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Biomedical subjects

Q Yu

Publications and source records attributed to Q Yu.

At least 19 recordsLinked to original sources

Inhibition of the hyaluronan-CD44 interaction by merlin contributes to the tumor-suppressor activity of merlin.

Mutation or loss of expression of merlin is responsible for neurofibromatosis type 2 (NF2), which is characterized by the development of schwannomas and other tumors of the nervous system. Like the ERM (ezrin-radixin-moesin) proteins, merlin interacts with CD44, a cell-surface receptor for hyaluronan (HA) that promotes tumorigenesis. However, the relationship between merlin and CD44 and the mechanism by which merlin exerts its tumor-suppressor function have not been elucidated. In the present study, we show that increased expression of wild-type merlin in Tr6BC1 schwannoma cells inhibits HA binding to CD44. Furthermore, we demonstrate that the residues required for this inhibitory effect and the interaction between CD44 and merlin lie within the first 50 amino acids of merlin. Overexpression of merlin inhibited subcutaneous growth of Tr6BC1 cells in immunocompromised Rag1 mice. In contrast, knocking down expression of endogenous merlin promoted tumor cell growth, as did overexpression of a merlin deletion mutant (merlinDel-1) that lacks the first 50 amino acids but not of other NH(2)-terminal deletion mutants. Together, our results demonstrate that inhibition of the CD44-HA interaction contributes to the tumor-suppressor function of merlin, and they suggest that merlin inhibits tumor growth, at least in part, by negatively regulating CD44 function.

Actins↗

Full-length ADAMTS-1 and the ADAMTS-1 fragments display pro- and antimetastatic activity, respectively.

The exact role of a disintegrin and metalloproteinase with thrombospondin motifs-1 (ADAMTS-1) and the underlying mechanism of its involvement in tumor metastasis have not been established. We have now demonstrated that overexpression of ADAMTS-1 promotes pulmonary metastasis of TA3 mammary carcinoma and Lewis lung carcinoma cells and that a proteinase-dead mutant of ADAMTS-1 (ADAMTS-1E/Q) inhibits their metastasis, indicating that the prometastatic activity of ADAMTS-1 requires its metalloproteinase activity. Overexpression of ADAMTS-1 in these cells promoted tumor angiogenesis and invasion, shedding of the transmembrane precursors of heparin-binding epidermal growth factor (EGF) and amphiregulin (AR), and activation of the EGF receptor and ErbB-2, while overexpression of ADAMTS-1E/Q inhibited these events. Furthermore, we found that ADAMTS-1 undergoes auto-proteolytic cleavage to generate the NH(2)- and COOH-terminal cleavage fragments containing at least one thrombospondin-type-I-like motif and that overexpression of the NH(2)-terminal ADAMTS-1 fragment and the COOH-terminal ADAMTS-1 fragment can inhibit pulmonary tumor metastasis. These fragments also inhibited Erk1/2 kinase activation induced by soluble heparin-binding EGF and AR. Taken together, our results suggest that the proteolytic status of ADAMTS-1 determines its effect on tumor metastasis, and that the ADAMTS-1E/Q and the ADAMTS-1 fragments likely inhibit tumor metastasis by negatively regulating the availability and activity of soluble heparin-binding EGF and AR.

ADAM Proteins↗

Therapeutic drug monitoring of mycophenolic acid can be used as predictor of clinical events for kidney transplant recipients treated with mycophenolate mofetil.

OBJECTIVE: This study was designed to investigate the relationship between clinical events and the pharmacokinetics of mycophenolic acid (MPA) in adult renal transplant patients. METHODS: Thirty-seven adult kidney transplant recipients received a cyclosporine, mycophenolate mofetil, and steroids. MPA-AUC(0-12) was obtained before and 12 days after grafting by RP-HPLC. Predose blood samples were measured for MPA-C(0) were gathered from all the recipients at 4, 12, and 21 days as well as 1, 1.5, 2, 2.5, 3, and 6 months after grafting. The clinical events at corresponding time points were recorded to correlate with each MPA-C(0) value. RESULTS: In addition to single-dose and multidose MPA-AUC(0-12), 357 MPA-C(0) values were obtained from 37 patients. The 357 units were divided into three subgroups: group A patients, including 239 units (66.9%), experienced uneventful outcomes; group B of 100 units (28.0%) showed MPA-related side effects, and group C, 18 units (5.0%) of acute rejection episodes. MPA-C(0) for groups A, B, and C were 0.8416 +/- 0.1373 mg/L, 1.5903 +/- 0.3741 mg/L and 0.6057 +/- 0.2338 mg/L, respectively (P < .001 between groups A and B, groups B and C, and P = .021 between groups A and C). The three groups were also divided into an initial phase (< or =1 month, 251 units) and a stable phase (>1 month, 106 units). The relationship between MPA-C(0) and associated clinical events was also investigated. CONCLUSION: Our results suggested a relationship between MPA pharmacokinetics and clinical events. The MPA-C(0) might be an appropriate pharmacokinetic monitoring parameter for kidney transplantation.

