Biomedical subjects

S Cheng

Publications and source records attributed to S Cheng.

At least 127 records · Page 7Linked to original sources

PubMed1999

A multilocus genotyping assay for candidate markers of cardiovascular disease risk.

A number of chronic diseases, including cardiovascular disease, appear to have a multifactorial genetic risk component. Consequently, techniques are needed to facilitate evaluation of complex genetic risk factors in large cohorts. We have designed a prototype assay for genotyping a panel of 35 biallelic sites that represent variation within 15 genes from biochemical pathways implicated in the development and progression of cardiovascular disease. Each DNA sample is amplified using two multiplex polymerase chain reactions, and the alleles are genotyped simultaneously using an array of immobilized, sequence-specific oligonucleotide probes. This multilocus assay was applied to two types of cohorts. Population frequencies for the markers were estimated using 496 unrelated individuals from a family-based cohort, and the observed values were consistent with previous reports. Linkage disequilibrium between consecutive pairs of markers within the apoCIII, LPL, and ELAM genes was also estimated. A preliminary analysis of single and pairwise locus associations with severity of atherosclerosis was performed using a composite cohort of 142 individuals for whom quantitative angiography data were available; evaluation of the potentially interesting associations observed will require analysis of an independent and larger cohort. This assay format provides a research tool for studies of multilocus genetic risk factors in large cardiovascular disease cohorts, and for the subsequent development of diagnostic tests.

Adult↗

PubMed1999

High-dose isoniazid therapy for isoniazid-resistant murine Mycobacterium tuberculosis infection.

The use of isoniazid (INH) for the treatment of INH-resistant Mycobacterium tuberculosis infection has been controversial. The purpose of the present studies was to determine if there is a dose response with INH for INH-susceptible M. tuberculosis Erdman (ATCC 35801), and whether high-dose INH (100 mg/kg of body weight) was more effective than standard-dose INH (25 mg/kg) for therapy of tuberculosis infections caused by INH-resistant mutants of M. tuberculosis Erdman. Six-week-old CD-1 mice were infected with approximately 10(7) viable mycobacteria. Early control groups of infected but untreated mice were euthanized by CO(2) inhalation 1 week later when treatment was initiated. INH (25, 50, 75, and 100 mg/kg) was given by gavage 5 days/week for 4 weeks. Late control groups of untreated mice and treated mice were sacrificed 2 days after the last dose of drug. Spleens and right lungs were removed aseptically and homogenized, and viable cell counts were determined by titration on 7H10 agar plates. In the next study, INH at 100 mg/kg was compared to INH at 25 mg/kg against an isogenic mutant of M. tuberculosis Erdman (INH MIC, 2 microg/ml) and the parent strain. This mutant was found to have a mutation in the KatG protein (Phe to Leu at position 183). In the first study, there was no dose response with increasing doses of INH. In the second study, there was no significant difference between the reduction of viable cell counts for mice treated with INH at 100 mg/kg and that for mice treated with INH at 25 mg/kg (parent or INH-resistant mutant). These preliminary results suggest that INH may be useful in combination therapy of M. tuberculosis infections caused by low-level INH-resistant organisms (INH MICs, 0.2 to 5 microg/ml) and that higher doses of INH are unlikely to be more efficacious than the standard 300-mg/day dose.

Animals↗

PubMed1999

Two year follow up of pulmonary function values among welders in New Zealand.

OBJECTIVES: To examine whether welding is a risk factor for an accelerated decline in pulmonary function. METHODS: 2 Year follow up of pulmonary function and respiratory symptoms among 54 welders and 38 non-welders in eight New Zealand welding sites. RESULTS: There were no significant differences in age, height, smoking habits, ethnicity, or total time in industrial work between welders and non-welders. No overall differences were noted in the changes of pulmonary function variables between the two study groups. However, when the comparison was restricted to smokers, welders had a significantly greater (p = 0.02) annual decline (88.8 ml) in FEV1 than non-welders, who had a slight non-significant annual increase (34.2 ml). Also, welders without respiratory protection or local exhaust ventilation while welding had a greater annual decline both in forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) than welders with protection (p = 0.001 and 0.04, respectively). Among welders a significant association was found between the acute across shift change and the annual decline in FEV1. Chronic bronchitis was more common among welders (24%) than non-welders (5%). Only one welder (2%) but eight non-welders (21%) reported having asthma. CONCLUSIONS: Welders who smoked and welders working without local exhaust ventilation or respiratory protection have an increased risk of accelerated decline in FEV1.

