Biomedical subjects

J Chung

Publications and source records attributed to J Chung.

At least 19 recordsLinked to original sources

PubMed2007

Missing data imputation in two phase III trials treating HIV1 infection.

In most longitudinal clinical trials, some patients drop out before the end of the planned follow-up, and, in order to allow an all-patient intent-to-treat analysis to be performed, it is common practice to use some method of imputation to estimate values for missing data. However, different imputation methods may provide different results, and it is essential to investigate the sensitivity of the analysis using different imputation rules. In our analysis of two trials of the new HIV1 fusion inhibitor enfuvirtide, we compared some standard methods of imputing and analyzing HIV1-RNA data with two novel alternatives, to check the robustness of the primary endpoint results. The standard methods were: (1) last-observation-carried-forward, (2) baseline carried forward, and (3) multiple imputation. These were compared with a nearest-neighbour hot-deck method, specifically proposed for imputation of missing HIV1-RNA data, and with a heuristic approach: censored regression analysis of the last-observation-carried-forward. To supplement this analysis of real clinical trial data, we investigated the performance of the same imputation methods on simulated datasets designed to cover a broader range of missing data patterns.

Algorithms↗

PubMed2006

Homotypic association between tumour-associated VHL proteins leads to the restoration of HIF pathway.

The von Hippel-Lindau (VHL) tumour suppressor gene encodes a substrate-specifying component of an E3 ubiquitin ligase that targets hypoxia-inducible factor (HIF) alpha subunits for degradation under normoxia. The VHL protein is composed of an N-terminal HIFalpha-binding beta domain and a C-terminal alpha domain, which is necessary and sufficient for the formation of the E3 multiprotein enzyme. A large number of disease-causing mutations in either the alpha or beta domain renders HIFalpha stable irrespective of oxygen tension, leading to the upregulation of numerous HIF-target genes, such as GLUT1 and VEGF. Here, we show that VHL forms a self-associated complex in vivo, but not in vitro, and demonstrate that coexpression of two different VHL missense mutants -- one in the alpha domain and the other in the beta domain -- restores HIF-mediated gene expression profile. These findings indicate that VHL homotypic complexes can function in vivo in a complementary fashion to target HIFalpha for ubiquitin-mediated proteolysis, and potentially explain why VHL-associated tumours with a missense mutation-carrying VHL allele is almost invariably accompanied by a second VHL allele harbouring a gross truncation or deletion.

Amino Acid Substitution↗

PubMed2006

In vivo protective performance of N95 respirator and surgical facemask.

BACKGROUND: The SARS outbreak in 2003 has spawned a major controversy concerning protective performance facemasks for healthcare workers. This study reports a study on in-vivo protective performance of surgical masks and N95 respirators. METHODS: Typical surgical masks and N95 respirators used in Hong Kong hospitals were tested in comparison with those treated with nano-functional materials (called nano-masks) on various physical properties and in-vivo wear filtration efficiency, as well as usability test in hospitals for surgical masks. RESULTS: Tests on physical properties showed that N95 respirators had significantly lower air permeability and water vapor permeability than surgical masks. The in-vivo filtration tests illustrated that N95 respirators filtered out 97% of potassium chloride (KCl) solution, while surgical masks filtered out 95% of KCl solution. Nano-masks show stronger water repellency and antibacterial activities, but no difference in usability, comparing with normal N95 and surgical masks. CONCLUSIONS: Surgical masks can provide in-vivo filtration protection of 95% filtration efficiency. N95 respirators provide higher in-vivo filtration efficiency of 97% with significant reduction of air permeability and water vapor permeability. Compared to normal surgical masks/respirators, the nano-masks can provide additional protective functions in stopping capillary diffusion and antibacterial activities.

Aerosols↗

PubMed2006

Backwash based methodology for the estimation of solids retention time in biological aerated filter.

The concept of solids retention time (SRT) was used for describing the growth of biofilm in a biological aerated filter (BAF) system. The SRT profile was obtained from the change in solids accumulation, estimated from the head loss profile data before and after backwash using the Carmen-Kozeny equation. The SRT profile along the filter bed depth showed the SRT of about 2 days for the lower layer and about 6 days for the upper layer. The overall SRT was determined by the direct estimation of excess solids mass during backwash and of solids retained in the filter bed. The ideal characteristic SRT distribution was maintained by regular backwash, for organic removal and nitrification. The SRT for high organic removal and nitrification is demonstrated by the SRT distribution along the filter bed in this BAF process.

