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T Duong

Publications and source records attributed to T Duong.

At least 19 recordsLinked to original sources
PubMed2004

Towards single molecule analysis in PDMS microdevices: from the detection of ultra low dye concentrations to single DNA molecule studies.

In this paper, we report on the performance of electrophoretical separation and laser-induced fluorescence (LIF) detection of dyes and fluorescently labeled biomolecules in poly(dimethylsiloxane) (PDMS) microdevices. The dyes fluorescein and fluorescein isothiocyanate (FITC) have been separated effectively in nM concentrations. Fluorescein injections gave linear concentration response in the range from 4 to 100 pM. As ultimate detection sensitivity, 100 fM injected fluorescein was obtained. Further, 100 fM injected fluorescein could be detected. This is to our knowledge the smallest electrokinetically injected dye concentration detected on a microchip. Injection studies of fluorescently labeled avidin revealed a theoretical detection limit of 25 nM for laser-induced fluorescence detection in good agreement with separations in glass chips. Furthermore, the injection of several and even one single DNA molecule using a PDMS cross injector has been demonstrated as well as free solution separation of lambda- and T2-DNA (60 pM each) in periodically structured channels.

Biopolymers↗
PubMed2003

Decline in mortality, AIDS, and hospital admissions in perinatally HIV-1 infected children in the United Kingdom and Ireland.

OBJECTIVE: To describe changes in demographic factors, disease progression, hospital admissions, and use of antiretroviral therapy in children with HIV. DESIGN: Active surveillance through the national study of HIV in pregnancy and childhood (NSHPC) and additional data from a subset of children in the collaborative HIV paediatric study (CHIPS). SETTING: United Kingdom and Ireland. PARTICIPANTS: 944 children with perinatally acquired HIV-1 under clinical care. MAIN OUTCOME MEASURES: Changes over time in progression to AIDS and death, hospital admission rates, and use of antiretroviral therapy. RESULTS: 944 children with perinatally acquired HIV were reported in the United Kingdom and Ireland by October 2002; 628 (67%) were black African, 205 (22%) were aged > or = 10 years at last follow up, 193 (20%) are known to have died. The proportion of children presenting who were born abroad increased from 20% in 1994-5 to 60% during 2000-2. Mortality was stable before 1997 at 9.3 per 100 child years at risk but fell to 2.0 in 2001-2 (trend P < 0.001). Progression to AIDS also declined (P < 0.001). From 1997 onwards the proportion of children on three or four drug antiretroviral therapy increased. Hospital admission rates declined by 80%, but with more children in follow up the absolute number of admissions fell by only 26%. CONCLUSION: In children with HIV infection, mortality, AIDS, and hospital admission rates have declined substantially since the introduction of three or four drug antiretroviral therapy in 1997. As infected children in the United Kingdom and Ireland are living longer, there is an increasing need to address their medical, social, and psychological needs as they enter adolescence and adult life.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Incident vertebral fractures and mortality in older women: a prospective study.

Older persons who have prevalent vertebral fractures have an increased risk of mortality. It is not known whether incident vertebral fractures are also associated with an increased risk of mortality. To determine whether older women with incident vertebral fractures have an increased risk of mortality, we conducted a prospective cohort study of 7233 community-dwelling older women aged 65 years or older who were enrolled in the Study of Osteoporotic Fractures. We measured incident vertebral fractures by radiographic morphometry of paired lateral spine X-rays taken an average of 3.7 years apart. We also collected information on baseline prevalent vertebral fractures; calcaneal bone density; anthropometric measures; and demographic, medical history, and lifestyle variables. Overall mortality was assessed and confirmed by receipt of death certificates. Over an average of 3.7 years, 389 (5.4%) women developed at least one incident vertebral fracture. During an additional 8 years of follow-up, 1617 (22%) women died. Women with at least one new fracture had an age-adjusted 32% increased risk of mortality (RH=1.32; 95% CI=1.10-1.58, P=0.003) compared to those without incident vertebral fractures. After adjustment for weight loss, physical frailty markers, and nine other predictors of mortality, there was no longer an independent association between incident vertebral fractures and mortality (RH=1.06; 95% CI=0.88 1.28). Older women with incident vertebral fractures have an increased risk of mortality that may be explained by weight loss and physical frailty.

Aged↗
PubMed2003

Tobramycin and gentamycin elution analysis between two in situ polymerizable orthopedic composites.

