Biomedical subjects

D Cao

Publications and source records attributed to D Cao.

At least 19 recordsLinked to original sources

PubMed2006

Further evidence that the chromogranin B gene confers predisposition to schizophrenia: a family-based association study in Chinese.

The Chromogranin B (CHGB) gene has been proposed as a candidate gene for predisposition to schizophrenia due to its location on the genome, the evidence of genetic studies, and its functional role in schizophrenia. To investigate its association with schizophrenia using case-control analysis, we genotyped eight single nucleotide polymorphisms (SNPs) and performed transmission disequilibrium tests (TDT) using 192 Han Chinese trios. The G allele of IVS4 + 808A > G showed a trend of over-transmission from heterozygous parents to affected offspring (P = 0.06), although no significant over-transmission was found for individual markers. Furthermore, a significant transmission was observed for the common haplotype G-G-A-G-C (P = 0.0018). Overall, our results suggest that at least one locus in or close to the CHGB gene confers risk of the disorder and strengthen the evidence that CHGB is a promising susceptibility gene for schizophrenia in Chinese population.

Asian People↗

PubMed2006

Comprehensive DNA methylation profiling in a human cancer genome identifies novel epigenetic targets.

Using a unique microarray platform for cytosine methylation profiling, the DNA methylation landscape of the human genome was monitored at more than 21,000 sites, including 79% of the annotated transcriptional start sites (TSS). Analysis of an oligodendroglioma derived cell line LN-18 revealed more than 4000 methylated TSS. The gene-centric analysis indicated a complex pattern of DNA methylation exists along each autosome, with a trend of increasing density approaching the telomeres. Remarkably, 2% of CpG islands (CGI) were densely methylated, and 17% had significant levels of 5 mC, whether or not they corresponded to a TSS. Substantial independent verification, obtained from 95 loci, suggested that this approach is capable of large scale detection of cytosine methylation with an accuracy approaching 90%. In addition, we detected large genomic domains that are also susceptible to DNA methylation reinforced inactivation, such as the HOX cluster on chromosome 7 (CH7). Extrapolation from the data suggests that more than 2000 genomic loci may be susceptible to methylation and associated inactivation, and most have yet to be identified. Finally, we report six new targets of epigenetic inactivation (IRX3, WNT10A, WNT6, RARalpha, BMP7 and ZGPAT). These targets displayed cell line and tumor specific differential methylation when compared with normal brain samples, suggesting they may have utility as biomarkers. Uniquely, hypermethylation of the CGI within an IRX3 exon was correlated with over-expression of IRX3 in tumor tissues and cell lines relative to normal brain samples.

Brain↗

PubMed2006

FOXP3 identifies regulatory CD25bright CD4+ T cells in rheumatic joints.

Regulatory T cells have recently been implicated in a number of human diseases, including rheumatoid arthritis. To investigate whether the presence of CD25+CD4+ regulatory T cells is a general finding in arthritic joints, synovial fluid of patients with different rheumatic diseases such as undifferentiated arthritides, systemic rheumatic diseases and reactive arthritis were investigated for the presence of such cells. In 95% of the patients, a higher frequency of CD25(bright)CD4+ T cells was found in synovial fluid as compared with peripheral blood. Both in vitro suppression experiments and FOXP3 mRNA analysis confirmed these cells to be natural regulatory T cells. Together with our previous data, we conclude that arthritic joints, irrespective of precise diagnosis and disease duration, are enriched with natural regulatory T cells. These results suggest that suppressor cells migrate to and/or multiply at the sites of inflammation as part of the immune responses' effort to combat injurious inflammation.

Adult↗

PubMed2005

Allopurinol safely and effectively optimizes tioguanine metabolites in inflammatory bowel disease patients not responding to azathioprine and mercaptopurine.

BACKGROUND: Many non-responders to azathioprine or mercaptopurine (6-mercaptopurine) have high normal thiopurine methyltransferase activity and preferentially metabolize mercaptopurine to produce 6-methylmercaptopurine instead of the active 6-tioguanine (6-tioguanine) metabolites. AIM: To describe the use of allopurinol in mercaptopurine/azathioprine non-responders to deliberately shunt metabolism of mercaptopurine towards 6-tioguanine. METHODS: Fifteen thiopurine non-responders whose metabolites demonstrated preferential metabolism towards 6-methylmercaptopurine are described. Subjects were commenced on allopurinol 100 mg po daily and mercaptopurine/azathioprine was reduced to 25-50% of the original dose. Patients were followed clinically and with serial 6-tioguanine and 6-methylmercaptopurine metabolite measurements. RESULTS: After initiating allopurinol, 6-tioguanine levels increased from a mean of 185.73 +/- 17.7 to 385.4 +/- 41.5 pmol/8 x 10(8) red blood cells (P < 0.001), while 6-methylmercaptopurine decreased from a mean of 10 380 +/- 1245 to 1732 +/- 502 pmol/8 x 10(8) RBCs (P < 0.001). Allopurinol led to a decrease in white blood cell from a mean of 8.28 +/- 0.95 to 6.1 +/- 0.82 x 10(8)/L (P = 0.01). CONCLUSIONS: The addition of allopurinol to thiopurine non-responders with preferential shunting to 6-methylmercaptopurine metabolites appears to be an effective means to shift metabolism towards 6-tioguanine.