Adult↗

PubMed1999

Relationship between fetal growth and the development of asthma and atopy in childhood.

BACKGROUND: A study was undertaken to investigate the relationship between birth anthropometric measures and the subsequent development of asthma, airway hyperresponsiveness, and atopy in later childhood. METHODS: A longitudinal study was performed on 734 subjects (71%) from a cohort of children born in Dunedin, New Zealand in 1972-73. The birth anthropometric measures were available from hospital records and the main outcome measures of reported asthma, skin prick tests, and methacholine hyperresponsiveness were measured at the age of 13 years, while the serum total IgE was measured at 11 years. RESULTS: After adjustment for other factors, infants with a larger head circumference at birth tended to have higher serum total IgE at 11 years of age (p = 0.02) but IgE was not associated significantly with birth length or birth weight. The adjusted odds ratio for raised serum IgE (>150 IU/ml) in infants with a head circumference of 37 cm or more was 3.4 (95% CI 1.4 to 7.9). In contrast, recent asthma symptoms were positively associated with birth length (p = 0. 04) but not with head circumference. The adjusted odds ratio for asthma in the previous two years in infants with a birth length of 56 cm or more was 6.4 (95% CI 2.0 to 19.8). Infants with a birth weight of less than 3.0 kg had an odds ratio for reported asthma of 0.2 (95% CI 0.0-0.6). There were no significant associations of any of the birth parameters with skin prick positivity, reported hay fever, or eczema. CONCLUSIONS: These results suggest that increased fetal growth is related to an increased risk of asthma and atopy in childhood. The precision of the findings is limited by the small numbers in the extreme categories of each birth parameter, but the results are consistent with intrauterine programming of the developing respiratory and immune systems.

Adolescent↗

PubMed1999

Components of human papillomavirus that activate transcription and support plasmid replication in human airway cells.

Human papillomaviruses (HPVs) such as types 6 and 11 can establish lifelong infections in airway epithelial cells in patients, and long-term infection can lead to pulmonary involvement and death. The mechanisms underlying this persistence depend on both the transcriptional activity of the viral enhancers and promoters and the ability of this virus to maintain its double-stranded circular DNA genome in infected tissues. We investigated the transcription and replication properties of HPV sequence elements and protein products in a human airway cell line. We showed that incorporation of the upstream regulatory region and cotransfection with expression vectors of two virus-encoded proteins, E1 and E2, conferred approximately 5,000-fold stimulation of reporter gene expression. Transient plasmid replication in transfected human airway cells and lungs of FVB/N-C57BL/6 mice was demonstrated by a modified transient replication assay. These results have important implications for viral pathogenesis in airway cells and the potential of HPV-based replicons for gene transfer into airway epithelium.

Animals↗

PubMed1999

Symptoms and cognition as predictors of community functioning: a prospective analysis.

OBJECTIVE: It has been suggested that level of cognitive functioning as assessed by formal neurocognitive tests may be as important as, or even more important than, symptoms in predicting level of community functioning for patients with schizophrenia. The results of past prospective studies, when carefully examined, do not consistently support this hypothesis. In the current study, the authors used symptom and neurocognitive data to predict subsequent level of functioning in the community. METHOD: Neurocognitive and symptom data collected as part of an earlier study were used to predict the community functioning of 50 patients with a diagnosis of schizophrenia. Using the Life Skills Profile, staff of a community mental health program assessed community functioning while blind to the earlier symptom ratings and neurocognitive performance. RESULTS: Symptoms were more predictive of community functioning than were neurocognitive measures. Disorganization symptoms were generally more predictive of community functioning than was either psychomotor poverty or reality distortion. CONCLUSIONS: The results of this study and of previous longitudinal studies suggest the importance of using symptom levels after optimal treatment, rather than symptoms during acute episodes, as predictors of community functioning. They also indicate the need to evaluate the effects of treatment on disorganization as a separable dimension of symptoms.

