Biomedical subjects

F Yang

Publications and source records attributed to F Yang.

At least 91 records · Page 5Linked to original sources

PubMed2001

A classification efficiency test of spectral karyotyping and multiplex fluorescence in situ hybridization: identification of chromosome homologies between Homo sapiens and Hylobates leucogenys.

Two digital fluorescence microscopy systems, spectral karyotyping (SKY) and multiplex fluorescence in situ hybridisation (M-FISH), are used with multicolour probe sets to assist in the detection of chromosome aberrations. We have compared the resolution of the two methods in their ability to identify karyotype rearrangements, which have occurred during the divergence of Homo sapiens and Hylobates leucogenys in evolution. A 24-color human paint kit distinguishes 74 conserved autosomal segments in H. leucogenys, some of which are difficult to resolve. We examined the extent to which the SKY and M-FISH techniques are able to detect the smallest of these bands. We have found this to be a rigorous test of multicolour chromosome classification systems. We conclude from our results that both systems are able invariably to classify the majority of conserved segments but differ in the efficiency of detection of small inserts.

Animals↗

PubMed2001

Reduced expression of the Aalpha subunit of protein phosphatase 2A in human gliomas in the absence of mutations in the Aalpha and Abeta subunit genes.

Protein phosphatase 2A (PP2A) consists of 3 subunits: the catalytic subunit, C, and the regulatory subunits, A and B. The A and C subunits both exist as 2 isoforms (alpha and beta) and the B subunit as multiple forms subdivided into 3 families, B, B' and B". It has been reported that the genes encoding the Aalpha and Abeta subunits are mutated in various human cancers, suggesting that they may function as tumor suppressors. We investigated whether Aalpha and Abeta mutations occur in human gliomas. Using single strand conformational polymorphism analysis and DNA sequencing, 58 brain tumors were investigated, including 23 glioblastomas, 19 oligodendrogliomas and 16 anaplastic oligodendrogliomas. Only silent mutations were detected in the Aalpha gene and no mutations in the Abeta gene. However, in 43% of the tumors, the level of Aalpha was reduced at least 10-fold. By comparison, the levels of the Balpha and Calpha subunits were mostly normal. Our data indicate that these tumors contain very low levels of core and holoenzyme and high amounts of unregulated catalytic C subunit.

Alleles↗

PubMed2001

Cell image segmentation with kernel-based dynamic clustering and an ellipsoidal cell shape model.

In this paper, we propose a novel approach to cell image segmentation under severe noise conditions by combining kernel-based dynamic clustering and a genetic algorithm. Our method incorporates a priori knowledge about cell shape. That is, an elliptical cell contour model is introduced to describe the boundary of the cell. Our method consists of the following components: (1) obtain the gradient image; (2) use the gradient image to obtain points which possibly belong to cell boundaries; (3) adjust the parameters of the elliptical cell boundary model to match the cell contour using a genetic algorithm. The method is tested on images of noisy human thyroid and small intestine cells.

Algorithms↗

PubMed2001

High-throughput sequence identification of gene coding variants within alcohol-related QTLs.

Low initial response to alcohol has been shown to be among the best predictors of development of alcoholism. A similar phenotypic measure, difference in initial sensitivity to ethanol, has been used for the genetic selection of two mouse strains, the Inbred Long-Sleep (ILS) and Inbred Short-Sleep (ISS) mice, and for the subsequent identification of four quantitative trait loci (QTLs) for alcohol sensitivity. We now report the application of high throughput comparative gene sequencing in the search for genes underlying these four QTLs. To carry out this search, over 1.7 million bases of comparative DNA sequence were generated from 68 candidate genes within the QTL intervals, corresponding to a survey of over 36,000 amino acids. Eight central nervous system genes, located within these QTLs, were identified that contain a total of 36 changes in protein coding sequence. Some of these coding variants are likely to contribute to the phenotypic variation between ILS/ISS animals, including sensitivity to alcohol, providing specific new genetic targets potentially important to the neuronal actions of alcohol.

Alcoholism↗

PubMed2001

Catalytic dechlorination of chlorophenols in water by palladium/iron.

Three isomer chlorophenols, o-, m-, p-chlorophenol, were dechlorinated by palladium/iron powder in water through catalytic reduction. The dechlorinated reaction is believed to take place on the surface site of the catalyst in a pseudo-first-order reaction. The reduction product for all the three isomers is phenol. The dechlorination rate increases with increase of bulk loading of palladium due to the increase of both the surface loading of palladium and the total surface area. The molecular structure also has an effect on the dechlorination rate. For conditions with 0.048% Pd/Fe, the rate constants are 0.0215, 0.0155 and 0.0112 min-1 for o-, m-, p-chlorophenol, respectively. Almost complete dechlorination is achieved within 5 h.