Allopurinol↗

PubMed2005

Fludarabine, melphalan, and alemtuzumab conditioning in adults with standard-risk advanced acute myeloid leukemia and myelodysplastic syndrome.

PURPOSE: This prospective phase II study evaluated toxicity, relapse rate, progression-free survival, and overall survival after allogeneic transplantation and conditioning with fludarabine, melphalan, and alemtuzumab in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). PATIENTS AND METHODS: Fifty-two consecutive adults with AML and MDS were enrolled onto the study. Median age was 52 years (range, 17 to 71 years) and the majority of patients had high-risk disease, comorbidities, and/or modest reduction in performance status. Fifty-six percent of patients had unrelated or mismatched related donors. RESULTS: After a median follow-up of 18 months (range, 2 to 34 months), 1-year survival was 48% (95% CI, 34% to 61%), progression-free survival was 38% (95% CI, 25% to 52%), relapse rate was 27% (95% CI, 15% to 40%), and treatment-related mortality was 33% (95% CI, 20% to 46%). The cumulative probability of extensive chronic graft-versus-host disease (GVHD) was only 18% (95% CI, 8% to 40%); extensive chronic GVHD was only observed in recipients of unrelated donor transplants. Performance score and disease status were the major predictors of outcome. High-risk disease (ie, active AML or MDS with > 5% blasts) or even modest decreases in performance status were associated with poor outcomes. Patients with standard-risk leukemia (first or second complete remission) or MDS (< 5% blasts) had excellent outcomes despite unfavorable disease characteristics. CONCLUSION: Fludarabine and melphalan combined with in vivo alemtuzumab is a promising transplantation regimen for patients with AML or MDS and low tumor burden. For patients with active disease, this regimen provides at best modest palliation. Despite a low incidence of GVHD, transplantation is still associated with considerable nonrelapse mortality in patients with decreased performance status.

Acute Disease↗

PubMed2005

Mechanisms of methanol decomposition on platinum: A combined experimental and ab initio approach.

The dual path mechanism for methanol decomposition on well-defined low Miller index platinum single crystal planes, Pt(111), Pt(110), and Pt(100), was studied using a combination of chronoamperometry, fast scan cyclic voltammetry, and theoretical methods. The main focus was on the electrode potential range when the adsorbed intermediate, CO(ad), is stable. At such "CO stability" potentials, the decomposition proceeds through a pure dehydrogenation reaction, and the dual path mechanism is then independent of the electrode-substrate surface structure. However, the threshold potential where the decomposition of methanol proceeds via parallel pathways, forming other than CO(ad) products, depends on the surface structure. This is rationalized theoretically. To gain insights into the controlling surface chemistry, density functional theory calculations for the energy of dehydrogenation were used to approximate the potential-dependent methanol dehydrogenation pathways over aqueous-solvated platinum interfaces.

Journal Article↗

PubMed2005

Engineering and characterisation of chimeric monoclonal antibody 806 (ch806) for targeted immunotherapy of tumours expressing de2-7 EGFR or amplified EGFR.

We report the generation of a chimeric monoclonal antibody (ch806) with specificity for an epitope on the epidermal growth factor receptor (EGFR) that is different from that targeted by all other anti-EGFR therapies. Ch806 antibody is reactive to both de2-7 and overexpressed wild-type (wt) EGFR but not native EGFR expressed in normal tissues at physiological levels. Ch806 was stably expressed in CHO (DHFR -/-) cells and purified for subsequent characterisation and validated for use in preliminary immunotherapy investigations. Ch806 retained the antigen binding specificity and affinity of the murine parental antibody. Furthermore, ch806 displayed enhanced antibody-dependent cellular cytotoxicity against target cells expressing the 806 antigen in the presence of human effector cells. Ch806 was successfully radiolabelled with both iodine-125 and indium-111 without loss of antigen binding affinity or specificity. The radioimmunoconjugates were stable in the presence of human serum at 37 degrees C for up to 9 days and displayed a terminal half-life (T(1/2beta)) of approximately 78 h in nude mice. Biodistribution studies undertaken in BALB/c nude mice bearing de2-7 EGFR-expressing or amplified EGFR-expressing xenografts revealed that (125)I-labelled ch806 failed to display any significant tumour retention. However, specific and prolonged tumour localisation of (111)In-labelled ch806 was demonstrated with uptake of 31%ID g(-1) and a tumour to blood ratio of 5 : 1 observed at 7 days postinjection. In vivo therapy studies with ch806 demonstrated significant antitumour effects on established de2-7 EGFR xenografts in BALB/c nude mice compared to control, and both murine 806 and the anti-EGFR 528 antibodies. These results support a potential therapeutic role of ch806 in the treatment of suitable EGFR-expressing tumours, and warrants further investigation of the potential of ch806 as a therapeutic agent.

