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Biomedical subjects

David Liu

Publications and source records attributed to David Liu.

At least 19 recordsLinked to original sources
PubMed2006

Multi-institutional clinical experience with the Calypso System in localization and continuous, real-time monitoring of the prostate gland during external radiotherapy.

PURPOSE: To report the clinical experience with an electromagnetic treatment target positioning and continuous monitoring system in patients with localized prostate cancer receiving external beam radiotherapy. METHODS AND MATERIALS: The Calypso System is a target positioning device that continuously monitors the location of three implanted electromagnetic transponders at a rate of 10 Hz. The system was used at five centers to position 41 patients over a full course of therapy. Electromagnetic positioning was compared to setup using skin marks and to stereoscopic X-ray localization of the transponders. Continuous monitoring was performed in 35 patients. RESULTS: The difference between skin mark vs. the Calypso System alignment was found to be >5 mm in vector length in more than 75% of fractions. Comparisons between the Calypso System and X-ray localization showed good agreement. Qualitatively, the continuous motion was unpredictable and varied from persistent drift to transient rapid movements. Displacements > or =3 and > or =5 mm for cumulative durations of at least 30 s were observed during 41% and 15% of sessions. In individual patients, the number of fractions with displacements > or =3 mm ranged from 3% to 87%; whereas the number of fractions with displacements > or =5 mm ranged from 0% to 56%. CONCLUSION: The Calypso System is a clinically efficient and objective localization method for positioning prostate patients undergoing radiotherapy. Initial treatment setup can be performed rapidly, accurately, and objectively before radiation delivery. The extent and frequency of prostate motion during radiotherapy delivery can be easily monitored and used for motion management.

Aged↗
PubMed2006

botXminer: mining biomedical literature with a new web-based application.

This paper outlines botXminer, a publicly available application to search XML-formatted MEDLINE data in a complete, object-relational schema implemented in Oracle XML DB. An advantage offered by botXminer is that it can generate quantitative results with certain queries that are not feasible through the Entrez-PubMed interface. After retrieving citations associated with user-supplied search terms, MEDLINE fields (title, abstract, journal, MeSH and chemical) and terms (MeSH qualifiers and descriptors, keywords, author, gene symbol and chemical), these citations are grouped and displayed as tabulated or graphic results. This work represents an extension of previous research for integrating these citations with relational systems. botXminer has a user-friendly, intuitive interface that can be freely accessed at http://botdb.abcc.ncifcrf.gov.

Computer Graphics↗
PubMed2006

Six characteristics of effective structured reporting and the inevitable integration with speech recognition.

The reporting of radiological images is undergoing dramatic changes due to the introduction of two new technologies: structured reporting and speech recognition. Each technology has its own unique advantages. The highly organized content of structured reporting facilitates data mining and billing, whereas speech recognition offers a natural succession from the traditional dictation-transcription process. This article clarifies the distinction between the process and outcome of structured reporting, describes fundamental requirements for any effective structured reporting system, and describes the potential development of a novel, easy-to-use, customizable structured reporting system that incorporates speech recognition. This system should have all the advantages derived from structured reporting, accommodate a wide variety of user needs, and incorporate speech recognition as a natural component and extension of the overall reporting process.

Humans↗
PubMed2006

Scaling of theory-of-mind understandings in Chinese children.

Prior research demonstrates that understanding of theory of mind develops at different paces in children raised in different cultures. Are these differences simply differences in timing, or do they represent different patterns of cultural learning? That is, to what extent are sequences of theory-of-mind understanding universal, and to what extent are they culture-specific? We addressed these questions by using a theory-of-mind scale to examine performance of 140 Chinese children living in Beijing and to compare their performance with that of 135 English-speaking children living in the United States and Australia. Results reveal a common sequence of understanding, as well as sociocultural differences in children's developing theories of mind.

Australia↗
PubMed2006

Luminogenic cytochrome P450 assays.

Luminogenic cytochrome P450 (CYP) assays couple CYP enzyme activity to firefly luciferase luminescence in a technology called P450-Glo(TM) (Promega). Luminogenic substrates are used in assays of human CYP1A1, -1A2, -1B1, -2C8, -2C9, -2C19, -2D6, -2J2, -3A4, -3A7, -4A11, -4F3B, -4F12 and -19. The assays detect dose-dependent CYP inhibition by test compounds against recombinant CYP enzymes or liver microsomes. Induction or inhibition of CYP activities in cultured hepatocytes is measured in a nonlytic approach that leaves cells intact for additional analysis. Luminogenic CYP assays offer advantages of speed and safety over HPLC and radiochemical-based methods. Compared with fluorogenic methods the approach offers advantages of improved sensitivity and decreased interference between optical properties of test compound and CYP substrate. These homogenous assays are sensitive and robust tools for high-throughput CYP screening in early drug discovery.

