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Biomedical subjects

F Yang

Publications and source records attributed to F Yang.

At least 109 records · Page 6Linked to original sources

Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer's disease.

The brain in Alzheimer's disease (AD) shows a chronic inflammatory response characterized by activated glial cells and increased expression of cytokines and complement factors surrounding amyloid deposits. Several epidemiological studies have demonstrated a reduced risk for AD in patients using nonsteroidal anti-inflammatory drugs (NSAIDs), prompting further inquiries about how NSAIDs might influence the development of AD pathology and inflammation in the CNS. We tested the impact of chronic orally administered ibuprofen, the most commonly used NSAID, in a transgenic model of AD displaying widespread microglial activation, age-related amyloid deposits, and dystrophic neurites. These mice were created by overexpressing a variant of the amyloid precursor protein found in familial AD. Transgene-positive (Tg+) and negative (Tg-) mice began receiving chow containing 375 ppm ibuprofen at 10 months of age, when amyloid plaques first appear, and were fed continuously for 6 months. This treatment produced significant reductions in final interleukin-1beta and glial fibrillary acidic protein levels, as well as a significant diminution in the ultimate number and total area of beta-amyloid deposits. Reductions in amyloid deposition were supported by ELISA measurements showing significantly decreased SDS-insoluble Abeta. Ibuprofen also decreased the numbers of ubiquitin-labeled dystrophic neurites and the percentage area per plaque of anti-phosphotyrosine-labeled microglia. Thus, the anti-inflammatory drug ibuprofen, which has been associated with reduced AD risk in human epidemiological studies, can significantly delay some forms of AD pathology, including amyloid deposition, when administered early in the disease course of a transgenic mouse model of AD.

Alzheimer Disease↗

Separation of gallic acid from Cornus officinalis Sieb. et Zucc by high-speed counter-current chromatography.

Gallic acid was separated from a n-butanol extract of the fruit of Cornus officinalis Sieb. et Zucc by high-speed countercurrent chromatography in two steps using two solvent systems composed of ethyl-acetate-ethanol n-butanol-water (5:1.8:6, v/v/v) and ethyl acetate-ethanol-water (5:0.5:6, v/v/v) successively. From 1 g of n-butanol extract the method produced 60 mg of gallic acid at a purity of 97%.

Chromatography, High Pressure Liquid↗

Preparative isolation and purification of notopterol and isoimperatorin from Notopterygium forbessi Boiss (Chinese traditional medicinal herb) by high-speed counter-current chromatography.

Preparative high-speed counter-current chromatography was successfully used for isolation and purification of coumarins from Chinese traditional medicinal herb Notopterygium forbessi Boiss (Qianghuo in Chinese) using stepwise elution with a pair of two-phase solvent systems composed of light petroleum-ethyl acetate-methanol-water at volume ratios of 5:5:4.8:5 and 5:5:5:4. Four major components including notopterol and isoimperatorin were isolated, each at over 98% purity.

Chromatography, Liquid↗

Intracellular Ca(2+) and Ca(2+)/calmodulin-dependent kinase II mediate acute potentiation of neurotransmitter release by neurotrophin-3.

Neurotrophins have been shown to acutely modulate synaptic transmission in a variety of systems, but the underlying signaling mechanisms remain unclear. Here we provide evidence for an unusual mechanism that mediates synaptic potentiation at the neuromuscular junction (NMJ) induced by neurotrophin-3 (NT3), using Xenopus nerve-muscle co-culture. Unlike brain-derived neurotrophic factor (BDNF), which requires Ca(2+) influx for its acute effect, NT3 rapidly enhances spontaneous transmitter release at the developing NMJ even when Ca(2+) influx is completely blocked, suggesting that the NT3 effect is independent of extracellular Ca(2+). Depletion of intracellular Ca(2+) stores, or blockade of inositol 1, 4, 5-trisphosphate (IP3) or ryanodine receptors, prevents the NT3-induced synaptic potentiation. Blockade of IP3 receptors can not prevent BDNF-induced potentiation, suggesting that BDNF and NT3 use different mechanisms to potentiate transmitter release. Inhibition of Ca(2+)/calmodulin-dependent kinase II (CaMKII) completely blocks the acute effect of NT3. Furthermore, the NT3-induced potentiation requires a continuous activation of CaMKII, because application of the CaMKII inhibitor KN62 reverses the previously established NT3 effect. Thus, NT3 potentiates neurotransmitter secretion by stimulating Ca(2+) release from intracellular stores through IP3 and/or ryanodine receptors, leading to an activation of CaMKII.

