Biomedical subjects

L Yan

Publications and source records attributed to L Yan.

At least 91 records · Page 5Linked to original sources

PubMed2000

Identification and characterization of the epithelial polarity receptor "Frizzled" in Hydra vulgaris.

The Wnt signaling pathway plays an important role in the specification of cell patterning during development in many species. Here we report the isolation and characterization of a putative Wnt receptor, Frizzled, in Hydra vulgaris. Analysis of the amino acid sequence of Frizzled in hydra reveals that this receptor contains many strong sequence similarities to other known Frizzled receptors. Hydra divergence is estimated to have occurred about one billion years ago; thus comparison of the Frizzled sequence of hydra with that of other species is likely to provide important information on the structure and function of those highly conserved regions. Northern and Southern blotting reveal that the Frizzled receptor in hydra has a 2.34-kb message size, and that it is encoded by a single gene. In situ hybridization using hydra frizzled as a probe reveals that the receptor message is restricted to the endoderm in adult hydra. This distribution supports the hypothesis that the Frizzled receptor is functioning in a pathway that controls cell differentiation in hydra.

Amino Acid Sequence↗

PubMed2000

Efficacy of vaccination with live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine against a variant (A/Sydney) not contained in the vaccine.

OBJECTIVE: To determine the safety, immunogenicity, and efficacy of revaccination of children with live attenuated influenza vaccine. STUDY DESIGN: A 2-year multicenter, double-blind, placebo-controlled, efficacy field trial of live attenuated, cold-adapted trivalent influenza vaccine administered by nasal spray to children. This report summarizes year 2 results, a year in which the epidemic strain of influenza A/Sydney was not well matched to the vaccine strains. Each year, vaccine strains were antigenically equivalent to the contemporary inactivated influenza vaccine. In year 2, a single intranasal revaccination was administered. Active surveillance for influenza was conducted during the influenza season by means of viral cultures. Influenza cases were defined as illnesses with wild-type influenza virus isolated from respiratory secretions. RESULTS: In year 2, 1358 (85%) children, 26 to 85 months of age, returned for revaccination. The intranasal vaccine was easily accepted, well tolerated, and immunogenic. Revaccination resulted in 82% to 100% of the vaccinated children in a subset studied for immunogenicity being seropositive as compared with 26% to 65% of placebo recipients, depending on the influenza strain tested. No serious adverse events were associated with the vaccine. In addition to the strains in the vaccine, antibody was induced to the variant strain A/Sydney/H3N2. In year 2, influenza A/Sydney/H3N2, a variant not contained in the vaccine, caused 66 of 70 cases of influenza A; nonetheless, intranasal vaccine was 86% efficacious in preventing A/Sydney influenza. Eight cases of lower respiratory tract disease were associated with A/Sydney influenza; all cases were in the placebo group. CONCLUSIONS: This live attenuated, cold-adapted influenza vaccine was safe, immunogenic, and efficacious against influenza A/H3N2 (including a variant, A/Sydney, not contained in the vaccine) and influenza B. The characteristics of this vaccine make it suitable for routine use in children to prevent influenza.

Administration, Intranasal↗

PubMed2000

From fold recognition to homology modeling: an analysis of protein modeling challenges at different levels of prediction complexity.

An analysis of different approaches to protein structure prediction is presented based solely on the range of models submitted to the third Critical Assessment of Protein Structure Prediction (CASP3) conference. CASP conferences evaluate the current state of the art of protein structure prediction by comparing blind prediction efforts of many groups for the same set of target sequences. Target sequences may be highly similar to those with known structure or can be totally (at least superficially) sequentially dissimilar. Techniques applied to those blind predictions (over 40 targets) ranges from a detailed homology prediction to the detection of remote homologues well below a twilight zone of protein sequence similarity. For the CASP3 conference, we have submitted predictions, totaling 35, with various levels of difficulty and complexity. For ten submitted homology targets, eight of them were determined by experiment so far. The RMSD of C-alpha atoms are 1.2-1.7, 2.3, and 4.6-17.9 A for the three easy targets, two hard targets, and three very hard homology targets, respectively. Out of 18-fold recognition predictions available for analysis, we got six correct predictions, five near misses, three tough near misses and four far misses. Here we analyze successes and failures of those predictions in an attempt to identify common problems and common achievements.

