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Biomedical subjects

F Yang

Publications and source records attributed to F Yang.

At least 127 records · Page 7Linked to original sources

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↗

Chromosome identification and assignment of DNA clones in the dog using a red fox and dog comparative map.

We have developed a novel method for identifying dog chromosomes and unambiguously mapping specific clones onto canine chromosomes. This method uses a previously established red fox/dog comparative chromosome map to guide the FISH mapping of cloned canine DNA. Mixing metaphase preparations of the red fox and dog enabled a single hybridization to be performed on both species. We used this approach to map the chromosomal locations of twenty-six canine cosmids. Each cosmid contains highly polymorphic microsatellite markers currently used by the DogMap project to compile the canine linkage map. All but two cosmids were successfully assigned to subchromosomal regions on red fox and dog chromosomes. For eight cosmids previously mapped on dog chromosomes, we confirmed and refined the canine chromosomal assignments of seven cosmids and corrected an erroneous assignment regarding cosmid CanBern1. These results demonstrate that the red fox and dog comparative chromosome map can greatly improve the accuracy and efficiency of chromosomal assignments of canine genetic markers by FISH.

Animals↗

Influence of 699C-->T and 1080C-->T polymorphisms of the cystathionine beta-synthase gene on plasma homocysteine levels.

The association of moderately elevated total homocysteine (tHcy) levels with coronary artery disease is increasingly being recognized. However, the role of genetic influence on plasma tHcy levels is not completely understood. We studied 1,055 individuals with respect to the effect of two silent polymorphisms, the 699C--> T and the 1080C-->T, of the cystathionine beta-synthase (CBS) gene on plasma tHcy levels. Individuals who were heterozygous or homozygous for the T699 allele had lower post-methionine load (PML) tHcy levels when compared to individuals with the C/C genotype. This association was statistically significant (p = 0.005) for the T/T genotype compared to the C/C genotype and became even more significant (p = 0.000002) when individuals carrying the 68-bp insertion (844ins68) and the T1080 allele were excluded from the analysis. With regard to the 1080C-->T polymorphism, the T1080 allele was associated with significantly lower PML tHcy levels only when individuals carrying the 844ins68 and T699 allele were excluded from the study (p = 0.01 for 1080T/T genotype compared to 1080C/C genotype). We speculate that the 699C-->T and 1080C-->T polymorphisms may be in linkage disequilibrium with regulatory elements that upregulate CBS gene transcription.

Adult↗

Novel fold and capsid-binding properties of the lambda-phage display platform protein gpD.

The crystal structure of gpD, the capsid-stabilizing protein of bacteriophage lambda, was solved at 1.1 A resolution. Data were obtained from twinned crystals in space group P21 and refined with anisotropic temperature factors to an R-factor of 0.098 (Rfree = 0. 132). GpD (109 residues) has a novel fold with an unusually low content of regular secondary structure. Noncrystallographic trimers with substantial intersubunit interfaces were observed. The C-termini are well ordered and located on one side of the trimer, relatively far from its three-fold axis. The N-termini are disordered up to Ser 15, which is close to the three-fold axis and on the same side as the C-termini. A density map of the icosahedral viral capsid at 15 A resolution, obtained by cryo-electron microscopy and image reconstruction, reveals gpD trimers, seemingly indistinguishable from the ones seen in the crystals, at all three-fold sites. The map further reveals that the side of the trimer that binds to the capsid is the side on which both termini reside. Despite this orientation of the gpD trimer, fusion proteins connected by linker peptides to either terminus bind to the capsid, allowing protein and peptide display.

Amino Acid Sequence↗

Cytokine requirement for the development of T-lymphoid lineage potential in clonal lymphohaematopoietic progenitors in vitro.

