Is voluntary counselling and testing of drug users in China feasible?
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China↗
Biomedical subjects
Y Lu
Publications and source records attributed to Y Lu.
Fhit protein is preferentially expressed in the nucleus of monocyte-derived cells and its possible biological significance.
The FHIT gene encompassing the most active common human fragile region, FRA3B, has been proposed as a tumour suppressor gene for important common human carcinomas. The mechanism in which Fhit protein exerts its tumour suppressor activity is still obscure. To further understand the Fhit function associated with its intracellular localization we have investigated its cellular localization and distribution in human normal and cancerous tissues. Data of 1500 samples from immunohistochemistry showed that Fhit protein was preferentially and stably expressed in the nucleus of monocyte-derived or histiocytic lineage cells including monocytes of the circulating blood cells, macrophages of the connective tissue, Kupffer cells of the liver, alveolar macrophages or dust cells of the lung, osteoclasts of bone, microglia of the brain, epithelioid cells under chronic inflammatory conditions, foreign-body giant cells, Langerhans cells of the epidermis and dendritic cells of various kinds of human tissue, although the protein could also be infrequently observed in the nucleus of some quiescent epithelial cells. In active cells other than histiocytes, Fhit protein was detected either in cytoplasm or was negative. Neurons expressed Fhit strongly and neuroglial cells did so moderately but only in the cytoplasm. There was no Fhit protein detected in the neutrophils, lymphocytes, plasma cells and lipocytes. The present data showes that the stable nuclear localization of Fhit is not only a special marker for histiocytes with various morphologies but also may suggest the other function concerning Fhit as a signaling molecule related to anti-proliferation function. The detailed biological function related to nuclear localization of Fhit protein in the histiocytes remains to be further studied.
Acid Anhydride Hydrolases↗
A pharmacokinetic model of the gastrointestinal tract consisting of two segments can describe the concentration-time course of itraconazole.
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Administration, Oral↗
Prospective study of a new serological test (ASSURE TB Rapid Test) for the diagnosis of pulmonary tuberculosis.
OBJECTIVE: To prospectively compare a rapid tuberculosis serological test, ASSURE TB Rapid Test, with traditional smear and culture methods for the diagnosis of pulmonary tuberculosis (PTB). DESIGN: All consecutive in-patients aged > or = 18 years suspected of having active PTB and admitted between June 2001 and March 2003 were tested with three sputum samples for smear and culture of Mycobacterium tuberculosis and serology (done within 3 days). RESULTS: Of 238 patients initially enrolled (male: female 2.5:1, mean age 56.6 years), the final analysis included 216 patients. For the final diagnosis of PTB, the sensitivity and specificity of the serological test were respectively 60.2% (95%CI 50.5-69.1) and 82.3% (95%CI 74.2-88.2) compared to 53.4% (95%CI 43.8-62.7) and 98.2% (95%CI 93.8-99.5) for the smear test. A combination of smear and serology provided an increased sensitivity of 74.8% (95%CI 65.6-82.2), but a lower specificity of 80.5% (95%CI 72.3-86.8). CONCLUSION: The new serological test showed a moderate increase in sensitivity but a decrease in specificity compared to smear examination. The combination (smear + serology) test further increased the sensitivity while maintaining a moderate specificity.
Adolescent↗
Gene therapeutic treatment of pancreatic cancer based on injection of pcDNA3.1/CCK plasmid with xenogeneic homologous cholecystokinin.
AIM: To study the therapeutic effect of recombinant plasmid pcDNA3.1/CCK containing porcine gene of cholecystokinin (CCK). METHODS: The confirmed fragments of porcine CCK cDNA were cloned into the pcDNA3.1 vector. Recombinant plasmid pcDNA3.1/CCK was injected into the muscles of Syrian golden hamsters. Before gene transfer, orthotopic tumor model and liver metastasis model of hamster pancreatic cancer have been established by injection of 1 x 10(6) PGHAM-1 cells into the pancreas and spleen of golden hamsters. Then the CCK expression in vivo and the tumor inhibiting effect were analyzed. RESULTS: Our data revealed that recombinant plasmid pcDNA3.1/CCK had long-term expression in hamsters and induced generation of specific antibody. Antibody level correlated with the number of inoculations. Compared to the control, significant reduction in tumor volume, decrease in number of liver metastasis and a remarkable enhancement of survival rate were detected. CONCLUSION: Intramuscular injection of recombinant plasmid pcDNA3.1/CCK has significant antitumor and antimetastatic effect in vivo.