Catalysis↗

PubMed2001

Quantitative structure-property relationship studies on direct photolysis of selected polycyclic aromatic hydrocarbons in atmospheric aerosol.

Based on some fundamental quantum chemical descriptors computed by PM3 Hamiltonian, by the use of partial least-squares analysis, a quantitative structure property relationship model for direct photolysis half-lives of 11 polycyclic aromatic hydrocarbons (PAHs) in atmospheric aerosol under UV irradiation was developed. PAHs with great molecular weight (bulkness) tend to photolyze fast, and PAHs with small absolute electronegativity values and large absolute hardness values, tend to photolyze fast.

Atmosphere↗

PubMed2001

Quantitative structure-property relationships (QSPRs) on direct photolysis quantum yields of PCDDs.

By the use of partial least squares (PLS) method and 16 fundamental quantum chemical descriptors computed by PM3 Hamiltonian, quantitative structure-property relationships (QSPRs) were obtained for direct photolysis quantum yields of selected polychlorinated dibenzo-p-dioxins (PCDDs). Direct photolysis quantum yields for PCDDs without experimental quantum yield values were predicted. The QSPR results showed that it was mainly the number of chlorine atoms bonded to the parent structure, the largest positive atomic charge on a chlorine atom, the dipole moment, and the frontier molecular orbital energies (Ehomo and Elumo) that determine the direct photolysis quantum yields of the PCDDs. Increasing the number of chlorine atoms, dipole moment, and the largest positive atomic charge on a chlorine atom, leads to decrease of photolysis quantum yields. Increasing Elumo, Ehomo and Elumo - Ehomo values lead to increase of log Y values.

Chlorine↗

PubMed2001

Quantitative structure-property relationship studies on n-octanol/water partitioning coefficients of PCDD/Fs.

Based on some fundamental quantum chemical descriptors computed by PM3 Hamiltonian, by the use of partial least-squares (PLS) analysis, a significant quantitative structure-property relationship (QSPR) model for logKow of polychlorinated dibenzo-p-dioxins and dibenzo-p-furans (PCDD/Fs) was obtained. The QSPR can be used for prediction. The intermolecular dispersive interactions and thus the bulkness of the PCDD/Fs are the main factors affecting the logKow. The more chlorines in the PCDD/F molecule, the greater the logKow values.

Benzofurans↗

PubMed2001

Quantitative structure-property relationship study on reductive dehalogenation of selected halogenated aliphatic hydrocarbons in sediment slurries.

In this study, by the use of partial least squares (PLS) method and 26 quantum chemical descriptors computed by PM3 Hamiltonian, a quantitative structure-property relationship (QSPR) model was developed for reductive dehalogenation rate constants of 13 halogenated aliphatic compounds in sediment slurry under anaerobic conditions. The model can be used to explain the dehalogenation mechanism. Halogenated aliphatic compounds with great energy of the lowest unoccupied molecular orbital (Elumo), total energy (TE), electronic energy (EE), the smallest bond order of the carbon-halogen bonds (BO) and the most positive net atomic charges on an atom of the molecule (q+) values tend to be reductively dehalogenated slow, whereas halogenated aliphatic compounds with high values of molecular weight (Mw), average molecular polarizability (alpha) and core-core repulsion energy (CCR) values tend to be reductively dehalogenated fastest.

Electrons↗

PubMed2001

Quantitative structure-property relationships (QSPRs) on direct photolysis of PCDDs.

By the use of partial least squares (PLS) method and 27 quantum chemical descriptors computed by PM3 Hamiltonian, a statistically significant QSPR were obtained for direct photolysis quantum yields (Y) of selected Polychlorinated dibenzo-p-dioxins (PCDDs). The QSPR can be used for prediction. The direct photolysis quantum yields of the PCDDs are dependent on the number of chlorine atoms bonded with the parent structures, the character of the carbonoxygen bonds, and molecular polarity. Increasing bulkness and polarity of PCDDs lead to decrease of log Y values. Increasing the frontier molecular orbital energies (Elumo and Ehomo) and heat of formation (HOF) values leads to increase of log Y values.

Carbon↗

PubMed2001

Multiple-label immunocytochemistry for the evaluation of nature of cell death in experimental models of neurodegeneration.