Computer Simulation↗

PubMed2000

Sequences of the waxy loci of wheat: utility in analysis of waxy proteins and developing molecular markers.

The waxy proteins from a number of genetic backgrounds of wheat and its progenitors were analyzed by SDS-PAGE. The deduced amino acid sequences of the waxy proteins of three diploid progenitor species indicated several key amino acid substitutions, which could explain the differences observed in the electrophoretic mobilities of the wheat waxy proteins. A slight difference observed in the apparent molecular weight of the WX-A1 protein of diploid and polyploid wheat was explained by amino acid substitutions or variations in predicted protein structures. Further, twelve different partial genomic clones, representing the individual waxy loci of the various diploid, tetraploid and hexaploid wheats, were isolated and compared. The results indicated significant variations in intron 4 and led to identification of sequences unique to the individual waxy genes and genomes of wheat and its proposed progenitors. The sequence variations observed have a great potential for development as molecular markers for identification of specific waxy loci and study of the various waxy mutants of wheat.

Base Sequence↗

PubMed2000

Vitamin D status and parathyroid hormone concentrations in Chinese women and men from north-east of the People's Republic of China.

STUDY OBJECTIVE: To evaluate vitamin D status of young and old women and men living in Shenyang, north-east People's Republic of China in early spring and to explore the relationship between vitamin D metabolites and parathyroid hormone (PTH) in this population. DESIGN: Cross-sectional study. SETTING: Shenyang, north-east China. SUBJECTS: 194 healthy volunteers: 48 young women and 48 young men aged 25-35 y, and 48 old women and 50 old men aged 65-75 y. RESULTS: Fasting blood samples were used to measure plasma 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D) and PTH using radioimmunoassays. The proportion of subjects who could be regarded as vitamin D deficient (<25 nmol/l) was 48%, 29%, 15% and 13% for old men, young men, old women and young women, respectively. There was no association between plasma 1,25(OH)2D and 25(OH)D concentrations. PTH concentrations were elevated in both old women and men compared with young subjects (P<0.01). A negative association between PTH and 25(OH)D was only found in old women (P<0. 001), but not in old men, nor in young subjects. CONCLUSIONS: Vitamin D status was poor in this population in early spring, especially in men. There was no clear evidence to show that the secretion of PTH and the conversion of 1,25(OH)2D were affected by the low 25(OH)D concentration. SPONSORSHIP: Partly supported by the Sandoz Foundation for Gerontological Research and the Nestlé Foundation, Switzerland, and Medical Research Council, UK. European Journal of Clinical Nutrition (2000) 54, 68-72

Adult↗

PubMed2000

Differential adrenergic regulation of the circadian expression of the clock genes Period1 and Period2 in the rat pineal gland.

Precise temporal regulation of transcription is pivotal to the role of the mammalian pineal gland as a transducer of circadian and seasonal information. The circadian clock genes Per1 and Per2 encode factors implicated in temporally gated transcriptional programmes in brain and pituitary. Here we show that the nocturnal circadian expression of Per1 and Per2 in the rat pineal gland parallels that of serotonin N-acetyltransferase (NAT) mRNA, which encodes the rate-limiting enzyme of melatonin biosynthesis. This rhythm is dependent upon an intact sympathetic innervation. Increases in rPer1 (r indicates rat) and rPer2, as well as rNAT, expression during subjective night were blocked completely by superior cervical ganglionectomy (SCGX). In SCGX rats, the beta-adrenergic receptor agonist isoproterenol rapidly induced the rPer1 mRNA with dynamics very similar to its effect on rNAT mRNA. In contrast, isoproterenol was without effect on expression of rPer2 mRNA. These findings demonstrate that circadian pineal expression of both rPer1 and rPer2 is controlled by sympathetic afferent innervation, but whereas beta-adrenergic signalling regulates rPer1 and rNAT, an alternative route mediates sympathetic regulation over rPer2 expression.

