Biomedical subjects

C Lu

Publications and source records attributed to C Lu.

At least 37 records · Page 2Linked to original sources

PubMed2004

Human chorionic gonadotrophin and progesterone levels in pregnancies of unknown location.

OBJECTIVE: To evaluate accuracy, user variability and impact of experience on the use of serum hCG and progesterone in women who have a pregnancy of unknown location (PUL's). MATERIALS AND METHODS: This was a retrospective study. Presenting 1932 consecutive women to an Early Pregnancy Unit had a transvaginal scan. The location of the pregnancy could not be found in 189 women (Pregnancy of unknown location, PUL), and so blood was taken to measure serum hCG and progesterone at presentation and subsequently after 48 h, according to the protocol. All women were monitored at regular intervals until the final outcome was known, which was a failing PUL, a viable or failing intra-uterine pregnancy, an ectopic pregnancy or a persisting PUL. The final study group comprised 185 PUL, as four cases of persisting PUL were treated and excluded from the analysis. Five investigators assessed the hormonal data independently. The investigator's experience as defined by the number of years working in obstetrics and gynecology ranged from 2 to 15 years. Each investigator knew the women were clinically stable and that the scan result was consistent with a PUL, i.e. there were no signs of intra- or extra-uterine pregnancy, and there was no hemoperitoneum on TVS. When assessing the PUL's, each investigator was given the hormonal results at time 0 and 48 h for serum hCG and progesterone and asked to classify the PUL's as failing PUL's, immediately viable intra-uterine PUL's and ectopic PUL's. No other clinical information about the women was made available. RESULTS: Complete data 185 women (89%): 102 failing PUL's, 63 immediately viable intra-uterine PUL's and 20 ectopic PUL's (total 185). The most experienced investigator obtained the best accuracy 163/185 (88.1%); not significantly different from those obtained by less experienced investigators (range 85.9-87.6%). Mean correct classification of failing PUL and immediately viable intra-uterine PUL's was 93% (range 89-95%); corresponding value for ectopic PUL's was 42% (range 25-60%). Agreement between observers for classification of failing PUL's and immediately viable intra-uterine PUL's was almost perfect (Cohen's kappa 0.86-0.90), whereas the value for ectopic PUL's group was fair to moderate (Cohen's kappa 0.39-0.67). All 5 investigators misdiagnosed same 35% of ectopic PUL's. CONCLUSIONS: Serum hCG and progesterone levels at defined times can be used to predict the immediate viability of a PUL, but cannot be used reliably to predict its location. Clinical experience does not significantly improve the ability to assess PUL outcome.

Chorionic Gonadotropin↗

PubMed2003

Normal retinal development and retinofugal projections in mice lacking the retina-specific variant of actin-binding LIM domain protein.

The actin-binding LIM domain protein (abLIM) is the mammalian homologue of UNC-115, a protein mediating axon guidance in C. elegans. AbLIM is widely expressed with three isoforms differing from one another by the length of their amino termini. Experiments utilizing dominant-negative mutants in the chick retina suggested a role for abLIM in axon path finding in retinal ganglion cells (RGCs). To investigate which variant is involved in the regulation of mammalian RGC axon guidance, we analyzed their expression profile in mice. The longest variant, abLIM-L, is highly enriched in the ganglion cell layer. AbLIM-L is up-regulated postnatally which temporally overlaps with the period of RGC axon remodeling. In contrast, the abLIM-M and abLIM-S variants are widespread and remain relatively constant through development. By selective gene targeting, we ablated abLIM-L to explore its functional significance in vivo. AbLIM-L mutant mice exhibit no apparent morphological or functional defects in photoreceptors and inner retinal neurons. Retinofugal projections and synaptic maturation also appear normal. These data suggest that abLIM-M is likely the isoform performing the essential function related to axon guidance.

Animals↗

PubMed2003

Preoperative prediction of malignancy of ovarian tumors using least squares support vector machines.

In this work, we develop and evaluate several least squares support vector machine (LS-SVM) classifiers within the Bayesian evidence framework, in order to preoperatively predict malignancy of ovarian tumors. The analysis includes exploratory data analysis, optimal input variable selection, parameter estimation, and performance evaluation via receiver operating characteristic (ROC) curve analysis. LS-SVM models with linear and radial basis function (RBF) kernels, and logistic regression models have been built on 265 training data, and tested on 160 newly collected patient data. The LS-SVM model with nonlinear RBF kernel achieves the best performance, on the test set with the area under the ROC curve (AUC), sensitivity and specificity equal to 0.92, 81.5% and 84.0%, respectively. The best averaged performance over 30 runs of randomized cross-validation is also obtained by an LS-SVM RBF model, with AUC, sensitivity and specificity equal to 0.94, 90.0% and 80.6%, respectively. These results show that the LS-SVM models have the potential to obtain a reliable preoperative distinction between benign and malignant ovarian tumors, and to assist the clinicians for making a correct diagnosis.