Adult↗

PubMed1999

Comparison of ultrasound and bone mineral density assessment of the calcaneus with different regions of interest in healthy early menopausal women.

This study investigated the effect of different sized regions of interest (ROIs) on quantitative ultrasound (QUS) variables of the calcaneus. The effect on QUS of using a fixed ROI as opposed to an ROI adjusted for foot length was also assessed. Eighty Caucasian women, aged 50-57 yr (mean 53 +/- 2) who were healthy and within 0. 5-5 yr of the onset of menopause participated in this study. Using the QUS-1(trade mark) Ultrasonometer (Metra Biosystems, Mountain View, CA), we assessed broadband ultrasound attenuation ([BUA] and UBI-4, dB/MHz), the average transit time through the heel ([TTH], mus) and a multiple-factor index (UBI-4T = UBI-4/TTH, dB/[MHz. mus]). The QUS measurement results were calculated from three different sizes of ROI as well as one in a fixed location and one adjusted for foot size. Bone thickness, bone width, bone mineral content ([BMC], g/cm), bone mineral density area ([BMD(a)], g/cm(2)), and bone mineral density volume ([BMD(v)], g/cm(3)) were measured by single-energy photon absorptiometry. Lateral radiography of the foot was used to ensure the QUS scanning location in a subgroup. The results showed that there was a 1.4-5.9% difference in QUS parameters among different ROIs (p = 0.076-0.001). No significant differences between fixed and adjusted location were found regarding the mean values of QUS. The correlation between the fixed and adjusted locations was very strong, although there was a 12-42% unexplained variation. On the other hand, QUS in the size-adjusted ROI increased the correlation with BMC/BMD compared to the fixed QUS assessments. After controlling for body weight and height, a significant correlation between QUS and bone mass variables remained, and in some cases correlations became stronger. Lateral radiography showed that when using a fixed location to scan a large foot, the scanning area might be close to the bone edge, an area of higher BMD and potential acoustic artifacts. When scanning a small foot, the scanning area was confined to the middle of the calcaneus. Our results indicate that bone size has a modest effect on BUA. There is a better correlation with BMD when the measurement region is appropriately located in the calcaneus. This suggests that measurement location based on foot size may improve the accuracy of the measurements, resulting in good diagnostic sensitivity.

Bone Density↗

PubMed1999

Multilocus approach to cardiovascular risk.

Until now, our familial studies have showed that shared genetic and environmental factors are involved on lipid parameters variability. More precisely, being working on 119 families we have showed that: a) The apolipoprotein E (apo E) common polymorphism is involved in the total cholesterol, low density lipoprotein cholesterol (LDL-Chol), apo E, apo B levels variability, b) the apolipoprotein A-IV gene had no effect on lipid metabolism parameters variability, apo A-IV levels included, c) the apolipoprotein B gene was associated with total cholesterol, high density lipoprotein cholesterol, LDL-Chol, triglycerides and apo B levels genetic variability, d) the lipoproteine lipase (LPL) gene was responsible for 6.5% of the triglycerides variability, e) the apo E and LPL 447 polymorphisms influence in conjunction lipid parameters. These preliminary results on effects and combination effects of polymorphic genes show the interest of a multilocus approach. We have used in a subgroup of 416 individuals of a familial cohort (Stanislas Cohort) a prototype assay that genotypes a panel of 35 polymorphic sites on 15 candidate genes of Cardiovascular diseases. Each sample is amplified by two multiplex polymerase chain reactions, then hybridized to an array of immobilized, oligonucleotide probes. The frequencies of the rare alleles were in agreement with those reported by others in caucasian populations. The realisation of this multiplex assay in the 1,006 families of the Stanislas Cohort, which is underway, will allow us a better understanding of the inter-individual variability of lipids and will contribute to the determination of the genetic susceptibility of one's individual to cardiovascular risk.

