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Biomedical subjects

P Fan

Publications and source records attributed to P Fan.

At least 55 records · Page 3Linked to original sources

[Clinical significance of cardiac axis determination in prenatal echocardiographic diagnosis of fetal congenital heart disease].

OBJECTIVE: To investigate the clinical significance of cardiac axis determined by echocardiography in prenatal diagnosis of fetal congenital heart disease (CHD). METHODS: 518 high risk fetuses for CHD were and 90 normal fetuses were examined by echocardiography. Cardiac axis was measured on four-chamber view and fetal cardiac anatomical structure was examined in multiple views to determine CHD. RESULTS: The 35 fetuses with CHD diagnosed by prenatal echocardiography. There is significant difference of caidiac axis between CHD group (58.1 +/- 15.7 degree) and normal group (44.8 +/- 10.3 degree, P < 0.01). Sensitivity of CHD diagnosis using four-chamber view alone is 68.5%, it will be elevated to 91.4% by combination of four-chamber view and cardiac axis determination (P < 0.05). CONCLUSION: Cardiac axis play an important role in fetal echocardiographic screening for CHD and it should be measured routinely as part of the four-chamber view of the fetal heart. The normal range of fetal cardiac axis is 20 to 75 degree. If it was more than 75 degree, the CHD should be suspected.

Adult↗

[Apolipoportein E polymorphism, serum lipids and apolipoproteins of 362 Han national subjects in Chengdu area].

This investigation was conducted to observe the frequency distribution of apoE phenotypes and alleles and to explore the relationship between apoE polymorphism and plasma lipids or apolipoproteins in Chinese population. ApoE phenotypes were assayed by isoelectric focusing and immunoblotting with serum. Serum lipids and apoA I, B100, C II, C III, E were determined in a random subset of 362 subjects including 268 males and 94 females with a mean age of 43.7 +/- 12.3 yrs from a population of Han Nationality in Chengdu area. The results showed that the frequencies of apoE phenotypes and alleles were: E3/3 72.93%, E2/3 12.98%, E3/4 11.33%, E2/4 1.38%, E4/4 1.38%, E2/2 0.00%; epsilon 3 0.8508, epsilon 2 0.0718, epsilon 4 0.0774. The results also showed that the apo E2(E2/3 + E2/2) group had lower levels of serum TC and apoB100 (P < 0.05) and a higher level of serum apoE (P < 0.001) when compared with the apoE3(E3/3) or apoE4(E3/4 + E4/4) group. No significant difference was observed in TG, apoA I, apoC II, and apoC III levels among the apoE2, E3 and E4 groups (P > 0.05).

Adult↗

[Plasma HDL subfractions in endogenous hypertriglyceridemia].

Our previous studies indicated that while the plasma triglycerides (TG) levels were significantly increased, HDL-C and apo A I levels were significantly decreased and abnormal HDL compositions were found in hypertriglyceridemic (HTG) patients. Whether the particle sizes of plasma HDL in HTG undergo a change has not yet been reported. This study was designed to observe the changes of plasma HDL subfractions in HTG patients. The plasma TG, total cholesterol (TC), HDL-C, apo A I, A II, B100, C II, C III, and E, HDL compositions and HDL subfractions--HDL2a, HDL2b, HDL3a, HDL3b and HDL3c were measured in 25 HTG patients (plasma TG > 2.26 mmol/L, TC < 6.72 mol/L) and 25 age-sex matched healthy subjects (plasma TG < 1.69 mmol/L, TC < 5.17 mmol/L). Plasma HDL was isolated by one step density gradient ultracentrifugation. Plasma and HDL TC, TC were determined by enzymatic methods; apo A I, A II, B100, C II, C III and E were measured by RID kits developed by ourselves. HDL subfractions were analyzed by a gradient gel electrophoresis method (GGE). The variation coefficients in one gel were 2.3% to 8.3% and the variation coefficients among gels were 3.5% to 9.3%. The results indicated that in the HTG group, the fasting plasma TG, apo B100, C II, C III and E levels were significantly higher (P < 0.001) and HDL-C, apo A I levels were lower (P < 0.05) as compared with those in the control group. TC in HDL in the HTG group were significantly increased (P < 0.05), while TG, apo A I, C II, C III and E were significantly decreased (P < 0.05, P < 0.01). Among HDL subfractions in the HTG group, HDL2b was significantly decreased (P < 0.02); HDL2a and HDL3a were increased (P < 0.05, P < 0.02). With the increase of plasma TG levels in the HTG group, the HDL particle sized tended to become smaller. According to the results, it is suggested that the changes of plasma HDL subfractions in HTG are related to the changes of the apolipoprotein compositions of HDL, which lead to the increase of HDL catabolism, therefore the plasma HDL2b content decreases and HDL2a, HDL3a contents increase.

