Biomedical subjects

H Cao

Publications and source records attributed to H Cao.

At least 91 records · Page 5Linked to original sources

PubMed2000

Human hepatocyte nuclear factor-1 beta (HNF1B) 1968A/G polymorphism.

We found a novel A-->G change at nucleotide 1968 within the 3'-untranslated region of the HNF1B gene encoding the hepatocyte nuclear factor-1 beta. The HNF1B 1968A/G polymorphism could be detected by digestion with endonuclease MspI. The frequency of the HNF1B 1968G allele was 0.060 in Caucasians and 0.129 in Canadian Oji-Cree. Because of the importance of the HNF1B gene product in the regulation of transcription of several hepatic proteins, this polymorphism may be useful in the study of associations with metabolic phenotypes such as diabetes.

3' Untranslated Regions↗

PubMed2000

Human C-reactive protein (CRP) 1059G/C polymorphism.

We found a novel G-->C change at nucleotide 1059 within exon 2 of the CRP gene encoding the C-reactive protein. The CRP 1059G/C polymorphism could be detected by digestion with endonuclease MaeIII. The frequency of the CRP 1059C allele was 0.109 in Caucasians, but it was absent from Canadian Oji-Cree. Because of the importance of the CRP gene product in inflammation and its recent association with ischemic heart disease syndromes, this polymorphism may be useful in the association studies of atherosclerosis and its related phenotypes.

Alleles↗

PubMed2000

The dynamin family of mechanoenzymes: pinching in new places.

The large GTPase dynamin is a mechanoenzyme that mediates the liberation of nascent clathrin-coated pits from the plasma membrane during endocytosis. Recently, this enzyme has been demonstrated to comprise an extensive family of related proteins that have been implicated in a large variety of vesicle trafficking events during endocytosis, secretion and even maintenance of mitochondrial form. The potential contributions by the dynamin family to these diverse but related functions are discussed.

Actins↗

PubMed2000

Gender, obesity, hepatic nuclear factor-1alpha G319S and the age-of-onset of type 2 diabetes in Canadian Oji-Cree.

Among the Oji-Cree of northern Ontario, women have both a higher prevalence and an earlier onset of type 2 diabetes compared to men. We studied the relationship between HNF1A S319 and both the presence of and the age-of-onset of type 2 diabetes in women and men separately. We found that: 1) in women, there was a significant difference in the mean age-of-onset of type 2 diabetes according to HNF1A genotype; and 2) in men, there was no difference in the mean age-of-onset of type 2 diabetes according to HNF1A genotype. The findings indicate that HNF1A S319 is associated with increased susceptibility to type 2 diabetes in both men and women, but with earlier age-of-onset in women only. One factor that might account for the gender difference in the onset of HNF1A S319-associated type 2 diabetes is the greater prevalence and severity, and earlier onset of, obesity among female Oji-Cree.

Adolescent↗

PubMed2000

In vitro generation of dendritic cells from human blood monocytes in experimental conditions compatible for in vivo cell therapy.

DC are professional APC that are promising adjuvants for clinical immunotherapy. Methods to generate in vitro large numbers of functional human DC using either peripheral blood monocytes or CD34+ pluripotent HPC have been developed recently. However, the various steps of their in vitro production for further clinical use need to fit good manufacturing practice (GMP) conditions. Our study focused on setting up such a full procedure, including collection of mononuclear cells (MNC) by apheresis, separation of monocytes by elutriation, and culture of monocytes with GM-CSF + IL-13 + autologous serum (SAuto) in sterile Teflon bags. The procedure was first developed with apheresis products from 7 healthy donors. Its clinical feasibility was then tested on 7 patients with breast cancer. The characteristics of monocyte-derived DC grown with SAuto (or in some instances with a pooled AB serum) were compared with those obtained in the presence of FBS by evaluation of their phenotype, their morphology in confocal microscopy, and their capacity to phagocytize latex particles and to stimulate allogeneic (MLR) or autologous lymphocytes (antigen-presentation tests). The results obtained demonstrate that the experimental conditions we set up are easily applicable in clinical trials and lead to large numbers of well-defined SAuto-derived DC as efficient as those derived with FBS.