Biofilms↗

PubMed2006

Multiple polyexponentials and quasipolynomials as empirical nonlinear regression models: a case study with HIV viral load data.

Measurements of HIV1-RNA plasma concentrations are an important method of assessing patient response to anti-HIV1 treatment, and in most clinical trials of such treatments HIV1-RNA levels are assessed at regular intervals of time. HIV1-RNA levels in successfully treated patients tend to follow a standard pattern of biphasic decline-a rapid early decline in viral load, followed by a period of slower decline or a steady level. Fitting nonlinear regression models to these patterns of declining HIV1-RNA levels can be of value in comparing different treatment regimes and in predicting treatment outcome. Simple exponential-decline models can give an adequate fit to the typical pattern of HIV1-RNA decline, but we have explored the extent to which curve-fitting can be improved by using two novel nonlinear model forms. Specifically, we describe the fitting of multiple polyexponential and quasipolynomial forms to longitudinal HIV1-RNA plasma data collected in two recent trials of the novel anti-HIV1 treatment Fuzeon. We comment on the practicalities of fitting these nonlinear models, and compare the fit using various criteria.

Data Interpretation, Statistical↗

PubMed2006

Contact with livestock--a protective effect against allergies and asthma?

BACKGROUND: A 'protective farm factor' possibly related to livestock exposure is hypothesized to reduce the risk for allergic sensitization. OBJECTIVE: The purpose of this study was to determine whether 4-H club youth, who have opportunities for contact with livestock through club activities, have reduced risks of respiratory and allergic symptoms according to residence on a farm or exposure to livestock. METHODS: A cross-sectional postal survey was completed by British Columbia 4-H members 8-20 years of age; a subset underwent skin prick testing as well. The association of farm residence and livestock exposure variables with symptoms were evaluated using logistic regression with adjustment for age, sex, cat and/or dog ownership, parental history of allergic disease, parental education, number of older siblings and exposure to smokers at home. RESULTS: Questionnaires were completed by 1158 participants (response rate 50.3%); of these, a subset of 317 had skin prick tests (SPTs) (response rate 64.4%). Current residence on a farm was associated with a lower prevalence of ever having wheeze and asthma, as well as symptoms of atopic dermatitis. Variables relating to residence in a farm or rural area with livestock were more strongly associated with respiratory and allergic symptoms than were the livestock exposure variables such as frequency of contact and hours of barn use. The adjusted odds ratios for living in a farm residence in comparison with a rural non-livestock area were 0.49 (95% confidence interval (CI) 0.27-0.89) for diagnosed asthma, 0.51 (95% CI 0.30-0.85) for allergic rhinitis and 0.45 (95% CI 0.24-0.84) for atopic dermatitis. CONCLUSION: Our findings suggest that some aspects of the farm environment, not just attributable to contact with livestock, were protective for respiratory and allergic conditions among 4-H youth.

Adolescent↗

PubMed2006

Effect of Weissella cibaria isolates on the formation of Streptococcus mutans biofilm.

The objective of this study was to isolate and identify lactic acid bacteria able to inhibit the in vitro formation of Streptococcus mutans biofilm as well as the in vivo formation of oral biofilm. Two strains, CMS1 and CMS3, exhibiting profound inhibitory effects on the formation of S. mutans biofilm and the proliferation of S. mutans, were isolated from children's saliva and identified as Weissella cibaria by 16S rDNA sequencing. The water-soluble polymers produced from sucrose by the W. cibaria isolates also inhibited the formation of S. mutans biofilm. According to the results of thin-layer chromatographic analysis, the hydrolysates of water-soluble polymers produced by the isolates were identical to those of dextran, forming mostly alpha-(1-6) glucose linkages. In the clinical study, the subjects mouthrinsed with a solution containing W. cibaria CMS1 evidenced plaque index reduction of approximately 20.7% (p < 0.001). These results indicate that the W. cibaria isolates possess the ability to inhibit biofilm formation, both in vitro and in vivo.

Adult↗

PubMed2006

Development of a new pulsatile extracorporeal life support device incorporating a dual pulsatile blood pump.