This research analyzed Tobramycin and Gentamycin elution characteristics for two antibiotic-impregnated bone composites: PMMA-based Simplex P and the novel, hybrid, bioactive, CORTOSS. Experimental results were correlated with composite hydrophilicity and antibiotic phase partitioning behaviors. The phase partitioning experiment was conducted to understand antibiotic solubility in aqueous environments. By comparing experimental results with calculated data, antibiotic release behavior was predicted. Total Tobramycin elution percentages from CORTOSS and Simplex P were 12.5 and 6.4%, respectively. Total Gentamycin elution percentages from CORTOSS and Simplex P were 6.95 and 10.17%, respectively. Phase partitioning data indicate 100% of Tobramycin remains in aqueous phases, being extremely hydrophilic. This is supported by its calculated theoretical value (log P = - 7.32). Results suggest that Tobramycin elution can be attributed to composite hydrophilicity as well as its high degree of hydrophilicity. Fifteen percent of Gentamycin distributes in hydrophobic phases (log P = - 4.22). Despite a lower Gentamycin hydrophilicity, its release was affected by its complexation with polar salts in the leaching buffer, thereby increasing its elution potential, making it appreciably water soluble. CORTOSS is more hydrophilic; therefore the migration of aqueous liquids into the polymer network of CORTOSS facilitates greater antibiotic elution compared with hydrophobic Simplex P.

Anti-Bacterial Agents↗
PubMed2002

Detunable transverse electromagnetic (TEM) volume coil for high-field NMR.

Most high-field MRI systems do not have the actively detuned body coils that are integral to clinical systems operating at 1.5T and lower field strengths. Therefore, many clinical applications requiring homogeneous volume excitation in combination with local surface coil reception are not easily implemented at high fields. To solve this problem for neuroimaging applications, actively detunable transverse electromagnetic (TEM) head coils were developed to be used with receive-only surface coils for signal-to-noise ratio (SNR) gains and improved spatial coverage from homogeneously excited regions. These SNR and field of view (FOV) gains were achieved by application of a detunable TEM volume coil to human brain imaging at 4T.

Brain↗
PubMed2001

Pneumocystis carinii pneumonia and cytomegalovirus infection in children with vertically acquired HIV infection.

OBJECTIVES: The outcome of Pneumocystis carinii pneumonia (PCP) in HIV-infected infants is poor, and the role of cytomegalovirus (CMV) co-infection in the course and outcome of PCP is unclear. This study describes the prevalence, clinical characteristics, management and changes in survival over time of vertically HIV-infected infants developing PCP and/or CMV infection. METHODS: Data on children with HIV, born in the UK and Ireland and reported to the National Study of HIV in Pregnancy and Childhood, with PCP and/or CMV were combined with clinical information collected from reporting paediatricians. RESULTS: By April 1998, 340 vertically HIV-infected children had been reported, of whom 93 had PCP and/or CMV, as their first AIDS indicator disease; 85 (91%) were infants. Among infants with PCP, 79% were born to mothers not diagnosed as HIV infected, and there was an independent and statistically significant association with breast-feeding, being black African, and developing CMV disease. Median survival after PCP and/or CMV was significantly better in those born between 1993 and 1998 compared with those born before 1993 (P = 0.009), and worse than after other AIDS diagnoses (P = 0.01). Infants with dual infection were more likely to be ventilated (P = 0.003) and receive corticosteroids (P = 0.002) than those with PCP alone. CONCLUSION: Although survival from PCP and CMV has improved over time, these remain serious and potentially fatal infections among infants in whom maternal HIV status is not recognized in pregnancy. Breast-feeding increases the risk of combined PCP and CMV infection, which is associated with severe disease.

AIDS-Related Opportunistic Infections↗
PubMed2001

Six and twelve month changes in bone turnover are related to reduction in vertebral fracture risk during 3 years of raloxifene treatment in postmenopausal osteoporosis.