Animals↗

Characterization of tBid-induced cytochrome c release from mitochondria and liposomes.

tBid, the cleaved form of Bid, can induce cytochrome c (Cyt. c) release from rat heart mitochondria more efficiently and reproducibly than that from liver or brain mitochondria. Unlike Bax, such release was not prevented by cyclosphorin A, an inhibitor of the opening of permeability transition pore. Carbonyl-cyanide m-chlorophenyl-hydrazone or oligomycin also have no obvious effect on the release of Cyt. c. In contrast to ceramide, tBid-mediated Cyt. c release from mitochondria is independent of the redox state of Cyt. c. Furthermore, Bid or tBid can directly trigger the efflux of encapsulated Cyt. c or trypsin within liposomes without involvement of other protein factors.

Animals↗

Amyloid beta-protein length and cerebral amyloid angiopathy-related haemorrhage.

The relationship between amyloid beta-protein (A beta) length and the apolipoprotein E (APOE) epsilon 2 allele, which is over-represented in cerebral amyloid angiopathy-related haemorrhage (CAAH), has not previously been examined. Of 57 CAA patients studied, 37 had CAAH. All patients, particularly those with CAAH had more blood vessels immunoreactive for A beta 40 than A beta 42 in both the leptomeninges and cerebral cortex. CAAH patients had more A beta 40-immunoreactive blood vessels in the leptomeninges (p < 0.001) and cortex (p = 0.027) than had non-haemorrhage patients. Cortical blood vessels, the usual source of haemorrhage in CAAH, were more frequently A beta 42 immunoreactive in APOE epsilon 2 carriers than in non-epsilon 2 carriers (p = 0.022). The APOE epsilon 2 allele may predispose to CAAH by increasing the seeding of cortical blood vessels by A beta 42.

Aged↗

Quantitative structure-property relationships for direct photolysis quantum yields of selected polycyclic aromatic hydrocarbons

By the use of partial least squares (PLS) method and 11 quantum chemical descriptors computed by PM3 Hamiltonian, Quantitative Structure-Property Relationships (QSPRs) for direct photolysis quantum yields of selected polycyclic aromatic hydrocarbons (PAHs) were obtained. Direct photolysis quantum yields were predicted for PAHs for which experimental quantum yield values were lacking. Based on the QSPR models, significant PAH molecular characters governing their direct photolysis quantum yields were identified. It can generally be concluded that PAHs with large average molecular polarizability, molecular weight, and heat of formation values tend to have small photolysis quantum yields. PAHs with large values of the energy of the lowest unoccupied molecular orbital (Elumo), small values of the energy of the highest occupied molecular orbital (Ehomo), and large Elumo-Ehomo values, tend to have great photolysis quantum yields.

Journal Article↗

Plaque-associated alpha-synuclein (NACP) pathology in aged transgenic mice expressing amyloid precursor protein.

Patients with the Lewy body variant (LBV) of Alzheimer's disease (AD) have ubiquitinated intraneuronal and neuritic accumulations of alpha-synuclein and show less neuron loss and tau pathology than other AD patients. Aged Tg2576 transgenic mice overexpressing human betaAPP695. KM670/671NL have limited neuron loss and tau pathology, but frequent ubiquitin- and alpha-synuclein-positive, tau-negative neurites resembling those seen in the LBV of AD.

Aging↗

Multiplex fluorescence in situ hybridization and cross species color banding of a case of chronic myeloid leukemia in blastic crisis with a complex Philadelphia translocation.