Animals↗
Reduction of sampling bias of odds ratios for vertebral fractures using propensity scores.
INTRODUCTION: Assessment of the predictive power of a newly introduced diagnostic technique with regard to fracture risk is frequently limited by the enormous costs and long time periods required for prospective studies. A preliminary estimate of predictive power usually relies on cross-sectional case-control studies in which bone measurements of normal and fractured subjects are compared. The measured discriminatory power is taken as an estimate of predictive power. Because of possible sample selection bias, study participants may have different bone mineral density (BMD) values, and fractured patients may have fractures of different severity levels. The same diagnostic techniques for the measured discriminatory power, expressed as odds ratios, will differ among studies with different patient and control populations. METHODS: In this paper, we propose a weighted logistic regression approach to adjust the odds ratio in order to reduce the effect of sampling bias. The weight is derived from age, deformity severity, BMD, and the interactions of these, using the propensity score theory and reference population data. RESULTS: Simulation examples using data from the Osteoporosis and Ultrasound Study (OPUS) demonstrate that such a procedure can effectively reduce the estimation bias of odds ratios introduced by sampling differences, such as for dual x-ray absorptiometry (DXA) scans of the spine and hip as well as various quantitative ultrasound techniques. The derived estimated odds ratios are substantially less biased, and the corresponding 95% confidence intervals contain the true odds ratios from the population data. CONCLUSIONS: We conclude that a statistical correction procedure based on propensity scores and weighted logistic regression can effectively reduce the effect of sampling bias on the odds ratios calculated from cross-sectional case-control studies. For a new diagnostic technique, hip BMD and deformity severity information are necessary and likely sufficient to derive the propensity scores required to adjust the measured standardized odds ratios.
Adult↗
3.0 vs 1.5 T MRI in the detection of focal cartilage pathology--ROC analysis in an experimental model.
OBJECTIVE: To use receiver operator characteristics (ROC) analysis for assessing the diagnostic performance of three cartilage-specific MR sequences at 1.5 and 3 T in detecting cartilage lesions created in porcine knees. DESIGN: Eighty-four cartilage lesions were created in 27 porcine knee specimens at the patella, the medial and lateral femoral and the medial and lateral tibial cartilage. MR imaging was performed using a fat saturated spoiled gradient echo (SPGR) sequence (in plane spatial resolution/slice thickness: 0.20 x 0.39 mm2/1.5 mm) and two fat saturated proton density weighted (PDw) sequences (low spatial resolution: 0.31 x 0.47 mm2/3 mm and high spatial resolution: 0.20 x 0.26 mm2/2 mm). The images were independently analyzed by three radiologists concerning the absence or presence of lesions using a five-level confidence scale. Significances of the differences for the individual sequences were calculated based on comparisons of areas under ROC curves (A(Z)). RESULTS: The highest A(Z)-values for all three radiologists were consistently obtained for the SPGR (A(Z) = 0.84) and the high-resolution (hr) PDw (A(Z) = 0.79) sequences at 3T. The corresponding A(Z)-values at 1.5 T were 0.77 and 0.69; the differences between 1.5 and 3 T were statistically significant (P < 0.05). A(Z)-values for the low-resolution PDw sequence were lower: 0.59 at 3 T and 0.55 at 1.5 T and the differences between 1.5 and 3T were not significant. CONCLUSION: With optimized hr MR sequences diagnostic performance in detecting cartilage lesions was improved at 3 T. For a standard, lower spatial resolution PDw sequence no significant differences, however, were found.