Adult↗

PubMed1999

[Transformation of human bronchial epithelium by EB virus gene LMP1 and EBNA2].

OBJECTIVE: To observe Epstein-Barr virus (EBV)-dependent transformation of human bronchial epithelium. METHODS: Eukaryotic expression plasmide pBS-LMP-Hyg and pSG5-EBNA2-Hyg were transfected into immortalized human bronchial epithelium cell line TR. RESULTS: In situ hybridization and Western blot confirmed EBNA2 and LMP1 expression in one hygromycine B resistant cell clone TR/LMP1-EBNA2. Growth curve and MTT value showed that transformed cells grew faster. Soft agar plating rate of TR/LMP1-EBNA2 was 50.1per thousand, 68.2per thousand, empty vector PBs-Hyg transfected cell strain TR/Hyg 2.0per thousand, 3.0per thousand, TR 11.0per thousand, 0.7per thousand. CONCLUSION: Expression of both LMP1 and EBNA2 led to decreased anchorage dependence and increased proliferation rate of TR, thereby further transformed immortalized human bronchial epithelium. Our results suggest that EBV may play a role in genesis of lung cancer.

Animals↗

PubMed1999

[Relationship between oxysterols and atherosclerosis].

Oxysterols, being oxygenated derivatives of cholesterol, are as many kinds as one hundred. They are found in the foodstuffs, the blood and arterial tissues of animals with hypercholesterolemia, the human atheroma, the foam cell from atherosclerotic tissues, as well as in the oxidized low density lipoprotein. The results of experiments have demonstrated that oxysterols are cytotoxic and they are injurious to a variety of cells including vascular endothelial cells, smooth muscle cells and monocyte/macrophages, suggesting that oxysterols could play a key role in the initiation and pathogenesis of atherosclerosis.

Animals↗

PubMed1999

[Study of cytotoxicity of bioprosthetic heart valve material and its store solution].

This study compared the cytotoxicities of bioprosthetic heart valve materials crosslinked by glutaraldehyde, stored in 4% formaldehyde or Hank's solution. Human embryonic pulmonary fibroblasts or L-929 cell culture in vitro were used. Cell proliferative inhibition index(CP II) was calculated for bioprosthetic heart valve materials using different store methods in different rinse periods(before, 10 days, 20 days, 30 days). The results demonstrate: (1) bioprosthetic heart valve materials stored in 4% formaldehyde or in Hank's solution both have significant cytotoxicity, and the longer the rinse time continues, the lower the cytotoxicity declines; (2) HEL cell is more sensitive than L-929 cell in detecting the cytotoxicity of toxic biomaterials but for weak toxic biomaterials the two cell lines are not significanth different; (3) formatldehyde solution increases the cytotoxicity of biomaterials stored in it, but the enhanced cytotoxicity can be easily relieved by rinse. The authors conclude that bioprosthetic heart valve materials have long term significant cytotoxicity and the biomaterial cytotoxicity test using human fibroblasts is more sensitive and precise than other tests.

Animals↗

PubMed1999

[Analysis of Chinese moxibustion in visible and infrared spectra in process of clinical application].

By use of the testing compartment which was made up and the spectrometer of visible or infrared light give expression to electromagnetic spectrum of that the heat is given by Chinese moxibustion in process of clinical application. Experimental results show that the heat wich is given when Chinese moxibustion is burnt is the continuous wave electromagnetic spectrum from about 600 millimicron to far infrared and diffrent electromagnetic spectrum are given out by diffrent kinds of Chinese moxibustion.

Humans↗

PubMed1998

On-line flow displacement immunoassay for fatty acid-binding protein.