Animals↗

PubMed2000

Opposing functional effects of cyclic GMP and cyclic AMP may act through protein phosphorylation in rabbit cardiac myocytes.

1. We tested the hypothesis that the negative functional effects of cyclic GMP (cGMP) oppose the positive effects of cyclic AMP (cAMP) in cardiac myocytes through interaction at the level of their respective protein kinases. 2. Cell shortening was studied using a video-edge detector. The O2 consumption of a suspension of rabbit ventricular myocytes was measured using O2 electrodes. Protein phosphorylation was measured autoradiographically following SDS-PAGE. Data were collected with: (1) 8-bromo-cGMP (8-Br-cGMP) 10(-7) or 10(-5) M; (2) 8-bromo-cAMP (8-Br-cAMP) 10(-7) or 10(-5) M; (3) 8-Br-cAMP 10(-5) M followed by 8-Br-cGMP 10(-7) or 10(-5) M; (4) 8-Br-cGMP 10(-5) M followed by 8-Br-cAMP 10(-7) or 10(-5) M; (5) 8-Br-cGMP 10(-7) or 10(-5) M followed by KT 5720 (cAMP-dependent protein kinase inhibitor) or KT 5823 (cGMP-dependent protein kinase inhibitor) 10(-6) M; and (6) 8-Br-cAMP 10(-7) or 10(-5) M followed by KT 5720 or KT 5823 10(-6) M. 3. 8-Br-cGMP 10(-5) M decreased percent shortening (Pcs) from 6.3+/-0.6 to 3.6+/-0.4% and rate of shortening (Rs) from 66.7+/-4.4 to 41.8+/-4.2 microm s(-1). 8-Br-cAMP 10(-5) M increased Pcs (from 3.7+/-0.2 to 4.8+/-0.2) and Rs (from 50.0+/-3.0 to 60.0+/-3.1). With 8-Br-cAMP 10(-5) M, 8-Br-cGMP 10(-5) M decreased Pcs and Rs less. The positive functional effects of 8-Br-cAMP 10(-7) or 10(-5) M were also diminished with 8-Br-cGMP 10(-5) M. Following 8-Br-cGMP 10(-7) or 10(-5) M, KT 5720 10(-6) M further decreased Pcs to 2.5+/-0.3 and Rs to 30.0+/-4.1. KT 5823 10(-6) M returned Pcs to 4.7+/-0.4 and Rs to 61.3+/-5.3. Following 8-Br-cAMP 10(-7) or 10(-5) M, KT 5720 decreased the elevated Pcs and Rs significantly and KT 5823 10(-6) M further increased these parameters. 4. cGMP and cAMP phosphorylated the same five protein bands. With KT 5720 or KT 5823, all of the bands were lighter at the same concentration of 8-Br-cAMP and 8-Br-cGMP. 5. We conclude that, in rabbit ventricular myocytes, the opposing functional effects of cGMP and cAMP are related to the interaction at the level of their respective protein kinases.

Animals↗

PubMed2000

Thiopurine methyltransferase polymorphic tandem repeat: genotype-phenotype correlation analysis.