Animals↗

PubMed2005

Local distortion induced metal-to-insulator phase transition in PrRu4P12.

Extended x-ray absorption fine structure (EXAFS) experiments have been carried out on PrRu(4)P(12) and PrOs(4)P(12) to study the metal-to-insulator (MI) phase transition in PrRu(4)P(12). No Pr displacement was observed across the MI transition temperature from the EXAFS data. Instead, our EXAFS data clearly show that a Ru displacement is associated with this MI transition. The very high Debye temperature for the Ru-P bond (Theta(D) = 690 K) suggests that a slight rotation/displacement of relatively rigid RuP(6) octahedra leads to this small Ru displacement, which accompanies the MI transition at 62 K in PrRu(4)P(12).

Journal Article↗

PubMed2005

[Compliance with a protocol of prevention of neonatal group B streptococcal sepsis in the Aurore perinatal network].

OBJECTIVE: Our purpose was to measure the compliance with the network hospitals protocol for preventing neonatal group B streptococcal sepsis. MATERIALS AND METHOD: All vaginal deliveries during a one-week period in 37 maternities of the perinatal network were reviewed retrospectively. RESULTS: A total of 752 records were reviewed. Compliance with the protocol regarding the time of culture was 91.1%. Overall, prevalence of group B streptococcal carriage was 14.2%. Among patients eligible for intrapartum antibiotics, 46.4% received adequate prophylaxis. Considering the length of labor, one out of two patients could have received intrapartum adequate antibiotics. Regarding newborns, 86.1% received adequate medical surveillance. There was no confirmed case of group B streptococcal sepsis during the week of study. CONCLUSION: All the maternities of network Aurore accepted and adopted evaluation principle. Some elements of protocol could be better applied, in particular delivering adequate intrapartum antibiotic prophylaxis.

Anti-Bacterial Agents↗

PubMed2004

[Calcium pyrophosphate dihydrate deposition disease in the transverse ligament of the atlas].

Calcium pyrophosphate dihydrate (CPPD) deposits, answerable for chondrocalcinosis, are frequently observed in elderly people. Involvement of the spine is not rare. We present the case of a woman hospitalised for an acute arthritis of the right knee related to CPPD crystal deposition disease who suffered from acute neck pain. The computerised tomography showed calcified deposits in the transverse ligament of the atlas highly suggestive of CPPD deposits. This localisation seems to be very common for CPPD deposits. These CPPD crystal deposits may induce pseudo-meningitic attacks or chronic mechanical neck pain. CPPD crystal deposits in the upper cervical spine should be diagnosed when the disease is quiet, in order to avoid unnecessary investigations and therapies when an acute cervical flare occurs.

Aged↗

PubMed2002

Frustrated soft modes and negative thermal expansion in ZrW2O8.

Negative thermal expansion (NTE) in cubic ZrW2O8 has generated much interest due to its large, isotropic, and temperature independent behavior. Here, x-ray absorption fine structure data are presented for various atom pairs, providing evidence that the low-energy modes causing NTE correspond to the correlated vibrations of a WO4 tetrahedron and its three nearest ZrO6 octahedra. This involves translations of the WO4 as a rigid unit along each of the four <111> axes. The interconnectivity of these modes prevents an anisotropic soft mode from developing, a new geometrical phenomenon that we call the "frustrated soft mode."

Journal Article↗

PubMed2002

[Worsening of heart failure during hospital course in myocardial infarction is a factor of poor prognosis. Apropos of a prospective cohort study of 2,507 patients hospitalized with myocardial infarction: the PRIMA study].

