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Biomedical subjects

K Wang

Publications and source records attributed to K Wang.

At least 235 records · Page 13Linked to original sources

[Changes in the pulmonary function of factory workers exposure to terephthalic acid].

The pulmonary function was examined in 140 workers exposed to terephthalic acid(TPA) and 70 controls in the same residence area as non-exposure workers. The exposed workers exhibited significant decrease in MVV, PEFR, V75, PEFR/H and V75/H(P < 0.05) in comparison with the controls. The decrease was found to be associated with increased TPA concentration by multiple regression analysis. The results of life table method analysis suggested that there was an exposure level-response relationship between accumulative TAP dust exposure and lower FEV1. According to the results reported here, an exposure limit for TPA dust was proposed to be 4.30 mg/m3.

Adult↗

Caspase cleaved BID targets mitochondria and is required for cytochrome c release, while BCL-XL prevents this release but not tumor necrosis factor-R1/Fas death.

"BH3 domain only" members of the BCL-2 family including the pro-apoptotic molecule BID represent candidates to connect with proximal signal transduction. Tumor necrosis factor alpha (TNFalpha) treatment induced a caspase-mediated cleavage of cytosolic, inactive p22 BID at internal Asp sites to yield a major p15 and minor p13 and p11 fragments. p15 BID translocates to mitochondria as an integral membrane protein. p15 BID within cytosol targeted normal mitochondria and released cytochrome c. Immunodepletion of p15 BID prevents cytochrome c release. In vivo, anti-Fas Ab results in the appearance of p15 BID in the cytosol of hepatocytes which translocates to mitochondria where it releases cytochrome c. Addition of activated caspase-8 to normal cytosol generates p15 BID which is also required in this system for release of cytochrome c. In the presence of BCL-XL/BCL-2, TNFalpha still induced BID cleavage and p15 BID became an integral mitochondrial membrane protein. However, BCL-XL/BCL-2 prevented the release of cytochrome c, yet other aspects of mitochondrial dysfunction still transpired and cells died nonetheless. Thus, while BID appears to be required for the release of cytochrome c in the TNF death pathway, the release of cytochrome c may not be required for cell death.

Amino Acid Sequence↗

Predictive medicine: computational techniques in therapeutic decision-making.

The current paradigm for surgery planning for the treatment of cardiovascular disease relies exclusively on diagnostic imaging data to define the present state of the patient, empirical data to evaluate the efficacy of prior treatments for similar patients, and the judgement of the surgeon to decide on a preferred treatment. The individual variability and inherent complexity of human biological systems is such that diagnostic imaging and empirical data alone are insufficient to predict the outcome of a given treatment for an individual patient. We propose a new paradigm of predictive medicine in which the physician utilizes computational tools to construct and evaluate a combined anatomic/physiologic model to predict the outcome of alternative treatment plans for an individual patient. The predictive medicine paradigm is implemented in a software system developed for Simulation-Based Medical Planning. This system provides an integrated set of tools to test hypotheses regarding the effect of alternate treatment plans on blood flow in the cardiovascular system of an individual patient. It combines an Internet-based user interface developed using Java and VRML, image segmentation, geometric solid modeling, automatic finite element mesh generation, computational fluid dynamics, and scientific visualization techniques. This system is applied to the evaluation of alternate, patient-specific treatments for a case of lower extremity occlusive cardiovascular disease.

Arterial Occlusive Diseases↗

Functional dissection of nebulette demonstrates actin binding of nebulin-like repeats and Z-line targeting of SH3 and linker domains.