A new pulsatile extracorporeal life support device (ECLS) has been developed, designed to sustain pulsatile blood flow during emergency cardiopulmonary resuscitations and cardiopulmonary operations. This device features two identical pulsatile pumps that operate alternately and can therefore provide blood inflow in a more uniform manner than similar systems featuring a single-pump configuration. In order to confirm the presumed benefits of this newly-developed dual pulsatile pump configuration, we have conducted a series of in vitro experiments designed to compare the properties of the new system with a single pump system, specifically with regard to pump delivery rate and active filling efficiency. Our results reveal that the dual pump configuration can, indeed, deliver a higher flow than can the single-pump system, and exhibits an active filling efficiency superior to that of the single-pump configuration. We performed a series of animal experiments to measure the pulsatility of the dual-pump configuration in terms of equivalent energy pressure (EEP). In order to measure EEP, we measured femoral arterial pressure and pump outflow. The results of our animal experiments revealed that the newly-developed pulstile ECLS exhibits sufficient pulsatility in terms of the EEP considerations.

Advanced Cardiac Life Support↗

PubMed2006

Wireless patient monitoring system for a moving-actuator type artificial heart.

In this study, we developed a wireless monitoring system for outpatients equipped with a moving-actuator type pulsatile bi-ventricular assist device, AnyHeart. The developed monitoring system consists of two parts; a Bluetooth-based short-distance self-monitoring system that can monitor and control the operating status of a VAD using a Bluetooth-embedded personal digital assistant or a personal computer within a distance of 10 meters, and a cellular network-based remote monitoring system that can continuously monitor and control the operating status of AnyHeart at any location. Results of in vitro experiments demonstrate the developed system's ability to monitor the operational status of an implanted AnyHeart.

Cell Phone↗

PubMed2006

Self-management protocol for a moving-actuator type artificial heart.

In this paper, we describe the development of a self-management protocol for a controller of a moving-actuator type artificial heart, AnyHeart. The developed protocol analyzes motor current signals and detects abnormal pumping statuses. If preset abnormal pumping statuses are detected by an implemented algorithm, a controller triggers an emergency management procedure and transmits an alarm message to predetermined medical and engineering staffs via a cellular phone network to notify them of an abnormal pumping status occurrence and its likely cause. Results of in vitro performance experiments showed that the developed protocol can detect simulated abnormalities in motor current, manage the operating status of the blood pump during an emergency, and transmit an alarm message as desired.

Algorithms↗

PubMed2005

JNK pathway mediates apoptotic cell death induced by tumor suppressor LKB1 in Drosophila.

Although recent progresses have unveiled the diverse in vivo functions of LKB1, detailed molecular mechanisms governing these processes still remain enigmatic. Here, we showed that Drosophila LKB1 negatively regulates organ growth by caspase-dependent apoptosis, without affecting cell size and cell cycle progression. Through genetic screening for LKB1 modifiers, we discovered the JNK pathway as a novel component of LKB1 signaling; the JNK pathway was activated by LKB1 and mediated the LKB1-dependent apoptosis. Consistently, LKB1-null mutant was defective in embryonic apoptosis and displayed a drastic hyperplasia in the central nervous system; these phenotypes were fully rescued by ectopic JNK activation as well as wild-type LKB1 expression. Furthermore, inhibition of LKB1 resulted in epithelial morphogenesis failure, which was associated with a decrease in JNK activity. Collectively, our studies unprecedentedly elucidate JNK as the downstream mediator of the LKB1-dependent apoptosis, and provide a new paradigm for understanding the diverse LKB1 functions in vivo.

AMP-Activated Protein Kinase Kinases↗

PubMed2005

Racial differences in the incidence of BRCA1 and BRCA2 mutations in a cohort of early onset breast cancer patients: African American compared to white women.

PURPOSE: To evaluate the frequency and distribution of BRCA1 and BRCA2 mutations in a cohort of young women with breast cancer and to compare the distribution of mutations as a function of race. METHODS: After IRB approved informed consent, 170 white women and 30 African American women with known breast cancer diagnosed at a young age (45 years or less) underwent complete sequencing of the BRCA1 and BRCA2 genes. Each cohort represented approximately 40% of women of the same ethnic background aged 45 years or younger in a breast cancer database. RESULTS: Of the 200 patients tested, 131 (65%) had wild type mutations, 34 (17%) had deleterious mutations, and 35 (18%) had variants of uncertain significance. There were no significant differences between the white and African American cohorts regarding the percentage of deleterious mutations (17% v 17%). However, most African American patients had mutations in BRCA2 (4/5, 80%), while most mutations in the white cohort were in BRCA1 (20/29, 69%). In addition, 46% of the African American women had variants of uncertain significance, compared to only 12% of the white cohort. CONCLUSIONS: Young African American women with breast cancer have a similar frequency of deleterious mutations as white women, but have a significantly higher frequency of variants of uncertain significance. Review of these variants revealed that the majority were unlikely to be associated with disease risk or were likely to be polymorphisms. The implications for genetic testing and counselling in young women with breast cancer are discussed.