Adolescent↗

Association of intercellular adhesion molecule 1 polymorphisms with retinopathy in Chinese patients with Type 2 diabetes.

AIMS: To investigate the relationship of the K469E and G241R polymorphisms of the intercellular adhesion molecule 1 (ICAM-1) gene with diabetic retinopathy in Chinese patients with Type 2 diabetes mellitus. PATIENTS AND METHODS: One hundred and seventy-two Chinese patients with Type 2 diabetes and 80 normal control subjects were recruited. Patients with diabetes were placed into two groups: the diabetic retinopathy (DR) group and the non-diabetic retinopathy (NDR) group. The DR group was subdivided into those with proliferative retinopathy (PDR) and non-proliferative retinopathy (NPDR). Genomic DNA was prepared using the hydroxybenzene-chloroform extraction method. Genotypes and alleles were detected by polymerase chain reaction-heteroduplex-single-strand conformation polymorphism (PCR-HA-SSCP) analysis combined with gene sequencing. RESULTS: The patients with retinopathy had an increased frequency of the K469K genotype compared with both the patients without retinopathy and the control subjects (61.4 vs. 40.0 and 35.0%, respectively; chi(2) = 8.280 and 13.952, respectively; P < 0.05). The frequency of the K allele in the DR group was higher than in the NDR group and control subjects (75.4 vs. 58.8 and 61.3%, respectively; chi(2) = 9.693 and 11.219, respectively; P < 0.05). Genotype and allele frequencies were similar in the NDR group and control subjects, and in the PDR and NPDR groups. CONCLUSION: The ICAM-1 gene K469E polymorphism is associated with diabetic retinopathy in Chinese patients with Type 2 diabetes. Patients with the K469K genotype were more likely to have diabetic retinopathy than patients with the K469E or E469E genotype.

Adult↗

Operative techniques and morbidity with subthalamic nucleus deep brain stimulation in 100 consecutive patients with advanced Parkinson's disease.

OBJECTIVE: Subthalamic nucleus (STN) stimulation for patients with medically refractory Parkinson disease (PD) is expanding. Reported experience has provided some indication of techniques, efficacy, and morbidity, but few centres have reported more than 50 patients. To expand this knowledge, we reviewed our experience with a large series of consecutive patients. METHODS: From March 1999 to September 2003, 191 subthalamic stimulator devices (19 unilateral) were implanted in 100 patients with PD at New York Presbyterian Hospital/Columbia University Medical Center. Sixteen patients had undergone a prior surgery for PD (pallidotomy, thalamotomy, or fetal transplant). Microelectrode guided implantations were performed using techniques similar to those described previously. Electrode implantation occurred 1-2 weeks before outpatient pulse generator implantation. RESULTS: Reductions of dyskinesias and off severity/duration were similar to prior published reports. Morbidity included: 7 device infections (3.7%), 1 cerebral infarct, 1 intracerebral haematoma, 1 subdural haematoma, 1 air embolism, 2 wound haematomas requiring drainage (1.0%), 2 skin erosions over implanted hardware (1.0%), 3 periprocedural seizures (1.6%), 6 brain electrode revisions (3.1%), postoperative confusion in 13 patients (6.8%), and 16 battery failures (8.4%). Of the 100 patients, there were no surgical deaths or permanent new neurological deficits. The average hospital stay for all 100 patients was 3.1 days. CONCLUSION: Subthalamic stimulator implantation in a large consecutive series of patients with PD produced significant clinical improvement without mortality or major neurological morbidity. Morbidity primarily involved device infections and hardware/wound revisions.

Adult↗

Noncontact atomic force microscopy studies of ultrathin films of amorphous solid water deposited on Au(111).

Noncontact atomic force microscopy was used to study the morphological changes of an ultrathin amorphous solid water (ASW) film as a function of deposition temperature, annealing temperature, and annealing time. ASW deposited at 80 or 108 K on Au(111) formed truncated hemispherical clusters of increasing size during annealing at 134 K; these clusters were inferred to be crystalline. The number of nuclei present at the outer surface of the film after deposition was greater for higher deposition temperature. For lower cluster densities, depletion of the ASW film around the clusters was observed when the clusters became larger and dendritic growth was observed when the apparent cluster footprint radius exceeded 100 nm.