BACKGROUND: Worsening of heart failure in patients with myocardial infarction is seldom studied, elderly patients often are not included, and multivariate analysis is uncommon. AIMS: The prospective PRIMA study (Prise en charge de l'Infarctus du Myocarde Aigu; management of acute myocardial infarction) sought to determine the incidence of heart failure worsening, its risk factors, and its prognostic importance in patients with myocardial infarction, regardless of age and hospital facilities, in the "real world" in a region in France, using multivariate analysis. METHODS: Data were prospectively collected in all patients with myocardial infarction admitted in all hospitals in three departments in the Rhône-Alpes region in France between September 1, 1993 and January 31, 1995. RESULTS: Among 2,507 patients, 33% were in Killip classes II-IV at admission. Four hundred and sixteen patients (17%) had worsening of Killip class during the first five days. In-hospital mortality (overall: 14%) increased dramatically with Killip class at admission (9% in class I; 62% in class IV) and with worsening of Killip class during the first five days (36% vs 8% if no worsening). In multivariate analysis, older age, diabetes mellitus and anterior Q-wave myocardial infarction were significant predictors of Killip class at admission and of its worsening. The significant predictors of in-hospital mortality were older age, Killip class III at admission and worsening of Killip class during the first five days. CONCLUSION: This large, unselected cohort revealed that among patients with myocardial infarction, heart failure and its worsening are frequent, especially in the elderly, and dramatically worsen the in-hospital mortality.

Aged↗

PubMed2002

Mouldy houses influence symptoms of asthma among atopic individuals.

BACKGROUND: The influence of current levels of indoor fungi on asthma is a controversial issue that needs to be resolved in order to advise patients appropriately. OBJECTIVE: To assess the seasonal variation in indoor fungal levels and the impact of these levels on asthma among mould-sensitized individuals. METHODS: Thirty-five young adults with current asthma and sensitization to fungi were visited four times over 1 year. At each home visit a questionnaire was administered and samples of dust and air were collected. Participants also recorded information on symptoms, peak expiratory flows (PEF) and medication use. Dust samples were analysed for house dust mite allergen (Der p 1) and total fungal biomass (ergosterol). Total and genus-specific fungal propagules were identified in air samples. Seasonal variation in allergen levels and significant independent effects of fungal levels on peak flow variability (PFV) were identified by repeated measures analysis of variance. RESULTS: Significant seasonal variations were observed in viable airborne fungi, ergosterol levels in the floor dust and PFV. PFV correlated significantly with symptom scores and the dose of reliever medication. PFV was also significantly associated with smoking and visible mould. The association between visible mould and PFV was independent of season, smoking and the dose of reliever medication. However, there was no association between total fungi, specific fungi or ergosterol and PFV. Der p 1 levels had no significant influence on asthma, even in HDM-sensitized individuals. CONCLUSIONS: Mouldy homes adversely influence asthma in asthmatics sensitized to fungi.

Air Pollution, Indoor↗

PubMed2002

Preferential location of sex chromosomes, their aneuploidy in human sperm, and their role in determining sex chromosome aneuploidy in embryos after ICSI.

BACKGROUND: In babies born after ICSI procedures, an increase of de-novo sex chromosome abnormalities has been observed. Several hypotheses have been proposed to explain these findings: an increased rate of sex chromosome aneuploidy in sperm of oligozoospermic men, or a preferential location of the sex chromosomes in the sub-acrosomal region of the sperm nucleus which leads to a reduced DNA decondensation of this region. In order to investigate which theory may be more reliable, we studied the localization of sex chromosomes and their aneuploidy rate in sperm in men undergoing ICSI. METHODS: Using fluorescent in-situ hybridization we studied sex chromosome localization and the aneuploidy rate for sex chromosomes and chromosome 18 in 20 oligospermic men undergoing ICSI and in 10 controls. RESULTS: In 40.94 and 52.92% of cases, the X and Y chromosomes respectively were localized in the sub-acrosomal region of the sperm nucleus compared with only 14.29% of cases of chromosome 18 (P < 0.001). An increase of sex chromosome aneuploidy in sperm of oligospermic men was observed; 2.91 versus 0.69% of controls (P < 0.001). CONCLUSIONS: Sex chromosomes are localized preferentially in the sub-acrosomal region of sperm and sex chromosome aneuploidy rate in the sperm of oligozoospermic men is higher than in controls.

Acrosome↗

PubMed2001

Alternatively folded choriogonadotropin analogs. Implications for hormone folding and biological activity.