Exciting new techniques in molecular cytogenetics--namely, spectral karyotyping, multiplex fluorescence in situ hybridization (M-FISH), and cross species color banding--have been recently developed. An increasing number of reports demonstrate the success of these procedures in providing additional cytogenetic information--identifying marker chromosomes and revealing the presence of previously undetected chromosomal changes. However, these procedures have their limitations, and their absolute sensitivity in the accurate identification of subtle chromosomal abnormalities remains to be established. M-FISH and color banding have been applied to a case of chronic myeloid leukemia with a complex Philadelphia translocation involving chromosomes 9, 17, and 22, which had initially been identified from G-banded chromosome analysis. The abnormalities were confirmed by chromosome "painting" and specific probes. Although M-FISH and color banding revealed no additional cryptic chromosomal changes, this study has clearly demonstrated the success of these multiple color FISH approaches in the accurate characterization of a complex rearrangement with subtle abnormalities.

Adolescent↗

The value of in-phase and opposed-phase T1-weighted breath-hold FLASH sequences for hepatic imaging.

The value of the combined in-phase (IP) and opposed-phase (OP) T1-weighted (T1-W) breath-hold FLASH sequences for hepatic imaging, especially for fat content, was evaluated. Non-contrast-enhanced IP and OP T1-W GRE breath-hold images were obtained in 76 patients refereed for abdominal MRI at 1.5T. 76 patients were divided into three groups for analysis: (1) liver without mass (n = 8); (2) liver with hepatoma (n = 34); (3) liver with haemangioma or cyst (n = 34). Liver/spleen and liver/lesion signal-to-noise (SNR) and contrast-to-noise ratio (CNR) were assessed for lesion detection. Images between IP and OP sequences were compared quantitatively. The results showed that there was not statistically significant difference in liver/spleen and liver/lesion SNR between IP and OP sequences. In the patients with fatty infiltration, the OP sequences yielded substantially lower values for liver/spleen and liver/lesion SNR than those of the IP sequences. Furthermore, OP imaging showed fatty infiltration in 14 cases and demonstrated hyperintense peritumor rim in 4 cases. In 14 cases of fatty infiltration, many lesions were identified using IP images. The use of IP and OP GRE sequences provides complementary diagnostic information for hepatic lesions and fat content. Focal hepatic lesions may be obscured in the setting of fatty infiltration if only OP sequences are employed. A complete assessment of the liver with MR should include both IP and OP imaging.

Adolescent↗

Cyclooxygenase 2 expression is increased in the stroma of colon carcinomas from IL-10(-/-) mice.

BACKGROUND & AIMS: The pathological and molecular changes associated with colitis-associated colorectal cancer and sporadic colorectal cancer are considered to be distinct. Therefore, we have used a mouse model of ulcerative colitis to determine if expression of the enzyme cyclooxygenase (COX)-2 is increased in colitis-associated tumors. METHODS: Reverse-transcription polymerase chain reaction and Western analysis were used to determine if COX-2 expression is increased in these tumors; in situ hybridization and immunohistochemistry were used to determine the localization of COX-2. RESULTS: Increased levels of COX-2 messenger RNA and protein were detected in interleukin (IL)-10 (-/-) tumors and in an inflamed region of the colon that contained no macroscopically detected tumors. This expression was localized to the inflammatory cells associated with ulcerated regions of the tumor by in situ hybridization and immunohistochemistry. Increased COX-2 expression was also associated with the areas of the tumor expressing alpha-smooth muscle actin, which is a molecular marker for subepithelial myofibroblasts. The association between COX-2 expression and subepithelial myofibroblasts was also noted in tumors derived from the multiple intestinal neoplasia mice (Min/+) and from carcinogen-induced tumors. CONCLUSIONS: These results indicate that COX-2 is expressed very early in the pathogenesis of colitis-associated tumors, and that the expression pattern is similar to that seen in tumors from azoxymethane-treated and Min/+ mice.