Adult↗

Extraperitoneal laparoscopic inguinal hernia repairs.

Totally extraperitoneal herniorrhaphy (TEP) is a highly technical procedure with a long learning curve for surgeons. It demands extra skills and may be frustrating, even to the experienced laparoscopic surgeon. The main eriticisms have been the higher costs, the need for general anesthesia, and the prolonged operating room time. When properly performed, TEP provides satisfaction to all involved, namely the patient, the surgeon and the third party payer. The initial concerns of safety, efficacy and efficiency are no longer valid issues as TEP has proved to be safe in numerous randomized trials. We find that there is increasing patient demand for this procedure.

Journal Article↗

[Establishment and identification of the monoepitopic monoclonal antibody of Plasmodium falciparum].

AIM: To prepare a monoepitopic monclonal antibody of Plasmoduim falciparum. METHODS: According to the theory of protein structure, a peptide with 6-9 residues representting the antigenicity of the original histidine-rich protein II (HRP-II) of P. falciparum was synthesized and used to immunize BALB/c mice after purity identification by capillary electrophoresis. RESULTS: Four hybridoma cell lines targeting a suitable peptide from pf HRP-II were obtained by using spleen embedment method and hybridoma technology. CONCLUSION: It is the first report to prepare a monoepitopic monoclonal antibody against original protein by selecting a suitable peptide from the primary sequence of protein.

Animals↗

[Transmission grating spectrograph for soft X-ray spectrum measurements with a pre-optics].

A novel diffraction spectroscopic instrument consisting of a large area transmission grating and a grazing-incidence pre-optics comprising of a toroidal mirror, a slit and a cylindrical mirror has been implemented. A nearly perfect stigmatism and a medium spectral resolution are due to the separation of the focusing and dispersing function. The experimental results show that it is possible to construct large area transmission grating spectrograph with high collecting efficiency and good spatial resolution.

English Abstract↗

Novel analogues of arachidonylethanolamide (anandamide): affinities for the CB1 and CB2 cannabinoid receptors and metabolic stability.

Several analogues of the endogenous cannabinoid receptor ligand arachidonylethanolamide (anandamide) were synthesized and evaluated in order to study (a) the structural requirements for high-affinity binding to the CB1 and CB2 cannabinoid receptors and (b) their hydrolytic stability toward anandamide amidase. The series reported here was aimed at exploring structure-activity relationships (SAR) primarily with regard to stereoelectronic requirements of ethanolamido headgroup for interaction with the cannabinoid receptor active site. Receptor affinities, reported as Ki values, were obtained by a standard receptor binding assay using [3H]CP-55,940 as the radioligand, while stability toward the amidase was evaluated by comparing the Ki of each analogue in the presence and absence of phenylmethanesulfonyl fluoride (PMSF), a serine protease blocker and inhibitor of anandamide amidase. Introduction of a methyl group in the 1'- and 2'-positions or substitution of the ethanolamido headgroup with a butylamido group gave analogues with vastly improved biochemical stability. This is accomplished in some cases with increased receptor affinity. Conversely, oxazolyl and methyloxazolyl headgroups led to low-affinity analogues. Substitution of the hydroxyl group with electronegative substituents such as fluoro, chloro, allyl, and propargyl groups significantly increased receptor affinity but did not influence the biochemical stability. The 2'-chloro analogue of anandamide was found to have the highest affinity for CB1. Additionally, reversing the positions of the carbonyl and NH in the amido group produces retro-anandamides possessing considerably higher metabolic stability. Replacement of the arachidonyl tail with oleyl or linoleyl results in analogues with low affinities for both receptors. All of the analogues in this study showed high selectivity for the CB1 receptor over the peripheral CB2 receptor. The most potent analogues were tested for their ability to stimulate the binding of [35S]GTPgammaS to G-proteins and were shown to be potent cannabimimetic agonists. The results are discussed in terms of pharmacophoric features affecting receptor affinity and enzymatic stability.