The early process of T-cell development prior to thymic colonization has been poorly investigated because of the lack of a sensitive assay. We have developed a two-step in vitro culture system by combining a clonal culture with a fetal thymus organ culture (FTOC) and analysed the early development of T cells from lymphohaematopoietic progenitors. Cells of immature colonies derived from bone marrow cells of 5-fluorouracil (5FU)-treated mice using various combinations of early acting cytokines were transferred into a FTOC. All the combinations of stem cell factor (SCF), interleukin (IL)-3 and IL-6 capable of inducing colony formation supported T-cell generation. IL-11 and the Flt3 ligand possessed T-lineage promotional effects similar to IL-6 and SCF respectively. However, there were some quantitative differences in the final T-cell yield among cytokine combinations. Thus, the commitment towards T lineage in lymphohaematopoietic progenitors may be an event determined intrinsically rather than induced by specific stimuli, but there may be a hierarchy between the activity of cytokines in further development. Furthermore, we examined the T-lineage potential of individual colonies derived from Lin(-)c-Kit(+)Sca-1(+) cells clone-sorted from post-5FU marrow cells. No colonies that contained only myelocytic progenitors showed T-lineage potential, but 23.3% of colonies with a haematopoietic multipotentiality did. Therefore, the divergence of the T lineage from other lineages such as myeloid potential may occur at an early stage of the hierarchy of haematopoiesis. The proposed method should prove valuable for exploring the molecular and cellular changes that occur during early T-cell development before thymic colonization.

Animals↗

Caspase-cleaved actin (fractin) immunolabelling of Hirano bodies.

Hirano bodies are eosinophilic rod-like inclusions that are found predominantly in neuronal processes in the hippocampal CA1 sector with increasing age and are particularly numerous in Alzheimer's disease. They contain a variety of cytoskeletal epitopes, especially actin and actin-binding proteins. Actin cleavage by cysteinyl aspartate-specific proteases (caspases) is a feature of apoptosis. Cleavage at aspartate 244 generates N-terminal 32 kDa and C-terminal 15 kDa actin fragments. This has led to the development of a rabbit polyclonal antibody specific for caspase-cleaved actin, directed to the last five C-terminal amino acids of the 32 kDa fragment of actin ('fractin'). Fractin immunohistochemistry was performed on hippocampal sections from Alzheimer's disease and control cases containing numerous Hirano bodies, in addition to immunolabelling with CM1 antiserum which recognizes activated caspase-3. The Hirano bodies showed strong diffuse fractin immunoreactivity. They did not label with CM1 antiserum, perhaps reflecting too low a level of activated caspase-3 for immunodetection, or involvement of a different member of the caspase family. The finding of fractin immunoreactivity of Hirano bodies suggests that caspase-like cleavage of actin may play a role in their formation and further supports caspase-like activity in neuronal processes, distinct from that associated with acute perikaryal apoptosis.

Actins↗

beta-amyloid (Abeta)42(43), abeta42, abeta40 and apoE immunostaining of plaques in fatal head injury.

beta-Amyloid (Abeta) deposits are found in the brains of approximately one-third of patients who die within days after a severe head injury; their presence correlating strongly with possession of an apolipoprotein E (apoE)-epsilon4 allele. The aim of the study was to investigate the relationship between Abeta42, Abeta40 and apoE immunostaining of Abeta plaques in the cerebral cortex and the relevance of apoE genotype in 23 fatally head-injured patients. These cases were known to have Abeta deposits from a previous study in which they were examined and semiquantified and related to apoE genotype. In the present study, the temporal cortex was probed using four different antibodies that recognize Abeta42(43), Abeta40 and an antibody to apoE. Abeta42(43)-positive plaques were observed in all of the 23 cases and Abeta40 immunoreactivity in only 11 of the 23 cases. In addition, semiquantitative analysis showed that relatively fewer plaques were detected with anti-Abeta40 than anti-Abeta42(43). ApoE-immunoreactive plaques were identified in 18 of the 23 cases. The number of plaques stained for apoE was relatively less than for Abeta42(43) but greater than for Abeta40. Furthermore, the density of Abeta plaques detected using either Abeta42(43), Abeta40 or apoE antibodies was associated with possession of apoE-epsilon4 in an allele dose-dependent manner. The results are consistent with Abeta42(43) as the initially deposited species in brain parenchyma and provide evidence that apoE is involved in the early stages of amyloid deposition. Further, the findings may be of relevance to the role of apoE genotype in influencing outcome after acute brain injury.

Adolescent↗