BACKGROUND: Thiopurine methyltransferase (TPMT) is a genetically polymorphic enzyme that catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine. Recently, a variable number tandem repeat (VNTR) within the TPMT promoter has been reported to "modulate" levels of this enzyme activity. METHODS: We set out to perform genotype-phenotype correlation analysis for the polymorphic TPMT tandem repeat in 1211 clinical laboratory samples in which red blood cell (RBC) TPMT activity had been measured and to compare those results with data for 279 control DNA samples. RESULTS: TPMT VNTR length varied from three to nine repeats ( *V3 to *V9), but the most common alleles were *V4 and *V5, with frequencies in the control samples of 0.54 and 0.36, respectively. The clinical laboratory samples were then stratified into those with "low," "intermediate," or "high" levels of RBC TPMT activity; that is, samples presumed to be homozygous for open reading frame (ORF)-based variant alleles, heterozygous for those alleles, or homozygous for the "wild-type" ORF sequence, respectively. TPMT VNTR genotype *V4/*V5 was associated with significantly higher RBC TPMT activity than were *V4/*V4 or *V5/*V5. Lowest activity levels were associated with genotypes that included an allele with more than 5 repeat elements. However, all of these effects were quantitatively small. Finally, there was linkage disequilibrium between VNTR allele *V5 and TPMT*3A, the most common ORF-based polymorphism associated with very low TPMT activity in white persons. CONCLUSIONS: These observations suggest that, in addition to the striking effects of ORF-based single nucleotide polymorphisms on TPMT activity, the VNTR within the 5'-flanking region of the TPMT gene also may modulate levels of RBC TPMT activity.

Adolescent↗

PubMed2000

Comparison of the safety, vaccine virus shedding, and immunogenicity of influenza virus vaccine, trivalent, types A and B, live cold-adapted, administered to human immunodeficiency virus (HIV)-infected and non-HIV-infected adults.

Fifty-seven human immunodeficiency virus (HIV)-infected (CDC class A1-2) and 54 non-HIV-infected adults, not prescreened for influenza susceptibility, were randomized to receive trivalent live attenuated influenza vaccine (LAIV) or placebo intranasally. LAIV was safe and well tolerated with no serious adverse events attributable to vaccine. Reactogenicity rates were similar in LAIV and placebo recipients except that runny nose/nasal congestion was significantly more common in LAIV recipients regardless of HIV status. No prolonged shedding of LAIV was observed in HIV-infected participants. HIV RNA levels were not increased and CD4 counts were not decreased in HIV-infected LAIV recipients compared with placebo recipients after immunization. Shedding of LAIV and increases in antibody titers were infrequent, consistent with prior experience in unscreened adults. The data suggest that inadvertent vaccination with LAIV in relatively asymptomatic HIV-infected adults would not be associated with frequent significant adverse events.

Adult↗

PubMed2000

Correlates of immune protection induced by live, attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine.

The authors conducted a 2-year, multicenter, double-blind, placebo-controlled efficacy field trial of live, attenuated, cold-adapted, trivalent influenza vaccine administered by nasal spray to children 15-71 months old. Overall, vaccine was 92% efficacious at preventing culture-confirmed infection by influenza A/H3N2 and influenza B. Because influenza A/H1N1 did not cause disease during the years in which this study was conducted, the authors sought to determine vaccine efficacy and correlates of immune protection against experimental challenge with 107 TCID50 of attenuated H1N1 (vaccine strain) by intranasal spray. Prechallenge assessments included serum hemaglutination-inhibiting (HAI) antibody and nasal wash IgA antibody to H1N1. Vaccine was 83% efficacious (95% confidence interval, 60%-93%) at preventing shedding of H1N1 virus after challenge. Any serum HAI antibody or any nasal wash IgA antibody was correlated with significant protection from H1N1 infection as indicated by vaccine-virus shedding, and high efficacy against H1N1 challenge was demonstrated.

Administration, Intranasal↗

PubMed2000

Flow modulation of pressure-sensitive tone in rat pial arterioles: role of the endothelium.