Antigen Presentation↗

PubMed2000

NAT2 polymorphism associated with plasma glucose concentration in Canadian Oji-Cree.

The prevalence of type 2 diabetes in the Oji-Cree of Northern Ontario is among the highest of any population in the world. We previously demonstrated that markers D8S264 and D22S683 were both linked and associated with type 2 diabetes in the Oji-Cree. Among the possible candidate genes for type 2 diabetes and related traits on chromosomes 8p and 22q were NAT2 and CYP2D6, respectively. We thus explored the possible association of NAT2 and CYP2D6 alleles and diabetes-related traits in a sample of 112 Oji-Cree subjects with type 2 diabetes and 481 Oji-Cree subjects without type 2 diabetes. We found no difference in the allele and genotype frequencies of the NAT2 G191A, C282T, C481T, G590A, A803G and G857A, and the CYP2D6 G1934A polymorphisms between Oji-Cree subjects with and without type 2 diabetes. However, we found a significant association between the NAT2 C282T polymorphism and plasma fasting glucose concentration. Specifically, NAT2 282T/T homozygotes had significantly higher plasma fasting glucose than 282C/C homozygotes, and heterozygotes had intermediate levels of this trait. Thus, variation in NAT2 or CYP2D6 was not associated with the presence of type 2 diabetes, and would not be causative for this phenotype in Oji-Cree. However, NAT2 might be a 'modifier gene' affecting the level of glycaemia in non-diabetic subjects.

Adolescent↗

PubMed2000

Association between nuclear lamin A/C R482Q mutation and partial lipodystrophy with hyperinsulinemia, dyslipidemia, hypertension, and diabetes.

Nuclear lamins A and C are encoded by LMNA and are present in terminally differentiated cells. Lamins participate in DNA replication, chromatin organization, arrangement of nuclear pores, nuclear growth, and anchorage of nuclear membranes. In several Canadian probands with partial lipodystrophy, since found to have a common ancestor, we identified a rare novel LMNA mutation, R482Q, that completely cosegregated with the partial lipodystrophy phenotype. We evaluated the relationship between quantitative metabolic phenotypes in both diabetic and nondiabetic carriers of LMNA R482Q and family controls, who were LMNA R482/R482 homozygotes. We found that when compared with LMNA R482/R482 homozygotes: (1) diabetic LMNA Q482/R482 heterozygotes had significantly higher glucose, glycosylated hemoglobin, triglycerides, insulin and C-peptide, and significantly lower HDL cholesterol; and (2) nondiabetic LMNA Q482/R482 heterozygotes had significantly higher triglycerides, insulin and C-peptide, and significantly lower HDL cholesterol. We also found that diabetic LMNA Q482/R482 heterozygotes were older and more likely to take antihypertensive medications. Thus, LMNA R482Q was associated with lipodystrophy, hyperinsulinemia, dyslipidemia, diabetes, and hypertension. The results indicate that perturbations in plasma lipids precede the plasma glucose abnormalities in LMNA Q482-associated hyperinsulinemia. Thus, rare mutations in a nuclear structural protein can be associated with markedly abnormal qualitative and quantitative metabolic phenotypes

Adolescent↗

PubMed2000

Transition from amplified spontaneous emission to laser action in strongly scattering media

In an active random medium, the combination of multiple scattering with light amplification may lead to random laser action. However, it is crucial but sometimes difficult to distinguish between amplified spontaneous emission and lasing. By varying the amount of scattering in an amplifying random medium, we have observed the transition from amplified spontaneous emission to lasing with coherent feedback. We have found out when the transition occurs through the measurement of the scattering mean free path. Our numerical simulation based on the direct solution to Maxwell equations clearly illustrates the transition from light amplification to laser oscillation due to an increase of the amount of scattering in active random medium.

Journal Article↗

PubMed2000

A new catheter design using needle electrode for subendocardial RF ablation of ventricular muscles: finite element analysis and in vitro experiments.