We studied the relationship between change in bone turnover and vertebral fracture risk during raloxifene therapy using 3-year data from the MORE trial, where 2622 of the 7705 randomized women had measurement of bone markers at baseline and after 6 and 12 months participation. Change in bone turnover was significantly related to future risk of vertebral fracture, also after adjusting for baseline vertebral fracture status and BMD. Thus, for a decrease of 9.3 pg/l in serum osteocalcin after 1 year's raloxifene therapy, the odds ratio (OR) for a new vertebral fracture during 3 years was 0.69 (0.54-0.88), p = 0.003. Similarly, for a decrease of 5.91 microg/l in serum bone alkaline phosphatase, OR was 0.75 (0.62-0.92), p = 0.005. The change in BMD over 12 and 24 months was not related to fracture risk in any of the analyses. The strongest predictor for vertebral fracture was prevalent vertebral fracture--even during therapy. The predictive value of baseline BMD was in the same order of magnitude as bone turnover change during raloxifene treatment. In conclusion, the change in bone turnover is related to fracture risk during raloxifene therapy. In contrast the change in BMD is not related to fracture risk. The strongest predictor for vertebral fracture is prevalent vertebral fracture.

Alkaline Phosphatase↗
PubMed2001

Effects of the selective oestrogen receptor modulator-raloxifene-on calcium and PTH secretory dynamics in women with osteoporosis.

OBJECTIVES: A possible mechanism for the maintenance of bone mass by oestrogens and the selective oestrogen receptor modulator (SERM)-raloxifene-is an interaction with calciotropic hormones. We studied the effects of raloxifene on calcium-PTH homeostasis. PATIENTS AND MEASUREMENTS: Calcium and EDTA infusions were performed in 32 post-menopausal women with osteoporosis (BMD T score < - 2.5). This cross-sectional study was performed in the third year of the MORE (Multiple Outcomes of Raloxifene Evaluation) trial, a double-blind, placebo-controlled study. After an overnight fast, calcium glubionate (5 mg/kg BW*h), and after 2.5 h of test-free interval, Na3EDTA (40 mg/kg BW*h) were given intravenously. The duration of infusions was based on individual plasma total calcium before the calcium infusion (t = 0), the target calcium (2.60 and 1.95 mmol/l, respectively), and desired mean calcium change (0.010 mmol/L*min). Blood samples were taken at 0 and every 5 minutes of both infusions. Plasma PTH levels were fitted into an inversed sigmoidal relation with plasma calcium. The effect of raloxifene on calcium-PTH homeostasis was tested in linear regression models adjusted for age and BMI. Nine patients used placebo, 13 raloxifene 60 mg/day and 10 raloxifene 120 mg/day. RESULTS: Raloxifene use was associated with lower plasma albumin (40.7 +/- 1.8 vs. 38.0 +/- 2.0 and 38.5 +/- 2.3 g/l, for placebo, raloxifene 60 mg/day and raloxifene 120 mg/day, respectively, P = 0.01), lower plasma total calcium at t = 0 (2.28 vs. 2.24 and 2.21; +/- 0.07 mmol/L; P = 0.03), lower plasma total calcium at 50% of maximal PTH secretion (PTH set-point: 2.23 +/- 0.06 vs. 2.18 +/- 0.07 and 2.16 +/- 0.08 mmol/l, P = 0.06), and lower plasma non-suppressible PTH (0.84 +/- 0.19 vs. 0.75 +/- 0.10 and 0.73 +/- 0.05 pmol/l, P = 0.02). After correction for plasma albumin, the differences for plasma calcium at t = 0 and at PTH set-point were no longer significant. In contrast, the difference in PTH suppression during calcium load was not explained either by differences in plasma albumin or calcium. CONCLUSION: Raloxifene did not have any detectable effect on the PTH set-point. An effect on non-suppressible PTH secretion cannot be excluded.

Aged↗
PubMed2001

A global study of vitamin D status and parathyroid function in postmenopausal women with osteoporosis: baseline data from the multiple outcomes of raloxifene evaluation clinical trial.