Amidohydrolases↗

Classical/nonclassical hybrid cannabinoids: southern aliphatic chain-functionalized C-6beta methyl, ethyl, and propyl analogues.

The stereoelectronic requirements for interaction of the southern aliphatic hydroxyl of cannabimimetic pharmacophores with the CB1 and CB2 receptors are explored. The stereoselective syntheses of three series of classical/nonclassical hybrid cannabinoids are described. These compounds were designed to investigate the importance of the southern aliphatic hydroxyl (SAH) pharmacophore for cannabimimetic activity. Variation in the chain length of the SAH moiety in these 6beta-(hydroxyalkyl)dihydrobenzopyran analogues, from 6beta-hydroxymethyl to 6beta-(omega-hydroxyethyl) and 6beta-(omega-hydroxypropyl), and the effects of replacing the hydroxyl functionality by hydride and iodide are reported. Our results indicate that the SAH pharmacophore has less pronounced effects than the C-3 aliphatic chain on cannabinoid activity. Furthermore, it appears that this southern molecular component is capable of interacting with two different subsites on the receptor and that the nature of this interaction is determined by the terminal substituent on the C-6beta alkyl group. One of the subsites can accommodate the relatively polar SAH pharmacophore, while the second subsite interacts with more hydrophobic C-6beta substituents and can accommodate large spherical pharmacophores separated by three methylene carbons from the tricyclic cannabinoid template.

Animals↗

A bait and switch hapten strategy generates catalytic antibodies for phosphodiester hydrolysis.

General base catalysis supplied by the histidine-12 (H-12) residue of ribonuclease (RNase) A has long been appreciated as a major component of the catalytic power of the enzyme. In an attempt to harness the catalytic power of a general base into antibody catalysis of phosphodiester bond hydrolysis, the quaternary ammonium phosphate 1 was used as a bait and switch hapten. Based on precedence, it was rationalized that this positively charged hapten could induce a counter-charged residue in the antibody binding site at a locus suitable for it to deprotonate the 2'-hydroxyl group of the anhydroribitol phosphodiester substrate 2. After murine immunization with hapten 1, mAb production yielded a library of 35 antibodies that bound to a BSA-1 conjugate. From this panel, two were found to catalyze the cyclization-cleavage of phosphodiester 2. Kinetic studies at pH 7.49 (Hepes, 20 mM) and 25 degreesC showed that the most active antibody, MATT.F-1, obeyed classical Michaelis-Menten kinetics with a Km = 104 microM, a kcat = 0.44 min-1, and a kcat/kuncat = 1.7 x 10(3). Hapten 1 stoichiometrically inhibits the catalytic activity of the antibody. MATT.F-1 is the most proficient antibody-catalyst (1.6 x 10(7) M-1) yet generated for the function of phosphodiester hydrolysis and emphasizes the utility of the bait and switch hapten paradigm when generating antibody catalysts for processes for which general-base catalysis can be exploited.

Antibodies, Catalytic↗

Cloning and characterization of a novel human chemokine receptor.