Nebulette, a 107 kDa protein associated with the I-Z-I complex of cardiac myofibrils, may play an important role in the assembly of the Z-line. Determination of the complete primary structure of 1011 residue human fetal nebulette reveals a four-domain layout similar to skeletal muscle nebulin: a short N-terminal domain, followed by 22 nebulin-like repeats that are linked to a C-terminal Src homology 3 (SH3) domain via a short linker domain. To elucidate the mechanisms of assembly for nebulette in the Z-line, the complete coding sequence or fusions of nebulette domains with green fluorescent protein (GFP) were expressed in cardiomyocytes and fibroblasts. The complete protein localized to Z-lines in cardiac cells and to dense bodies in nonmuscle cells. The GFP-repeat domain forms bundles that are associated with actin filaments in both cell types and disrupts the microfilament network. In contrast, the GFP-repeat plus linker shows limited interaction with dense bodies in nonmuscle cells and the Z-lines of cardiomyocytes. Interestingly, the tagged linker or SH3 is diffusely distributed in nonmuscle cells, but localizes to the Z-lines in cardiomyocytes. Supporting the cellular localization work, recombinant nebulette fragments bind to actin, tropomyosin, and alpha-actinin in in vitro binding assays. These results suggest the repeat domain contains actin binding functions and that the linker domain may target this interaction to Z-lines and dense bodies. Our data also indicate that the linker and SH3 domains can distinguish between dense bodies and Z-lines, suggesting that the ligands for their interactions are specific to these muscular substructures.

Actins↗

A Bayesian approach to replication of linkage findings.

A novel Bayesian approach to replication studies, allowing for locus heterogeneity, is introduced. Compared with currently used approaches to replication, it offers a natural way to accumulate evidence across independently collected data sets and yields more interpretable results. Using for replicates (one as initial study and the other three as replication studies) from Problem 2 of the Genetic Analysis Workshop 11 data, we show the performance of this method. All four disease susceptibility loci (D1G009, D1G024, D3G045, D5G035) are identified and accurately mapped, with no false positive signals.

Bayes Theorem↗

Perioperative cimetidine application modulates natural killer cells in patients with colorectal cancer: a randomized clinical study.

Thirty-eight colorectal cancer patients were randomly assigned to treatment group, which took cimetidine in the perioperative period, and control group to which no drug was given. Twenty healthy volunteers served as normal controls. NK cells were measured by immunocytochemical technique. The results showed that NK percentages before treatment in both groups of patients were significantly lower than those in normal controls (P < 0.05). NK cell percentages at admission, before operation, on the 2nd and the 10th postoperative days were 14.84 +/- 4.41, 15.74 +/- 3.75, 17.21 +/- 3.69, 21.05 +/- 4.54, respectively, for the treatment group, and 15.00 +/- 2.77, 13.05 +/- 2.46, 14.21 +/- 2.19, 15.58 +/- 1.68, respectively, for control group. The difference was statistically significant (P < 0.01), suggesting that the perioperative administration of cimetidine could help restore NK cells in colorectal cancer patients.

Cimetidine↗

The transport kinetics of lanthanide species in a single erythrocyte probed by confocal laser scanning microscopy.

A novel method has been developed to visualize and follow the temporal course of lanthanide transport across the membrane into a single living erythrocyte. By means of confocal scanning microscopy and the optical section technique, the entry of lanthanide ions was followed by the fluorescence quenching of fluorescein isothiocyanate (FITC)-labeled membrane and cytosol. From the difference of the quenching kinetics of the whole section and the central area, the time for diffusion through the membrane and the diffusion in the extracellular and intracellular media can be deduced. To clarify the mechanism of lanthanide-induced fluorescence quenching of FITC-labeled erythrocytes and to ensure that this reaction can be used in this method, the reaction was investigated by steady-state fluorescence techniques. The results showed that the lanthanides strongly quenched the florescence emitted by FITC covalently bound to membrane proteins and cytosolic proteins. The static quenching mechanism is responsible for the fluorescence quenching of FITC-labeled proteins by Ln species. The quenching mechanism is discussed on the basis of complex formation. The dependence of fluorescence quenching on both ion size and the total orbital angular momentum L supports the complexation mechanism. The transport time across the membrane is strikingly correlated with Ln species and extracellular concentration. For a given concentration, the transport time of [Ln(cit)2]3- is much shorter than that of Ln3+, since they enter the cells via the anion channel. This is supported by the inhibition effect of 4,4'-diisothiocyanato-2,2'-stilbenendisulfonate on the transport of [Ln(cit)2]3-. On the other hand, the transport of free Ln3+ might be attributed to the enhanced permeability of erythrocytes owing to Ln3+ binding. These findings strongly demonstrate the existence of the non-internalization mechanism of Ln species uptake by erythrocytes.