Vitamin D deficiency leads to secondary hyperparathyroidism, increased bone turnover, and bone loss and, when severe, to osteomalacia. Vitamin D deficiency is common in elderly people, especially the institutionalized. The definition of vitamin D deficiency is hampered by the fact that large interlaboratory differences exist in assays for serum 25-hydroxyvitamin D (25OHD), the main circulating metabolite. The international Multiple Outcomes of Raloxifene Evaluation study, a large prospective intervention trial in postmenopausal women with osteoporosis, offered the opportunity to compare vitamin D status and parathyroid function throughout many countries over the world. For this study, baseline data were available from 7564 postmenopausal women from 25 countries on 5 continents. All women had osteoporosis, i.e. bone mineral density (BMD) at femoral neck or lumbar spine was lower than t-score -2.5, or they had 2 vertebral fractures. Serum 25OHD was measured by RIA, and serum PTH was measured by immunoradiometric assay. BMD was measured by dual x-ray absorptiometry. The mean (+/-SD) serum 25OHD was 70.8 +/- 30.9 nmol/L. A low serum 25OHD (<25 nmol/L) was observed in 4.1% of all women in the Multiple Outcomes of Raloxifene Evaluation study, ranging from 0% in south east Asia (very few patients) to 8.3% in southern Europe. Serum 25OHD was between 25-50 nmol/L in 24.3% of the women. Serum 25OHD showed a significant seasonal relationship, with lower values in all regions in winter. Serum PTH correlated negatively with serum 25OHD (r = -0.25; P < 0.001). This significant negative correlation was observed in all regions. When serum 25OHD was less than 25, 25-50, or more than 50 nmol/L, respectively, mean serum PTH levels were 4.8, 4.1, and 3.5 pmol/L, respectively (by ANOVA, P < 0.001). Similarly, mean alkaline phosphatase levels were 83.7, 79.1, and 75.7 U/L (P < 0.001), respectively, with increasing serum 25OHD. The effect of serum 25OHD on BMD was only significant for the BMD of the trochanter where a serum 25OHD level less than 25 nmol/L was associated with a 4% lower BMD. After 6 months of treatment with vitamin D(3) (400-600 IU/day) and calcium (500 mg/day), serum 25OHD increased from 70.8 +/- 29.8 to 92.3 +/- 28.6 nmol/L. Serum PTH decreased significantly after 6 months of treatment, and this decrease depended on baseline serum 25OHD. When baseline serum 25OHD was less than 25, 25-50, or more than 50 nmol/L, respectively, serum PTH decreased by 0.8, 0.5, or 0.2 pmol/L, respectively (P < 0.001). In conclusion, serum 25OHD was less than 25 nmol/L in 4% of the women, and this was associated with a 30% higher serum PTH. In 24% of the women serum 25OHD was between 25-50 nmol/L, associated with a 15% higher level of serum PTH compared with women with a serum 25OHD greater than 50 nmol/L. A low serum 25OHD level was also associated with higher serum alkaline phosphatase and lower BMD of the trochanter. Treatment with vitamin D(3) and calcium increased serum 25OHD and decreased serum PTH significantly; the effect was greater for lower baseline serum 25OHD.

Absorptiometry, Photon↗
PubMed2001

Effects of the selective estrogen receptor modulator, raloxifene, on the somatotropic axis and insulin-glucose homeostasis.

Raloxifene is the first selective estrogen receptor modulator registered for the prevention and treatment of postmenopausal osteoporosis. In addition to direct effects on bone cells, estrogen and raloxifene may act indirectly via changes in hormonal homeostasis. However, the menopause-related decrease in serum insulin-like growth factor I (IGF-I) and the increase in insulin or glucose are not always reversed by estrogen replacement. Especially orally administered estrogen was reported to decrease serum IGF-I levels. Understanding the effects of estrogens and raloxifene on the GH-IGF axis and insulin-glucose homeostasis are important because of their link to bone metabolism and cardiovascular health. We investigated the effects of raloxifene on the GH-IGF-I axis and insulin-glucose homeostasis in a cross-sectional study in the third year of the Multiple Outcomes of Raloxifene Evaluation trial, a double blind, placebo-controlled, prospective study in postmenopausal women with osteoporosis (T-score of -2.5 or less or at least two moderate vertebral fractures). Patients with diabetes mellitus were excluded from this additional study. A fasting blood sample was obtained (0 h), and women received an sc injection of 0.05 mg recombinant human GH (Humatrope)/kg BW. The second blood sample was obtained 24 h later (24 h). GH, IGF-I, IGF-binding protein-3 (IGFBP-3), insulin, and glucose were measured. Group characteristics were tested by nonparametric ANOVA. The dose-response to raloxifene was tested by linear regression models, with age and body mass as covariates. Seven women were taking placebo, 16 were taking raloxifene (60 mg/day), and 9 were taking raloxifene (120 mg/day). Patients from the 60 mg raloxifene group were the oldest (mean +/- SD, 64.4 +/- 4.2 vs. 69.3 +/- 6.9 and 63.3 +/- 5.9 yr for placebo, 60 mg/day raloxifene, and 120 mg/day raloxifene, respectively; P = 0.05). Compared with placebo users, patients taking raloxifene had higher body mass index (24.7 +/- 1.7 vs. 25.0 +/- 3.1 and 28.8 +/- 5.8 kg/m(2); P = 0.03). At 0 h, raloxifene use was associated with lower IGF-I/IGFBP-3 ratio (4.3 +/- 0.7 vs. 2.9 +/- 0.7 and 3.0 +/- 0.7 nmol/mg; P = 0.001) and insulin/glucose ratio (13.7 +/- 5.2 vs. 11.9 +/- 5.9 and 9.5 +/- 2.3 pmol/mmol; P = 0.04). Similarly, raloxifene use was associated with lower IGF-I/IGFBP-3 and insulin/glucose ratios at 24 h (P = 0.01 and 0.07). Glucose, GH, and IGFBP-3 levels were similar among the groups (0.12 < P < 0.67). In conclusion, raloxifene use is associated with decreased serum IGF levels and insulin/glucose ratio before and 24 h after one rhGH injection in nondiabetic postmenopausal women with osteoporosis. Therefore, raloxifene may decrease liver sensitivity to GH. Other explanations are increased clearance or increased tissue sensitivity to IGF-I or insulin. The raloxifene-induced increases in bone mineral density do not appear to be mediated by reversing the age- and menopause-related decreases in IGF-I levels. The results of this small cross-sectional study need confirmation by longitudinal studies.