Radio-frequency (RF) cardiac ablation has been very successful for treating arrhythmias related with atrioventricular junction and accessory pathways with successful cure rates of more than 90%. Even though ventricular tachycardia (VT) is a more serious problem, it is known to be rather difficult to cure VT using RF ablation. In order to apply RF ablation to VT, we usually need to create a deeper and wider lesion. Conventional RF ablation electrodes often fail to produce such a lesion. We propose a catheter-electrode design including one or more needle electrodes with a diameter of 0.5-1.0 mm and length of 2.0-10 mm to create a lesion large enough to treat VT. One temperature sensor could be placed at the middle of the needle electrode for temperature-controlled RF ablation. From finite element analyses and in vitro experiments, we found that the depth of a lesion is 1-2 mm deeper than the insertion depth of the needle and the width increases as we increase the diameter of the needle and the time duration. We showed that a single needle electrode can produce a lesion with about 10-mm width and any required depth. If a wider lesion is required, more than one needle with suggested structures can be used. Or, repeated RF ablations around a certain area using one needle could produce a cluster of lesions. In some cases, a catheter with both conventional electrode and needle electrode at its tip may be beneficial to take advantage of both types of electrode.

Animals↗

PubMed2000

Finite element analyses of uniform current density electrodes for radio-frequency cardiac ablation.

The high current density at the edge of a metal electrode causes hot spots, which can lead to charring or blood coagulation formation during radio-frequency (RF) cardiac ablation. We used finite element analysis to predict the current density distribution created by several electrode designs for RF ablation. The numerical results demonstrated that there were hot spots at the edge of the conventional tip electrode and the insulating catheter. By modifying the shape of the edge of the 5-mm tip electrode, we could significantly reduce the high current density at the electrode-insulator interface. We also studied the current density distribution produced by a cylindrically shaped electrode. We modified the shape of a cylindrical electrode by recessing the edge and filled in a coating material so that the overall structure was still cylindrical. We analyzed the effects of depth of recess and the electrical conductivity of the added material. The results show that more uniform current density can be accomplished by recessing the electrode, adding a curvature to the electrode, and by coating the electrode with a resistive material.

Catheter Ablation↗

PubMed2000

Dependence of apparent resistance of four-electrode probes on insertion depth.

The apparent resistance of a finite-thickness layer measured with a four-electrode plunge probe depends on the electrode insertion depth, electrode spacing, and layer thickness, as well as the resistivity ratio of an underlying layer. A physical model consisting of air, a saline solution layer, and an agar layer simulates the real situation of resistivity measurement. The saline layer represents the finite-thickness layer whose resistivity is to be measured by a plunge electrode probe, and the agar layer represents an underlying perturbing layer. A micropositioner controls the insertion depth of the four electrodes into the saline solution. With the apparent resistance measured on a semi-infinite-thickness layer of saline solution as standard, measurement results show decreasing apparent resistance and increasing error with increasing electrode insertion depth. This information is important for correct measurement of myocardial resistivity in vivo and in vitro.

Calibration↗

PubMed2000

Temperature measurement within myocardium during in vitro RF catheter ablation.

While most commercial ablation units and research systems can provide catheter tip temperature during ablation, they do not provide information about the temperature change inside the myocardium, which determines the lesion size. We present the details of a flow simulation and temperature measurement system, which allows the monitoring of the temperature change inside the myocardium during in vitro radio frequency (RF) cardiac catheter ablation at different blood flow rates to which the catheter site may be exposed. We set up a circulation system that simulated different blood flow rates of 0 to 5 L/min at 37 degrees C. We continuously measured the temperature at the catheter tip using the built-in thermistor and inside the myocardium using a three-thermocouple probe. The system provides a means for further study of the temperature inside myocardium during RF catheter ablation under different flow conditions and at different penetration depths.

Animals↗

PubMed2000

Exposure assessment of heavy metals resulting from farmland application of wastewater sludge in Tianjin, China: the examination of two existing national standards for soil and farmland-used sludge.

