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Biomedical subjects

H Cao

Publications and source records attributed to H Cao.

At least 55 records · Page 3Linked to original sources

Polymorphisms in PNLIP, encoding pancreatic lipase, and associations with metabolic traits.

Pancreatic lipase (EC 3.1.1.3) is an exocrine secretion that hydrolyzes dietary triglycerides in the small intestine. We developed genomic amplification primers to sequence the 13 exons of PNLIP, which encodes pancreatic lipase, in order to screen for possible mutations in cell lines of four children with pancreatic lipase deficiency (OMIM 246600). We found no missense or nonsense mutations in these samples, but we found three silent single-nucleotide polymorphisms (SNPs), namely, 96A/C in exon 3, 486C/T in exon 6, and 1359C/T in exon 13. In 50 normolipidemic Caucasians, the PNLIP 96C and 486T alleles had frequencies of 0.083 and 0.150, respectively. The PNLIP 1359T allele was absent from Caucasian, Chinese, South Asian, and North American aboriginal samples, but had a frequency of 0.085 in an African sample, suggesting that it is a population-specific variant. In an association analysis of 185 African neonates, the PNLIP 1359C/T SNP genotype was significantly associated with concentrations of plasma lipoproteins. These associations were most likely due to linkage disequilibrium with another functional variant at or near PNLIP. Thus, we report three new SNPs for the PNLIP, which may serve as markers for association analyses and for pharmacogenetic studies of pancreatic lipase inhibitors.

Africa↗

Single-nucleotide polymorphisms of the nuclear lamina proteome.

Familial partial lipodystrophy (FPLD) has been shown to be due to mutations in the LMNA gene encoding nuclear lamins A and C, indicating that defective structure of the nuclear envelope can produce this unique phenotype. Some patients with inherited partial lipodystrophy have normal LMNA coding, promoter, and 3'-untranslated region sequences. This suggests that the FPLD phenotype is genetically heterogeneous. Among the candidate genes to consider for the non-LMNA-associated forms of FPLD are other components of the inner nuclear membrane, such as lamin B1 and B2 and the lamin B receptor. We developed amplification primers for the coding regions of LMNB1, LMNB2, and LBR, which encode lamin B1, lamin B2, and the lamin B receptor, respectively. We found no putative disease mutations in any of these proteins in subjects with non-LMNA FPLD, but, through the screening of diseased and normal subjects, we identified several single-nucleotide polymorphisms (SNPs); specifically, five SNPs in LMNB1 and four SNPs in LBR. The LMNB2 gene was monomorphic in screening experiments. We conclude that mutations in other constituent proteins of the nuclear envelope are not present in subjects with non-LMNA-associated FPLD. However, the identification of amplification primers and SNPs provides tools to investigate these proteins for their association with other phenotypes.

Base Sequence↗

Modeling and prediction for discharge lifetime of battery systems using hybrid evolutionary algorithms.

A hybrid evolutionary modeling algorithm (HEMA) is proposed to build the discharge lifetime models with multiple impact factors for battery systems as well as make predictions. The main idea of the HEMA is to embed a genetic algorithm (GA) into genetic programming (GP), where GP is employed to optimize the structure of a model, while a GA is employed to optimize its parameters. The experimental results on lithium-ion batteries show that the HEMA works effectively, automatically and quickly in modeling the discharge lifetime of battery systems. The algorithm has some advantages compared with most existing modeling methods and can be applied widely to solving the automatic modeling problems in many fields.

Algorithms↗

An approach to metal-assisted DNA base pairing: novel beta-C-nucleosides with a 2-aminophenol or a catechol as the nucleobase.

The metal-chelating beta-C-nucleoside having a phenylenediamine moiety as the nucleobase was previously found to form a stable 2:1 complex with a Pd(2+) ion in aqueous media, where hydrogen bonding is replaced by metal coordination in the base pairing, thereby creating a novel hybridization motif in duplex DNA. In this regard, we have further designed two types of artificial beta-C-nucleosides possessing a metal-chelating site (a 2-aminophenol or a catechol) as the nucleobase moiety. These artificial nucleosides are directed toward controlling the net charges of the metal-assisted base pairs. This paper describes convenient syntheses of the artificial nucleosides bearing a 2-aminophenol or a catechol moiety. Each nucleoside was directly synthesized through 2'-deoxy derivative via a Friedel-Crafts coupling reaction as the key step between the aromatic ring and ribose moiety, whereas the nucleoside having a phenylenediamine moiety was prepared in rather longer steps through an RNA type intermediate followed by the removal of 2'-hydroxyl group.

Aminophenols↗

Association of a single nucleotide polymorphism in CPB2 encoding the thrombin-activable fibrinolysis inhibitor (TAF1) with blood pressure.