Algorithms↗
PubMed2005

Preschoolers' understanding of knowing-that and knowing-how in the United States and Hong Kong.

Two experiments on preschoolers' understanding of the effects of exposure on knowing-that and knowing-how were conducted with 3-, 4-, and 5-year-old children (N=388) in 2 locations: a small midwestern city in the United States and a suburban area of Hong Kong, China. By using both English- and Chinese-speaking samples, the authors examined differences in children's understanding of knowing-that and knowing-how as well as the impact of different types of linguistic markers on the understanding of these concepts. Across both studies, in both locations, and for judging the knowledge of self or of others, children's understanding for knowing-that preceded their understanding for knowing-how. Implications of these findings both for universal patterns of theory-of-mind development and for how culture may impact on that development are discussed.

Child, Preschool↗
PubMed2005

Smad3 and extracellular signal-regulated kinase 1/2 coordinately mediate transforming growth factor-beta-induced expression of connective tissue growth factor in human fibroblasts.

Connective tissue growth factor (CTGF) is secreted by fibroblasts stimulated with transforming growth factor-beta (TGF-beta). CTGF is a potent enhancer of fibroblast proliferation, chemotaxis, and extracellular matrix deposition, and it is thought to mediate some of the fibrogenic effects of TGF-beta. Here, we have elucidated signaling pathways involved in regulating the TGF-beta-induced production of CTGF in primary fibroblasts. TGF-beta induced the expression of CTGF messenger RNA and protein in human gingival fibroblasts after 2 h of treatment. Adenoviral overexpression of Smad3 enhanced the TGF-beta-elicited expression of CTGF, whereas Smad7 and dominant-negative Smad3 suppressed the effects of TGF-beta on CTGF and Cyr61 expression. Pre-treatment of cells with PD98059, an inhibitor for extracellular signal-regulated kinase (ERK)1/2-activator mitogen-activated protein kinase (MAPK)/ERK kinase (MEK)1, potently inhibited the TGF-beta-induced expression of CTGF. Furthermore, co-expression of Smad3 with constitutively active MEK1 resulted in potent induction of CTGF production without exogenous TGF-beta stimulation. Together, these results demonstrate that Smad3 and ERK1/2 coordinately mediate TGF-beta-induced release of CTGF by fibroblasts. It is conceivable that the crosstalk between Smad3 and ERK1/2 signaling cascades plays an important role in regulating CTGF expression, e.g., in wound repair and tissue fibrosis and could be exploited in therapeutic targeting of fibrotic conditions.

Cells, Cultured↗
PubMed2005

Acupuncture for acute postoperative pain relief in a patient with pregnancy-induced thrombocytopenia--a case report.

A 39 year old woman, scheduled for elective caesarean section in her second pregnancy, developed thrombocytopenia. Therefore, at the time of surgery, spinal anaesthesia and non-steroidal analgesic drugs were avoided and she was given a standard general anaesthetic procedure including fentanyl 100 microg and morphine 10 mg. In the early postoperative period she received tramadol 100 mg and a further 10 mg of morphine. These drugs did not control her pain, but caused side effects--in particular nausea and retching. Acupuncture to LI4 and PC6 on the right side produced dramatic pain relief within minutes.

Acupuncture Analgesia↗
PubMed2004

Selective inhibitors of type I receptor kinase block cellular transforming growth factor-beta signaling.

Transforming growth factor (TGFbeta) is a 25-kDa dimeric polypeptide that plays a key role in a variety of physiological processes and disease states. Blocking TGFbeta signaling represents a potentially powerful and conceptually novel approach to the treatment of disorders in which the signaling pathway is constitutively activated, such as cancer, chronic inflammation with fibrosis and select immune disorders. In this paper, we describe the biological properties of a novel series of quinazoline-derived inhibitors of the type I transforming growth factor receptor kinase (TbetaKIs) that bind to the ATP-binding site and keep the kinase in its inactive conformation. These compounds effectively inhibited TGFbeta-induced Smad2 phosphorylation in cultured cells in vitro with an IC(50) between 20 and 300 nM. Moreover, TbetaKIs were able to broadly block TGFbeta-induced reporter gene activation. Finally, TbetaKIs inhibited TGFbeta-mediated growth inhibition of normal murine mammary epithelial cells (NMuMG) and mink lung epithelial cells (Mv1Lu), and TGFbeta-induced epithelial-mesenchymal transdifferentiation (EMT) of NMuMG cells. Thus, these chemical TbetaKIs have the potential to be further developed as anti-cancer and -fibrosis agents. In addition, they represent valuable new tools for dissecting the biochemical mechanisms of TGFbeta signal transduction and understanding the role of TGFbeta signaling pathways in different physiological and disease processes.