Animals↗
Congenital heart defects and genetic variants in the methylenetetrahydroflate reductase gene.
BACKGROUND: Most non-syndromic congenital heart defects (CHD) are caused by a complex interaction between maternal lifestyle factors, environmental exposures, and maternal and fetal genetic variants. Maternal periconceptional intake of folic acid containing vitamin supplements is reported to decrease the risk of CHD. The 677C-->T and 1298A-->C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene decrease enzyme activity. OBJECTIVE: To examine the relation between CHD and maternal and fetal MTHFR polymorphisms. METHODS: 375 nuclear families were studied. The transmission/disequilibrium test was used to test for transmission distortion in complete triads. A log-linear approach was used to test for associations between CHD and maternal and offspring polymorphisms, and to estimate independently the contributions of maternal and fetal variants to relative risks. Haplotype frequencies were estimated and a haplotype transmission disequilibrium test carried out. RESULTS: The 1298C allele was transmitted less often than expected (p = 0.0013). There was no distortion in the transmission of the 677T allele, neither was there evidence of a parent of origin effect in the transmission of either of the single nucleotide polymorphisms. The 677C-1298C haplotype was also transmitted less often than expected (p = 0.0020). The relative risk associated with inheriting one copy of the 1298C allele was 0.64 (95% confidence interval, 0.48 to 0.87) and the that associated with inheriting two copies of the 1298C allele, 0.38 (0.21 to 0.70). CONCLUSIONS: The apparent protective effect of the MTHFR 1298C allele against CHD could have several explanations and further study is needed.
Alleles↗
Towards standardization of dual X-ray absorptiometry (DXA) at the forearm: a common region of interest (ROI) improves the comparability among DXA devices.
Manufacturer-implemented regions of interest (ROIs) to determine the bone mineral density (BMD) at the forearm are currently not standardized across dual X-ray absorptiometry (DXA) devices. We hypothesized that their differences introduce considerable variation in measurement results for forearm BMD when taken on different devices, and that a ROIs common to all devices with standardized placement and size significantly improve device comparability. The common ROI was defined to have a fixed length of 2 cm and to extend proximally from the location where the ulna and radius bones superimpose on the DXA image. The effects of universal standardization of forearm BMD were combined with and compared to those of the common ROI. They were drawn on 91 female study participants (ages 20-80 years, 10 per decade) who were scanned on Hologic QDR-4500, Aloka DCS-600EX, GE Lunar PIXI and Norland pDEXA DXA scanners. For all device combinations, manufacturer-implemented ROI root mean-square errors were significantly higher than for the common ROI, suggesting that implementing an ROI with common design on all scanners is a good way to reduce interdevice variability. When manufacturer-implemented ROIs were universally standardized root mean-square error (RMSE) values were less different from that of the nonstandardized Common ROI, suggesting that universal standardization can further improve interdevice comparability even when a common ROI such as the one implemented here is used. ROI standardization dramatically improves interdevice comparability.
Absorptiometry, Photon↗
Antioxidant activity in lingonberries (Vaccinium vitis-idaea L.) and its inhibitory effect on activator protein-1, nuclear factor-kappaB, and mitogen-activated protein kinases activation.
Lingonberry has been shown to contain high antioxidant activity. Fruits from different cultivars of lingonberry (Vaccinium vitis-idaea L.) were evaluated for fruit quality, antioxidant activity, and anthocyanin and phenolic contents. The fruit soluble solids, titratable acids, antioxidant capacity, and anthocyanin and phenolic contents varied with cultivars. Lingonberries contain potent free radical scavenging activities for DPPH*, ROO*, *OH, and O2*- radicals. Pretreatment of JB6 P+ mouse epidermal cells with lingonberry extracts produced a dose-dependent inhibition on the activation of activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) induced by either 12-O-tetradecanoylphorbol-13-acetate (TPA) or ultraviolet-B (UVB). Lingonberry extract blocked UVB-induced phosphorylation of the mitogen-activated protein kinase (MAPK) signaling members ERK1, ERK2, p38, and MEK1/2 but not JNK. Lingonberry extract also prevented TPA-induced phosphorylation of ERK1, ERK2, and MEK1/2. Results of soft agar assays indicated that lingonberry extract suppressed TPA-induced neoplastic transformation of JB6 P(+) cells in a dose-dependent manner. Lingonberry extract also induced the apoptosis of human leukemia HL-60 cells in a dose-independent manner. These results suggest that ERK1, ERK2, and MEK1/2 may be the primary targets of lingonberry that result in suppression of AP-1, NF-kappaB, and neoplastic transformation in JB6 P(+) cells and causes cancer cell death by an apoptotic mechanism in human leukemia HL-60 cells.
