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Biomedical subjects

S Cheng

Publications and source records attributed to S Cheng.

At least 55 records · Page 3Linked to original sources
PubMed2002

Influence of region of interest and bone size on calcaneal BMD: implications for the accuracy of quantitative ultrasound assessments at the calcaneus.

There is considerable technological diversity among quantitative ultrasound (QUS) devices used to assess osteoporosis. Because the distance between the transducer and the footplate remains constant, the location of the calcaneus measured will vary with foot size. This study was designed to quantify the variation in bone mineral density (BMD) between a manufacturer's region of interest (ROI_M), which is fixed relative to the footplate, and an anatomical region of interest (ROI_A), which is defined as 20% of calcaneal length. The effect of foot length and width on QUS variables measured using two Food and Drug Administration cleared QUS devices, the Sahara (Hologic) and the Achilles+ (Lunar) was assessed. 26 healthy subjects (12 male and 14 female), aged 22-54 years (35.6+/-10 years) and with foot lengths of 21.5 cm to 29.7 cm (25.1+/-2.3 cm) were recruited. QUS assessments were performed at the right calcaneus. In addition, a Hologic 4500 densitometer was used to measure the BMD of the calcaneus in the ROI_M and ROI_A. The sizes of the ROIs were approximated to the sizes of the transducers of the Sahara and Achilles+ devices. The results showed a significant difference in BMD between the two ROI locations for the Sahara device (BMD 0.642+/-0.135 g cm(-2) vs 0.616+/-0.114 g cm(-2), p=0.014), but no significant difference was found in BMD between the two locations for the Achilles device (BMD 0.661+/-0.120 g cm(-2) vs 0.662+/-0.123 g cm(-2), p=0.818). At the ROI_A, there was a significant difference in BMD between the two QUS devices (p<0.001). The correlation between QUS variables and BMD was slightly higher for the ROI_M (r=0.68-0.79, since this is site-matched) than the ROI_A (r=0.59-0.70) for the Achilles device, while for the Sahara device the correlations were r=0.35-0.40 and r=0.51-0.54, respectively. The smaller ROI of the Sahara device resulted in more than 50% of the subjects having BMD differences of greater than 5% between the ROI_A and the ROI_M, compared with only 20% of the subjects on the Achilles device. ROIs containing cortical bone edge and other soft tissues were found in 58% of cases for the Achilles device and 46% of cases for the Sahara device. The greatest differences occurred in very small and very large feet. Calcaneal length correlated significantly with Sahara speed of sound (SOS), and heel width correlated significantly with Achilles SOS. Heel width also correlated significantly with Sahara broadband ultrasound attenuation (BUA) but not Achilles+ BUA. These results suggest that variation in ROI and bone size might affect the accuracy of QUS measurements, since the calcaneus is heterogeneous both in terms of its external geometry and its internal structure and density.

Adult↗
PubMed2002

Spatial and dynamic simulation for Miyun Reservoir waters in Beijing.

In order to assist the water quality management in Miyun Reservoir, a spatial and dynamic simulation model system was built. In the model system, GIS was integrated with the WASP5 model. The integrated model system was then calibrated and verified in different sets of field data. The result showed that the integrated model system could characterize the Miyun Reservoir waters. Two scenarios were then designed and analyzed with the integrated model system. It was indicated that the water quality would improve if the cage fishery was banned, the algae blooms might occur in Miyun Reservoir if the low water stage ocurred but loads remained unchanged.

Animals↗
PubMed2001

A targeted dominant negative mutation of the thyroid hormone alpha 1 receptor causes increased mortality, infertility, and dwarfism in mice.