Animals↗
PubMed2004

Case-control study of factors associated with intrauterine fetal deaths.

OBJECTIVE: To study the characteristics of pregnancies that resulted in stillbirth and to determine which may possibly predict intrauterine fetal death (IUFD). STUDY DESIGN: A total of 161 singleton pregnancies resulting in stillbirth at Nottingham City Hospital from 1991 to 1997 were compared with 499 live births randomly selected from the same period of time. The variables studied were the following: customized birth weight for gestational age, fetal sex, histopathologic cause of IUFD, maternal age, ethnic group, parity, maternal body mass index (BMI), smoking habit, and maternal blood group. RESULTS: In 54.7% of the cases of stillbirth at our institution women presented with reduction or absence of fetal movements before the diagnosis of IUFD. Almost half of the stillbirths (48.4%) were small for gestational age (< 10th percentile) on the basis of gestational age-specific weight. The difference in customized birth weight between stillbirths and live births was statistically significant (P <.0001). Increased maternal body mass index (BMI) was positively associated with stillbirth rate (P <.001), as was increased maternal age (P =.0012). Women with blood group O (P =.014) had an even higher stillbirth rate. There was no association between stillbirth rate and maternal ethnic group, maternal smoking, maternal Rhesus status, or fetal sex. CONCLUSIONS: This study found that almost half of stillborn babies were small for gestational age. Reduced fetal activity should be investigated thoroughly, with formal measurement of fetal growth as part of this assessment. Maternal blood group and maternal age were found to be important factors in IUFD. Smoking was not confirmed in this study to be a significant factor.

Adolescent↗
PubMed2004

Decoupling beliefs from reality in the brain: an ERP study of theory of mind.

Theory of mind, attributing behaviors to mental states, is a cognitive ability central to human social interactions. To investigate the neural substrates of theory of mind reasoning, we recorded human event-related brain potentials (ERP) while participants made judgments about belief and judgments about reality. A late ERP component (peaking around 800 ms post-stimulus) with a left frontal scalp distribution, which was inconsistent with a source in the anterior paracingulate cortex and consistent with a source possibly in the left orbitofrontal cortex, differentiated judgments about belief and about reality. This late left frontal component is probably associated with the decoupling mechanism that distinguishes mental states from reality.

Adult↗
PubMed2003

ERK(MAPK) activity as a determinant of tumor growth and dormancy; regulation by p38(SAPK).

After dissemination from a primary tumor, cancer cells may resume growth, leading to overt metastasis, or enter a state of protracted dormancy. However, mechanisms that determine their fate, or markers that predict it, are mostly unavailable. We previously showed that in HEp3 human head and neck carcinoma, the extracellular signal-regulated kinase (ERK)(MAPK)/p38(SAPK) activity ratio predicts whether the cells will proliferate or enter a state of dormancy in vivo. The proliferative balance of high ERK/p38 ratio was induced by high urokinase (uPA) receptor (uPAR) expression, which activated alpha5beta1-integrin and epidermal growth factor receptor. This signaling pathway was additionally enhanced by uPA binding to uPAR and fibronectin binding to alpha5beta1-integrin. We tested whether the ERK/p38 balance is predictive of in vivo behavior in other cancer cell types and whether altering the balance will shift their phenotype between proliferation and dormancy. ERK and p38 activities were determined using either phospho-specific monoclonal antibodies or a trans-reporting system where GAL4-Elk and GAL4-CHOP trans-activation of luciferase gene served as reporters for ERK and p38 activities, respectively. We show that in breast, prostate, melanoma, and fibrosarcoma cell lines, the level of active phospho-ERK and the ERK/p38 activity ratio predict for the in vivo behavior in approximately 90% of the cell lines tested. Modulation of ERK/p38 activity ratio by multiple pharmacological and genetic interventions confirms that high ERK/p38 ratio favors tumor growth, whereas high p38/ERK ratio induces tumor growth arrest (dormancy) in vivo and that ERK is negatively regulated by p38. A melanoma cell line appeared to have developed an escape mechanism to avoid the growth inhibitory effect of high p38 activity. Mechanistic analysis implicated high uPAR expression and its interaction with and activation of alpha5beta1-integrin as determinants of the in vivo growth promoting high ERK/p38 ratio in several cell lines. The small GTPase, Cdc42, was implicated in activation of p38 and growth arrest. These results suggest that even cells that originate in advanced cancers retain a degree of dependence on surface receptors and matrix for their proliferative signals in vivo and provide a therapeutic opportunity to change their phenotype from tumorigenic to dormant.

