Biomedical subjects

P Fan

Publications and source records attributed to P Fan.

At least 73 records · Page 4Linked to original sources

PubMed1998

[Comparison of nuclear accumulation of p53 protein with mutations in the p53 gene on the tissues of human breast cancer].

OBJECTIVE: To compare nuclear accumulation of p53 protein with mutations in the p53 gene on the tissues of human breast cancer. METHOD: Fifty-four invasive ductal carcinomas of breast were analyzed by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) silver stain and strep-avidin-biotin-peroxidase complex (SABC) immunohistochemistry. RESULT: A highly significant association between the presence of p53 gene mutation and nuclear accumulation of p53 protein was found (r = 0.714, P < 0.01). All 22 tumors with p53 gene mutations showed nuclear accumulation of p53 protein. Of the 32 tumors with gene mutations undetected, 9(28%) showed nuclear accumulation of p53 protein. Both p53 mutation protein and p53 gene mutations were prevalent in steroid and progesterone receptors negative tumors (P < 0.05). There was a statistically significant association between the nuclear accumulation of p53 protein and lymph node invasion (P < 0.05). So did p53 gene mutations (P < 0.05). Therefore, p53 abnormalities might be associated with an aggressive phenotype in breast cancer. CONCLUSION: The immunohistochemical detection of nuclear p53 protein accumulation is highly associated with p53 gene mutations in breast cancer tissues. This method is useful for rapid screening of p53 abnormalities. In some cases of slightly positive for p53 nuclear protein we must observe p53 genemutations to avoid the false positive reaction.

Breast Neoplasms↗

PubMed1997

Isolation, characterization, and mapping of two human potassium channels.

Two novel human genes encoding putative potassium channels, kH1 and kH2, were identified from a human fetal brain cDNA library. Sequence analysis showed that kH1 and kH2 are homologous to rat IK8 and rat K13, respectively. The kH1 encodes a polypeptide of 495 amino acids, which shares 88% and 95% identity to IK8 at the nucleotide and amino acid level, respectively. The kH2 encodes a polypeptide of 515 amino acids with 86% and 92% identity to K13 at the nucleotide and amino acid level, respectively. Northern blot studies revealed that one mRNA species, approximately 5kb, of the kH1 was expressed abundantly in tissues examined, including the heart, skeletal muscle, and less abundant in the brain, liver, kidney, and pancreas. Interestingly, an alternative spliced form of 2.4 kb mRNA species of the kH1 was also found in the brain. Unlike kH1, 2.4 kb of kH2 was expressed predominantly in the brain, placenta, and the skeletal muscle where it shared a differently spliced form of the kH2 mRNA, approximately 2.0 kb. Fluorescence in situ hybridization localized kH1 to the human chromosome 2p25 and kH2 to the human chromosome 20q13.

Amino Acid Sequence↗

PubMed1997

Purification and characterization of a silica-induced bronchoalveolar lavage protein with fibroblast growth-promoting activity.

Experimentally induced silicosis provides a good model for chronic interstitial pulmonary inflammation and fibrosis. In the present study, a specific single polypeptide with an apparent molecular mass of 58,000 and a pl of 4.5 was purified and characterized from the bronchoalveolar lavage fluid of silicotic rats. The same protein was also isolated from both the extract and conditioned medium of alveolar macrophages of silicotic rats. Therefore, this protein was termed an inducible silicotic (rat) bronchoalveolar lavage protein-p58 (iSBLP58) or an inducible silicotic (rat) pulmonary macrophage factor (iSPMF-p58). iSBLP58 has been purified to homogeneity by a combination of gel permeation, Mono Q ion exchange, and reverse-phase high performance liquid chromatography. This polypeptide displayed a potent fibroblast growth-promoting activity in vitro. The sequence of the first 15 NH2-terminal amino acids was determined and was found to have high sequence homology with members of the mammalian chitinase-like protein family, which includes human cartilage gp39, mammalian oviduct-specific glycoprotein, and a secretory protein from activated mouse macrophages.

Amino Acid Sequence↗

PubMed1997

Structure, recognition and adaptive binding in RNA aptamer complexes.

Novel features of RNA structure, recognition and discrimination have been recently elucidated through the solution structural characterization of RNA aptamers that bind cofactors, aminoglycoside antibiotics, amino acids and peptides with high affinity and specificity. This review presents the solution structures of RNA aptamer complexes with adenosine monophosphate, flavin mononucleotide, arginine/citrulline and tobramycin together with an example of hydrogen exchange measurements of the base-pair kinetics for the AMP-RNA aptamer complex. A comparative analysis of the structures of these RNA aptamer complexes yields the principles, patterns and diversity associated with RNA architecture, molecular recognition and adaptive binding associated with complex formation.