Thrombin-activable fibrinolysis inhibitor (TAFI) is a hepatically secreted zymogen, whose substrates include bradykinin. The CPB2 gene encoding TAFI is a candidate gene for blood pressure. A recently identified single nucleotide polymorphism (SNP) in the CPB2 coding region, designated as 1057C > T, results in an amino acid change at TAFI residue 325 (Ile > Thr325). We found that the genotype based on this SNP was significantly associated with blood pressure in aboriginal Canadians. Specifically, analysis of variance showed that homozygotes for CPB2 1057T had significantly lower diastolic blood pressure than subjects with other CPB2 genotypes. CPB2 genotype accounted for approximately 3% of the total variation in diastolic blood pressure. consistent with the expected magnitude of a modest genetic effect in a complex trait such as blood pressure. Although the mechanism underlying the association is unclear, the findings are of interest because TAFI may provide a link between coagulation and blood pressure regulation.

Adolescent↗

In vitro production of dendritic cells from human blood monocytes for therapeutic use.

Dendritic cells (DC) are professional antigen-presenting cells 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 hematopoietic progenitor cells have been now developed. For this purpose, their in vitro production for further clinical use need to fit good manufacturing practice (GMP) conditions. In the present review, we give our experience of such a procedure: it includes collection of mononuclear cells by apheresis, separation of monocytes by elutriation, and culture of monocytes with GM-CSF + IL-13 + human serum (autologous patient's serum or AB serum) or in a serum-free medium (AIM V). The characteristics of monocyte-derived DC grown in these various conditions varied mainly regarding their phenotype and their morphology in confocal microscopy, whereas no significant differences were found in their capacity to phagocytize latex particles and to stimulate allogeneic (MLR) or autologous lymphocytes (antigen-presentation tests). The DC were also cryopreserved in bags (either by putting the bags directly in a -80 degrees C mechanical freezer or using a classical liquid nitrogen controlled-rate freezer at -1 degrees C/min) in a solution containing 10% dimethyl sulfoxide (Me(2)SO) and 2% human albumin in doses of DC available for several infusions. The mean recoveries after freezing and thawing were not statistically different (around 70%). The immunophenotype of DC, as well as the T lymphocyte-stimulating capacity, were not modified by the freezing--thawing procedure. 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 DC. Clinical trials using DC already published will be discussed.

Adjuvants, Immunologic↗

Guidelines for predicting lesion size at common endocardial locations during radio-frequency ablation.

We used the finite element method to study the effect of radio-frequency (RF) catheter ablation on tissue heating and lesion formation at different intracardiac sites exposed to different regional blood velocities. We examined the effect of application of RF current in temperature- and power-controlled mode above and beneath the mitral valve annulus where the regional blood velocities are high and low respectively. We found that for temperature-controlled ablation, more power was delivered to maintain the preset tip temperature at sites of high local blood velocity than at sites of low local blood velocity. This induced more tissue heating and larger lesion volumes than ablations at low velocity regions. In contrast, for power-controlled ablation, tissue heating was less at sites of high compared with low local blood velocity for the same RF power setting. This resulted in smaller lesion volumes at sites of low local velocity. Our numerical analyzes showed that during temperature-controlled ablation at 60 degrees C, the lesion volumes at sites above and underneath the mitral valve were comparable when the duration of RF current application was 10 s. When the duration of RF application was extended to 60 s and 120 s, lesion volumes were 33.3% and 49.4% larger above the mitral valve than underneath the mitral valve. Also, with temperature-controlled ablation, tip temperature settings of 70 degrees C or greater were associated with a risk of tissue overheating during long ablations at high local blood velocity sites. In power-controlled ablation (20 W), the lesion volume formed underneath the mitral valve was 165.7% larger than the lesion volume above the mitral valve after 10 s of ablation. We summarized the guidelines for energy application at low and high flow regions.

Blood Flow Velocity↗

Measurement of directional thermal properties of biomaterials.

This paper presents an experimental technique to measure the directional thermal conductivity and thermal diffusivity of materials. A heated thermistor heats the sample and a sensing thermistor placed about 2.5 mm away measures the temperature rise due the heating pulse at the heated thermistor. An empirical relation between the power delivered by the first thermistor and the temperature rise recorded by the sensing thermistor is used to measure the thermal conductivity of the material along the line joining the thermistors. Diffusivity of the material is determined from the delay between the power pulse in the heated thermistor and the temperature pulse at the sensing thermistor. Signal processing was done to eliminate errors in the measurement due to change of base line temperature. Uncertainty of the measurement technique was found to be 5% when tested in media of known thermal properties. The thermal conductivity and thermal diffusivity of swine left ventricle in normal and ablated conditions were measured using this technique. The thermal conductivity of the tissue dropped significantly from 0.61 to 0.50 W.m(-1).K(-1) after ablation while the diffusivity dropped from 2.1 x 10(-7) to 1.7 x 10(-7)m2.s(-1).