Journal Article↗

Intrinsic vacancy-induced nanoscale wire structure in heteroepitaxial Ga2Se3/Si(001).

A highly anisotropic growth morphology is found for heteroepitaxial gallium sesquiselenide (Ga2Se3) on the lattice matched substrate, arsenic-terminated Si(001). Scanning tunneling microscopy of Ga2Se3 films reveals nanoscale, wirelike structures covering the surface in parallel lines, less than 1 nm wide and up to 30 nm long. Core-level photoemission spectroscopy and diffraction reveals the local structure of buried Ga and Se atoms to reflect the bulk, defected zinc-blende structure of beta-Ga2Se3, which contains ordered 110 arrays of Ga vacancies. These ordered vacancy lines are proposed to be responsible for the observed growth anisotropy in heteroepitaxial Ga2Se3.

Journal Article↗

Molecular genetic analysis for Ax phenotype of the ABO blood group system in Chinese.

BACKGROUND AND OBJECTIVES: To elucidate the molecular genetic background of the Ax phenotype in the Chinese population. MATERIALS AND METHODS: The ABO genes of eight Ax phenotype samples, four Ax and four AxB, were amplified by polymerase chain reaction (PCR) and were cloned, along with those of 10 random A(1) Chinese subjects. We analysed the ABO gene transcript structure and the sequences of two exons and one intron at the ABO locus. RESULTS: Among the four Ax phenotype samples, we identified one Ax02, two Ax03 and one novel Ax allele with the 543G > T mutation in the A102 background. Two of five family members also carry the allele. Of the four AxB phenotypes, one was designated as cis-AB-1/B101; the other three were shown to carry one B allele and one O with the nt261G deletion. The B alleles of the latter three were identical to B101 except for single point mutation at nt700C > G, nt640A > G and nt641T > C, respectively. The novel B101-like alleles were first associated with A(weak)B phenotypes. CONCLUSIONS: Two ABO*B(A) alleles and an Ax allele clearly differ from all previously reported ABO alleles, suggesting that the molecular genetic background of Ax is heterogeneous in the Chinese population.

ABO Blood-Group System↗

Variation in RNA expression and genomic DNA content acquired during cell culture.

Specific chromosomal abnormalities are increasingly recognised to be associated with particular tumour subtypes. These cytogenetic abnormalities define the sites of specific genes, the alteration of which is implicated in the neoplastic process. We used comparative genomic hybridisation (CGH) to examine DNA from different breast and ovarian cancer cell lines for variations in DNA sequence copy number compared with the same normal control. We also compared different sources of the MCF7 breast line by both CGH and cDNA expression arrays. Some of the differences between the subcultures were extensive and involved large regions of the chromosome. Differences between the four subcultures were observed for gains of 2q, 5p, 5q, 6q, 7p, 7q, 9q, 10p, 11q, 13q, 14q, 16q, 18p and 20p, and losses of 4q, 5p, 5q, 6q, 7q, 8p, 11p, 11q, 12q, 13q, 15q, 19p, 19q, 20p, 21q, 22q and Xp. However, few variations were found between two subcultures examined, 5 months apart, from the same initial source. The RNA arrays also demonstrated considerable variation between the three different subcultures, with only 43% of genes expressed at the same levels in all three. Moreover, the patterns of the expressed genes did not always reflect our observed CGH aberrations. These results demonstrate extensive genomic instability and variation in RNA expression during subculture and provide supportive data for evidence that cell lines do evolve in culture, thereby weakening the direct relevance of such cultures as models of human cancer. This work also reinforces the concern that comparisons of published analyses of cultures of the same name may be dangerous.

Breast Neoplasms↗

Correlation of ph dependant equilibrium isotherms of heavy metal biosorption with a modified Freundlich model.

Equilibrium isotherms of heavy metal biosorption are commonly correlated with adsorption models such as the Freundlich model. On the other hand, the adsorption properties of heavy metal biosorption are strongly influenced by the solution pH of the biosorption system. Therefore, standard adsorption models are limited to the correlation of equilibrium isotherms under constant pH values. In this paper, a modified Freundlich model was developed for the correlation of pH dependent equilibrium isotherms of heavy metal biosorption. The model was based on the mechanism that the functional groups for heavy metal interactions are weakly acidic groups and the uptake capacities of the biomass are affected through the association and dissociation equilibrium between two apparent ionic forms. Both the standard and the modified Freundlich models were tested with isotherm data for Cd2+, Cu2+ and Ni2+ biosorption onto pre-treated biomass of marine alga Durvillaea potatorum under various solution pH values. Regression analyses indicated that the developed model correlated the experimental data well.