Mutations in the thyroid hormone receptor beta (TRbeta) gene result in resistance to thyroid hormone. However, it is unknown whether mutations in the TRalpha gene could lead to a similar disease. To address this question, we prepared mutant mice by targeting mutant thyroid hormone receptor kindred PV (PV) mutation to the TRalpha gene locus by means of homologous recombination (TRalpha1PV mice). The PV mutation was derived from a patient with severe resistance to thyroid hormone that has a frameshift of the C-terminal 14 aa of TRbeta1. We knocked in the same PV mutation to the corresponding TRalpha gene locus to compare the phenotypes of TRalpha1(PV/+) mice with those of TRbeta(PV/+) mice. TRalpha1(PV/+) mice were viable, indicating that the mutation of the TRalpha gene is not embryonic lethal. In drastic contrast to the TRbeta(PV/+) mice, which do not exhibit a growth abnormality, TRalpha1(PV/+) mice were dwarfs. These dwarfs exhibited increased mortality and reduced fertility. In contrast to TRbeta(PV/+) mice, which have a hyperactive thyroid, TRalpha1(PV/+) mice exhibited mild thyroid failure. The in vivo pattern of abnormal regulation of T3 target genes in TRalpha1(PV/+) mice was unique from those of TRbeta(PV/+) mice. The distinct phenotypes exhibited by TRalpha1(PV/+) and TRbeta(PV/+) mice indicate that the in vivo functions of TR mutants are isoform-dependent. The TRalpha1(PV/+) mice may be used as a tool to uncover human diseases associated with mutations in the TRalpha gene and, furthermore, to understand the molecular mechanisms by which TR isoforms exert their biological activities.

Animals↗
PubMed2001

A comparison between microsatellite analysis and cytology of urine for the detection of bladder cancer.

We have studied, in a blinded fashion, cytology and microsatellite analysis on urine sediments of 143 Chinese with or without bladder lesions. Microsatellite analysis succeeded in all 143 individuals, while cytology could not be performed on 42 subjects due to insufficient urine samples. Both microsatellite analysis and routine urine cytology succeeded in 81 bladder cancer patients. Seventy-three patients (90%) were identified by microsatellite analysis, while only 41 patients (51%) were identified by cytology. However, four patients were identified by routine cytology but not by microsatellite analysis. Our results proved that microsatellite analysis is more sensitive than routine cytology but the two methods are complementary to each other.

Adult↗
PubMed2001

Effect of templated quenched disorder on fluid phase equilibrium.

Templating offers a means to direct the structure of quenched disorder. We show here that changes in phase equilibrium due to the presence of quenched disorder can themselves be altered by templating. We calculate the phase diagram of a fluid in a collection of template-directed, quenched particles by solving a set of replica Ornstein-Zernike equations within the mean spherical approximation and show templating to enhance phase behavior, that is, shift the phase envelope upward from its location for a nontemplated system of identical available volume. This enhancement is due to an augmented number of fluid-fluid interactions.

Journal Article↗
PubMed2001

A man who inherited his SRY gene and Leri-Weill dyschondrosteosis from his mother and neurofibromatosis type 1 from his father.

We report on a man with neurofibromatosis type 1 (NF1) and Leri-Weill dyschondrosteosis (LWD). His father had NF1. His mother had LWD plus additional findings of Turner syndrome (TS): high arched palate, bicuspid aortic valve, aortic stenosis, and premature ovarian failure. The proband's karyotype was 46,X,dic(X;Y)(p22.3;p11.32). Despite having almost the same genetic constitution as 47,XXY Klinefelter syndrome, he was normally virilized, although slight elevation of serum gonadotropins indicated gonadal dysfunction. His mother's karyotype was mosaic 45,X[17 cells]/46,X,dic(X;Y)(p22.3;p11.32)[3 cells].ish dic(X;Y)(DXZ1 +,DYZ1 + ). The dic(X;Y) chromosome was also positive for Y markers PABY, SRY, and DYZ5, but negative for SHOX. The dic(X;Y) chromosome was also positive for X markers DXZ1 and a sequence < 300 kb from PABX, suggesting that the deletion encompassed only pseudoautosomal sequences. Replication studies indicated that the normal X and the dic(X;Y) were randomly inactivated in the proband's lymphocytes. LWD in the proband and his mother was explained by SHOX haploinsufficiency. The mother's female phenotype was most likely due to 45,X mosaicism. This family segregating Mendelian and chromosomal disorders illustrates extreme sex chromosome variation compatible with normal male and female sexual differentiation. The case also highlights the importance of karyotyping for differentiating LWD and TS, especially in patients with findings such as premature ovarian failure or aortic abnormalities not associated with isolated SHOX haploinsufficiency.

Adult↗
PubMed2001

Dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma: meta-analysis.