Analysis of Variance↗

Flow effect on lesion formation in RF cardiac catheter ablation.

This study investigated the flow effect on the lesion formation during radio-frequency cardiac catheter ablation in temperature-controlled mode. The blood flow in heart chambers carries heat away from the endocardium by convection. This cooling effect requires more power from the ablation generator and causes a larger lesion. We set up a flow system to simulate the flow inside the heart chamber. We performed in vitro ablation on bovine myocardium with three different flow rates (0 L/min, 1 L/min and 3 L/min) and two target temperatures (60 degrees C and 80 degrees C). During ablation, we also recorded the temperatures inside the myocardium with a three-thermocouple temperature probe. The results show that lesion dimensions (maximum depth, maximum width and lesion volume) are larger in high flow rates (p<0.01). Also, the temperature recordings show that the tissue temperature rises faster and reaches a higher temperature under higher flow rate.

Animals↗

Common mechanisms for pathogens of plants and animals.

The vast evolutionary gulf between plants and animals--in terms of structure, composition, and many environmental factors--would seem to preclude the possibility that these organisms could act as receptive hosts to the same microorganism. However, some pathogens are capable of establishing themselves and thriving in members of both the plant and animal kingdoms. The identification of functionally conserved virulence mechanisms required to infect hosts of divergent evolutionary origins demonstrates the remarkable conservation in some of the underlying virulence mechanisms of pathogenesis and is changing researchers' thinking about the evolution of microbial pathogenesis.

Animals↗

Identification of inhibitors of bacterial transcription/translation machinery utilizing a miniaturized 1536-well format screen.

This report presents the miniaturization of a HTS screen to identify inhibitors of prokaryotic transcription-translation in a 1536-well format. The in vitro assay design utilized the bacterial expression machinery to drive expression of a firefly luciferase reporter gene, which was read as an endpoint luminesence measurement. This multicomponent system permits identification of inhibitors at different steps in this pathway. Successful miniaturization required integration of homogeneous assay formats, robust liquid-handling workstations, and second-generation imaging systems. Comparison of data from a triplicate 1536-well screen of a subset of a target library that had been previously validated and followed up for hit confirmation in a 384-well plate format confirmed that triplicate screening yields data of higher confidence and quality, eliminates the time-consuming and potentially error-prone step of cherry-picking, and reduces the number of false positives and negatives. The substantial savings of reagents and reduction of the numbers of plates to process obtained in a 1536-well format as compared to a 384-well format allowed a full triplicate evaluation of the entire library of 183,000 compounds at lower cost and in less time. The triplicate-screen statistics are consistent with a highly reliable data set with a coefficient of variation of 14.8% and Z' and Z values of 0.57 and 0.25, respectively. This screen resulted in the identification of 1,149 hits (0.63% hit rate), representing a compound population at 2.5 standard deviations from the mean cutoff. Furthermore, the data demonstrate good agreement between IC(50) values derived for this assay in a 1536-well format and 384-well format.

Bacteria↗

Molecular analysis of medicinally-used Chinese and Japanese Curcuma based on 18S rRNA gene and trnK gene sequences.

Curcuma drugs have been used discriminatingly for invigorating blood circulation, promoting digestion, and as a cholagogic in China. However, there is confusion about the drug's botanical origins and clinical uses because of morphological similarity of Curcuma plants and drugs. In order to develop an ultimate identification, molecular analysis based on 18S rRNA gene and trnK gene sequences were performed on 6 Curcuma species used medicinally in China and Japan. The 18S rRNA gene sequences were found to be of 1810 bps in length. In comparison with the common sequence of C. longa, C. phaeocaulis, C. wenyujin and C. aromatica, that of C. kwangsiensis had one base substitution, and the same base difference was observed between the Chinese and the Japanese populations of C. zedoaria. The trnK gene sequences were found to span 2698-2705 bps. There were base substitutions, small deletions or insertions at some sites between the trnK coding region and matK region among each species. Based on the base substitutions, C. zedoaria and C. kwangsiensis specimens were divided into two groups, respectively. An identical sequence was detected in C. phaeocaulis and in the Chinese population of C. zedoaria, as well as in the Japanese population of C. zedoaria and in one group of C. kwangsiensis with a purple-colored band in leaves. New taxonomic information to be used for authenticating Curcuma drugs was obtained.