Adenosine Monophosphate↗

PubMed1997

Cloning, mapping, and tissue distribution of a human homologue of the mouse jerky gene product.

Inactivation of the jerky gene by insertion of a transgene into the mouse genome results in epileptic seizures in transgenic mice. This finding indicates that the jerky gene plays an important role in inducing epilepsy syndromes in mice. We report here our efforts in cloning, chromosomal mapping, and analysis of tissue distribution of a novel human gene, the HHMJG, a homologue to the mouse jerky gene product. We have successfully identified a full length cDNA clone encoding a novel human protein homologous to the mouse jerky gene product. The finding was based on the result of an analysis of EST (expressed sequence tag) sequences of a clone from a human tonsil cDNA library. A 4.0 kb mRNA species of the HHMJG is abundantly expressed in the majority of human tissues examined, including brain and skeletal muscle. However, in the testes, two mRNA species of the HHMJG, approximately 2.0 and 4.0 kb, are abundantly expressed. Sequence analysis of the HHMJG cDNA indicates that it encodes a putative protein of 51 kD, which shares significant sequence homology to not only the mouse jerky gene product but also some nuclear regulatory proteins, such as centromere binding protein-B. The predicted nuclear localization of the HHMJG product suggests that this protein may function as a nuclear regulatory protein. The result of human chromosomal mapping shows that the HHMJG is located on human chromosome 11q21. Our identification of the HHMJG cDNA provides a potential gene candidate to further investigate the biological significance and clinical implications of the HHMJG in human epilepsy.

Amino Acid Sequence↗

PubMed1997

Comparison of multiplane and biplane transesophageal echocardiography in the assessment of aortic stenosis.

The aim of the study was to compare the accuracy of multiplane transesophageal echocardiography (TEE) with the more conventional biplane technique in the direct assessment of aortic valve area in patients with aortic stenosis. Short-axis images of the aortic valve adequate for measuring aortic valve area were obtained in all 81 patients studied by multiplane TEE but in only 56 of 64 patients (88%) using the biplane approach. The correlation coefficient for aortic valve area determined by multiplane TEE (r = 0.89; SEE = 0.04 cm2) was higher (p < 0.01) than biplane TEE (r = 0.74; SEE = 0.06 cm2). Correlations were higher for bicuspid valves (multiplane, r = 0.93; biplane, r = 0.75) than tricuspid valves (multiplane, r = 0.87; biplane, r = 0.75). Our study has demonstrated the superiority of multiplane TEE to both biplane TEE and transthoracic echocardiography (TTE) in the direct evaluation of aortic valve area in patients with aortic stenosis.

Adult↗

PubMed1997

[DNA polymorphisms of apolipoprotein A I gene in Chinese endogenous hypertriglyceridemics].

The restriction fragment length polymorphisms (RFLPs) of apolipoprotein(apo) A I gene were studied using polymerase chain reaction (PCR) in 69 endogenous hypertriglyceridemics (HTG) and 74 healthy subjects from a population of Chinese Han nationality in Chengdu area. The loci studied included Msp 1 within intron 3 of the apo A I gene; Xmn I, 5' to the apo A I gene; and Pst I, 3' to the apo A I gene. The results showed that both in HTG group and control group M1, X1 and P1 alleles were the major alleles and homozyous M1M1, X1X1 and P1P1 genotypes were the most frequent ones. The frequencies of rare M2 and X2 alleles in Chinese were significantly higher than those in European Caucasians (0.293 vs 0.111, P < 0.0006, 0.286 vs 0.130, P < 0.004), but no differences were found in the frequency of rare P2 allele (0.071 vs 0.046, P > 0.05). The frequency of rare M2 tended to increase in the HTG group when compared with the control group (0.353 vs 0.275, P > 0.05). Both in the HTG group and control group, subjects with genotype M2M2 had a higher serum mean concentration of TC, apo C II and higher serum TG/HDL-C ratio compared with the subjects with the genotypes M1M1 and M1M2 (P = 0.05, P < 0.03, P < 0.04), and the serum TG, apo C II and apo E levels had a tendency to increase. The subjects with the genotypes P1P2 and P2P2 had a higher serum apo A II levels compared with the subjects with the genotype P1P1 (P < 0.04). The data show that the only Msp I RFLP within the intron 3 of apo A I gene is associated with endogenous hypertriglyceridemia to some extent in Chinese population.

Adult↗

PubMed1997

[Serum apolipoprotein C II, C III and E levels in 437 male healthy subjects aged 40-70 in Chengdu area].

