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Biomedical subjects

Q Wang

Publications and source records attributed to Q Wang.

At least 343 records · Page 19Linked to original sources

Altered G protein-coupling functions of RNA editing isoform and splicing variant serotonin2C receptors.

Different isoforms of serotonin subtype 2C receptor (5-HT(2C)R) with altered G protein-coupling efficacy are generated by RNA editing, which converts genomically encoded adenosine residues into inosines. In combination, editing of five sites all located within the second intracellular loop region of 5-HT(2C)R mRNA changes the gene-encoded Ile, Asn, and Ile at positions 156, 158, and 160, respectively. We analyzed the G protein-coupling functions of previously unreported editing isoform receptors. An approximately 13-fold reduction in the agonist potency for G protein-coupling stimulation as well as a significantly reduced basal level activity was observed with the thalamus-specific isoform carrying Ile156, Gly158, and Val160 (5-HT(2C)R-IGV). In contrast, the agonist was four- to five-fold less potent with 5-HT(2C)R-MSV and -IDV, detected in the amygdala and choroid plexus, respectively, indicating a dominant role for the amino acid residue at position 158 in receptor functions. We also identified a splicing variant receptor with a truncated C terminus that displayed no ligand binding capacity or G protein-coupling activity. Examination of the alternatively spliced RNA encoding this truncated receptor suggests that editing of this variant RNA occurs after completion of splicing, resulting in complete editing at all five sites.

3T3 Cells↗

Effect of CT digital image compression on detection of coronary artery calcification.

PURPOSE: To test the effect of digital compression of CT images on the detection of small linear or spotted high attenuation lesions such as coronary artery calcification (CAC). MATERIAL AND METHODS: Fifty cases with and 50 without CAC were randomly selected from a population that had undergone spiral CT of the thorax for screening lung cancer. CT image data were compressed using JPEG (Joint Photographic Experts Group) or wavelet algorithms at ratios of 10:1, 20:1 or 40:1. Five radiologists reviewed the uncompressed and compressed images on a cathode-ray-tube. Observer performance was evaluated with receiver operating characteristic analysis. RESULTS: CT images compressed at a ratio as high as 20:1 were acceptable for primary diagnosis of CAC. There was no significant difference in the detection accuracy for CAC between JPEG and wavelet algorithms at the compression ratios up to 20:1. CT images were more vulnerable to image blurring on the wavelet compression at relatively lower ratios, and "blocking" artifacts occurred on the JPEG compression at relatively higher ratios. CONCLUSION: JPEG and wavelet algorithms allow compression of CT images without compromising their diagnostic value at ratios up to 20:1 in detecting small linear or spotted high attenuation lesions such as CAC, and there was no difference between the two algorithms in diagnostic accuracy.

Adult↗

Differentiated thyroid carcinomas. Prediction of tumor invasion with MR imaging.

PURPOSE: To assess diagnostic accuracy for tumor invasion of surrounding organs by measurement of tumor circumferences on MR images in patients with differentiated thyroid carcinomas. MATERIAL AND METHODS: Surgical and MR imaging findings in 50 patients with differentiated thyroid carcinoma (43 primary, 7 recurrent lesions) were retrospectively reviewed. The degrees of circumference of tumor encroachment to the organs were measured, and the measurements and morphologic diagnosis of tumor invasion made by a head and neck radiologist were compared with surgical and pathologic findings using receiver operating characteristic curves. RESULTS: Diagnosis of tumor invasion by the radiologist was superior to the measurements of the carotid artery and cartilage, while the reverse was true for the trachea and esophagus. However, no statistical differences were noted between them for each structure. Optimal thresholds for tumor invasion were 90 degrees or more for the cartilage (94% accuracy) and esophagus (86% accuracy), 135 degrees or more for the trachea (86% accuracy), and 225 degrees or more for the carotid artery (90% accuracy). CONCLUSION: Tumor invasion was more accurately diagnosed by measurement of tumor circumferences of each organ on MR images.

Adenocarcinoma, Follicular↗

Sharing memories and telling stories: American and Chinese mothers and their 3-year-olds.