OBJECTIVE: To examine the dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma. DESIGN: Meta-analysis of placebo controlled, randomised clinical trials that presented data on at least one outcome measure of asthma and that used at least two different doses of fluticasone. SETTING: Medline, Embase, and GlaxoWellcome's internal clinical study registers. MAIN OUTCOME MEASURES: FEV(1), morning and evening peak expiratory flow, night awakenings, beta agonist use, and major exacerbations. RESULTS: Eight studies, with 2324 adolescents and adults with asthma, met the inclusion criteria. Data on doses of >500 microg/day were limited. The dose-response curve for the raw data began to reach a plateau at around 100-200 microg/day and peaked by 500 microg/day. A negative exponential model for the data, without meta-analysis, indicated that 80% of the benefit at 1000 microg/day was achieved at doses of 70-170 microg/day and 90% by 100-250 microg/day. A quadratic meta-regression showed that the maximum achievable efficacy was obtained by doses of around 500 microg/day. The odds ratio for patients remaining in a study at a dose of 200 microg/day, compared with higher doses, was 0.73 (95% confidence interval 0.49 to 1.08). Comparison of the standardised difference in FEV(1 )for an inhaled dose of 200 microg/day against higher doses showed a difference in FEV(1) of 0.13 of a standard deviation (-0.02 to 0.29). CONCLUSIONS: In adolescent and adult patients with asthma, most of the therapeutic benefit of inhaled fluticasone is achieved with a total daily dose of 100-250 microg, and the maximum effect is achieved with a dose of around 500 microg/day. However, these findings were limited by the lack of data on individual patients and by the paucity of dose-response studies that included doses of >500 microg/day.

Administration, Inhalation↗
PubMed2001

Inhaled human insulin treatment in patients with type 2 diabetes mellitus.

BACKGROUND: Despite demonstrated benefits, intensive insulin therapy has not gained widespread clinical acceptance for several reasons: Multiple daily injections are inconvenient, adherence is a concern, and the time-activity profile may not mimic normal insulin secretion. As such, alternate means of administering insulin are being evaluated. OBJECTIVE: To assess the efficacy and safety of pulmonary delivery of insulin in type 2 diabetic patients who require insulin. DESIGN: Randomized, open-label, 3-month study consisting of a screening visit, a 4-week baseline lead-in phase, and a 12-week treatment phase. SETTING: General clinical research center and outpatient research clinics. PATIENTS: 26 patients (16 men, 10 women) with type 2 diabetes (average age, 51.1 years; average duration of diabetes, 11.2 years). INTERVENTION: Patients received inhaled insulin before each meal plus a bedtime injection of ultralente insulin, performed home glucose monitoring, and had weekly adjustment of insulin dose; target level for preprandial plasma glucose was 5.55 to 8.88 mmol/L (100 to 160 mg/dL). MEASUREMENTS: Glycemic control (hemoglobin A(1c) level) obtained at baseline and monthly for 3 months. Pulmonary function tests were done at baseline and at the end of the study. RESULTS: Inhaled insulin treatment for 3 months significantly improved glycemic control compared with baseline: Mean hemoglobin A(1c) levels decreased by 0.0071 +/- 0.0072 (0.71% +/- 0.72%). Patients experienced an average of 0.83 mild to moderate hypoglycemic event per month; no severe events were recorded. Patients showed no significant weight gain or change in pulmonary function compared with baseline. CONCLUSIONS: Pulmonary delivery of insulin in type 2 diabetic patients who require insulin improved glycemic control, was well tolerated, and demonstrated no adverse pulmonary effects. Larger-scale studies are ongoing to provide long-term efficacy and safety data.

Administration, Inhalation↗
PubMed2001

Detecting bladder cancer in the Chinese by microsatellite analysis: ethnic and etiologic considerations.