Apolipoprotein (apo) C II, C III and E levels of 437 male healthy subjects aged 40-70 [with fasting serum triglyceride (TG levels < 2.26 mmol/L, total cholesterol (TC) levels < 6.21 mmol/L and plasma glucose levels < 6.10 mmol/L] in Changdu area were determined by radial immunodiffusion assay (RID). The results showed that the concentrations of apoC II, C III and E were 41.6 +/- 13.1, 112.8 +/- 31.0 and 38.7 +/- 8.2 mg/L (mean +/- s) respectively. No difference in the serum levels of apoC II, C III and E was noted between the men of different ages. The results of the linear correlation showed that there was a positive correlation of apoC II, C III, E with TG, TC, LDL-C; of apoC II, C III with BMI; and of apoE with ages.

Adult↗

PubMed1997

[The serum lipid and apolipoprotein levels of middle-aged male hyperlipidemics in Chengdu district].

It has been evidenced that cardiovascular diseases (CVD) relate with many risk factors and serum lipids play and essential role in the development of CVD. In order to further study hyperlipidemia (HL) in the middle-aged males, we analysed the body mass index (BMI), fast blood sugar (FBS), serum lipids and apolipoproteins A I, A II, B100, C II, C III and E in 223 male HL patients aged 41-60 and 349 normal male subjects who matched the HL patients in age. The result showed that the increase of serum triglycerids (TG), was as might be expected, the major characteristic of the middle-aged male HL patients in Chengdu District. Besides the serum lipid and apolipoprotein B100, C II, C III and E levels, the BMI and FBS levels in the IIb, IV and V types of HL patients were significantly higher than those in the normal subjects. It also showed that in TG increased patients the increased percentages of serum lipids were significantly higher than those of apolipoproteins. The age distribution in HL patients revealed that only 25% of the HL patients were between 41 to 50 years old, while 50% in the 56-60 year-old group. The relationship between apolipoprotein levels and serum lipid metabolism is also discussed. The results suggest that the 51-60 year-old males should pay attention to diet and increase physical activities to reduce incidence of HL which is directly associated with CVD.

Adult↗

PubMed1997

[Clinical valuation color Doppler echocardiography for diagnosis of coronary artery fistula].

The purpose of this study was to investigate the advantages of color Doppler echocardiography in the diagnosis of congenital coronary artery fistula. Twenty-one patients with coronary artery fistula ranging in age from 3 to 28 years underwent color Doppler echocardiographic study 1991.4-1996.8. When a coronary artery fistula was found, the origin, the course and the drainage site were carefully searched for to make a precise diagnosis. Color Doppler echocardiographic diagnosis of all patients were confirmed by cardiac operation on cardioangiography. The results indicate that color Doppler echocardiography can provide a panoramic view of coronary artery and the fistulous vessel with precise definition of the origin, the course of draingae site of the fistula. Therefore, it is the noninvasive method of first choice to diagnose congenital coronary artery fistula.

Adolescent↗

PubMed1997

[Color Doppler echocardiography in the diagnosis for ruptured aneurysm of sinus of Valsalva].

Twenty-five cases with ruptured aneurysm of sinus of Valsava were detected by color Doppler sonography and twenty-four cases undenwent surgical repair. In twenty-three cases, the sonographic findings of the site of the aneurysm and the chambers into which aneurysm ruptured were coincident with the surgical findings. The accuracy was 95.8%. The size of the aneurysm and the diameter of the ruptured site detected by ultrasound were correlated well with surgical findings. The associated lesions obtained by ultrasound were completely identical with surgical findings. Color Doppler flowing imaging has special value in diagnosing the ruptured aneurysm of sinus of Valsalva.

Adolescent↗

PubMed1996

Head group analogs of arachidonylethanolamide, the endogenous cannabinoid ligand.

Several analogs of an endogenous cannabimimetic, arachidonylethanolamide (anandamide), were synthesized to study the structural requirements of the ethanolamide head group. CB1 receptor affinities of the analogs were evaluated by a standard receptor binding assay using tritiated CP-55,940 as the radioligand and compared to anandamide which was shown to have a Ki of 78 nM. Replacement of the amide carbonyl oxygen by a sulfur atom had a detrimental effect on the CB1 affinity. The thio analogs of both anandamide and (R)-methanandamide showed very weak affinity for CB1. The secondary nature of the amidic nitrogen was also shown to be important for affinity, indicating a possible hydrogen-bonding interaction between the amide NH and the receptor. Introduction of a phenolic moiety in the head group resulted in the loss of receptor affinity except when a methylene spacer was introduced between the amidic nitrogen and the phenol. A select group of analogs were also tested for their affinity for the CB2 receptor using a mouse spleen preparation and were found to possess low affinities for the CB2 sites. Notably, anandamide and (R)-methanandamide demonstrated high selectivity for the CB1 receptor. Overall, the data presented here show that structural requirements of the head group of anandamide are rather stringent.