American and Chinese mothers were asked to talk with their 3-year-old children at home about two shared past events and a story (41 mother-child dyads). Results revealed between-culture variation in the content and style of mother-child conversations when sharing memories and telling stories. American mothers and children showed a high-elaborative, independently oriented conversational style in which they co-constructed their memories and stories by elaborating on each other's responses and focusing on the child's personal predilections and opinions. In contrast, Chinese Mother-child dyads employed a low-elaborative, interdependently oriented conversational style where mothers frequently posed and repeated factual questions and showed great concern with moral rules and behavioural standards with their children. Findings suggest that children's early social-linguistic environments shape autobiographical remembering and contribute to cultural differences in the age and content of earliest childhood memories.

Adult↗

VCP, a weak ATPase involved in multiple cellular events, interacts physically with BRCA1 in the nucleus of living cells.

BRCA1, a breast/ovarian cancer susceptibility gene, undergoes mutations in as many as 50% of familial breast tumors. Recent studies indicate that BRCA1 may be involved in DNA damage repair. Here, we demonstrate that the BRCA1 protein physically associates with valosin-containing protein (VCP), a member of the ATPases associated with a variety of cellular activities (AAA) superfamily. In vitro studies revealed that VCP, via its N- terminal region, binds to amino acid residues 303-625 in the BRCA1 protein. Although found predominantly in the cytoplasm and, less abundantly, in the nucleus, VCP can be translocated from the nucleus after stimulation with epidermal growth factor. Collectively, our results suggest that VCP, by binding to BRCA1, participates in the DNA damage-repair function as an ATP transporter, possibly facilitating the transcription-coupled repair.

Adenosine Triphosphatases↗

Primary thyroid lymphoma: diagnosis of immunoglobulin heavy chain gene rearrangement with polymerase chain reaction in ultrasound-guided fine-needle aspiration.

We present a case of primary thyroid lymphoma coexisting with Hashimoto's thyroiditis in a 75-year-old woman in whom B-cell lymphoma was substantiated based on the findings of immunophenotyping and polymerase chain reaction (PCR) gene rearrangement in specimens that had been obtained by ultrasound (US)-guided fine-needle aspiration biopsy (FNAB). The immunophenotyping technique showed A light chain restriction, and PCR-based assays showed a discrete narrow band, which was diagnostic for clonal B-cell proliferation. Analyses of PCR gene rearrangement in US-guided FNAB may be a useful ancillary technique to pathological findings for diagnosis of primary thyroid lymphoma, especially for differentiation between low-grade B-cell lymphomas and Hashimoto's thyroiditis.

Aged↗

Translation of maternal messenger ribonucleic acids encoding transcription factors during genome activation in early mouse embryos.

Embryonic genome activation (EGA) in mice is sensitive to treatment with cycloheximide, indicating that protein synthesis plays an important role in mediating EGA. We hypothesized that regulated maternal mRNA recruitment may control the time of EGA by controlling the time of appearance of certain transcription factors (TFs). We also hypothesized that synthesis of other TFs may contribute to EGA independently of controlling the timing of EGA. To test these hypotheses, we used sucrose density gradient fractionation coupled to a quantitative reverse transcription-polymerase chain reaction method to compare polysomal mRNA abundances of specific TF mRNAs between metaphase II oocytes, 1-cell-stage embryos, and 2-cell-stage embryos. We observed a 2-cell-stage-specific increase in polysomal abundance of mouse TEA DNA binding domain 2 (mTEAD-2) mRNA, coincident with the first appearance of mTEAD activity in the early embryo. The mRNAs encoding Sp1, TATA binding protein, and cyclic AMP response element binding protein did not undergo translational recruitment, but exhibited differences in polysomal abundance. We also observed a continuous, high proportion in the polysomal fraction for the mRNA encoding ribosomal protein L23 mRNA, which contrasted with the patterns observed for other maternal transcripts. These observations are consistent with the hypothesis that regulated recruitment of maternal TF mRNAs may control the time of activation of some genes during EGA, and that continuous synthesis of other TFs, like Sp1, may facilitate EGA.