Animals↗

Polygenic influence on plasma homocysteine: association of two prevalent mutations, the 844ins68 of cystathionine beta-synthase and A(2756)G of methionine synthase, with lowered plasma homocysteine levels.

A moderately elevated plasma total homocysteine (tHcy), whether measured during fasting or post-methionine load (PML), is increasingly being recognized as a risk factor for coronary artery diseases (CAD). However, etiologies for moderately elevated plasma tHcy, particularly with regard to the role of genetic influence on plasma tHcy levels, are still not well understood. In the current investigation, we studied 1025 individuals with respect to the effect of the 68-bp insertion (844ins68 variant) of the cystathionine beta-synthase (CBS) gene, the A(2756)G transition of the B(12)-dependent methionine synthase (MS) gene and the C(677)T transition of the methylenetetrahydrofolate reductase (MTHFR) gene on fasting and 4 h PML tHcy. Of these individuals, 153 (14.9%) were heterozygous for the 68-bp insertion, 329 (32.1%) were heterozygous for the G(2756) allele and 122 (11.9%) were homozygous for the C(677)T transition. Individuals heterozygous for the insertion had significantly lower PML increase in tHcy concentrations, while individuals homozygous for the A(2756)G transition had significantly lower fasting tHcy levels. A 2-way ANOVA showed that there was no interaction between the 844ins68 and the A(2756)G transition for either fasting tHcy or PML increase in tHcy, confirming the fact that the effect of these two genotypes on plasma tHcy levels are additive. The effects are opposite but additive with the C(677)50% of all individuals in this study carried polymorphic traits, which predisposed them to either higher or lower plasma tHcy concentrations, thus providing new evidence of the importance of genetic influences as determinants of tHcy levels.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

The use of PLS algorithms and quantum chemical parameters derived from PM3 hamiltonian in QSPR studies on direct photolysis quantum yields of substituted aromatic halides.

The Partial Least-Squares (PLS) method was used to further study Quantitative Structure-Property Relationship (QSPR) for photohydrolysis quantum yields of selected aromatic halides. The cluster of substituted bromobenzenes and iodobenzenes was further grouped into two clusters, substituted bromobenzenes and substituted iodobenzenes, for which QSPRs were obtained, respectively. The QSPRs obtained by PLS are more significant than those obtained in previous studies. The studies showed that only when the compounds belonging to different groups are studies separately, inherent relationships between molecular properties and their structure characteristics can be revealed. It can be generally concluded that the photohydrolysis quantum yields of the substituted aromatic halides are dependent on the overall characters of the molecules, the characters of the carbon-halogen bonds to be broken in the photolysis, and the character of the halogen atoms to be replaced in the photolysis. Electronegativity has great relevance to the photohydrolysis processes of the compounds. Substituted aromatic halides with large average molecular polarizability and molecular weight values tend to have low photolysis quantum yields.

Algorithms↗

Pain response in Chinese and non-Chinese Canadian infants: is there a difference?

This study was designed to compare the behavioural pain responses of 2-month-old Canadian-born Chinese babies receiving a routine immunization to those of non-Chinese infants in similar situations. Two groups of 26 infants were obtained from a pediatric clinic held by a Chinese pediatrician and a suburban pediatric practice of a large Canadian city. Facial expression using the Neonatal Facial Coding System (Grunau, R.V.E., Craig, K.D., 1987. Pain expression in neonates: facial action and cry. Pain, 28, 395-410.) and cry using the Fast Fourier Transform were measured during 30 s following the insertion of the needle. Acculturation in Chinese mothers, circadian rhythm, gender, height and weight in infants were assessed. Multivariate analysis of variance revealed significant differences in pain response between these two groups with the Chinese babies showing greater response. No significant effect of circadian rhythm and gender was identified. These results suggest the presence of differences in acute pain response in relation to culture by at least 2 months of age.

Adult↗

Changes of transmembrane Ca2+ gradient in the formation of macrophage-derived foam cells.