Adnexal Diseases↗

PubMed2003

Effects of the farnesyl transferase inhibitor R115777 on normal and leukemic hematopoiesis.

Patients with acute myelogenous leukemia or myelodysplastic syndrome may respond to farnesyl transferase inhibitors (FTIs) with partial or complete response rates noted in about 30% of such patients. FTIs prevent the attachment of a lipid farnesyl moiety to dependent proteins prior to their insertion into the plasma membrane and thereby prevent activity of these prenylation-dependent proteins, but their mechanism of tumor suppression remains unknown. Many patients receiving FTIs do experience myelosuppression. In this work, the in vitro effects of the FTI, R115777 on normal and leukemic hematopoiesis have been examined as have its effects on apoptosis induction and cell cycle profile in both leukemic blasts and normal CD34+ cells. R115777 was inhibitory to normal CD34+ cell proliferation and to leukemic blast cells, but did not affect long-term culture initiating cell frequency nor NOD-SCID reconstituting capacity. No induction of apoptosis or cell cycle changes were noted in AML blasts. These data suggest that myelosuppression with R115777 occurs largely at the intermediate to late progenitor stage of hematopoiesis and that cyclic use might avoid long-term marrow suppression.

Alkyl and Aryl Transferases↗

PubMed2003

The interpretation of 131I scans in the evaluation of thyroid cancer, with an emphasis on false positive findings.

Radioiodine has aided the management of differentiated thyroid cancer for several decades. Most thyroid cancers retain the ability to trap iodine, and radionuclides of iodine can be used both diagnostically and therapeutically. The availability of sensitive diagnostic tests, coupled with the ability to deliver targeted therapy, gives physicians the ability to manage thyroid cancer better than with any other type of cancer. The correct interpretation of radioiodine scans is critical in the appropriate management of patients with thyroid cancer. False positive findings do occur. A radioiodine scan showing abnormal uptake outside the thyroid bed must be studied carefully and alternative reasons for the finding must be considered. The scan should be analysed systematically. Is there residual thyroid? If so, what is the 48 or 72 h neck uptake? Radioiodine uptake in the salivary glands, stomach, gastrointestinal and urinary tracts should be acknowledged as physiological. Diffuse uptake is seen in the liver in most patients with functioning thyroid at the time of their post-therapy scan. When there is uptake of the radioiodine outside these regions, contamination must be considered. A variety of cases illustrating true positive, true negative, and false positive findings is presented in this review, and the causes and consequences of misinterpretation of radioiodine scans are discussed.

Adolescent↗

PubMed2003

TrialDB: A web-based Clinical Study Data Management System.

Clinical Study Data Management Systems (CSDMSs) are a class of software that support centralized management of data generated during the conduct of clinical studies. Commercial CSDMSs include Oracle Clinical, ClinTrial and MetaTrial. Such systems, which are typically deployed at an institutional or organizational level, must accommodate diverse types of data from different clinical domains that is generated by different groups of clinical investigators. Large-scale CSDMSs typically employ a high-end database engine that is usually accessed over an intranet or the Internet using Web-based technologies. CSDMSs in institution-wide use for a variety of clinical domains are best served by entity-attribute-value (EAV) modeling for the clinical data: all the commercial CSDMSs that we are aware of use EAV design. However, de novo development of EAV databases for data management is a challenging task. A large body of generic metadata-driven code must be developed before a basic EAV application can be written. Clearly, the availability of pre-existing software with the requisite functionality would be very valuable. We will discuss the benefits of such software being in open-source form.

Clinical Trials as Topic↗

PubMed2002

Mitogen-activated protein kinase signaling in postgermination arrest of development by abscisic acid.

Abscisic acid (ABA) mediates plant responses to environmental stress, particularly to water status. During germination, the embryo emerges from dormancy as the ABA concentration declines. Exposure to exogenous ABA during germination arrests development rapidly, but reversibly, enabling seedlings to withstand early water stress without loss of viability. Postgermination proteolytic degradation of the essential ABI5 transcription factor is interrupted by perception of an increase in ABA concentration, leading to ABI5 accumulation and reactivation of embryonic genes. Making use of the ABA-hypersensitive hyl1 mutant of Arabidopsis, we show that the ABA signal is transmitted to the transcriptional apparatus through mitogen-activated protein kinase signaling.