Antioxidants↗
Modified anthrax fusion proteins deliver HIV antigens through MHC Class I and II pathways.
T cell-based HIV vaccine candidates have focused on eliciting both CD4- and CD8-mediated responses. One challenge in vaccine development is the successful introduction and presentation of exogenous antigen to elicit an immune response. Modified bacterial toxins have been studied extensively as intracellular delivery agents because of their unique capability to translocate antigen across the cell membrane without affecting cell viability. Modified anthrax toxin lethal factor (LFn) fusion protein is able to effectively induce anti-HIV cytotoxic T lymphocytes in the absence of protective antigen (PA) and is being evaluated as a vaccine candidate. Here we describe, for the first time, the processing and presentation of LFn fusion proteins by the MHC Class II pathway. The ability of LFn--HIV to induce both CD8- and CD4-mediated responses may have relevance in current approaches to vaccine design. Furthermore, the translocation and presentation of antigens occurs in the absence of PA, which proposes a modified molecular mechanism of antigen presentation by the anthrax toxin model. Additionally, we found that LFn--HIV is specific and sensitive in detecting HIV-specific CD4(+) and CD8(+) T cell responses in T cell assays, further broadening the value of this antigen delivery system as a useful immunologic tool.
Antigen Presentation↗
Dye sensitization of the anatase (101) crystal surface by a series of dicarboxylated thiacyanine dyes.
Dye sensitization of the single crystal anatase (101) surface was studied using a structurally similar series of dicarboxylated thiacyanine dyes that bind to the oxide surface through their carboxylate groups. An ultraviolet (UV) light treatment of the anatase (101) surfaces, immediately prior to dye adsorption, improved both the reproducibility of dye coverage and the incident photon-to-current efficiencies (IPCE) for sensitization. The UV treatment does not pit or roughen the anatase surface and results in high IPCEs of more than 1% in some cases and absorbed photon current efficiencies (APCE) from 5 to 100%. The photocurrent spectra showed features associated with surface-bound dye monomers and H-dimers that could be followed as a function of the dye surface coverage. Models for the surface structures of the adsorbed dye layers that are consistent with the measurements are presented, along with a discussion of adsorption isotherms.
Journal Article↗
Residues of organic chlorinated pesticides in agricultural soils of Beijing, China.
Concentration of organic chlorinated pesticides (OCPs) were measured in topsoils of a selected farm (NK farm) in Beijing in 1993 and 2003. The results indicated that OCPs, mainly 1,2,3,4,5,6-hexachlorocyclohexane (HCH) and 1,1,1,-trichloro-2,2-bis(p-chlorophenyl) ethane (DDT), degraded greatly in the 20 years after the prohibition of their use. DDT was the major contributors of pollution on the farm with 92.23% and 81.28% contributions of total OCP load in soils in 2003 and 1993 respectively. The levels of total DDT and HCH in the old orchard group, in which cultivation began in 1962, were significantly higher (p < 0.05) than those in the new orchard group in which cultivation began in 1991, and all data were higher than the level of barren land (p < 0.05). Studying the isomeric and parent substance metabolite ratios indicated there was more application and accumulation of DDT in the old orchard and that DDT in the new orchard had undergone a different degradation time period or perhaps had been applied more recently, but no new input of HCH was detected. Pollution potential was assessed on the basis of China Soil Environmental Quality Standard.