Animals↗

Fetal esophageal transplantation in rats: a treatment option for long-gap esophageal atresia.

PURPOSE: The aim of this study is to determine if fetal esophageal transplantation can create viable esophageal tissue that may be used for treating long gap esophageal atresia. METHODS: Fetuses of gestational age 19 to 20 days were obtained by hysterotomy of pregnant 15-week-old Lewis rats. A 10-mm long segment of esophagus was obtained from each fetus by thoracolaparotomy and transplanted by wrapping it in a pouch created in the distal omentum of a 5-week-old Lewis rat (syngeneic transplantation: n = 15). Transplanted fetal esophageal grafts were harvested 10 days post-transplantation and fixed in 10% formalin and embedded in paraffin. H&E was used for histological examination, and PGP 9.5 (a neuronal antibody) was used for immunohistochemistry. Esophageal segments obtained from 10-day-old Lewis rats were used as controls. RESULTS: Thirteen of 15 (87%) grafts were transplanted successfully. The successfully transplanted graft could be mobilized to the thoracic cavity without tension or compromising of vascularity, because of the long omental pedicle. H&E staining and PGP 9.5 immunohistochemistry showed normal esophageal structure with intact esophageal nervous system, comparable with control specimens. CONCLUSIONS: Fetal esophageal transplantation produces viable esophageal tissue that may find application for treating long gap esophageal atresia providing rejection can be controlled adequately.

Animals↗

Complications after sigmoidocolocystoplasty: review of 100 cases at one institution.

BACKGROUND/PURPOSE: The aim of this study was to review complications after sigmoidocolocystoplasty (SCP) performed at a single institution from 1984 to 1997. METHODS: The medical records of 100 patients who underwent SCP were reviewed retrospectively. RESULTS: Mean age at SCP was 10.8 years. Urinary control was improved in 75 cases and unchanged in 25. Post-SCP complications included death, abdominal wound infection or dehiscence, adhesive bowel obstruction, vesical calculi, vesicocolonic anastomosis stenosis, metabolic acidosis, and transient renal hypertension. Fifty-one patients underwent ureteric re-implantation (URI) at the time of, or before, SCP, and 7 had recurrence of VUR post-URI (spontaneous regression in 6); 3 patients had new onset of contralateral VUR post-URI (spontaneous regression in 2). Transient pleural effusion was seen after reinsertion of ventriculo-pleural shunts to ventriculo-thoracic in 12 cases, but there was no incidence of infection. Squamous metaplasia of the bladder mucosa was identified in 5 patients on routine mucosal biopsy results but resolved in all cases after regular bladder irrigation was commenced. Preoperative constipation or fecal incontinence was better managed after sigmoidectomy in approximately one third of cases (38%). CONCLUSIONS: SCP with or without URI can improve the quality of life of patients with neurogenic or small-capacity bladder, but it can be associated with long-term complications. Regular bladder irrigation is recommended to maintain bladder mucosa integrity.

Adolescent↗

Existence and global attractivity of positive periodic solutions of periodic n-species Lotka-Volterra competition systems with several deviating arguments.

In this paper, we study the existence and global attractivity of positive periodic solutions of periodic n-species Lotka-Volterra competition systems. By using the method of coincidence degree and Lyapunov functional, a set of easily verifiable sufficient conditions are derived for the existence of at least one strictly positive (componentwise) periodic solution of periodic n-species Lotka-Volterra competition systems with several deviating arguments and the existence of a unique globally asymptotically stable periodic solution with strictly positive components of periodic n-species Lotka-Volterra competition system with several delays. Some new results are obtained. As an application, we also examine some special cases of the system we considered, which have been studied extensively in the literature. Some known results are improved and generalized.

Animals↗

Knowledge, attitude and practice survey on immunization service delivery in Guangxi and Gansu, China.

