transesterification reaction, an acyl shift has never been observed with this residue. When the activities of this bacterial intein-like element were studied, protein splicing was not observed and N-terminal cleavage predominated. Mutation of Tyr+1 to Phe or Ala indicated that the Tyr side-chain hydroxyl was not necessary for N-terminal cleavage. Protein splicing activity could be rescued by "reversion" of Tyr+1 to Cys.

Alanine↗

Inhibitory effects of stress on postprandial gastric myoelectrical activity and vagal tone in healthy subjects.

The aim was to investigate gastric myoelectrical activity (GMA) and vagal activity in response to stress. The study was performed in 10 healthy subjects in three sessions (control, relaxation and stress). The control session was composed of 30-min recordings before and 30-min recordings after a test meal. The protocol of two other sessions was similar except that the fasting recording was extended to 60 min and the subjects were continuously watching a horror movie (stress) or guided meditation tape (relaxation) after the 30-min baseline. GMA was recorded using electrogastrography and heart rate variability (HRV) was derived from the electrocardiogram. Meal resulted in a postprandial increase in the dominant frequency (2.91 cpm vs 3.17 cpm, P < 0.007), dominant power (30.0 dB vs 32.5 dB, P < 0.05), and percentage of normal slow waves (79.8%vs 87.4%, P = 0.09). Similar responses were found in the relaxation session. Stress inhibited all these normal postprandial response and reduced the regularity of gastric slow waves (82.0%vs 66.0%, P < 0.01). In addition, spectral analysis of the HRV demonstrated an inhibition of postprandial vagal activity and an increase of postprandial sympathetic activity with stress. Stress has an inhibitory effect on postprandial GMA and this may involve both vagal and sympathetic pathway.

Adult↗