Adult↗

PubMed2005

Effects of wearing N95 and surgical facemasks on heart rate, thermal stress and subjective sensations.

AIM: The study was aimed at investigating the effects of wearing N95 and surgical facemasks with and without nano-functional treatments on thermophysiological responses and the subjective perception of discomfort. METHOD: Five healthy male and five healthy female participants performed intermittent exercise on a treadmill while wearing the protective facemasks in a climate chamber controlled at an air temperature of 25 degrees C and a relative humidity of 70%. Four types of facemasks, including N95 (3M 8210) and surgical facemasks, which were treated with nano-functional materials, were used in the study. RESULTS: (1) The subjects had significantly lower average heart rates when wearing nano-treated and untreated surgical facemasks than when wearing nano-treated and untreated N95 facemasks. (2) The outer surface temperature of both surgical facemasks was significantly higher than that of both N95 facemasks. On the other hand, the microclimate and skin temperatures inside the facemask were significantly lower than those in both N95 facemasks. (3) Both surgical facemasks had significantly higher absolute humidity outside the surface than both N95 facemasks. The absolute humidity inside the surgical facemask was significantly lower than that inside both N95 facemasks. (4) Both surgical facemasks were rated significantly lower for perception of humidity, heat, breath resistance and overall discomfort than both N95 facemasks. The ratings for other sensations, including feeling unfit, tight, itchy, fatigued, odorous and salty, that were obtained while the subjects were wearing the surgical facemasks were significantly lower than when the subjects were wearing the N95 facemasks. (5) Subjective preference for the nano-treated surgical facemasks was the highest. There was significant differences in preference between the nano-treated and untreated surgical facemasks and between the surgical and N95 facemasks. DISCUSSION: We discuss how N95 and surgical facemasks induce significantly different temperature and humidity in the microclimates of the facemasks, which have profound influences on heart rate and thermal stress and subjective perception of discomfort.

Blood Pressure↗

PubMed2005

An African American family with early-onset Alzheimer disease and an APP (T714I) mutation.

The occurrence of an APP T174I mutation is described in a large American family of African descent with Alzheimer disease. The clinical characteristics were an unusually early onset of disease (early 30s), similar to a previously reported age at onset of this mutation in an Austrian family. Distinct from that family, seizures and myoclonus were prominent features of the disease in this kindred.

Adult↗

PubMed2005

Comparison of influence of free ammonia and dissolved oxygen on nitrite accumulation between suspended and attached cells.

The shortcut biological nitrogen removal (SBNR) hybrid (suspended cells combined with attached cells) process is an innovative technology that nitrosofies ammonium to nitrite and then denitrifies nitrite to nitrogen gas. Theoretically, this results in a 25% savings of the oxygen needed for nitrification and a 40% of savings in carbon source needed for denitrification. In this study, the influences of free ammonia (FA) and dissolved oxygen (DO) concentrations on nitrite accumulation were investigated to find the optimal operational factors for stable nitrite accumulation over a long period. The maximum specific utilization rates for ammonium (qa) and nitrite (qn) were determined for suspended and attached cells taken from a bench-scale SBNR reactor and a pilot-scale livestock wastewater treatment plant reactor. For the ammonium and nitrite oxidations in both reactors, the attached cells were more resistant to the FA concentration, but were more significantly influenced by the DO concentration than the suspended cells. In addition, the effect of the DO concentration was more significant than that of the FA concentration for both types of cells from both reactors. In this SBNR hybrid system, a simultaneous manipulation of DO concentration (<1.5 mg l(-1)) and FA concentration (10-20 mg l(-1)) was required for maintaining high levels of nitrite accumulation.

Ammonia↗

PubMed2005

Calibration of 6q subtelomere deletions to define genotype/phenotype correlations.