Aged↗
PubMed2000

Low fractional calcium absorption increases the risk for hip fracture in women with low calcium intake. Study of Osteoporotic Fractures Research Group.

BACKGROUND: Decreased ability to absorb calcium with age limits adaptation to low calcium intake and is thought to lead to secondary hyperparathyroidism and increased risk for hip and other fractures. However, the associations between fractional calcium absorption, dietary calcium intake, and risk for fracture have never been studied. OBJECTIVE: To determine whether low fractional calcium absorption in women with low calcium intake increases the risk for subsequent hip and other nonspine fractures. DESIGN: Prospective cohort study. SETTING: Four clinical centers in Baltimore County, Maryland; Portland, Oregon; Minneapolis, Minnesota; and the Monongahela Valley, Pennsylvania. PARTICIPANTS: 5452 nonblack women 69 years of age or older participating in the fourth examination of the Study of Osteoporotic Fractures. MEASUREMENTS: Fractional calcium absorption was measured by using a 3-hour single isotope (45Ca) technique. Incident fractures were identified prospectively and were confirmed by radiographic report. RESULTS: During an average of 4.8 years, 729 women (13%) experienced at least one nonspine fracture; 153 of these women had hip fractures. After adjustment for age, women with lower fractional calcium absorption were at increased risk for hip fracture (relative risk per 1-SD [7.7%] decrease in fractional calcium absorption, 1.24 [95% CI, 1.05 to 1.48]). Women with low fractional calcium absorption and low calcium intake were at greatest risk for subsequent hip fracture; among women whose dietary calcium intake was less than 400 mg/d, those who had fractional calcium absorption at or below the median value of 32.3% had a 2.5-fold (CI, 1.29-fold to 4.69-fold) increase in risk for hip fracture compared with those who had greater absorption efficiency. Fractional calcium absorption was not related to risk for other nonspine fractures (relative risk per 1-SD [7.7%] decrease in fractional calcium absorption, 1.05 [CI, 0.96 to 1.14]). CONCLUSIONS: In elderly women, low fractional calcium absorption in the setting of low calcium intake increases the risk for hip fracture. Our findings support the hypothesis of type II osteoporosis, which postulates that decreased calcium absorption is an important risk factor for hip fracture in older persons.

Aged↗
PubMed2000

Epidemiology of pneumothorax in England.