Animals↗

Assessment of differential gene expression patterns in human colon cancers.

OBJECTIVE: To use a novel genomic approach to determine differential gene expression patterns in colon cancers of different metastatic potential. SUMMARY BACKGROUND DATA: Colorectal cancer is the third leading cause of cancer deaths in the United States; despite aggressive treatment strategies, the 5-year survival rate for metastatic cancer has not changed in 50 years. The analysis of changes in gene expression patterns associated with metastasis may provide new treatment strategies. METHODS: Human colon cancer cells KM12C (derived from a Dukes B colon cancer), KML4A (a metastatic variant derived from KM12C), and KM20 (derived from a Dukes D colon cancer) were extracted for RNA. In addition, RNA was extracted from normal colon, primary cancer, and liver metastasis in a patient with metastatic colon cancer. Gene expression patterns for approximately 1,200 human genes were analyzed and compared by cDNA array techniques. RESULTS: Of the roughly 1,200 genes assessed in the KM cell lines, 9 genes were noted to have a more than threefold change in expression (either increased or decreased) in the more metastatic KML4A and KM20 cells compared with KM12C. Assessment of tissues from a patient with metastatic colon cancer demonstrated a more than threefold change in the expression of 14 genes in the primary cancer and liver metastasis compared with normal mucosa. CONCLUSIONS: Using cDNA expression array technology, the authors identified genes with expression levels that are altered with metastasis. The ability to analyze and compare the expression patterns of multiple genes simultaneously provides a powerful technique to identify potential molecular targets for novel therapeutic strategies.

Blotting, Northern↗

Head and neck lesions: determination of an optimal MT technique for prediction of malignancies.

RATIONALE AND OBJECTIVES: To determine an optimal magnetization transfer (MT) technique for diagnosis of malignancies in the head and neck. METHODS: Lesion magnetization transfer ratios (MTRs) and lesion-to-muscle MTRs were prospectively measured in 52 head and neck lesions of 52 patients at frequency offsets of 0.3, 0.5, and 1 kHz from water resonance. The diagnostic capability for each MT pulse was calculated by using receiver operating characteristic (ROC) curves, and an optimal MT technique was determined for diagnosis of malignancies. RESULTS: The lesion MTRs and the lesion-to-muscle MTRs in malignant tumors were statistically significantly greater than those in benign lesions at both 0.5- and 1-kHz MT pulses, but no significant differences were noted between them at the 0.3-kHz MT pulse. Diagnosis with the lesion-to-muscle MTRs was better than that with the lesion MTRs at each MT pulse. Among all MTRs, lesion-to-muscle MTRs at the 1-kHz MT pulse showed the highest diagnostic capability for malignancies (area under the ROC curve = 0.82+/-0.06). With a lesion-to-muscle MTR at a 1-kHz MT pulse of 0.61 or greater, the highest accuracy of 85% was attained with 90% sensitivity and 77% specificity. CONCLUSIONS: Lesion-to-muscle MTRs at a 1-kHz MT pulse were optimal for diagnosis of malignancies in the head and neck.

False Positive Reactions↗

Cardiac hypertrophy depends upon sleep blood pressure: a study in rats.