BACKGROUND: Microsatellite analysis of urine sediments has shown promise as a highly sensitive and specific technique for the detection of bladder cancer. However, most studies have been conducted in Western countries with Caucasian subjects. We explored the potential of microsatellite analysis for detecting bladder cancer in Chinese people. METHODS: We performed microsatellite analysis of surgical specimens and urine sediment cells collected from Chinese patients with bladder tumors. Those microsatellite markers giving clearly readable patterns and showing susceptibility to alterations were used as a panel to detect primary tumors. A blinded study of additional patients with bladder cancer was performed to investigate the practical value of this panel for detecting bladder cancer. All statistical tests were two-sided. RESULTS: Thirty-eight bladder tumors and corresponding urine sediment specimens were initially screened for 60 microsatellite markers from 18 chromosomes. Nine markers, most of which were different from those that had been used for Western patients, with frequent alterations in the initial patients were selected for further analysis. In the subsequent blinded experiment, microsatellite alterations were observed in urine sediments from 22 (96%) of 23 patients with bladder cancer and from all three patients with inverted papilloma. None of the urine sediments from the one patient with bladder lipoma, from the one patient with neurofibroma, or from the 12 individuals without evidence of bladder tumor showed any microsatellite alterations. CONCLUSIONS: Microsatellite analysis of urine sediments could be a practical method for detecting bladder cancer in the Chinese. Our identification of different microsatellite markers highlights possible ethnic and etiologic disparities between the Chinese and Western bladder cancer patients.

Adult↗
PubMed2001

Molecular cloning, expression analysis, and functional characterization of connexin44.1: a zebrafish lens gap junction protein.

The connexin family of genes codes for proteins that oligomerize into a connexon of six subunits to form one half of the gap junction channel. Gap junctions are plasma membrane structures that mediate intercellular communication by joining the cytoplasm of two cells, allowing the passage of small molecules and metabolites, and contributing significantly to the maintenance of tissue homeostasis. The signaling mediated by these junctions appears to be necessary for the correct timing of key developmental events. This communication is especially important in the avascular lens where the intercellular passage of metabolites, second messengers, and ions is necessary to maintain the correct ionic balance in the lens fibre cells, and prevent cataract formation. To characterize the role that the connexin genes play in development, a novel connexin was cloned from zebrafish. A genomic clone was isolated that contained a 1,173 base open reading frame. The nucleotide sequence in this open reading frame shows extensive sequence similarity to mouse connexin50 (Cx50), chicken Cx45.6, sheep Cx49, and human Cx50. The protein encoded by this open reading frame contains 391 amino acids, with a predicted molecular weight of 44.1 kDa and a typical connexin transmembrane topology. By using the LN54 radiation hybrid panel, the Cx44.1 gene was mapped to linkage group 1. Whole-mount in situ hybridization and Northern blot analyses were performed on zebrafish embryos at various developmental stages to characterize the developmental expression of the Cx44.1 message. The ocular lens was the only tissue in which Cx44.1 transcripts were detected. The transcripts were first detected in the lens around 24 hr post fertilization and remained detectable until 120 hr post fertilization. Electrophysiological analysis of Cx44.1 channels revealed gating properties that were virtually identical to the mouse and chicken orthologues of Cx44.1.

Animals↗
PubMed2001

Clinical performance of a highly portable, scanning calcaneal ultrasonometer.

The aim of this study was to establish a normative database, assess precision, and evaluate the ability to identify women with low bone mass and to discriminate women with fracture from those without for a highly portable, scanning calcaneal ultrasonometer: the QUS-2. Fourteen hundred and one Caucasian women were recruited for the study. Among them were 794 healthy women 25-84 years of age evenly distributed per 10-year period to establish a normative database. Of these, 171 aged 25-34 years were defined as the young normal group for the purpose of T-score determination. Precision was assessed within 1 day (short-term) and over a 16-week period (long-term) in 79 women aged 25-84 years. Five hundred twenty-eight women ranging from 50 to 84 years of age with or without prevalent fractures of the spine, hip or forearm were measured to compare the QUS-2 with bone mineral density (BMD) of the hip and spine. Mean calcaneal broadband ultrasound attenuation (BUA) was constant in healthy women from 25 to 54 years of age and decreased with increasing age thereafter. Short-term precision, with and without repositioning of the heel, and long-term precision yielded comparable results (BUA SDs of 2.1-2.4 dB/MHz, coefficients of variations (CVs) of 2.5-2.9%). Calcaneal BUA was significantly correlated with BMD of the total hip (TH), femoral neck (FN) and lumbar spine (LS) in 698 women (r = 0.6-0.7, all p < 0.0001). A similar relationship was observed for LS BMD compared with either TH or FN BMD (r = 0.7, p < 0.0001). Prevalence of osteoporosis in our population (WHO criteria) was 20%, 17%, 21%, and 24% for BUA, BMD of the TH, FN and LS, respectively. Age-adjusted values for a 1 SD reduction in calcaneal BUA and TH and FN BMD predicted prevalent fractures of the spine, forearm, and hip with significant (p < 0.05) odds ratios of 2.3, 2.0 and 2.1, respectively. Areas under the receiver operating characteristic curves for age-adjusted bone mass values predicting prevalent fracture were 0.62 for BUA, 0.59 for TH BMD, 0.60 for FN BMD, and 0.57 for LS BMD; all statistically equivalent. We conclude that the QUS-2 calcaneal ultrasonometer exhibits reproducible clinical performance that is similar to BMD of the spine and hip in identifying women with low bone mass and discriminating women with fracture from those without.