Agriculture↗
Up-regulation of site-specific remodeling without accumulation of microcracking and loss of osteocytes.
Functional adaptation of bone normally protects the skeleton from fracture during daily activity. Accumulation of microcracking and loss of osteocytes have been implicated in the regulation and initiation of targeted (reparative) remodeling of bone and, in certain situations, the development of fatigue or stress fracture. We performed a histologic study of the dorsal cortex of the mid-diaphysis of the third metacarpal (Mc-III) bone of Thoroughbred racehorses after bones were bulk-stained in basic fuchsin and transverse calcified sections were prepared. The Thoroughbred racehorse is an extreme athlete whose Mc-III bone experiences particularly high cyclic strains during training and racing. A group of non-athletic horses was also included in the experiment. The following variables were quantified: activation frequency (Ac.f); bone formation rate (BFR); resorption space density (Rs.N/T.Ar); microcrack density (Cr.Dn); microcrack mean length (Cr.Le); microcrack surface density (Cr.S.Dn); osteocyte density (Ot.N/T.Ar; Ot.N/B.Ar); and bone volume fraction (B.Ar/T.Ar). Ac.f and BFR were estimated using a mathematical algorithm. Using confocal microscopy, bones were examined for fine microcracks, diffuse matrix injury, and disruption of the osteocyte syncytium. Low values for Cr.Dn (#/mm2) were found in both groups (0.022+/-0.008 and 0.013+/-0.006 for racing Thoroughbreds and non-athletic horses, respectively). There was no significant relationship between Cr.Dn and Ot.N/T.Ar; Ot.N/B.Ar, B.Ar/T.Ar, and Ot.N/T.Ar; Ot.N/B.Ar, and remodeling (Ac.f, Rs.N/T.Ar) and Ot.N/T.Ar; Ot.N/B.Ar. Intense remodeling of the Mc-III dorsal cortex was found in the racing Thoroughbreds (Ac.f 12.8+/-7.4 #/mm2/year; BFR 31.5+/-15.6%; Rs.N/T.Ar 0.19+/-0.09 #/mm2) and was significantly increased compared with non-athletic horses. Overall, remodeling was weakly correlated with Cr.Dn (r2=0.15, P<0.05). Subtle matrix injury, not detectable by bright-field microscopy, was particularly evident adjacent to resorption spaces in Thoroughbred bone. In non-athletic horses, disruption of the dendritic cell processes of osteocytes associated with cement lines and interstitial fragments was more evident. Taken together, these findings suggest that site-specific (targeted) induction of remodeling during functional adaptation of bone in a high-strain skeletal site is not dependent on accumulation of microcracking or loss of osteocytes. We hypothesize that athleticism can directly influence bone turnover in this extreme athlete through pathways that do not involve classical linear microcracks.
Age Factors↗
Common burden of chronic skin diseases? Contributors to psychological distress in adults with psoriasis and atopic dermatitis.
BACKGROUND: Chronic skin diseases, such as atopic dermatitis and psoriasis, are known to affect quality of life by heightening psychological distress. Knowledge about factors contributing to psychological distress is essential for supporting physicians in diagnostic and multidisciplinary treatment options for patients psychologically at risk. OBJECTIVES: To examine whether generic physical, psychological and social factors relevant to patients with chronic diseases might contribute to psychological distress in adults with psoriasis and atopic dermatitis. METHODS: Self-report data on clinical skin status, physical symptoms of itching and fatigue, impact of the disease on daily life, illness cognitions and social support were collected from 128 patients with psoriasis and 120 patients with atopic dermatitis (aged over 16 years). RESULTS: For patients with either skin disease, clinical status and physical symptoms of itching scarcely affected psychological distress. Instead, higher levels of fatigue, perceived helplessness and less social support best predicted psychological distress in patients with both skin diseases in multiple regression analyses. CONCLUSIONS: Results demonstrate that generic physical, psychological and social aspects play a role in chronic skin diseases and suggest that multidisciplinary care for patients with psoriasis and atopic dermatitis can be greatly improved by integrating common screening and treatment components for chronic diseases.