OBJECTIVE: The objective of this study was to determine whether cardiac hypertrophy in hypertensive rats could be reduced and normalized by intermittent reduction of blood pressure, and to determine whether left ventricular hypertrophy was related to 24 h workload or peak blood pressure responses. METHODS: Hypertension was created by the application of a 0.20 mm clip to the left renal artery. Blood pressure response was monitored using a telemetry system (Data Science International). Blood pressure was reduced for varying periods of the day by giving different doses of captopril in the drinking water or by intra-peritoneal administration. Cardiac size was measured by weighing the ventricles and factoring by the body weight to obtain a cardiac index. RESULTS: Captopril 75 mg/kg per day and 25 mg/kg per day in the drinking water administered between 1800 and 2000 h lowered the 24 h blood pressure more than captopril 15 mg/kg per day or 5 mg/kg per day intra-peritoneally given at 0800 h. Captopril 75 mg/kg per day and captopril 15 mg/kg per day (intra-peritoneal) caused regression of cardiac hypertrophy whereas the other doses had no effect The best predictor of the cardiac hypertrophy response was the blood pressure between 0800 and 1200 h (i.e. the sleeping blood pressure). Twenty-four hour cardiac work did not correlate with the response. CONCLUSION: Cardiac hypertrophy can be reduced by intermittent treatment of elevated blood pressure. It is also caused by intermittent elevation of blood pressure. It appears that the crucial factor is when these alterations in blood pressure take place. An elevated blood pressure during the sleeping hours causes left ventricular hypertrophy, whereas a normal blood pressure during the sleeping hours allows reduction. It is suggested that acute wall stress is the signal to initiate the events that lead to cardiac hypertrophy but this only occurs if the hormonal milieu is appropriate.

Animals↗

Activation of NF-kappaB varies in different regions of the gastrointestinal tract during endotoxemia.

The transcription nuclear factor-kappaB (NF-kappaB) regulates a large number of genes involved in the inflammatory response to sepsis and endotoxemia. We recently found that NF-kappaB is activated in the jejunal mucosa during endotoxemia, but the response of NF-kappaB in other parts of the gastrointestinal tract is not known. We hypothesized that NF-kappaB is differentially activated in different regions of the gastrointestinal tract during endotoxemia. NF-kappaB DNA binding activity was determined by electrophoretic mobility shift assay in mucosa of the stomach, jejunum, ileum, and colon from endotoxemic and saline-injected mice. Cytoplasmic levels of the NF-kappaB inhibitory proteins IkappaB-alpha and IkappaB-beta were determined by Western blot analysis. Endotoxemia increased NF-kappaB activity in mucosa of stomach, jejunum, and ileum, with jejunum responding to smaller doses of endotoxin than the other parts of the gastrointestinal tract. NF-kappaB DNA binding activity was not induced in colonic mucosa, even following administration of high doses of endotoxin. IkappaB-alpha and IkappaB-beta levels decreased in jejunal mucosa of endotoxin injected mice, concomitant with activation of NF-kappaB. The results suggest that during endotoxemia, NF-kappaB is activated in mucosa of stomach and small intestine, but not in colon, and that the jejunum is particularly sensitive to endotoxin.

Animals↗

Exact banded patterns from a Doi-Marrucci-Greco model of nematic liquid crystal polymers.

Elements of pattern formation in nematic liquid crystal polymers are presented using the Doi-Marrucci-Greco (DMG) moment-averaged theory. The theory yields a full tensor orientation equation, accounting for excluded-volume and distortional elasticity potentials, with rotational molecular diffusion. Spinodal decomposition associated with unstable homogeneous phases is described first by way of an exact solution of the linearized DMG model. A variety of uniaxial and biaxial banded spatial patterns are then explicitly constructed from the DMG model. Exact solutions are given that possess order parameter spatial variations as well as solutions whose banded intensity patterns arise from sinuous director heterogeneity. These constructions pose as analytical models for banded structures observed during and after cessation of simple shear or elongation.

Journal Article↗

Comparison of methods for detection of Erysipelothrix spp. and their distribution in some Australasian seafoods.

For many years, Erysipelothrix rhusiopathiae has been known to be the causative agent of the occupationally related infection erysipeloid. A survey of the distribution of Erysipelothrix spp. in 19 Australasian seafoods was conducted, and methodologies for the detection of Erysipelothrix spp. were evaluated. Twenty-one Erysipelothrix spp. were isolated from 52 seafood parts. Primary isolation of Erysipelothrix spp. was most efficiently achieved with brain heart infusion broth enrichment followed by subculture onto a selective brain heart infusion agar containing kanamycin, neomycin, and vancomycin after 48 h of incubation. Selective tryptic soy broth, with 48 h of incubation, was the best culture method for the detection of Erysipelothrix spp. with PCR. PCR detection was 50% more sensitive than culture. E. rhusiopathiae was isolated from a variety of different fish, cephalopods, and crustaceans, including a Western rock lobster (Panulirus cygnus). There was no significant correlation between the origin of the seafoods tested and the distribution of E. rhusiopathiae. An organism indistinguishable from Erysipelothrix tonsillarum was isolated for the first time from an Australian oyster and a silver bream. Overall, Erysipelothrix spp. were widely distributed in Australasian seafoods, illustrating the potential for erysipeloid-like infections in fishermen.