BACKGROUND: Cerebral arteriolar tone is modulated in response to changes in transmural pressure and luminal flow. The effect of flow on the relation between pressure and diameter has not been fully evaluated in these vessels. This study was conducted to investigate this interaction and to determine the role of the endothelium in mediating it. METHODS: Rat pial arterioles from the territory of the posterior cerebral artery were mounted in a perfusion myograph. In some arterioles, the endothelium was removed by air perfusion. Diameters were recorded at pressures from 20 to 200 mmHg in the presence and absence of flow (10 microl/min). The response to flow (0-30 microl/min) was recorded at 60 and 120 mmHg. RESULTS: In the absence of flow, endothelium-intact arterioles demonstrated tone at distending pressures between 40 and 140 mmHg. In the presence of flow, tone did not develop until pressure exceeded 100 mmHg, and the vessels remained active at pressures up to 200 mmHg. Endothelium-denuded arterioles developed tone at the same pressure when perfused as when unperfused, but perfused vessels were able to maintain active tone at higher pressures. At 60 mmHg, flow caused dilation if the endothelium was intact and constriction if it had been removed. At 120 mmHg, flow caused constriction. Endothelium-dependent flow-relaxation was inhibited by N(G)-nitro-L-arginine methyl ester (10(-5) M) and abolished by indomethacin (10(-5) M). CONCLUSION: Flow inhibits the development of pial arteriolar tone at low intraluminal pressures through endothelium-dependent mechanisms. Conversely, perfusion extends the upper limit of the myogenically regulated pressure range through endothelium-independent activation of arteriolar smooth muscle contraction.

Animals↗

PubMed2000

Histamine N-methyltransferase pharmacogenetics: association of a common functional polymorphism with asthma.

Histamine is involved in the pathophysiology of asthma, and histamine N-methyltransferase (HNMT) plays the dominant role in histamine metabolism in human bronchial epithelium. Levels of HNMT activity in human tissues are controlled, in part, by inheritance. A common C314T polymorphism within the HNMT gene results in a Thr105Ile change in encoded amino acid, and the T314 allele is associated with decreased levels of both HNMT enzymatic activity and immunoreactive protein. Therefore, presence of the T314 allele would be expected to result in reduced histamine metabolism and increased bronchoconstriction. We characterized this common, functionally significant polymorphism in DNA samples from 237 randomly selected Caucasian control subjects and 192 samples from Caucasian asthmatic patients. Allele frequencies for the T314 HNMT allele were 0.08 in the control samples and 0.14 in samples from Caucasian asthmatic patients (odds ratio = 1.9, P < 0.01), indicating a significant increase in the frequency of subjects with low HNMT activity among asthmatics. The association between a common, functionally significant genetic polymorphism for HNMT and asthma suggests that individual variation in histamine metabolism might contribute to the pathophysiology and/or response to therapy of this disease.

Adult↗

PubMed2000

Role of DBP in the circadian oscillatory mechanism.

Transcript levels of DBP, a member of the PAR leucine zipper transcription factor family, exhibit a robust rhythm in suprachiasmatic nuclei, the mammalian circadian center. Here we report that DBP is able to activate the promoter of a putative clock oscillating gene, mPer1, by directly binding to the mPer1 promoter. The mPer1 promoter is cooperatively activated by DBP and CLOCK-BMAL1. On the other hand, dbp transcription is activated by CLOCK-BMAL1 through E-boxes and inhibited by the mPER and mCRY proteins, as is the case for mPer1. Thus, a clock-controlled dbp gene may play an important role in central clock oscillation.

ARNTL Transcription Factors↗

PubMed2000

Vav3 mediates receptor protein tyrosine kinase signaling, regulates GTPase activity, modulates cell morphology, and induces cell transformation.