Abscisic Acid↗

PubMed2002

Removal of acrylonitrile and styrene mixtures from waste gases by a trickle-bed air biofilter.

The trickle-bed air biofilter (TBAB) performance for treating acrylonitrile (AN) and styrene (SR) mixtures was evaluated under different influent carbon loadings. In the pseudo steady state conditions, the elimination capacities of AN and SR increased but the removal efficiencies decreased with increased influent carbon loading. The removal efficiencies of AN were higher than those of SR, indicating that AN is a preferred substrate in the ANSR waste gas. More than 80% removal efficiencies were achieved with influent carbon loadings of AN and SR below 28 and 22 g/m(3)/h, respectively. The TBAB appears to be efficient for controlling ANSR emission with low to medium carbon loadings, and the effectiveness could be maintained over 175 days of laboratory operation. The elimination capacities of AN and SR for a pure volatile organic compound (VOC) feed were higher than those for a mixed VOC feed and the differences increased with increased influent VOC loading.

Journal Article↗

PubMed2002

Color Doppler and gray-scale ultrasound evaluation of the postpartum uterus.

OBJECTIVES: To evaluate the color Doppler and gray-scale sonographic appearance of the uterus after pregnancy, with special attention to the occurrence of areas of enhanced vascularity and placental remnants. PATIENTS AND METHODS: Cross-sectional observational study involving 385 consecutive women presenting at their first visit after pregnancy. The uterus was evaluated using ultrasound with color Doppler. In the presence of placental remnants, blood was sampled for measurement of beta human chorionic gonadotropin (beta hCG), hemoglobin (Hb) and infectious parameters. If indicated, a dilatation and curettage was performed. RESULTS: In 8.3% of women, areas of enhanced vascularity were detected with color Doppler examination. Most cases (68.9%) were focal areas of one or more vessels. In 2.6% of patients abnormal vascularity extended over a large area of the whole myometrium. In 6.75% of cases, placental remnants were detected. In 46% of these, blood sampling revealed beta hCG levels below 30 mIU/mL; serological infection parameters and Hb concentration were within the normal range. CONCLUSIONS: Areas of enhanced vascularity of the uterus, ranging from a focal vascular pedicle to a larger area of the myometrium, are relatively common after pregnancy. They are predominantly seen in the presence of placental remnants, in the early postpartum period and after instrumental or manual delivery of the placenta. There are no clear risk factors for retained placental tissue, besides the history of blood transfusion in the early postpartum, and perhaps multigravidity. Serology is of little help in the diagnosis of retained gestational products. The knowledge of the ultrasound and color Doppler features of the uterus after pregnancy may prove of practical value for the management of abnormal uterine bleeding in the postpartum period.

Adolescent↗

PubMed2002

Removal of acetone and methylacetate mixtures from waste gases by a trickle-bed air biofilter.

The biofilter process is a relatively new technology that has been proven more cost-effective than traditional technologies for treating low-strength and some high-strength volatile organic compounds (VOCs) from waste gases. Acetone (AT) and methylacetate (MA) mixtures are commonly encountered from the manufacture of artificial rubber or polyurethane resin. This research attempts to employ a trickle-bed air biofilter (TBAB) for treating AT and MA mixtures under different influent carbon loadings. In the pseudo-steady-states, the elimination capacities of AT and MA increased but the removal efficiencies decreased with increased influent carbon loading. The removal efficiencies of MA were higher than those of AT showing that MA is a preferred substrate in the ATMA waste gas and the differences were enhanced at a high carbon loading. Greater than 95% AT removal and nearly complete MA removal were achieved with influent carbon loadings of AT and MA below 20 and 27 g m(-1) h(-1), respectively. The TBAB appears very efficient for treating ATMA emission with low to medium carbon loadings.

Acetates↗

PubMed2002

Modelling the cost-effectiveness of sentinel lymph node mapping and adjuvant interferon treatment for stage II melanoma.