A prominent feature of neurodegenerative diseases is a loss of specific neuronal populations. The pathophysiological mechanisms responsible are, however, poorly understood. Primary cultures of rodent embryonic neurons represent a useful experimental system for investigation of molecular pathways of neurodegeneration and mechanisms of cell death. Here, we report a technique utilizing triple-label immunocytochemistry with confocal immunofluorescence detection designed to simultaneously assess multiple parameters of cell injury in individual hippocampal neurons in primary culture. This method combines detection of DNA damage (TUNEL or Klenow assay) with double-label immunocytochemistry for the activated form of caspase-3 or, alternatively, caspase-cleaved actin (fractin), and microtubule-associated protein-2 (MAP-2) or beta-tubulin. The combined evaluation of the form of nuclear damage (karyorrhexis, pyknosis), the presence or absence of activated caspase-3, and the extent of the damage to cell cytoskeleton, allows for precise assessment of the extent of injury and the mode of cell death (apoptosis, oncosis) for individual neurons.

Animals↗

PubMed2001

Variations in transmembrane Ca2+ gradient and apoptosis of macrophages induced by oxidized low density lipoprotein.

While Ca2+ has been proposed to be a messenger in OxLDL-induced cell death, few studies have addressed the possibility that it may influence the occurrence of apoptosis and necrosis of macrophages induced by OxLDL in virtue of change of transmembrane Ca2+ gradient including that across plasma membrane and intracellular organelle membranes. In this paper, various lipophilic Ca2+ fluorescent indicators and specific organelle markers were used to study the relationship between the changes of the transmembrane Ca2+ gradients and the OxLDL induced apoptosis of macrophages. Our results showed that following exposure of low dose OxLDL to macrophages, the transmembrane Ca2+ gradient across the plasma membrane, as well as the membrane-proximal Ca2+ gradient, the transnuclear, and the transmitochondrial membrane Ca2+ gradient were all changed significantly. These data suggested that changes in transmembrane Ca2+ gradients might be involved in the apoptosis of macrophages induced by OxLDL.

Animals↗

PubMed2001

Karyotype relationships between distantly related marsupials from South America and Australia.

Reciprocal chromosome painting and G-banding were used to compare the karyotypes of three Australian marsupials (Sminthopsis crassicaudata, Macropus eugenii, Trichosurus vulpecula) and one South American marsupial (Monodelphis domestica). The results revealed only a limited number of rearrangements between these species and that the four karyotypes can be described as different combinations of fifteen conserved segments. Five chromosomes are totally conserved between M. domestica (pairs 1, 2, 5, 8 and the X) and the presumed 2n = 14 Australian ancestral karyotype, while M. domestica pairs 3 and 6 and 4 and 7 would have been involved in fusion/fission rearrangements. Chromosome comparisons are presented in a chromosome homology map. Although the species studied diverged 70 million years ago, the karyotype of Monodelphis domestica is highly conserved in relation to those of Australian marsupials.

Animals↗

PubMed2001

Renin angiotensin system gene polymorphisms in pediatric renal transplant recipients.

Genetic variability in the renin angiotensin system may modify renal responses to injury and disease progression. We therefore examined whether the insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene, the Met235-->Thr polymorphism of the angiotensinogen (AGT) gene, and the A1166-->C polymorphism of the angiotensin II type 1 receptor gene (ATR1) were associated with disease progression and outcome after renal transplantation (Tx) in 100 Caucasian pediatric renal transplant recipients. The observed allele frequencies were: DD 31%, DI 41% and II 28%, for ACE; MM 42%, MT 37% and TT 21%, for the methionine (Met)235-->threonine (Thr) polymorphism of AGT; and AA 51%, AC 38% and CC 11%, for the adenine (A)1166-->cytosine (C) gene polymorphism. The slope of 1/creatinine was determined by linear regression analysis of a median of 12 points before and after renal Tx, and the population was divided in two equal groups, according to the slope, both before and after Tx. There were no statistically significant differences for AGT, ACE, and ATR1 polymorphisms with regard to the slope of 1/creatinine before renal Tx. After renal Tx, the ACE II genotype (p = 0.024, chi-square test) and the presence of the I allele (p=0.033, chi-square test) were associated with a favorable slope of 1/creatinine. There was no association of the AGT or the ATR1 polymorphism with outcome after renal Tx, and none of the genotypes were associated with hypertension before or after renal Tx. We suggest that the beneficial association of disease progression after renal Tx with the II genotype and/or the presence of the I allele in our pediatric cohort might be explained by a lower activity of the circulating ACE enzyme associated with the I allele.

Adolescent↗

PubMed2001

PI-3 kinase and IP3 are both necessary and sufficient to mediate NT3-induced synaptic potentiation.