Animals↗
PubMed2002

Beta-amyloid precursor protein transgenic mice that harbor diffuse A beta deposits but do not form plaques show increased ischemic vulnerability: role of inflammation.

beta-amyloid (A beta), derived form the beta-amyloid precursor protein (APP), is important for the pathogenesis of Alzheimer's disease (AD), which is characterized by progressive decline of cognitive functions, formation of A beta plaques and neurofibrillary tangles, and loss of neurons. However, introducing a human wild-type or mutant APP gene to rodent models of AD does not result in clear neurodegeneration, suggesting that contributory factors lowering the threshold of neuronal death may be present in AD. Because brain ischemia has recently been recognized to contribute to the pathogenesis of AD, we studied the effect of focal brain ischemia in 8- and 20-month-old mice overexpressing the 751-amino acid isoform of human APP. We found that APP751 mice have higher activity of p38 mitogen-activated protein kinase (p38 MAPK) in microglia, the main immune effector cells within the brain, and increased vulnerability to brain ischemia when compared with age-matched wild-type mice. These characteristics are associated with enhanced microglial activation and inflammation but not with altered regulation of cerebral blood flow, as assessed by MRI and laser Doppler flowmetry. Suppression of inflammation with aspirin or inhibition of p38 MAPK with a selective inhibitor, SD-282, abolishes the increased neuronal vulnerability in APP751 transgenic mice. SD-282 also suppresses the expression of inducible nitric-oxide synthase and the binding activity of activator protein 1. These findings elucidate molecular mechanisms of neuronal injury in AD and suggest that antiinflammatory compounds preventing activation of p38 MAPK in microglia may reduce neuronal vulnerability in AD.

Alzheimer Disease↗
PubMed2002

EGFR is a transducer of the urokinase receptor initiated signal that is required for in vivo growth of a human carcinoma.

Urokinase plasminogen activator receptor (uPAR) activates alpha5beta1 integrin and ERK signaling, inducing in vivo proliferation of HEp3 human carcinoma. Here we demonstrate that EGFR mediates the uPAR/integrin/fibronectin (FN) induced growth pathway. Its activation is ligand-independent and does not require high EGFR, but does require high uPAR expression. Only when uPAR level is constitutively elevated does EGFR become alpha5beta1-associated and activated. Domain 1 of uPAR is crucial for EGFR activation, and FAK links integrin and EGFR signaling. Inhibition of EGFR kinase blocks uPAR induced signal to ERK, implicating EGFR as an important effector of the pathway. Disruption of uPAR or EGFR signaling reduces HEp3 proliferation in vivo. These findings unveil a mechanism whereby uPAR subverts ligand-regulated EGFR signaling, providing cancer cells with proliferative advantage.

Blotting, Northern↗
PubMed2002

Traumatic pneumothorax detection with thoracic US: correlation with chest radiography and CT--initial experience.

PURPOSE: To prospectively compare the accuracy of ultrasonography (US) with that of supine chest radiography in the detection of traumatic pneumothoraces, with computed tomography (CT) as the reference standard. MATERIALS AND METHODS: Thoracic US, supine chest radiography, and CT were performed to assess for pneumothorax in 27 patients who sustained blunt thoracic trauma. US and radiographic findings were compared with CT findings, the reference standard, for pneumothorax detection. For the purpose of this study, the sonographers were blinded to the radiographic and CT findings. RESULTS: Eleven of 27 patients had pneumothorax at CT. All 11 of these pneumothoraces were detected at US, and four were seen at supine chest radiography. In the one false-positive US case, the patient was shown to have substantial bullous emphysema at CT. Sensitivity and negative predictive value of US were 100% (11 of 11 and 15 of 15 patients, respectively), specificity was 94% (15 of 16 patients), and positive predictive value was 92% (11 of 12 patients). Chest radiography had 36% (four of 11 patients) sensitivity, 100% (16 of 16 patients) specificity, a 100% (four of four patients) positive predictive value, and a 70% (16 of 23 patients) negative predictive value. CONCLUSION: In this study, US was more sensitive than supine chest radiography and as sensitive as CT in the detection of traumatic pneumothoraces.

Adolescent↗