Adult↗
PubMed2001

Ultrasound velocity and cortical bone characteristics in vivo.

Axial transmission of ultrasound along cortical bone may reflect a combination of material and structural properties of long bone cortices. The goal of this study was to determine the association of speed of sound (SOS) with cortical density (CoD), cortical wall thickness (CWT), and total cortical area (CoA). Quantitative ultrasound (QUS) and peripheral quantitative computed tomography (pQCT) were used to measure the above variables in the distal third of radius and the midshaft of tibia in 51 postmenopausal women aged 62 to 71 years. Univariate regression analysis showed that the site-specific CoD accounted for 34% of the variability in the radial SOS and 29% of that in the tibial SOS (p < 0.001 both). SOS was only moderately associated with radial CWT (R2 = 0.14, p < 0.05) and CoA (R2 = 0.12, p < 0.05), but not with tibial CWT nor CoA. After controlling for CoD, these dimension-related associations disappeared. Stepwise multiple regression analysis showed that CoD was the only significant determinant of radial SOS (adjusted R2 = 0.31), whereas for tibia, not only CoD but also the years since menopause were associated with SOS (adjusted R2 = 0.41). In conclusion, out of the studied macroscopic cortical variables, CoD (an apparent surrogate for material properties of bone) was the only determinant of SOS measured in vivo at radial and tibial shafts. The key question that still needs to be answered is whether the SOS information obtained from the peripheral long bone cortical shafts can be translated to describe the mechanical competence and quality of clinically pertinent bones (e.g. proximal femur) of a given individual.

Aged↗
PubMed2001

Molecular and cytogenetic alterations in early stage of carcinogenesis of human lung.

In an attempt to reveal the genetic and epigenetic abnormalities in early stage of carcinogenesis of human lung cancer, a human bronchial epithelial cell line was immortalized by transfection with the Simian virus early region genes (SV40T); the biological features of the stable transfected cells were compared to human non-small cell lung cancer (NSCLC) specimens. The immortalized bronchial epithelial cells did not develop tumors but premalignant lesions in animal models. However, several genetic changes, including chromosome deletion and aneuploidy, altered expression of oncogenes and tumor suppressor genes occur not only in invasive NSCLC (human specimens) but also in the early stage of lung carcinogenesis (premalignant lesions) in this transfection model.

Animals↗
PubMed2001

A novel multilocus genotyping assay to identify genetic predictors of stroke in sickle cell anaemia.

We describe a novel multilocus genotyping assay permitting simultaneous identification of 60 candidate markers for stroke in sickle cell anaemia (SCA). Based on cerebral magnetic resonance imaging (MRI), 69 patients were divided into stroke and control groups. The variant allele, CBS 278thr, showed protection from stroke, whereas the apoE3 allele showed a trend towards association with increased stroke risk. Several other variant alleles [TNFalpha (-308)A, CETP (-628)A, apoCIII (-641)A] showed a trend towards significant associations with stroke risk. These preliminary results on a small group of patients suggest that a multilocus genotyping assay may be valuable in identifying genes that increase the risk of stroke in SCA.

Adolescent↗
PubMed2001

Recurrent miscarriage and variant alleles of mannose binding lectin, tumour necrosis factor and lymphotoxin alpha genes.