A recently reported new member of the Vav family proteins, Vav3 has been identified as a Ros receptor protein tyrosine kinase (RPTK) interacting protein by yeast two-hybrid screening. Northern analysis shows that Vav3 has a broad tissue expression profile that is distinct from those of Vav and Vav2. Two species of Vav3 transcripts, 3.4 and 5.4 kb, were detected with a differential expression pattern in various tissues. Transient expression of Vav in 293T and NIH 3T3 cells demonstrated that ligand stimulation of several RPTKs (epidermal growth factor receptor [EGFR], Ros, insulin receptor [IR], and insulin-like growth factor I receptor [IGFR]) led to tyrosine phosphorylation of Vav3 and its association with the receptors as well as their downstream signaling molecules, including Shc, Grb2, phospholipase C (PLC-gamma), and phosphatidylinositol 3 kinase. In vitro binding assays using glutathione S-transferase-fusion polypeptides containing the GTPase-binding domains of Rok-alpha, Pak, or Ack revealed that overexpression of Vav3 in NIH 3T3 cells resulted in the activation of Rac-1 and Cdc42 whereas a deletion mutant lacking the N-terminal calponin homology and acidic region domains activated RhoA and Rac-1 but lost the ability to activate Cdc42. Vav3 induced marked membrane ruffles and microspikes in NIH 3T3 cells, while the N-terminal truncation mutants of Vav3 significantly enhanced membrane ruffle formation but had a reduced ability to induce microspikes. Activation of IR further enhanced the ability of Vav3 to induce membrane ruffles, but IGFR activation specifically promoted Vav3-mediated microspike formation. N-terminal truncation of Vav3 activated its transforming potential, as measured by focus-formation assays. We conclude that Vav3 mediates RPTK signaling and regulates GTPase activity, its native and mutant forms are able to modulate cell morphology, and it has the potential to induce cell transformation.

3T3 Cells↗

PubMed2000

The genes encoding granule-bound starch synthases at the waxy loci of the A, B, and D progenitors of common wheat.

Three genes encoding granule-bound starch synthase (wx-TmA, wx-TsB, and wx-TtD) have been isolated from Triticum monococcum (AA), and Triticum speltoides (BB), by the polymerase chain reaction (PCR) approach, and from Triticum tauschii (DD), by screening a genomic DNA library. Multiple sequence alignment indicated that the wx-TmA, wx-TsB, and wx-TtD genes had the same extron and (or) intron structure as the previously reported waxy gene from barley. The lengths of the three wx-TmA, wx-TsB, and wx-TtD genes were 2834 bp, 2826 bp, and 2893 bp, respectively, each covering 31 bp in the untranslated leader and the entire coding region consisting of 11 exons and 10 introns. The three genes had identical lengths of exons, except exonl, and shared over 95% identity with each other within the exon regions. The majority of introns were significantly variable in length and sequence, differing mainly in length (1-57 bp) as a result of insertion and (or) deletion events. The deduced amino acid sequence from these three genes indicated that the mature WX-TMA, -TSB, and -TTD proteins contained the same number of amino acids, but differed in predicted molecular weight and isoelectric point (pI) due to amino acid substitutions (13-18). The predicted physical characteristics of the WX proteins matched the respective proteins in wheat very closely, but the match was not perfect. Furthermore the exon5 sequences of the wx-TmA, wx-TsB, and wx-TtD genes were different from a cDNA encoding a waxy gene of common wheat previously reported. The striking difference was that an insertion of 11 amino acids occurred in the cDNA sequence that could not be observed in the exons of the A, B, and D genes. It was noted, however, that the 3' end of intron4 of these genes could account for the additional 11 amino acids. The sequence information from the available waxy genes identified the intron4-exon5-intron5 region as being diagnostic for sequence variation in waxy. The sequence variation in the waxy genes provides the basis for primer design to distinguish the respective genes in common wheat, and its progenitors, using PCR.