Clinical studies have demonstrated that high dose adjuvant interferon therapy improves disease-free and overall survival among high risk (stage IIb and III) melanoma patients. Sentinel lymph node mapping (SLM) has been shown to accurately detect micrometastasis and may be used to identify higher risk stage II patients, who might benefit most from adjuvant interferon therapy. We modelled the cost-effectiveness of first testing with SLM and then treating with adjuvant interferon (IFN) therapy for stage II melanoma. We used a decision analytical model to compare four strategies for stage II patients after surgical excision of their melanoma: (1) treat all with low dose IFN; (2) test first with SLM and then treat only those with positive micrometastasis with high dose IFN; (3) test first with SLM and treat positives with high dose IFN and negatives with low dose IFN (test and treat appropriately); and (4) surgery only. Treatment, toxicity, follow-up and relapse costs were included over a 5 year time period. The primary outcome was cost per quality-adjusted relapse-free life year saved. Our analysis shows that, compared with the current surgery-only strategy, all three treatment strategies provide incremental benefits. The test and treat appropriately strategy is the most effective, with an incremental improvement of 0.64 quality-adjusted life-years (QALY). The cost-effectiveness of test and treat some with high dose IFN compared with the surgery-only strategy is $18,700/QALY. The test and treat appropriately strategy is also cost-effective compared with test and treat some at $31,100/QALY. In conclusion appropriate dosing of IFN therapy based on the results of SLM is a cost-effective strategy for stage II melanoma patients.

Adjuvants, Immunologic↗

PubMed2002

Fluorescent tracer evaluation of chemical protective clothing during pesticide applications in central Florida citrus groves.

Chemical protective clothing (CPC) is often recommended as a method of exposure mitigation among pesticide applicators. This study evaluated four CPC regimens (cotton work shirts and work pants, cotton/polyester coveralls, and two non-woven garments) during 33 airblast applications of the organophosphorus insecticide ethion in central Florida citrus groves. CPC performance was determined by measurement of fluorescent tracer deposition on skin surfaces beneath garments with a video imaging analysis instrument (VITAE system), and by alpha-cellulose patches placed outside and beneath the garments. Non-woven coveralls allowed significantly greater exposure than did traditional woven garments, primarily because of design factors (e.g., large sleeve and neck openings). The greatest exposure occurred on the forearms beneath the non-woven garments. Fabric penetration was detected for all test garments; 5% to 7% of the ethion measured outside the garments was found beneath the garments. The clothing materials tested were not chemically resistant under these field conditions. Exposurepathways that would probably be undetected by the patch technique were characterized effectively with fluorescent tracers and video imaging analysis. However, the patch technique was more sensitive in detecting fabric penetration. CPC garments have been improved since this study was conducted, but performance testing under field conditions is not widespread. Workers conducting airblast applications would be better protected by closed cab systems or any technology that places an effective barrier between the worker and the pesticide spray.

Aerosols↗

PubMed2001

Telomerase protects developing neurons against DNA damage-induced cell death.

In mitotic cells, telomerase adds repeats of a DNA sequence (TTAGGG) to the ends of chromosomes (telomeres) thereby maintaining their length and preventing cellular senescence. We recently reported that the catalytic subunit of telomerase (TERT) is expressed in neuronal progenitor cells and in early postmitotic neurons in the developing rodent brain. We now report that TERT can protect cultured PC12 cells and embryonic hippocampal neurons against death induced by DNA damage. Overexpression of TERT in PC12 cells increases their resistance to the topoisomerase inhibitors camptothecin and etoposide. Hippocampal neurons in which TERT levels are decreased using antisense technology exhibit increased vulnerability to the DNA-damaging agents. Emerging findings suggest that DNA damage may trigger the death of neurons during brain development and in neurodegenerative disorders. Our data therefore suggest roles for TERT in modulating such cell deaths.

Animals↗

PubMed2001

Circumvention of MHC class II restriction by genetic immunization.

The fate of T cell responses to peptide-based vaccination is subject to constraints by the major histocompatibility complex (MHC), MHC restriction. Using as a model system of T and B cell epitopes from the circumsporozoite protein of Plasmodium falciparum malaria parasite, we show that vaccination by somatic transgene immunization readily primes Balb/c mice (H-2(d)) a strain previously reported to be non-responder to immunization with a synthetic peptide vaccine encompassing these epitopes. Following genetic vaccination Balb/c mice developed a primary T cell response comparable to that of the responder strain C57Bl/6 (H-2(b)). Following booster immunization on day 45 Balb/c mice responded with a typical T cell memory response. Priming induced the formation of specific antibodies, which rose sharply after booster immunization. These findings suggests that genetic immunization can circumvent MHC class II restriction.

Animals↗

PubMed2001

mua-3, a gene required for mechanical tissue integrity in Caenorhabditis elegans, encodes a novel transmembrane protein of epithelial attachment complexes.