In standard displacement flow immunoassays the analyte in the sample creates an active dissociation of labelled antigens (or antigen homologues) from an antigen binding site of an immobilized antibody, after which the labelled substance is measured downstream. Such systems have been described for molecules up to 1 kDa. In this study, we demonstrate displacement in a flow system for the detection of a small protein, cytoplasmic heart-type fatty acid-binding protein (15 kDa), a plasma marker for myocardial injury. The displacement system uses an inverse set-up: enzyme labelled monoclonal antibodies are associated to immobilized antigen, and are displaced by analyte in the sample. The system permits detection of both physiological (2-12 microg l(-1)) and pathological concentrations (12-2000 microg l(-1)) of fatty acid-binding protein in an on-line flow system.

Animals↗

PubMed1998

Structural and enzymatic studies of a new analogue of coenzyme B12 with an alpha-adenosyl upper axial ligand.

A new analogue of coenzyme B12 (5'-deoxyadenosylcobalamin, AdoCbl), in which the configuration of the N-glycosidic bond in the Ado ligand is inverted [(alpha-ribo)AdoCbl], has been synthesized and its crystal structure determined by X-ray diffraction [MoKalpha, lambda = 0.71073 A, monoclinic P212121, a = 16.132(12) A, b = 21. 684(15) A, c = 27.30(3) A, 9611 independent reflections, R1 = 0. 0708]. As suggested by molecular mechanics modeling before the structure was known, the Ado ligand lies over the southern quadrant of the molecule, as is the case for AdoCbl. The most striking feature of the structure is disorder in the orientation of the adenine (Ade) moiety relative to the ribose of the Ado ligand. This was resolved with a two-state model in which in the major (0.57 occupancy) conformer the A16(O)-A11-A9(N)-A8 dihedral angle is 1.9 degrees and the Ade is virtually perpendicular to the corrin ring; in the minor conformer, the Ade is tilted down, and this dihedral is -48.7 degrees. The Co-C and axial Co-N bond lengths and the Co-C-C bond angle are quite similar to those in AdoCbl. The corrin ring is considerably flatter than that of AdoCbl, with a fold angle of 11.7 degrees. The molecule was successfully modeled by molecular mechanics (MM), and rotation of the Ado ligand relative to the corrin gave rise to four locally minimum structures with the Ado in the southern, eastern, northern, or western quadrant, with the southern conformation as the global minimum, as is the case with AdoCbl itself. Nuclear Overhauser effects (nOe's) observed by two-dimensional (2D) NMR were incorporated as restraints in molecular dynamics (MD) and simulated annealing (SA) calculations. A MD simulation at 300 K showed that only the southern conformation is populated with the Ado ligand confined to an arc from over C15 to over C12, while the Ade ring oscillates from perpendicular to parallel to the corrin ring. Twenty-seven structures were collected by MD-SA. Most of these annealed into the southern conformation, but examples of the other conformations were also found. The new analogue is a partially active coenzyme for the ribonucleotide reductase from Lactobacillus leichmanii with maximal activity that is 9.7% of that of AdoCbl itself, and a very high Km value (245 microM compared to 0.54 microM for AdoCbl). In addition, the rate constant for enzyme-induced carbon-cobalt bond cleavage of (alpha-ribo)AdoCbl is 160-fold smaller than that for AdoCbl, and only 1/3 as much cob(II)alamin is produced at the active site.

Adenosine↗

PubMed1998

Autonomous regulation of growth cone filopodia.

The fan-shaped array of filopodia is the first site of contact of a neuronal growth cone with molecules encountered during neuronal pathfinding. Filopodia are highly dynamic structures, and the "action radius" of a growth cone is strongly determined by the length and number of its filopodia. Since interactions of filopodia with instructive cues in the vicinity of the growth cone can have effects on growth cone morphology within minutes, it has to be assumed that a large part of the signaling underlying such morphological changes resides locally within the growth cone proper. In this study, we tested the hypothesis that two important growth cone parameters-namely, the length and number of its filopodia-are regulated autonomously in the growth cone. We previously demonstrated in identified neurons from the snail Helisoma trivolvis that filopodial length and number are regulated by intracellular calcium. Here, we investigated filopodial dynamics and their regulation by the second-messenger calcium in growth cones which were physically isolated from their parent neuron by neurite transection. Our results show that isolated growth cones have longer but fewer filopodia than growth cones attached to their parent cell. These isolated growth cones, however, are fully capable of undergoing calcium-induced cytoskeletal changes, suggesting that the machinery necessary to perform changes in filopodial length and number is fully intrinsic to the growth cone proper.