Macrophages from C57BL/6J mice, an animal susceptible to atherosclerosis, were chosen as target cells to study changes in the transmembrane Ca2+ gradient during the formation of macrophage-derived foam cells. The transmembrane Ca2+ gradients of single living cells were examined-using Fura-2/AM combined with Fluo-3/AM by laser scanning confocal microscopy. Exposure to Oxidized Low Density Lipoprotein, decreases the Ca2+ gradient across macrophage plasma membrane, but increases that across the nuclear membrane. The altered transmembrane Ca2+ gradients could induce the up-regulation of scavenger receptor in macrophages, resulting in the formation of foam cells.

Animals↗

Comparative chromosome map of the laboratory mouse and Chinese hamster defined by reciprocal chromosome painting.

Cross-species reciprocal chromosome painting was used to determine homologous chromosomal regions between the laboratory mouse and Chinese hamster. When mouse chromosome-specific paints were hybridized to Chinese hamster chromosomes, paints specific for mouse chromosomes 3, 4, 9, 14, 18, 19 and X each painted a single chromosomal region, whilst other mouse paints delineated multiple discrete chromosomal regions. The mouse Y paint produced non-specific signals on Chinese hamster chromosomes. Nineteen mouse autosome paints identified a total of 47 homologous chromosome regions in the genome of the Chinese hamster. Hybridization of Chinese hamster paints to mouse chromosomes not only confirmed the above results, but also identified which of the chromosomal regions of these two species were homologous. In total, 10 Chinese hamster autosomal paints detected 38 homologous autosomal segments in the mouse genome. A comparative chromosome map was established based on these reciprocal chromosome painting patterns. This map forms the basis for exchanging gene mapping information between the species and for studying genome evolution.

Animals↗

Reciprocal chromosome painting illuminates the history of genome evolution of the domestic cat, dog and human.

Domestic cats and dogs are important companion animals and model animals in biomedical research. The cat has a highly conserved karyotype, closely resembling the ancestral karyotype of mammals, while the dog has one of the most extensively rearranged mammalian karyotypes investigated so far. We have constructed the first detailed comparative chromosome map of the domestic dog and cat by reciprocal chromosome painting. Dog paints specific for the 38 autosomes and the X chromosomes delineated 68 conserved chromosomal segments in the cat, while reverse painting of cat probes onto red fox and dog chromosomes revealed 65 conserved segments. Most conserved segments on cat chromosomes also show a high degree of conservation in G-banding patterns compared with their canine counterparts. At least 47 chromosomal fissions (breaks), 25 fusions and one inversion are needed to convert the cat karyotype to that of the dog, confirming that extensive chromosome rearrangements differentiate the karyotypes of the cat and dog. Comparative analysis of the distribution patterns of conserved segments defined by dog paints on cat and human chromosomes has refined the human/cat comparative genome map and, most importantly, has revealed 15 cryptic inversions in seven large chromosomal regions of conserved synteny between humans and cats.

Animals↗

A comparative chromosome map of the Arctic fox, red fox and dog defined by chromosome painting and high resolution G-banding.

A complete set of paint probes, with each probe specific for a single type of dog chromosome, was generated by DOP-PCR amplification of flow-sorted chromosomes. These probes have been assigned to high-resolution G-banded chromosomes of the dog and Arctic fox by fluorescence in-situ hybridization. On the basis of these results we propose improved nomenclature for the G-banded karyotypes of the dog and Artic fox. A comparative map between the Arctic fox, red fox and dog has been established based on results from chromosome painting and high-resolution G-banding. This map demonstrates that the euchromatic complements of these three canid species consists of 42 conserved segments. Thirty-four of these 42 segments are each represented by a single dog chromosome with dog chromosomes 1, 13, 18 and 19 each retaining two segments, respectively. The autosomes of the Arctic fox and red fox could be reconstructed from these 42 blocks in different combinations through chromosomal fusions. Our findings suggest that chromosome fusion has been the principal mechanism of karyotype evolution occuring during speciation in canids.

Animals↗