Land application is one of the major methods of managing municipal sludge in China. The sludge is used for fertilizing and conditioning soil, but due to the high concentration of heavy metals and other chemicals that it contains, improper use of sludge will lead to the contamination of farmland soil. To provide guidance on the application of sludge in China, the Control Standards for Pollutants in Sludge for Agricultural Use (CSPSAU) were enacted, and implemented in 1985. Afterwards, the National Environment Quality Standards for Soil (NEQSS) were also formulated and put into effect in 1996. In this article, these two national standards were examined by means of exposure assessment. The main exposure pathway to humans that was considered was dietary intake of crops grown on the sludge-applied farmland. Five major types of agricultural crops (rice, wheat, tuber roots, vegetables, and fruits) and three groups of exposure population (the urban individual group, the rural sludge-applying individual group, and the rural sludge nonapplying individual group) were assessed. This case study in Tianjin, China, shows the necessity of reexamining the national standards of the CSPSAU and the NEQSS in the context of risk assessment. More comprehensive surveys and monitoring programs assessing heavy metals contained in farmland soils and crop tissues will be necessary for examining the risks to human health.

Agriculture↗

PubMed2000

Differential narrow focusing of immunodominant human immunodeficiency virus gag-specific cytotoxic T-lymphocyte responses in infected African and caucasoid adults and children.

Cytotoxic T-lymphocyte (CTL) activity plays a central role in control of viral replication and in determining outcome in cases of human immunodeficiency virus type 1 (HIV-1) infection. Incorporation of important CTL epitope sequences into candidate vaccines is, therefore, vital. Most CTL studies have focused upon small numbers of adult Caucasoid subjects infected with clade-B virus, whereas the global epidemic is most severe in sub-Saharan African populations and predominantly involves clade-C infection in both adults and children. In this study, sensitive enzyme-linked immunospot (elispot) assays have been utilized to identify the dominant Gag-specific CTL epitopes targeted by adults and children infected with clade-B or -C virus. Cohorts evaluated included 44 B-clade-infected Caucasoid American and African American adults and children and 37 C-clade-infected African adults and children from Durban, South Africa. The results show that 3 out of 46 peptides spanning p17(Gag) and p24(Gag) sequences tested contain two-thirds of the dominant Gag-specific epitopes, irrespective of the clade, ethnicity, or age group studied. However, there were distinctive differences between the dominant responses made by Caucasoids and Africans. Dominant responses in Caucasoids were more often within p17(Gag) peptide residues 16 to 30 (38 versus 12%; P < 0.01), while p24(Gag) peptide residues 41 to 60 contained the dominant Gag epitope more often in the African subjects tested (39 versus 4%; P < 0.005). Within this 20-mer p24(Gag), an epitope presented by both B42 and B81 is defined which represents the dominant Gag response in >30% of the total infected population in Durban. This epitope is closely homologous with dominant HIV-2 and simian immunodeficiency virus Gag-specific CTL epitopes. The fine focusing of dominant CTL responses to these few regions of high immunogenicity is of significance to vaccine design.

Adult↗

PubMed2000

Mutations in the E1 hydrophobic domain of rubella virus impair virus infectivity but not virus assembly.

Rubella virus (RV) virions contain three structural proteins, a capsid protein that interacts with viral genomic RNA to form a nucleocapsid and two membrane glycoproteins, E2 and E1. We found that substitution of either an aspartic acid residue at Gly93 (G93D) or a glycine residue at Pro104 (P104G) in the internal hydrophobic domain of E1 affected virus infectivity but not virus assembly. Viruses carrying G93D and P104G mutations had impaired infectivity, reduced 1,000-fold and 10-fold, respectively. A revertant was isolated from the G93D mutant. Sequencing analysis showed that the substituted aspartic acid residue in G93D mutant had reverted to the original glycine residue, suggesting the involvement of Gly93 in membrane fusion during viral entry.

Amino Acid Substitution↗

PubMed2000

The private hepatocyte nuclear factor-1alpha G319S variant is associated with plasma lipoprotein variation in Canadian Oji-Cree.