Variant alleles of the mannose binding lectin (MBL) gene are associated with increased susceptibility to infection and polymorphisms of tumour necrosis factor and lymphotoxin alpha genes (TNF, LTA) are associated with increased severity of infection. Studies have associated recurrent miscarriage with low serum mannose binding lectin concentrations and premature membrane rupture and preterm delivery with elevated maternal and fetal levels of TNF and the TNF (- 308) polymorphism. In this study the frequencies of variant MBL, TNF and LTA alleles in 76 Caucasian couples with idiopathic recurrent miscarriage were compared with those in 69 Caucasian control couples with no history of miscarriage and at least one previous live birth. A new assay based on hybridization to immobilized sequence-specific oligonucleotides (SSO) was used to rapidly detect nine MBL, two TNF and two LTA sequence variants. The assay genotyped all the structural and promoter MBL variants known to influence serum MBL concentrations. This assay was more reliable than restriction digestion or nested allele-specific PCR for the structural variants at codon 54 or 52, respectively. Reliability for codon 57 alleles was not assessed because of the low frequency in this population. The MBL haplotype frequencies in antenatal controls were similar to those reported in other control populations. The frequencies of structural variant MBL genes and of low, medium and high MBL level haplotypes were similar in the recurrent miscarriage and control couples. The TNF and LTA haplotype frequencies were similar in the recurrent miscarriage and control couples. In this carefully defined population no association has been found between recurrent miscarriage and variant alleles of the MBL, TNF or LTA genes.

Abortion, Habitual↗
PubMed2001

Color Doppler imaging of the prostate: important adjunct to endorectal ultrasound of the prostate in the diagnosis of prostate cancer.

The purpose of this article is to evaluate color Doppler imaging (CDI) as an adjunctive tool to gray-scale ultrasound (US) in the diagnosis of prostate cancer and to correlate CDI-positive lesions to cancer grade. We retrospectively analyzed 619 consecutive patients who underwent prostate US, CDI, and biopsy because of abnormal digital rectal examination results or prostate-specific antigen levels. All had directed (into a specific lesion) biopsies or directed biopsies along with systematic four-quadrant or sextant biopsies, or systematic biopsy alone. Color Doppler imaging was compared with gray-scale findings and histologic results. There were 222 (35.9%) biopsy-proven cancers (n = 197) or prostatic intraepithelial neoplasia (n = 25). Of these, 106 (47.7%) had color-flow abnormalities. Of these 106 patients, 26 (24.5%), or 11.7% of all cancer patients, had relatively normal gray-scale US findings but had focal CDI abnormalities as the method of identification. Overall, 76.9% of these were moderate to high Gleason grades and were considered clinically significant lesions. Color Doppler imaging can identify a large number (11.7%) of clinically significant prostate cancers that are poorly seen by gray-scale US. Positive lesions on CDI are of clinical importance because 76.9% are histologically, moderately, or poorly differentiated. We recommend that CDI be used in all diagnostic and biopsy-guided US examinations of the prostate.

Journal Article↗
PubMed2001

The effect of delipidated deglycolipidated (DDMV) and heat-killed Mycobacterium vaccae in asthma.

Experimental and epidemiological evidence supports the hypothesis that exposure to mycobacteria has the potential to suppress the development of asthma and/or atopy and there are reports in the Chinese medical literature of repeated vaccination with inactivated BCG being effective in the management of asthma. Forty-three patients with stable moderately severe asthma who were skin prick test positive to house dust mite were randomized to receive two intradermal injections of either phosphate-buffered saline (placebo), heat-killed Mycobacterium vaccae (0.5 mg), or delipidated deglycolipidated Mycobacterium vaccae (DDMV) (0.05 mg). Markers of asthma severity were measured for 3 mo and blood eosinophil, IgE levels, and the T cell proliferative and cytokine responses were monitored. There were no significant differences between either treatment group and the placebo group for any of the outcome variables. There was also no difference between the treatment groups and placebo for eosinophil, IgE levels, or the T cell proliferative and cytokine response. The results indicate no effect of low dose intradermal DDMV or M. vaccae on asthma severity in patients with established asthma.

Adult↗