BACKGROUND: Little is known of the epidemiology of pneumothorax. Routinely available data on pneumothorax in England are described. METHODS: Patients consulting in primary care with a diagnosis of pneumothorax in each year from 1991 to 1995 inclusive were identified from the General Practice Research Database (GPRD). Emergency hospital admissions for pneumothorax were identified for the years 1991-4 from the Hospital Episode Statistics (HES) data. Mortality data for England & Wales were obtained for 1950-97. Analyses of pneumothorax rates by age and sex were performed for all data sources. Seasonal and geographical analyses were carried out for the HES data. RESULTS: The overall person consulting rate for pneumothorax (primary and secondary combined) in the GPRD was 24. 0/100 000 each year for men and 9.8/100 000 each year for women. Hospital admissions for pneumothorax as a primary diagnosis occurred at an overall incidence of 16.7/100 000 per year and 5.8/100 000 per year for men and women, respectively. Mortality rates were 1. 26/million per year for men and 0.62/million per year for women. The age distribution in both men and women showed a biphasic distribution for both GP consultations and hospital admissions. Deaths showed a single peak with highest rates in the elderly. There was an urban-rural trend observed for hospital admissions in the older age group (55+ years) with admission rates in the conurbations significantly higher than in the rural areas. Analysis for trends in mortality data for 1950-97 showed a striking increase in the death rate for pneumothorax in those aged 55+ years between 1960 and 1990, with a steep decline in the 1990s. Mortality in the younger age group (15-34 years) remained low and constant. CONCLUSION: There is evidence of two epidemiologically distinct forms of spontaneous pneumothorax in England. The explanation for the rise and fall in mortality for secondary pneumothorax is obscure.

Adolescent↗
PubMed1999

Vertical transmission rates for HIV in the British Isles: estimates based on surveillance data.

OBJECTIVE: To estimate and interpret time trends in vertical transmission rates for HIV using data from national obstetric and paediatric surveillance registers. DESIGN: Prospective study of HIV infected women reported through obstetric surveillance. HIV infection status of the child and onset of AIDS were reported through paediatric surveillance. Rates of vertical transmission and progression to AIDS rate were estimated by methods that take account of incomplete follow up of children with indeterminate infection status and delay in AIDS reporting. SETTING: British Isles. SUBJECTS: Pregnant women infected with HIV whose infection was diagnosed before delivery, and their babies. MAIN OUTCOME MEASURES: Mother to child transmission of infection and progression to AIDS in children. RESULTS: By January 1999, 800 children born to diagnosed HIV infected women who had not breast fed had been reported. Vertical transmission rates rose to 19.6% (95% confidence interval 8. 0% to 32.5%) in 1993 before falling to 2.2% (0% to 7.8%) in 1998. Between 1995 and 1998 use of antiretroviral treatment increased significantly each year, reaching 97% of live births in 1998. The rate of elective caesarean section remained constant, at around 40%, up to 1997 but increased to 62% in 1998. Caesarean section and antiretroviral treatment together were estimated to reduce risk of transmission from 31.6% (13.6% to 52.2%) to 4.2% (0.8% to 8.5%). The proportion of infected children developing AIDS in the first 6 months fell from 17.7% (6.8% to 30.8%) before 1994 to 7.2% (0% to 15. 7%) after, coinciding with increased use of prophylaxis against Pneumocystis carinii pneumonia. CONCLUSIONS: In the British Isles both HIV related morbidity and vertical transmission are being reduced through increased use of interventions.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Functional and structural diversity of the human Dickkopf gene family.

Wnt proteins influence many aspects of embryonic development, and their activity is regulated by several secreted antagonists, including the Xenopus Dickkopf-1 (xDkk-1) protein. xDkk-1 inhibits Wnt activities in Xenopus embryos and may play a role in induction of head structures. Here, we characterize a family of human Dkk-related genes composed of Dkk-1, Dkk-2, Dkk-3, and Dkk-4, together with a unique Dkk-3 related protein termed Soggy (Sgy). hDkks 1-4 contain two distinct cysteine-rich domains in which the positions of 10 cysteine residues are highly conserved between family members. Sgy is a novel secreted protein related to Dkk-3 but which lacks the cysteine-rich domains. Members of the Dkk-related family display unique patterns of mRNA expression in human and mouse tissues, and are secreted when expressed in 293T cells. Furthermore, secreted hDkk-2 and hDkk-4 undergo proteolytic processing which results in cleavage of the second cysteine-rich domain from the full-length protein. Members of the human Dkk-related family differ not only in their structures and expression patterns, but also in their abilities to inhibit Wnt signaling. hDkk-1 and hDkk-4, but not hDkk-2, hDkk-3 or Sgy, suppress Wnt-induced secondary axis induction in Xenopus embryos. hDkk-1 and hDkk-4 do not block axis induction triggered either by Xenopus Dishevelled (Xdsh) or Xenopus Frizzled-8 (Xfz8), both of which function to transduce signals from Wnt ligands. Thus, hDkks 1 and 4 may inhibit Wnt activity by a mechanism upstream of Frizzled. Our findings highlight the structural and functional heterogeneity of human Dkk-related proteins.