The present study reports the identification of a human gene, HCR, which encodes a novel human chemokine receptor. The partial sequence of the HCR gene was first found in a human neutrophil cDNA library. With the use of an expressed sequence tag (EST) probe from the neutrophil library, the full length HCR cDNA was isolated. The open reading frame of HCR cDNA predicts a protein of 345 amino acids with seven transmembrane domain topography. The HCR gene exhibits good homology to human MIP-1a receptor with 43.1% amino acid identity and 64.4% amino acid similarity and also shows considerable sequence homology to other human chemokine receptors such as the MCP-3 receptor, MCP-5 receptor, and MCP-1 receptor. Northern blot analysis suggests that HCR gene is expressed abundantly in immunal tissues such as spleen, fetal liver, lymph node, and bone marrow. Strong expression was also found in human lung and heart. A chromosome mapping study indicated that HCR gene is positioned within human chromosome band Xq13. Our result suggests that HCR gene is a novel putative chemokine receptor.

Amino Acid Sequence↗

Cloning of a putative human neurotransmitter receptor expressed in skeletal muscle and brain.

With the use of the degenerated nucleotides that contain the conserved sequence of G protein-coupled receptor, we have identified a 648-bp clone (HDGRC02) from human genomic DNA with significant sequence homology to human neurotransmitter receptors. HDGRC02 was then used as a probe for the screening of full length gene. From human Lambda DASH II genomic library, a 1.6 Kb clone encoded a full length gene was isolated and named putative neurotransmitter receptor (PNR). PNR has a single open reading frame which predicts a 38.3 KD protein of 338 amino acids with seven transmembrane domain topography. The amino acid sequence of PNR exhibits considerable homology to the rat 5-HR1D receptor with 35% amino acid identity and 56% amino acid similarity. PNR also shows significant sequence homology to the 5-HT1D receptor from Japanese puffer fish fugu, to the 5-HT4L receptor from mouse, to the alpha-2 adrenergic receptor and to the D2 dopamine receptor. Northern blot analysis indicates that PNR is expressed in skeletal muscle and selected areas of the brain. A chromosome mapping study located the PNR gene with human chromosome band of 6q23. The findings in the present study demonstrate that PNR is a putative neurotransmitter receptor.

Amino Acid Sequence↗

Common genetic variants of lipoprotein lipase and apolipoproteins AI-CIII that relate to coronary artery disease: a study in Chinese and European subjects.

The large ethnic differences in prevalence of coronary artery disease between China and Europe may relate to both genetic and environmental differences. To assess possible genetic factors we have therefore studied the frequencies of disease-related variants of genes involved in lipid transport in 69 hypertriglyceridemic Chinese subjects and 74 healthy Chinese controls. The loci studied include lipoprotein lipase (Asp9Asn, Asn291Ser, Ser447Ter, and Thr361Thr); apolipoprotein A1 (restriction sites at MspI, XmnI, and PstI); and apolipoprotein (apo) CIII (G3175C). All these variants have been shown in previous literature publications to relate to either dyslipidemia and/or premature coronary heart disease in Caucasians. Two disease-related genetic variants in Europeans (Asp9Asn and Asn291Ser) were not found in the Chinese sample. The apo CIII G3175C variant was found more frequently in the upper tertile distributions for apolipoprotein CIII, apolipoprotein E, and plasma triglyceride/HDL ratios (P < 0.05). The rare allele of the apo AI MspI restriction site polymorphic variant was also found more frequently in the upper tertiles for apo CIII, apo E, and plasma triglyceride/HDL ratios (P < 0.04). Eleven of the most lipaemic Chinese subjects (with fasting plasma triglycerides >700 mg/dl) were analyzed for DNA sequence variation. One novel mutation was observed C1338A (which is a silent mutation at Thr361) and two others that are also found in European subjects (Ala261Thr and Ser447Ter). We conclude that genetic differences between Chinese and Europeans may have an effect on the prevalence of coronary artery risk factors involved in lipid transport, and further extended study is warranted.

Alleles↗

Cloning, characterization, and mapping of human homolog of mouse T-cell death-associated gene.