BACKGROUND: a knowledge, attitude and practice (KAP) survey on immunization service delivery among providers and parents was conducted in Guangxi and Gansu, Provinces in China. PURPOSE: provide baseline information for a health education program. METHODS: KAP surveys were conducted in 12 randomly selected counties from high and low quality immunization service delivery area in Guangxi and Gansu Provinces. Caretakers of 2520 children born in 1995 and 637 immunization providers were selected by probability proportional to size sampling. RESULTS: the level of immunization knowledge among parents was positively associated with attitude and practices of immunization. Immunization coverage was 89.3% in the high and 63.8% in the low service areas. Low coverage was associated (p < 0.01) with the number of immunization service sessions per year, fee for immunization services and health insurance schemes for immunization services. CONCLUSIONS: immunization coverage can be improved by ensuring sufficient immunization service sessions per year, reducing the cost of immunization services and increasing the participation in health insurance schemes for immunization services.

China↗

Chain-length determination mechanism of isoprenyl diphosphate synthases and implications for molecular evolution.

In the synthesis of isoprenoids, isoprenyl diphosphate synthases catalyze the consecutive condensation of isopentenyl diphosphate with allylic diphosphates to produce a variety of prenyl diphosphates with well-defined chain lengths. Site-directed mutagenesis in conjunction with X-ray crystallographic studies have identified specific amino acid residues responsible for chain-length determination. Simple combinations of these residues within a characteristic motif are not only sufficient to confer product specificities to all isoprenyl diphosphate synthases but represent structural features that reflect the enzyme family's evolutionary course.

Alkyl and Aryl Transferases↗

A mini binary vector series for plant transformation.

A streamlined mini binary vector was constructed that is less than 1/2 the size of the pBIN19 backbone (3.5 kb). This was accomplished by eliminating over 5 kb of non-T-DNA sequences from the pBIN19 vector. The vector still retains all the essential elements required for a binary vector. These include a RK2 replication origin, the nptIII gene conferring kanamycin resistance in bacteria, both the right and left T-DNA borders, and a multiple cloning site (MCS) in between the T-DNA borders to facilitate cloning. Due to the reduced size, more unique restriction sites are available in the MCS, thus allowing more versatile cloning. Since the traF region was not included, it is not possible to mobilize this binary vector into Agrobacterium by triparental mating. This problem can be easily resolved by direct transformation. The mini binary vector has been demonstrated to successfully transform Arabidopsis plants. Based on this mini binary vector, a series of binary vectors were constructed for plant transformation.

Agrobacterium tumefaciens↗

Artifact detection in the PO2 and PCO2 time series monitoring data from preterm infants.

BACKGROUND: Artifacts in clinical intensive care monitoring lead to false alarms and complicate later data analysis. Artifacts must be identified and processed to obtain clear information. In this paper, we present a method for detecting artifacts in PCO2 and PO2 physiological monitoring data from preterm infants. PATIENTS AND DATA: Monitored PO2 and PCO2 data (1 value per minute) from 10 preterm infants requiring intensive care were used for these experiments. A domain expert was used to review and confirm the detected artifact. METHODS: Three different classes of artifact detectors (i.e., limit-based detectors, deviation-based detectors, and correlation-based detectors) were designed and used. Each identified artifacts from a different perspective. Integrating the individual detectors, we developed a parametric artifact detector, called ArtiDetect. By an exhaustive search in the space of ArtiDetect instances, we successfully discovered an optimal instance, denoted as ArtiDetector. RESULTS: The sensitivity and specificity of ArtiDetector for PO2 artifacts is 95.0% (SD = 4.5%) and 94.2% (SD = 4.5%), respectively. The sensitivity and specificity of ArtiDetector for PCO2 artifacts is 97.2% (SD = 3.6%) and 94.1% (SD = 4.2%), respectively. Moreover, 97.0% and 98.0% of the artifactual episodes in the PO2 and PCO2 channels respectively are confirmed by ArtiDetector. CONCLUSIONS: Based on the judgement of the expert, our detection method detects most PO2 and PCO2 artifacts and artifactual episodes in the 10 randomly selected preterm infants. The method makes little use of domain knowledge, and can be easily extended to detect artifacts in other monitoring channels.