Amino Acid Sequence↗

PubMed2000

beta-adrenergic receptor/cAMP-mediated signaling and apoptosis of S49 lymphoma cells.

beta-Adrenergic receptor (betaAR) activation and/or increases in cAMP regulate growth and proliferation of a variety of cells and, in some cells, promote cell death. In the current studies we addressed the mechanism of this growth reduction by examining betaAR-mediated effects in the murine T-lymphoma cell line S49. Wild-type S49 cells, derived from immature thymocytes (CD4(+)/CD8(+)) undergo growth arrest and subsequent death when treated with agents that increase cAMP levels (e.g., betaAR agonists, 8-bromo-cAMP, cholera toxin, forskolin). Morphological and biochemical criteria indicate that this cell death is a result of apoptosis. In cyc(-) and kin(-) S49 cells, which lack G(s)alpha and functional protein kinase A (PKA), respectively, betaAR activation of G(s)alpha and cAMP action via PKA are critical steps in this apoptotic pathway. S49 cells that overexpress Bcl-2 are resistant to cAMP-induced apoptosis. We conclude that betaAR activation induces apoptosis in immature T lymphocytes via G(s)alpha and PKA, while overexpression of Bcl-2 prevents cell death. betaAR/cAMP/PKA-mediated apoptosis may provide a means to control proliferation of immature T cells in vivo.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2000

Decreasing cyclic GMP exerts similar positive functional effects on cardiac myocytes regardless of initial level.

We tested the hypothesis that lowering the level of cyclic GMP would have positive functional effects on isolated rabbit ventricular myocytes regardless of the basal cyclic GMP level. Cell shortening data were collected with a video detector; O(2) consumption data were obtained with a Clark electrode; intracellular cyclic GMP levels were obtained by radioimmunoassay. Data were obtained: (1) at baseline; (2) after the addition of 1H-[1,2,4]oxadiazolo[4, 3-alpha]quinoxaline-1-one (ODQ) 10(-6) and 10(-4) mol/l, a selective soluble guanylyl cyclase inhibitor, and (3) after zaprinast 10(-6) mol/l, a cyclic GMP phosphodiesterase inhibitor, followed by ODQ 10(-6) and 10(-4) mol/l. We found that ODQ 10(-4) mol/l significantly decreased the cyclic GMP level from 493 +/- 75 to 301 +/- 78 (fmol/100,000 myocytes) and increased percent shortening (Pcs, %; 4.9 +/- 0.3 vs. 5.8 +/- 0.6) and maximum rate of shortening (Rs, microm/s; 58.7 +/- 5.7 vs. 73.6 +/- 4.9). Zaprinast significantly increased the cyclic GMP level from 419 +/- 140 to 599 +/- 241 and decreased Pcs (6.2 +/- 0.5 vs. 4.4 +/- 0.4) and Rs (65.5 +/- 5.3 vs. 49.6 +/- 4.3). After zaprinast, ODQ 10(-4) mol/l decreased the cyclic GMP level to 439 +/- 139 and increased percent shortening and rate of shortening by a similar percentage compared to the non-zaprinast treated myocytes. We conclude that in rabbit ventricular myocytes, a reduction in the level of myocyte cyclic GMP increases myocyte function independent of the initial cyclic GMP level.

Animals↗

PubMed2000

Approximate maximum entropy joint feature inference consistent with arbitrary lower-order probability constraints: application to statistical classification

We propose a new learning method for discrete space statistical classifiers. Similar to Chow and Liu (1968) and Cheeseman (1983), we cast classification/inference within the more general framework of estimating the joint probability mass function (p.m.f.) for the (feature vector, class label) pair. Cheeseman's proposal to build the maximum entropy (ME) joint p.m.f. consistent with general lower-order probability constraints is in principle powerful, allowing general dependencies between features. However, enormous learning complexity has severely limited the use of this approach. Alternative models such as Bayesian networks (BNs) require explicit determination of conditional independencies. These may be difficult to assess given limited data. Here we propose an approximate ME method, which, like previous methods, incorporates general constraints while retaining quite tractable learning. The new method restricts joint p.m.f. support during learning to a small subset of the full feature space. Classification gains are realized over dependence trees, tree-augmented naive Bayes networks, BNs trained by the Kutato algorithm, and multilayer perceptrons. Extensions to more general inference problems are indicated. We also propose a novel exact inference method when there are several missing features.

Journal Article↗