Normal locomotion of the nematode Caenorhabditis elegans requires transmission of contractile force through a series of mechanical linkages from the myofibrillar lattice of the body wall muscles, across an intervening extracellular matrix and epithelium (the hypodermis) to the cuticle. Mutations in mua-3 cause a separation of the hypodermis from the cuticle, suggesting this gene is required for maintaining hypodermal-cuticle attachment as the animal grows in size postembryonically. mua-3 encodes a predicted 3,767 amino acid protein with a large extracellular domain, a single transmembrane helix, and a smaller cytoplasmic domain. The extracellular domain contains four distinct protein modules: 5 low density lipoprotein type A, 52 epidermal growth factor, 1 von Willebrand factor A, and 2 sea urchin-enterokinase-agrin modules. MUA-3 localizes to the hypodermal hemidesmosomes and to other sites of mechanically robust transepithelial attachments, including the rectum, vulva, mechanosensory neurons, and excretory duct/pore. In addition, it is shown that MUA-3 colocalizes with cytoplasmic intermediate filaments (IFs) at these sites. Thus, MUA-3 appears to be a protein that links the IF cytoskeleton of nematode epithelia to the cuticle at sites of mechanical stress.

Animals↗

PubMed2001

[Experimental study of pBMP/MPTCP in bone defects therapy].

To develop a new substitute of bone graft, which is composed of porcine bone morphogenetic protein (pBMP) and the magnetic porous tricalcium phosphate (MPTCP), we investigated the effects of pBMP/MPTCP (Group A), autologous red bone marrow/porus tricalcium phosphate (BM/PTCP) (Group B), pBMP/PTCP(Group C) on the repair of bone defects created surgically in rabbits. By gross inspection, roentgenography examination, histological examination, immunohistochemistry test of osteocalcim, quantitive histological measurement of new bone formation and biomechanical test, three kinds of substitutes were proved to be biocompatible. Group A induced more new bone formation than other two groups, and showed a better biomechanical function(P < 0.01). It is believed that pBMP/MPTCP has characteristics of strong osteoinductive capacity, good biocompatibility, excellent filling of bone defects and gradual biodegradation.

Animals↗

PubMed2001

Site-specific mutations of FtsZ--effects on GTPase and in vitro assembly.

BACKGROUND: FtsZ, the major cytoskeletal protein in bacterial cytokinesis, assembles in vitro into protofilaments, which can further associate into sheets, bundles or tubes. We have constructed 16 site-directed mutants of E. coli ftsZ, and tested them for GTP hydrolysis and assembly in vitro, and for their ability to complement the temperature sensitive ftsZ84 mutation in E. coli. RESULTS: The mutants were grouped into three classes. Benign mutants, which mapped mostly to the front and back surface of the protofilament, were able to complement ftsZ84 in vivo and showed normal assembly in vitro. GTP contact mutations had less than 10% of wild type GTPase activity. They could all assemble in vitro, and several of these mutants could complement ftsZ84. A third, and newly discovered, class of mutations mapped to the sides of the protofilaments. These lateral mutants had mostly normal GTPase and assembly in vitro, but none of them complemented ftsZ84. The non-complementing mutants showed greatly reduced expression from the pBS58 vector, suggesting possible dominant negative effects. CONCLUSIONS: Several mutants with greatly reduced GTPase could still complement ftsZ84, suggesting that the high level of GTPase observed in vitro is not essential for in vivo function. All of the lateral mutants failed to complement ftsZ84, which suggests that these surfaces of the protofilaments are important for function in cell division. These lateral surfaces may mediate association of FtsZ protofilaments into pairs or small sheets, although their structure is apparently different from the sheets assembled in DEAE dextran or calcium.

Cell Division↗

PubMed2001

Species comparison in P450 induction: effects of dexamethasone, omeprazole, and rifampin on P450 isoforms 1A and 3A in primary cultured hepatocytes from man, Sprague-Dawley rat, minipig, and beagle dog.

Induction of P450 isoforms 1A (CYP1A) and 3A (CYP3A) by model inducers dexamethasone, omeprazole and rifampin was evaluated in primary cultured hepatocytes from man and laboratory animals. Inducer-specific species-differences were observed. Results with human hepatocytes from six human donors consistently show that both rifampin and dexamethasone were inducers of CYP3A activity (measured as testosterone 6beta-hydroxylase activity), with rifampin being more potent. Conversely, in rat hepatocytes, dexamethasone was a potent CYP3A inducer while rifampin was not an inducer. Rifampin but not dexamethasone induced CYP3A in minipig and beagle dog hepatocytes. Omeprazole was a potent inducer of CYP1A activity (measured as ethoxyresorufin-O-deethylase activity) in human, beagle dog and minipig hepatocytes, and not an inducer in rat hepatocytes. The species-differences observed suggest that human hepatocytes represent the most appropriate preclinical experimental system for the evaluation of P450 induction in human.

Adult↗