Amino Acid Sequence↗
PubMed1999

Characterization of NFkappaB activation by detection of green fluorescent protein-tagged IkappaB degradation in living cells.

Activation of the transcription factor NFkappaB requires rapid degradation of its inhibitor, IkappaBalpha. To facilitate the study of IkappaBalpha degradation, we fused IkappaBalpha protein to enhanced green fluorescent protein to construct IkappaBalpha-enhanced green fluorescent protein (IG). We demonstrated by both flow cytometry and Western blot analysis that the half-life of IG in the presence of human tumor necrosis factor (TNF) alpha is approximately 5 min, which is similar to the half-life of native IkappaBalpha. The degradation coincided with NFkappaB translocation from the cytoplasm to the nucleus and NFkappaB-mediated induction of transcription. Phorbol 12-myristate 13-acetate (PMA), but not forskolin, also induces degradation of IG fusion protein. The half-life of IG in the presence of PMA is approximately 15 min, longer than when induced with TNFalpha. Co-treatment with TNFalpha and PMA did not result in a synergistic effect on IG degradation, although they stimulate different kinases in two different signaling pathways. Degradation of IG was inhibited by mutations at serine residues 32 and 36, which are the target sites of the phosphorylation modification that initiates degradation of IkappaBalpha. We also demonstrated that basal degradation of IG in the presence of cycloheximide is inhibited by such mutations, suggesting that basal degradation of IkappaBalpha also requires phosphorylation as the signal for degradation. Finally, we showed that the rate of TNFalpha-induced degradation of IG remains almost constant throughout the cell cycle, except at the mitotic phase, in which IG degrades more slowly.

DNA-Binding Proteins↗
PubMed1999

Selective versus universal antenatal HIV testing: epidemiological and implementational factors in policy choice.

OBJECTIVE: To develop an epidemiological basis for economic analyses of selective and universal antenatal screening strategies, and to apply it to the UK. METHODS: The prevalence of higher-risk women and the prevalence of undiagnosed infection within groups of high-risk and low-risk women was estimated from surveillance and survey data. The numbers of women tested and the numbers of infected women who would be identified by universal and selective strategies were then calculated under a range of assumptions about the identification of higher-risk women and acceptance of testing. RESULTS: In higher-risk women estimated prevalence of undiagnosed infection was between 0.06% and 2.8%, comparing well with independent estimates. In low-risk women, estimates ranged from 0.014% in London to 0.002% in the rest of the UK. If uptake among the high-risk women was the same in selective and universal strategies, universal testing would entail testing between 7100 (London) and 50000 (rest of England) additional women to detect an additional case. However, if selective screening identified only 60% of those at high risk and achieved only 60% acceptance compared with a universal programme, then universal screening would require only 1150 additional women to identify one additional case in London, compared to 6470 in Scotland and 13140 in the rest of the UK. CONCLUSIONS: Overall prevalence does not form an adequate basis for determining screening strategy. Instead, universal screening can be justified either because the prevalence of HIV in the low-risk group is sufficiently high, or because it achieves sufficiently higher uptake relative to selective screening among those at higher risk.

Female↗
PubMed1999

Non-participation bias in unlinked anonymous HIV-prevalence surveys in England and Wales.

The objective was to assess the potential bias in unlinked anonymous HIV-seroprevalence surveys from objections to specimens being included. Objection rates in seroprevalence surveys were examined. Statistically large clusters of objections were considered to be the result of health care worker behaviour, and were disregarded. Underlying objection rates were estimated from remaining data and compared to seroprevalence. Overall objection rates approached or exceeded seroprevalence in many participating centres. However, underlying objection rates declined with time while prevalences were generally unchanging. Also, underlying rates correlated poorly with observed seroprevalences. Findings were therefore consistent with processes producing the clusters of objections and underlying objection rates independently of serostatus of individuals. Although national seroprevalence estimates produced by the surveys are reasonably free from objection bias, regional seroprevalence estimates outside London remain vulnerable to bias as a result of some centres returning data whose quality cannot be guaranteed.

Bias↗