Testing for subtelomere abnormalities in patients with idiopathic mental retardation has become a useful diagnostic tool. However, limited data exist regarding genotype/phenotype correlations for specific subtelomere imbalances. We have ascertained five patients with 6q subtelomere deletions either as a result of an isolated deletion or as a result of an unbalanced translocation, and developed a molecular ruler assay utilizing BAC or PAC clones and determined the size of the deleted regions to range from <0.5 to 8 Mb. To establish genotype/phenotype correlations for distal 6q, we compared the clinical features of these patients to previously reported cases of 6q subtelomere and cytogenetically visible deletions and found that they shared multiple abnormalities, suggesting that the causative genes may lie in the region of the smallest 6q subtelomeric deletion, approximately 400 kb from the telomere. However, multiple unique features were present only in patients with cytogenetically visible 6q deletions, indicative that genes involved in the development of these features may lie more proximally on 6q. These initial studies demonstrate the ability to develop genotype/phenotype correlations for subtelomere rearrangements, which will aid in the diagnosis and prognosis of these patients and may help narrow the search for relevant developmental genes.

Calibration↗

PubMed2004

CD44 and tenascin play critical roles in growth and vascular development of the chick chorioallantoic membrane and are targets of cigarette smoke.

Chorioallantoic membranes (CAMs) were used to determine which extracellular matrix molecules play essential roles in growth and vascular development in vivo and whether expression of critical molecules is affected by cigarette smoke exposure. Treatment of CAMs on day 5 of development with antibodies to CD44 or tenascin, but not to other matrix molecules, inhibited CAM growth and affected various aspects of blood vessel development including normal growth and branching of vessels, migration of vessels, and formation and differentiation of the capillary plexus. DNA synthesis was inhibited by antibodies to both C44 and tenascin which probably accounted for many of the phenotypic changes observed in treated CAMs. CD44 was located on all cells in day 5 CAMs, and tenascin, while present throughout the CAM, was especially abundant around large, non-migratory mesodermal blood vessels and endodermal cells that were positioned away from the direction of blood vessel migration. These data suggest that while tenascin is required for normal blood vessel migration, high levels of tenascin inhibit migration. The different distributions of CD44 and tenascin in CAMs and the observation that antibodies to either CD44 or tenascin produced similar phenotypes indicate that CD44 and tenascin were not functionally redundant. Mainstream smoke solutions, which produce a phenotype similar to that seen with anti-tenascin and anti-CD44, inhibited expression of CD44 mRNA and increased tenascin mRNA expression. 3-Ethylpyridine, a chemical in cigarette smoke that produced changes in CAM development similar to anti-CD44 and anti-tenascin treatment, also increased tenascin mRNA expression, but did not affect CD44. Together these data show that tenascin and CD44 play critical roles in early growth and vascular development of the CAM and support the idea that 3-ethylpyridine in mainstream smoke impairs CAM growth and vascular development by targeting expression of tenascin. 3-Ethylpyridine is generally regarded as safe and is used in many consumer products including food and tobacco.

Animals↗

PubMed2004

Fluorescence resonance energy transfer (FRET)-based specific labeling of Cryptosporidium oocysts for detection in environmental samples.

BACKGROUND: Accurate detection and quantification of Cryptosporidium oocysts in water are a challenge to the water industry. This article demonstrates a way to fluorescently label Cryptosporidium oocysts, based on fluorescence resonance energy transfer (FRET). Labeled oocysts can then be applied to environmental waters and their movement followed by flow cytometric detection and enumeration of the FRET-labeled oocysts, as demonstrated here with environmental water samples. METHODS: Cryptosporidium oocysts were labeled with three fluorochromes, FITC, Texas red, and Cy7, that through FRET yielded a Stokes shift of approximately 272 nm with excitation from a standard argon laser emitting at 488 nm. Defined flow cytometric settings and gatings were used to select FITC/green (530-nm), Texas red/red (650-nm), and Cy7/infrared (780-nm) fluorescing particles with light scatter properties similar to oocysts. Water concentrates were seeded with 10 tri-labeled oocysts and were analyzed using flow cytometry. Unseeded water concentrates were also analyzed. RESULTS: Analysis of unseeded water concentrates detected no autofluorescent particle similar to the labeled oocysts. Labeled oocysts were detected successfully with up to 85% recovery in water concentrates spiked with 10 tri-labeled oocysts. CONCLUSIONS: Low numbers of FRET-labeled oocysts can be quantified and clearly distinguished from autofluorescing background in environmental water concentrates.

Animals↗