Artifacts↗

Local polynomial estimate of surface Laplacian.

This paper describes a method for estimating the surface Laplacian of brain potentials. The method consists of two steps: local surface approximation by its tangent plane and local polynomial fitting. Compared to previous methods for estimating surface Laplacian, this method has some new features. First, it can estimate the surface Laplacian at any point of the scalp, including the locations of the peripheral electrodes. Secondly, it estimates the brain potential and the surface Laplacian at any point simultaneously. This reduces the risk of error propagation, which occurs when the brain potential is interpolated first and the surface Laplacian is then computed based on the interpolated brain potential. Finally, the method automatically adapts to noisy data by using more or less measurements at neighboring electrodes based on estimated noise level. Simulations suggest that this method is effective. Application to event-related potentials are also presented.

Action Potentials↗

Glutathione S-transferases in wild-type and doxorubicin-resistant MCF-7 human breast cancer cell lines.

1. Overexpression of glutathione S-transferases (GST) in breast cancer cells is hypothesized to be a component of the multifactorial doxorubicin-resistant phenotype. 2. We have characterized the expression of GST enzymes at the catalytic activity, protein and mRNA levels in wild-type MCF-7 (MCF-7/WT) human breast cancer cells and a line selected for resistance to doxorubicin (MCF-7/ADR), with the goal of modulating GST activity to overcome resistance. 3. The MCF-7/ADR cells were 30-65-fold more resistant to doxorubicin than the MCF-7/WT cells. 4. Total cytosolic GST catalytic activity was elevated 23-fold in the MCF-7/ADR cells as compared with the MCF-7/WT cells, and the MCF-7/ADR cells also showed 3-fold increases in catalytic activity toward GST mu and alpha class-selective substrates. Neither cell line showed detectable catalytic activity with a GST mu class-selective substrate. 5. MCF-7/ADR cells showed pronounced overexpression of GST mu protein and GST P1 mRNA in comparison with the wild-type cell line. Neither cell line displayed detectable GST alpha or mu at the protein level. 6. A glutathione analogue that functions as a selective GST alpha inhibitor was more potent at inhibiting total cytosolic GST catalytic activity in the MCF-7/ADR cell line than GST alpha and mu class-selective inhibitory glutathione analogues and the non-selective GST inhibitor ethacrynic acid. 7. The multidrug resistance-associated protein, which can function as a glutathione-conjugate transporter, appeared weakly overexpressed in the MCF-7/ADR cells in comparison with the MCF-7/WT cells.

ATP-Binding Cassette Transporters↗

Somatic PKD2 mutations in individual kidney and liver cysts support a "two-hit" model of cystogenesis in type 2 autosomal dominant polycystic kidney disease.

An intriguing feature of autosomal dominant polycystic kidney disease (ADPKD) is the focal and sporadic formation of renal and extrarenal cysts. Recent documentation of somatic PKD1 mutations in cystic epithelia of patients with germ-line PKD1 mutations suggests a "two-hit" model for cystogenesis in type 1 ADPKD. This study tests whether the same mechanism for cystogenesis might also occur in type 2 ADPKD. Genomic DNA was obtained from 54 kidney and liver cysts from three patients with known germ-line PKD2 mutations, using procedures that minimize contamination of cells from noncystic tissue. Using intragenic and microsatellite markers, these cyst samples were screened for loss of heterozygosity. The same samples were also screened for somatic mutations in five of the 15 exons in PKD2 by single-stranded conformational polymorphism analysis. Loss of heterozygosity was found in five cysts, and unique intragenic mutations were found in seven other cysts. In 11 of these 12 cysts, it was also determined that the somatic mutation occurred nonrandomly in the copy of PKD2 inherited from the unaffected parent. These findings support the "two-hit" model as a unified mechanism for cystogenesis in ADPKD. In this model, the requirement of a somatic mutation as the rate-limiting step for individual cyst formation has potential therapeutic implications.

Base Sequence↗