Curcuma↗

[Identification of notoginseng(Panax notoginseng) and its adulterants using DNA sequencing].

OBJECTIVE: To analyze the nuclear ribosomal RNA small subunit (18S rRNA) and chloroplast matK gene sequence of notoginseng (Panax notoginseng) in order to provide molecular evidence for its genuine origin identification. METHODS: To sequence 18S rRNA and matK genes of Panax notoginseng and its four adulterants such as P. japonicus, Curcuma phaeocaulis, C. wenyujin, C. kwangsiensis using PCR direct sequencing and to detect their variation of sequences. RESULTS: The sequence length of notoginseng and its adulterants is 1809-1811 bp for 18S rRNA gene and 1259-1548 bp for matK gene, respectively. Multiple sequence alignment shows that there are much sequence variation between notoginseng and its adulterants. CONCLUSION: DNA sequencing is an accurate and reliable method in origin identification of the genuine notoginseng.

Amino Acid Sequence↗

An experimental study on drugs for improving blood circulation and removing blood stasis in treating mild chronic hepatic damage.

Large and small doses of drugs for improving blood circulation and removing blood stasis were used in model rats to treat mild chronic hepatic damage induced by carbon tetrachloride (CCl4). The results show that large dose of Dang Gui ([symbol: see text] Radix Angelicae Sinensis) and Dan Shen ([symbol: see text] Radix Salviae Miltiorrhizae) (drugs for regulating blood flow) and small dose of Yu Jin ([symbol: see text] Radix Curcumae) and Niu Xi ([symbol: see text] Radix Achyranthis Bidentatae) (drugs for activating blood flow) can significantly elevate the activity of SOD (P < 0.05) and/or lower the T/K ratio, markedly reduce the MDA content (P < 0.05 or P < 0.01) and significantly decrease the activities of ALT and AST (P < 0.05 or P < 0.01), demonstrating that these drugs are effective in combating oxygen free radicals (OFR) in chronic liver damage. On the contrary, large dose of Tu Bie Chong ([symbol: see text] Eupolyphaga seu Steleophaga) and E Zhu ([symbol: see text] Rhizoma Curcumae) (drugs for removing blood stasis) tend to increase the ALT and AST (P < 0.05) activities. The results suggest that the synergism of elevation of the SOD activity and reduction of T/K ratio contributes to the action of drugs for improving blood circulation and removing blood stasis in combating the liver damage induced by CCl4.

Alanine Transaminase↗

[Nuclear ribosomal RNA small subunit (18S rRNA) nucleotide sequencing and characterization of sailonggu(whole bone of Myospalax baileyi Thomas)].

OBJECTIVE: Sequencing the nuclear ribosomal RNA small subunit (18S rRNA) gene of Myospalax baileyi (Cricetidae) to develop an ultimate and definitive means for origin identification of genuine Sailonggu. METHODS: The total DNA was prepared from dried tail tissues. The nuclear 18S rRNA gene region was amplified by PCR using a consensus primer set and its nucleotide sequence was determined by PCR direct sequencing. The characteristic analysis of 18S rRNA sequences was generated using software program Genetyx-SV/R Version 10.1. RESULTS: The entire 18S rRNA gene region of M. baileyi spanded 1851 bp in length. Although multiple alignment of sequence indicates that there are only lower homology (72.04%-72.18%) comparing with its two alias Mus musculus (GenBank Accession number X00686) and Rattus norvegicus (M11188) (Muridae), their highly conservative domain is located in 1020-1509 nt. There are many variable sites from upstream of 5'-end, which could provide a novel information for molecular recognition of Sailonggu. CONCLUSION: DNA sequencing could be a useful and reliable tool in the origin identification of genuine Sailonggu.

Animals↗

[Pharmacological study on Tianxiong (tuber of Aconitum carmichaeli Debx.), a Chinese drug for reinforcing the kidney yang retail in Hong Kong market].

OBJECTIVE: To explore the pharmacodynamic mechanism of Tianxiong (Aconitum carmichaeli) in tonifying the kidney and supporting Yang, so as to provide evidences for further development of new drugs treating Yang-eficiency of the kidney. METHOD: Observing parameters such as visceral index, survival time of low-temperature swimming for hydrocortisone-induced Yang-deficiency model mouse and testis-removed kidney-deficiency model rat. RESULT: The decoction of processed Tianxiong could strengthen the antifatigual ability and prolong the survival time of low-temperature swimming for mice, and promote immunization in rats. CONCLUSION: Tianxiong is able to reinforce the kidney Yang, which reconforms the conclusion of "replenishing the fire of vital gate and the Qi of kidney" recorded in Chinese historical literature and proved by overseas clinical practice.

Aconitum↗