Animals↗

Nitrate assimilation genes of the marine diazotrophic, filamentous cyanobacterium Trichodesmium sp. strain WH9601.

A 4.0-kb DNA fragment of Trichodesmium sp. strain WH9601 contained gene sequences encoding the nitrate reduction enzymes, nirA and narB. A third gene positioned between nirA and narB encodes a putative membrane protein with similarity to the nitrate permeases of Bacillus subtilis (NasA) and Emericella nidulans (CrnA). The gene was shown to functionally complement a DeltanasA mutant of B. subtilis and was assigned the name napA (nitrate permease). NapA was involved in both nitrate and nitrite uptake by the complemented B. subtilis cells. napA is distinct from the nrt genes that encode the nitrate transporter of freshwater cyanobacteria.

Amino Acid Sequence↗

Specific structural motifs determine TRAP220 interactions with nuclear hormone receptors.

The TRAP coactivator complex is a large, multisubunit complex of nuclear proteins which associates with nuclear hormone receptors (NRs) in the presence of cognate ligand and stimulates NR-mediated transcription. A single subunit, TRAP220, is thought to target the entire complex to a liganded receptor through a domain containing two of the signature LXXLL motifs shown previously in other types of coactivator proteins to be essential for mediating NR binding. In this work, we demonstrate that each of the two LXXLL-containing regions, termed receptor binding domains 1 and 2 (RBD-1 and RBD-2), is differentially preferred by specific NRs. The retinoid X receptor (RXR) displays a weak yet specific activation function 2 (AF2)-dependent preference for RBD-1, while the thyroid hormone receptor (TR), vitamin D(3) receptor (VDR), and peroxisome proliferator-activated receptor all exhibit a strong AF2-dependent preference for RBD-2. Using site-directed mutagenesis, we show that preference for RBD-2 is due to the presence of basic-polar residues on the amino-terminal end of the core LXXLL motif. Furthermore, we show that the presence and proper spacing of both RBD-1 and RBD-2 are required for an optimal association of TRAP220 with RXR-TR or RXR-VDR heterodimers bound to DNA and for TRAP220 coactivator function. On the basis of these results, we suggest that a single molecule of TRAP220 can interact with both subunits of a DNA-bound NR heterodimer.

Amino Acid Motifs↗

Gastric hyperplasia in mice lacking the putative Cdc42 effector IQGAP1.

Human IQGAP1 is a widely expressed 190-kDa Cdc42-, Rac1-, and calmodulin-binding protein that interacts with F-actin in vivo and that can cross-link F-actin microfilaments in vitro. Recent results have implicated IQGAP1 as a component of pathways via which Cdc42 or Rac1 modulates cadherin-based cell adhesion (S. Kuroda et al., Science 281:832-835, 1998), whereas yeast IQGAP-related proteins have been found to play essential roles during cytokinesis. To identify critical in vivo functions of IQGAP1, we generated deficient mice by gene targeting. We demonstrate that IQGAP1 null mutants arise at normal frequency and show no obvious defects during development or for most of their adult life. Loss of IQGAP1 also does not affect tumor development or tumor progression, but mutant mice exhibit a significant (P < 0.0001) increase in late-onset gastric hyperplasia relative to wild-type animals of the same genetic background. While we cannot exclude that functional redundancy with IQGAP2 contributes to the lack of developmental phenotypes, the restricted expression pattern of IQGAP2 is not obviously altered in adult IQGAP1 mutant mice. Thus, IQGAP1 does not serve any essential nonredundant functions during murine development but may serve to maintain the integrity of the gastric mucosa in older animals.

Amino Acid Sequence↗