To establish immunologic autotolerance, self-reactive immature thymocytes are eliminated by negative selection during T-cell development in the thymus. Self-reactive clones undergo apoptosis after stimulation via the T-cell receptor (TCR). The process of cell selection is determined by the dedication of the TCR for tolerogenic antigen/major histocompatibility complex. We have cloned a novel human gene that is highly homologous in the transmembrane and G protein-coupling domains to mouse T-cell death-associated gene 8 (TDAG8). The gene, human TDAG8 (hTDAG8), which belongs to the G protein-couple receptor superfamily, encodes a protein of 337 amino acids. An expressed sequence tag (EST) corresponding to hTDAG8 was identified from a human thyroid cDNA library and subsequently used to isolate a full-length genomic clone. Northern blot analysis revealed that the hTDAG8 gene is expressed predominantly in lymphoid tissues, including peripheral blood leukocytes, spleen, lymph nodes, and thymus. Stably transfected mammalian CHO cells were generated, and heterologous expression of hTDAG8 was confirmed by Northern blot analysis. Fluorescent in situ hybridization (FISH) revealed that hTDAG8 maps to human chromosome 14q31-32.1, a region in which abnormalities associated with human T-cell lymphoma or leukemia are found. Taken together, these data implicate the hTDAG8 gene in T-cell-associated diseases in humans, but its actual physiological and pathological role in the human immune system needs further investigation.

Amino Acid Sequence↗

Intrapulmonary shunting in primary pulmonary hypertension: an observation in two patients treated with epoprostenol sodium.

Continuous intravenous infusion of epoprostenol sodium in selected patients with primary pulmonary hypertension improves symptoms and survival. This report describes two patients with primary pulmonary hypertension treated with epoprostenol in whom intrapulmonary shunting and severe hypoxemia occurred. Intrapulmonary shunting was confirmed by contrast echocardiography showing delayed appearance of bubbles in the left cardiac chambers after peripheral venous injection of agitated saline solution.

Antihypertensive Agents↗

[Clinical significance of pulmonary valvular resistance in children determined by color Doppler echocardiography].

Pulmonary valvular resistance (PVR) of 40 children with pulmonary valvular stenosis was determined by color Doppler echocardiography before and after percutaneous balloon pulmonary valvuloplasty as well as during their follow-up. The correlation coefficient of PVR between Doppler method and catheterization method was 0.85 ( P <0.01) and the correlation coefficient between PVR determined by former method and pulmonary valvular area determined by the latter was -0.80 ( P <0.01). This study indicates that color Doppler echocardiography can take the place of catheterization to determine PVR in assessing the severity of pulmonary valvular stenosis in children.

Adolescent↗

[The value of color Doppler ultrasonography in diagnosing aneurysm].

Using Doppler ultrasound, we detected 59 patients with aneurysm, 54 cases were confirmed by angiography or operation or both. Among them, 33 cases (63%) showed true aneurysm, 18 cases (33%) pseudoaneurysm, and 2 cases (4%) superficial congenital arterio-venous aneurysm. Eight cases were associated with dissected stripping. One case was falsely diagnosed by ultrasonography. The diagnostic accuracy was 98%. The results suggest that color Doppler ultrasonography is useful in detecting aneurysm.

Adult↗

[Isoelectric focusing and immunoblotting identification of human ApoE phenotype].

A simple, rapid and accurate method for phenotyping sera apoE has been developed. In this method 10 microliters serum or plasma are incubated with Dithiothreitol and Tween-20 for 15 min and then applied to 5% polyacrylamid gel containing pH 4-8 ampholyte and 3 mol/L urea. After 2 h focusing, the apoE bands are transferred to Nitrocellulose membrane. apoE bands are made visible by immunoblotting and TMB is used as the substrate. Identification phenotype is easily accomplished by noting the location and number of protein bands. 56 samples shows apoE 3/3 in 47 cases, apoE 2/3 in 2 cases, and apoE 3/4 in 7 cases. This method is well suited for large-scale population studies and clinical labs.

Apolipoproteins E↗