Animals↗

PubMed1998

Induction of bone formation using a recombinant adenoviral vector carrying the human BMP-2 gene in a rabbit spinal fusion model.

Bone marrow-derived mesenchymal stem cells are pluripotential cells that have the capacity to differentiate into an osteoprogenitor line. It has been demonstrated that BMP-2 can enhance this differentiation process. In an attempt to prolong the transforming effect of BMP-2, we used an adenoviral vector carrying the human BMP-2 gene to transduce marrow-derived mesenchymal stem cells of New Zealand white rabbits. Assays on tissue culture demonstrated that these cells indeed produced the BMP-2 protein. These transduced stem cells were then autologously reimplanted into the donor rabbits. The cells were placed in the intertransverse process area of five rabbits. In one out of the five rabbits, this resulted in the production of new bone which was demonstrable on both radiographic and histologic examination. We conclude that it is possible to successfully transduce mesenchymal stem cells with the gene for BMP-2 such that these cells will produce the BMP-2 protein in vitro. Further, the transduction results in transformation of these cells into an osteoprogenitor line capable of producing bone in vivo. These data suggest the feasibility of employing gene therapy using recombinant adenoviral vectors as a tool for enhancing spine fusion. Further work to improve the fidelity and longevity of the gene transfer is warranted.

Adenoviridae↗

PubMed1998

A synoptic climatological approach to forecast concentrations of sulfur dioxide and nitrogen oxides in Hong Kong.

The objective of this study is to develop an automated synoptic climatological procedure to forecast high air pollution concentrations in the most polluted synoptic categories. The procedure is able to identify air masses historically associated with high air pollution concentrations. The arrival of air mass can be predicted 24 or 48 h in advance with the use of the weather forecast data. The development and statistical basis of the procedure are discussed, and an analysis of the procedure's ability to forecast weather conditions associated with high air pollution concentrations is presented. In addition, the dataset of 24 weather variables from 1993 to 1995 is used to validate the procedure. The procedure predicts that 70.3 and 83.3% of total high and severe SO2 concentration days fall into the identified most polluted categories, and the corresponding figures for NOx are 47.8 and 73.7%. The agreement between observed and predicted values is generally good. The prediction models can explain about 58 and 45% of total variance for NOx and SO2 with RMSEs of 42.5 and 16.5 microg m(-3), respectively. They are smaller than 1 SD of the observations.

Journal Article↗

PubMed1998

NAGLU mutations underlying Sanfilippo syndrome type B.

Sanfilippo syndrome type B (mucopolysaccharidosis III B) is a rare autosomal recessive disease caused by deficiency of alpha-N-acetylglucosaminidase, one of the enzymes required for the lysosomal degradation of heparan sulfate. The gene for this enzyme, NAGLU, recently was isolated, and several mutations were characterized. We have identified, in amplified exons from nine fibroblast cell lines derived from Sanfilippo syndrome type B patients, 10 additional mutations: Y92H, P115S, Y140C, E153K, R203X, 650insC, 901delAA, P358L, A664V, and L682R. Four of these mutations were found in homozygosity, and only two were seen in more than one cell line. Thus, Sanfilippo syndrome type B shows extensive molecular heterogeneity. Stable transfection of Chinese hamster ovary cells, by cDNA mutagenized to correspond to the NAGLU missense mutations, did not yield active enzyme, demonstrating the deleterious nature of the mutations. Nine of the 10 amino acid substitutions identified to date are clustered near the amino or the carboxyl end of alpha-N-acetylglucosaminidase, suggesting a role for these regions in the transport or function of the enzyme.

Acetylglucosaminidase↗