Adjuvants, Immunologic↗

PubMed1996

Unsaturated side chain beta-11-hydroxyhexahydrocannabinol analogs.

The cannabinoid side chain is a key pharmacophore in the interaction of cannabinoids with their receptors (CB1 and CB2). To study the stereochemical requirements of the side chain, we synthesized a series of cannabinoids in which rotation around the C1'-C2' bond is blocked. The key steps in the synthesis were the cuprate addition of a substituted resorcinol to (+)-apoverbenone, the TMSOTf-mediated formation of the dihydropyran ring, and the stereospecific introduction of the beta-11-hydroxymethyl group. All the analogs tested showed nanomolar affinity for the receptors, the cis-hept-1-ene side chain having the highest affinity for CB1 (Ki = 0.89 nM) and showing the widest separation between CB1 and CB2 affinities. The parent n-heptyl-beta-11-hydroxyhexahydrocannabinol was the least potent binding to CB1 (Ki = 8.9 nM) and had the lowest selectivity between CB1 and CB2.

Animals↗

PubMed1996

Molecular recognition in the FMN-RNA aptamer complex.

We report on a combined NMR-molecular dynamics calculation approach that has solved the solution structure of the complex of flavin mononucleotide (FMN) bound to the conserved internal loop segment of a 35 nucleotide RNA aptamer identified through in vitro selection. The FMN-RNA aptamer complex exhibits exceptionally well-resolved NMR spectra that have been assigned following application of two, three and four-dimensional heteronuclear NMR techniques on samples containing uniformly 13C, 15N-labeled RNA aptamer in the complex. The assignments were aided by a new through-bond NMR technique for assignment of guanine imino and adenine amino protons in RNA loop segments. The conserved internal loop zippers up through the formation of base-pair mismatches and a base-triple on complex formation with the isoalloxazine ring of FMN intercalating into the helix between a G.G mismatch and a G.U.A base-triple. The recognition specificity is associated with hydrogen bonding of the uracil like edge of the isoalloxazine ring of FMN to the Hoogsteen edge of an adenine at the intercalation site. There is significant overlap between the intercalated isoalloxazine ring and its adjacent base-triple platform in the complex. The remaining conserved residues in the internal loop participate in two G.A mismatches in the complex. The zippered-up internal loop and flanking stem regions form a continuous helix with a regular sugar-phosphate backbone except at a non-conserved adenine, which loops out of the helix to facilitate base-triple formation. Our solution structure of the FMN-RNA aptamer complex is to our knowledge the first structure of an RNA aptamer complex and outlines folding principles that are common to other RNA internal and hairpin loops, and molecular recognition principles common to model self-replication systems in chemical biology.

Base Sequence↗

PubMed1996

Structure-activity relationships of the antimalarial agent artemisinin. 3. Total synthesis of (+)-13-carbaartemisinin and related tetra- and tricyclic structures.

Provided by total synthesis, endoperoxides 18, 20, and 22 underwent intramolecular oxymercuration-demercuration leading respectively to formation of an isomeric tetracycle, (1aS, 3S, 5aS, 6R, 8aS, 9R, 12S)-10-deoxo-13-carbaartemisinin (19), (+)-10-deoxo-13-carbaartemisinin (21), and (+)-13-carbaartemisinin (4). Structure assignment to 19 and 21 was based on single-crystal X-ray crystallographic analysis. Tricyclic endoperoxide 20 was converted to methyl and benzyl ethers 23 and 24 and reduced to saturated analog 25 which was also converted to ethers 26 and 27. In vitro antimalarial screening of both tri- and tetracyclic analogs was conducted using the W-2 and D-6 clones of Plasmodium falciparum. Neither target 4 nor 21 displayed substantial antimalarial potency in vitro against P. falciparum, but the diastereomeric peroxide 19 possessed good antimalarial potency in vitro. Tricyclic analogs were uniformly impotent. Iron(II) bromide-promoted rearrangement of 21 gave, in 79% yield, the unique tetracyclic alcohol 35, while 19 provided ring-opened cyclohexanone 41 (39%) along with the tricyclic epoxide 42 (20%). Neither 41 nor 42 possessed in vitro antimalarial activity, suggesting that epoxide-like intermediates are not responsible for the mode of action of this subclass of antimalarials. Rearrangement of 10-deoxoartemisinin (43) with FeBr2 gave a major product (79%) not encountered in the rearrangement of artemisinin that resulted from unraveling of the tetracyclic system cyclohexanone 46. Minor amounts of 1,10-dideoxoartemisinin (49) (8%) were also produced in this reaction.