Most heterodimeric proteins are stabilized by intersubunit contacts or disulfide bonds. In contrast, human chorionic gonadotropin (hCG) and other glycoprotein hormones are secured by a strand of their beta-subunits that is wrapped around alpha-subunit loop 2 "like a seatbelt." During studies of hCG synthesis in COS-7 cells, we found that, when the seatbelt was prevented from forming the disulfide that normally "latches" it to the beta-subunit, its carboxyl-terminal end can "scan" the surface of the heterodimer and become latched by a disulfide to cysteines substituted for residues in the alpha-subunit. Analogs in which the seatbelt was latched to residues 35, 37, 41-43, and 56 of alpha-subunit loop 2 had similar lutropin activities to those of hCG; that in which it was latched to residue 92 at the carboxyl terminus had 10-20% the activity of hCG. Attachment of the seatbelt to alpha-subunit residues 45-51, 86, 88, 90, and 91 reduced lutropin activity substantially. These findings show that the heterodimer can form before the beta-subunit has folded completely and support the notions that the carboxyl-terminal end of the seatbelt, portions of alpha-subunit loop 2, and the end of the alpha-subunit carboxyl terminus do not participate in lutropin receptor interactions. They suggest also that several different architectures could have been sampled without disrupting hormone activity as the glycoprotein hormones diverged from other cysteine knot proteins.

Alanine↗

PubMed2001

p53-dependent suppression of uridine phosphorylase gene expression through direct promoter interaction.

Uridine phosphorylase (UPase) is a key enzyme in the pyrimidine salvage pathway. It reversibly catalyzes the catabolism of uridine to uracil; controls the homeostatic regulation of uridine concentration in plasma and tissues; and plays a role in the intracellular activation of 5-fluorouracil. We cloned the murine UPase gene promoter, a 1703-bp fragment, and determined the transcription initiation sites located at +1 and +92 bp of the cDNA sequence. Through transient expression analysis of the 5'-flanking region of UPase gene, we have evaluated the promoter activity for a series of fragments with 5'- to 3'-deletion in murine breast cancer EMT-6 cells and immortalized murine fibroblast NIH 3T3 cells. Cotransfection of the UPase promoter constructs (from -1619 to -445) containing p53 binding motif with the wild-type p53 construct resulted in a significant reduction of luciferase activity; however, this effect disappeared with the additional deletion of the -445 to -274 sequence to suggest the existence in this promoter region of a putative p53 recognition element. Similar cotransfection in murine embryo fibroblasts p53-/- confirmed the inhibitory role of p53 on the UPase promoter activity. The specificity of the interaction is demonstrated by nuclear protein-specific binding to the putative p53 recognition sequence using gel mobility shift assay and DNase I footprinting analysis. These data indicate the UPase gene is a novel target of p53, and its expression is down-regulated by p53 at the promoter level.

3T3 Cells↗

PubMed2001

Magnetic-field modulation experiments on colossal magnetoresistance samples: first results.

Recently we have observed a small change in the width, sigma, of the Mn-O pair distribution function when a IT magnetic field is applied. To improve our sensitivity to magnetic-field-induced changes, we have developed a magnetic field modulation technique. At each X-ray energy we collect two data points, one with field on and the other with field off: as a result we collect two scans simultaneously. The difference in these two traces provides a measure of the magnetic-field-induced change. The results for the modulation measurements will be compared to the earlier work using static magnetic fields.

Calcium Compounds↗

PubMed2001

Uridine phosphorylase association with vimentin. Intracellular distribution and localization.

Uridine phosphorylase (UPase), a key enzyme in the pyrimidine salvage pathway, is associated with the intermediate filament protein vimentin, in NIH 3T3 fibroblasts and colon 26 cells. Affinity chromatography was utilized to purify UPase from colon 26 and NIH 3T3 cells using the uridine phosphorylase inhibitor 5'-amino benzylacyclouridine linked to an agarose matrix. Vimentin copurification with UPase was confirmed using both Western blot analysis and MALDI-MS methods. Separation of cytosolic proteins using gel filtration chromatography yields a high molecular weight complex containing UPase and vimentin. Purified recombinant UPase and recombinant vimentin were shown to bind in vitro with an affinity of 120 pm and a stoichiometry of 1:2. Immunofluorescence techniques confirm that UPase is associated with vimentin in both NIH 3T3 and colon 26 cells and that depolymerization of the microtubule system using nocodazole results in UPase remaining associated with the collapsed intermediate filament, vimentin. Our data demonstrate that UPase is associated with both the soluble and insoluble pools of vimentin. Approximately 60-70% of the total UPase exists in the cytosol as a soluble protein. Sequential extraction of NIH 3T3 or colon 26 cells liberates an additional 30-40% UPase activity associated with a detergent extractable fraction. All pools of UPase have been shown to possess enzymatic activity. We demonstrate for the first time that UPase is associated with vimentin and the existence of an enzymatically active cytoskeleton-associated UPase.

3T3 Cells↗