Adolescent↗
A survey of haplotype variants at several disease candidate genes: the importance of rare variants for complex diseases.
BACKGROUND: The haplotype based association method offers a powerful approach to complex disease gene mapping. In this method, a few common haplotypes that account for the vast majority of chromosomes in the populations are usually examined for association with disease phenotypes. This brings us to a critical question of whether rare haplotypes play an important role in influencing disease susceptibility and thus should not be ignored in the design and execution of association studies. METHODS: To address this question we surveyed, in a large sample of 1873 white subjects, six candidate genes for osteoporosis (a common late onset bone disorder), which had 29 SNPs, an average marker density of 13 kb, and covered a total of 377 kb of the DNA sequence. RESULTS: Our empirical data demonstrated that two rare haplotypes of the parathyroid hormone (PTH)/PTH related peptide receptor type 1 and vitamin D receptor genes (PTHR1 and VDR) with frequencies of 1.1% and 2.9%, respectively, had significant effects on osteoporosis phenotypes (p = 4.2 x 10(-6) and p = 1.6 x 10(-4), respectively). Large phenotypic differences (4.0 approximately 5.0%) were observed between carriers of these rare haplotypes and non-carriers. Carriers of the two rare haplotypes showed quantitatively continuous variation in the population and were derived from a wide spectrum rather than from one extreme tail of the population phenotype distribution. CONCLUSIONS: These findings indicate that rare haplotypes/variants are important for disease susceptibility and cannot be ignored in genetics studies of complex diseases. The study has profound implications for association studies and applications of the HapMap project.
Apolipoproteins E↗
The growth hormone receptor gene is associated with mandibular height in a Chinese population.
Genetic influences are important in the determination of mandibular morphology, and growth hormone receptor (GHR) is believed to have an important influence on the growth of craniofacial bone. In this study, we used quantitative trait locus methods to evaluate the relationship between craniofacial morphology and single-nucleotide polymorphisms (SNPs) in GHR in an unselected healthy Chinese population. We systematically screened the 10 exons and nearby introns of GHR and identified 6 SNPs. Using 4 SNPs as markers, we studied the relationships between genotypes and craniofacial linear measurements. Individuals with the genotype CC of polymorphism I526L had a significantly greater mandibular ramus length (condylion-gonion/ articulare-gonion) than those with genotype AC or AA. Haplotype analysis showed that there were also significant differences between the long and short mandibular height groups in an extreme population. Our results indicate that the GHR gene polymorphism I526L is associated with mandibular height in the Chinese population.
Adenine↗
Concentration polarization of hyaluronan on the surface of the synovial lining of infused joints.
Hyaluronan (HA) in joints conserves the lubricating synovial fluid by making trans-synovial fluid escape almost insensitive to pressure elevation (e.g. effusions, joint flexion). This phenomenon, 'outflow buffering', was discovered during HA infusion into the rabbit knee joint cavity. It was also found that HA is partially reflected by the joint lining (molecular sieving), and that the reflected fraction R decreases as trans-synovial filtration rate Q is increased. It was postulated therefore that outflow buffering is mediated by HA reflection. Reflection creates a HA concentration polarization layer, the osmotic pressure of which opposes fluid loss. A steady-state, cross-flow ultrafiltration model was previously used to explain the outflow buffering and negative R-vs.-Q relation. However, the steady-state, cross-perfusion assumptions restricted the model's applicability for an infused, dead-end cavity or a non-infused joint during cyclical motion. We therefore developed a new, non-steady-state model which describes the time course of dead-end, partial HA ultrafiltration. The model describes the progressive build-up of a HA concentration polarization layer at the synovial surface over time. Using experimental parameter values, the model successfully accounts for the observed negative R-vs.-Q relation and shows that the HA reflected fraction (R) also depends on HA diffusivity, membrane area expansion and the synovial HA reflection coefficient. The non-steady-state model thus explains existing experimental work, and it is a key stage in understanding synovial fluid turnover in intact, moving, human joints or osteoarthritic joints treated by HA injections.
Animals↗