Animals↗

PubMed1996

Direct NMR measurement of folding kinetics of a trimeric peptide.

Direct NMR measurements of the folding kinetics are performed on a collagen-like triple helical peptide. The triple helical peptide was designed to model a biologically important region of collagen and has the sequence (POG)3ITGARGLAG(POG)4. Triple helical peptides were synthesized with specifically labeled 15N amino acid residues in key positions, and the kinetics of folding of the individual residues were monitored directly by measuring the loss of monomer intensity and the increase in trimer intensity. The residues at the terminal ends and central region could be followed independently and quantitated directly. Residues located at the terminal ends have rates and kinetics of folding that are distinct from residues in the central region of the peptide. This allows the monitoring of different steps in the folding mechanism and the postulation of the existence of a kinetic intermediate. The NMR data are consistent with a mechanism of association/nucleation and propagation. Hereditary connective tissue diseases are associated with mutations that result in abnormal folding of collagen, and the NMR folding experiments on a collagen-like peptide provide a basis for characterizing the molecular defect in folding mutations.

Amino Acid Sequence↗

PubMed1996

Neonatal mortality and length of newborn hospital stay.

OBJECTIVE: To investigate the effect of hospital discharge time on neonatal mortality of term newborns. DESIGN: Infants who were discharged home at 5 days of age of younger and who subsequently died were compared with control infants using a retrospective case-control design. Descriptive information was collected from records of infants who were not discharged home from the hospital of birth (because of death or transfer to a tertiary care hospital) to determine the age at which their illnesses presented. METHODS: We reviewed death certificates for all infants with birth weights of 2500 g or greater born at 37 weeks' gestational age or greater who died in the first 28 days of life and who were born in one of four Utah counties (1985 through 1989). Of the 109,256 eligible births, 115 infants were found who had died in the neonatal period. Eighty-four infants had not been discharged home from the hospital of birth, 5 infants had had hospital stays of more than 5 days, 9 records could not be located, 17 presumed healthy infants were discharged from the hospital at 5 days of age or younger. These 17 infants were each matched with 3 control infants. Newborn nursery charts were reviewed to determine hospital discharge times for case and control infants. Descriptive information regarding the time of presentation of illness was collected for the other 89 infants. RESULTS: The mean age of hospital discharge was 43 +/- 21 hours for the 17 case infants and 47 +/- 25 hours for the 51 control infants. The odds ratio for neonatal mortality for discharge at less than 24 hours was 1.65 (95% confidence interval, 0.42 to 3.34) and for discharge at less than 48 hours was 1.16 (95% confidence interval, 0.4 to 3.34). Of the 84 infants who were not discharged home from the hospital of birth, 93% had been symptomatic by 12 hours of age, and 99% were symptomatic by 18 hours. CONCLUSIONS: Most full-term infants who die in the neonatal period are symptomatic within the first 18 hours after birth. We could not demonstrate an association between early hospital discharge and neonatal mortality in those infants who died after discharge home.

Age of Onset↗

PubMed1995

Effect of cocaine on the 5-HT3 receptor-mediated ion current in Xenopus oocytes.

The cloned 5-HT3 receptor from NCB-20 neuroblastoma cells was expressed in Xenopus oocytes. In these oocytes, 5-HT, the selective 5-HT3 receptor agonists, 2-methyl-5-HT and m-chlorophenylbiguanide activated an inward current which was sensitive to the specific 5-HT3 receptor antagonist LY278584. Cocaine (0.1 to 10 microM) reversibly inhibited the current activated by 1 microM 5-HT in a concentration-dependent manner. The IC50 value is 0.7 microM and the apparent Hill coefficient is 1.55. This effect of cocaine was not dependent on membrane potential. Cocaine also produced a parallel shift of the 5-HT concentration-response curve to the right and did not reduce the maximal current induced by 5-HT. In the presence of 3 microM cocaine, the EC50 value of 5-HT was increased from 3.08 microM to 6.1 microM. Other local anesthetics such as tricaine and lidocaine also inhibited the current induced by 5-HT. These results suggest that the 5-HT3 receptors expressed in Xenopus oocytes exhibit properties similar to those in sensory neurons and neuroblastoma cells and were blocked by cocaine in a competitive manner.

Animals↗