Adsorption↗

Subthalamic nucleus stimulation in advanced Parkinson's disease: blinded assessments at one year follow up.

OBJECTIVE: To measure the effect of deep brain stimulation (DBS) of the subthalamic nucleus in patients with advanced Parkinson's disease. DESIGN: Open label follow up using blinded ratings of videotaped neurological examinations. PATIENTS: 30 patients with advanced Parkinson's disease (19 male, 11 female; mean age 58.8 years; mean disease duration 12.8 years), complicated by intractable wearing off motor fluctuations and dopaminergic dyskinesias. MAIN OUTCOME MEASURES: Unified Parkinson's disease rating scale (UPDRS), part III (motor), score at one year, from blinded reviews of videotaped neurological examinations. Secondary outcomes included the other UPDRS subscales, Hoehn and Yahr scale, activities of daily living (ADL) scale, mini-mental state examination (MMSE), estimates of motor fluctuations and dyskinesia severity, drug intake, and patient satisfaction questionnaire. RESULTS: Subthalamic nucleus stimulation was associated with a 29.5% reduction in motor scores at one year (p<0.0001). The only important predictors of improvement in UPDRS part III motor scores were the baseline response to dopaminergic drugs (p = 0.015) and the presence of tremor (p = 0.027). Hoehn and Yahr scores and ADL scores in the "on" and "off" states did not change, nor did the mean MMSE score. Weight gain occurred in the year after surgery, from (mean) 75.8 kg to 78.5 kg (p = 0.028). Duration of daily wearing off episodes was reduced by 69%. Dyskinesia severity was reduced by 60%. Drug requirements (in levodopa equivalents) declined by 30%. CONCLUSIONS: The 30% improvement in UPDRS motor scores was a more modest result than previously reported. DBS did not improve functional capacity independent of drug use. Its chief benefits were reduction in wearing off duration and dyskinesia severity.

Activities of Daily Living↗

Evolutionary computing for knowledge discovery in medical diagnosis.

One of the major challenges in medical domain is the extraction of comprehensible knowledge from medical diagnosis data. In this paper, a two-phase hybrid evolutionary classification technique is proposed to extract classification rules that can be used in clinical practice for better understanding and prevention of unwanted medical events. In the first phase, a hybrid evolutionary algorithm (EA) is utilized to confine the search space by evolving a pool of good candidate rules, e.g. genetic programming (GP) is applied to evolve nominal attributes for free structured rules and genetic algorithm (GA) is used to optimize the numeric attributes for concise classification rules without the need of discretization. These candidate rules are then used in the second phase to optimize the order and number of rules in the evolution for forming accurate and comprehensible rule sets. The proposed evolutionary classifier (EvoC) is validated upon hepatitis and breast cancer datasets obtained from the UCI machine-learning repository. Simulation results show that the evolutionary classifier produces comprehensible rules and good classification accuracy for the medical datasets. Results obtained from t-tests further justify its robustness and invariance to random partition of datasets.

Adolescent↗

Development of flexible fibre biofilm reactor for treatment of food processing wastewater.

Biological treatment methods are usually effective and commonly used in the treatment of organic wastewater. However, there are a number of problems for conventional biological treatment methods in treating wastewater from industries such as food processing. For example, microorganisms in the aeration tank in an activated sludge process cannot survive a continuous series of shock loads and the process could become operationally unstable. The associated problem of sludge bulking often occurs when the organic loading to the treatment process is high. In this paper, a new flexible fibre biofilm reactor was developed for the treatment of wastewater from fruit and vegetable processing plants. Experiments were carried out to evaluate the performance of the treatment process. Acclimatisation characteristics of the treatment process were also evaluated. The removal efficiencies for COD and BOD5 for different influent organic strengths evaluated. Results indicated that over 90% COD removal and 95% BOD5 removal could be achieved. The performance parameters were also compared with a conventional activated sludge process under similar conditions, operated in parallel. It was found that the biofilm reactor exhibited a number of advantages over the conventional reactor. These include (a) high organic loading rate, (b) long sludge retention times and low sludge discharge rate in the settling tank (about 10%), (c) elimination of the sludge recycle stream, and (d) no sludge bulking problem at high organic loading rates. Therefore, the flexible fibre biofilm reactor can provide a more efficient and cost effective treatment for wastewater from food processing industries.

Biofilms↗