Signaling mechanisms underlying neurotrophic regulation of synaptic transmission are not fully understood. Here we show that neurotrophin-3 (NT3)-induced potentiation of synaptic transmission at the neuromuscular synapses is blocked by inhibition of phosphoinositide-3 kinase, phospholipase C-gamma or the downstream IP3 receptors of phospholipase C-gamma, but not by inhibition of MAP kinase. However, neither stimulation of Ca2+ release from intracellular stores by photolysis of caged IP3, nor expression of a constitutively active phosphoinositide-3 kinase (PI3K*) in presynaptic motoneurons alone is sufficient to enhance transmission. Photo-uncaging of IP3 in neurons expressing PI3K* elicits a marked synaptic potentiation, mimicking the NT3 effect. These results reveal an involvement of PI3 kinase in transmitter release, and suggest that concomitant activation of PI3 kinase and IP3 receptors is both necessary and sufficient to mediate the NT3-induced synaptic potentiation.

Animals↗

PubMed2001

An abundance of X-linked genes expressed in spermatogonia.

Spermatogonia are the self-renewing, mitotic germ cells of the testis from which sperm arise by means of the differentiation pathway known as spermatogenesis. By contrast with hematopoietic and other mammalian stem-cell populations, which have been subjects of intense molecular genetic investigation, spermatogonia have remained largely unexplored at the molecular level. Here we describe a systematic search for genes expressed in mouse spermatogonia, but not in somatic tissues. We identified 25 genes (19 of which are novel) that are expressed in only male germ cells. Of the 25 genes, 3 are Y-linked and 10 are X-linked. If these genes had been distributed randomly in the genome, one would have expected zero to two of the genes to be X-linked. Our findings indicate that the X chromosome has a predominant role in pre-meiotic stages of mammalian spermatogenesis. We hypothesize that the X chromosome acquired this prominent role in male germ-cell development as it evolved from an ordinary, unspecialized autosome.

Animals↗

PubMed2001

GDNF acutely modulates excitability and A-type K(+) channels in midbrain dopaminergic neurons.

Glial cell line-derived neurotrophic factor (GDNF) prevents lesion-induced death of midbrain dopaminergic neurons, but its function in normal brain remains uncertain. Here we show that GDNF acutely and reversibly potentiated the excitability of cultured midbrain neurons by inhibiting transient A-type K(+) channels. The effects of GDNF were limited to large, tyrosine hydroxylase (TH)-positive dopaminergic neurons, and were mediated by mitogen associated protein (MAP) kinase. Application of GDNF also elicited a MAP kinase-dependent enhancement of the excitability in dopaminergic neurons in midbrain slice. These results demonstrate an acute regulation of GDNF on ion channels and its underlying signaling mechanism, and reveal an unexpected role of GDNF in normal midbrain dopaminergic neurons.

4-Aminopyridine↗

PubMed2001

Leakage and aggregation of phospholipid vesicles induced by the BH3-only Bcl-2 family member, BID.

BID is a BH3 domain-only member of the Bcl-2 family that acts as an apoptotic agonist in programmed cell death. After cleavage by caspase-8, the N-terminal of BID (N-BID) stays in the cytosol while the C-terminal of BID (C-BID) translocates to mitochondria, leading to cytochrome c release in vivo and in vitro. We have previously reported that BID or truncated BID (tBID) can induce the release of entrapped trypsin and cytochrome c from large unilamellar vesicles (LUVs). Further studies have been performed and are presented here; the results demonstrate that C-BID, like BID and tBID, induces vesicle leakage, whereas N-BID or the BID mutants BID (D59A) and BID (G94E) fail to have any significant effects. The affinity of the above-mentioned proteins for soybean phospholipid LUVs (SLUVs) decreased in an order similar to their leakage-inducing capability: tBID > BID > BID (D59A), while N-BID and BID (G94E) were unable to bind to the vesicles at all. BID-induced leakage was dependent on the lipid composition of vesicles. Acidic phospholipid (e.g. phosphatidic acid or phosphatidylglycerol) was necessary for BID-induced leakage while the presence of phosphatidylethanolamine or cholesterol reduced the leakage. It was also found C-BID is better able to penetrate the soybean phospholipid monolayer than BID or tBID. A further finding was that tBID, but not full-length BID, could stimulate the aggregation of SLUVs. Finally, Bcl-x(L), an apoptotic antagonist in programmed cell death, can prevent the aggregation of LUVs induced by tBID, but not the release of entrapped trypsin. It is postulated that two separate domains of tBID are responsible for inducing leakage and aggregation of phospholipid vesicles.

BH3 Interacting Domain Death Agonist Protein↗