We previously showed an extremely strong association between type 2 diabetes and a private polymorphism, namely G319S, in the hepatocyte nuclear transcription factor (HNF)-1alpha. Because HNF-1alpha is involved in the transcription of several apolipoprotein genes, we tested for an association between the private HNF1A G319S variant and plasma lipoproteins in a sample of 55 unrelated Oji-Cree subjects with type 2 diabetes and 175 unrelated Oji-Cree subjects without type 2 diabetes. In Oji-Cree subjects with type 2 diabetes, we found that the HNF1A G319S genotype was significantly associated with lower plasma concentrations of total cholesterol, low density lipoprotein cholesterol, and apolipoprotein (apo) B. In Oji-Cree subjects without type 2 diabetes, we found that the HNF1A G319S genotype was significantly associated with higher plasma concentrations of high density lipoprotein cholesterol and apo AI. There were no associations with plasma triglycerides or lipoprotein(a). Regression analysis indicated that the HNF1A genotype accounted for approximately 10% of the variation in the apo B-related traits in the diabetic subjects and for approximately 5% of the variation in the apo AI-related traits in the nondiabetic subjects. Furthermore, the regression model indicated that the HNF1A S319 allele affected these traits in a dominant manner in subjects with and without type 2 diabetes. These findings provide the first evidence that a rare variant in a nuclear transcription factor is associated with variation in plasma lipoprotein traits.

Adolescent↗

PubMed2000

Peroxisome proliferator-activated receptor-gamma2 P12A and type 2 diabetes in Canadian Oji-Cree.

Among the Oji-Cree of northern Ontario, we previously identified a novel variant in the HNF1A gene, namely G319S, that was strongly associated with type 2 diabetes. However, the majority of subjects with diabetes did not have the HNF1A S319 variant, suggesting that there might be other genetic determinants of diabetes susceptibility. In the course of sequencing candidate genes in diabetic subjects who were homozygous for HNF1A G319/G319, we found that some of them had the PPARG A12 variant. After genotyping PPARG in the entire adult Oji-Cree population, we found that: 1) PPARG A12 was strongly associated with type 2 diabetes in women, but not men; 2) among women, the odds of being affected for carriers of PPARG A12 compared with noncarriers was 2.3 (95% confidence interval, 1.4-3.8); and 3) among women, affected carriers of PPARG A12 had a significantly earlier age-of-onset and/or age-at-diagnosis compared with noncarriers. When taken together with the previously reported association of diabetes with HNF1A in both men and women, the gender-specific association with PPARG A12 confirms that type 2 diabetes is etiologically complex in the Oji-Cree and that at least two genes are involved in determining susceptibility to the disease in these people.

Adult↗

PubMed2000

LMNA R482Q mutation in partial lipodystrophy associated with reduced plasma leptin concentration.

Mutations in LMNA, which encodes lamins A and C, have been found in patients with autosomal dominant Dunnigan-type familial partial lipodystrophy (FPLD). We analyzed the relationship between plasma leptin and the rare LMNA R482Q mutation in 23 adult FPLD subjects compared with 25 adult family controls with normal LMNA in an extended Canadian FPLD kindred. We found that the LMNA Q482/R482 genotype was a significant determinant of plasma leptin, the ratio of plasma leptin to body mass index (BMI), plasma insulin, and plasma C peptide (P= 0.015, P = 0.0007, P = 0.0004, and P < 0.0001, respectively), but not BMI (P = 0.67). Family members who were heterozygous for LMNA Q482/R482 had significantly lower plasma leptin and leptin:BMI ratio than unaffected R482/R482 homozygotes. Fasting plasma concentrations of insulin and C peptide were both significantly higher in LMNA Q482/R482 heterozygotes than in R482/R482 homozygotes. Multivariate regression analysis revealed that the LMNA R482Q genotype accounted for 40.9%, 48.2%, 86.9%, and 81.0%, respectively, of the attributable variation in log leptin, leptin:BMI ratio, log insulin, and log C peptide (P = 0.013, P = 0.0007, P = 0.0002 and P < 0.0001, respectively). The results indicate that a rare FPLD mutation in LMNA determines the plasma leptin concentration. It remains to be established whether the reduction in leptin results from the reduced adipose tissue mass in FPLD or from another subcellular effect of mutant LMNA. It also remains to be established whether the insulin resistance in FPLD is a consequence of the reduced plasma leptin or of another functional change resulting from mutant LMNA.

Adult↗