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Biomedical subjects

B Zheng

Publications and source records attributed to B Zheng.

At least 91 records · Page 5Linked to original sources
PubMed1999

Reduction in atherosclerotic lesion size in pigs by alphaVbeta3 inhibitors is associated with inhibition of insulin-like growth factor-I-mediated signaling.

Insulin-like growth factor-I (IGF-I) is a potent stimulant of smooth muscle cell (SMC) migration and proliferation and has been implicated in the development of experimental atherosclerotic lesions. Because optimal stimulation of SMC in vitro by IGF-I requires ligand occupancy of alphaVbeta3, these studies were conducted to determine whether alphaVbeta3 antagonists would result in a change in lesion size and whether they could alter IGF-I-mediated actions. Clamps were placed on the carotid and femoral arteries of normal pigs that had been fed a high-cholesterol diet for 4 weeks. alphaVbeta3 inhibitors (SC-69000, SC-65811) (10(-6) mol/L) or saline were infused for 2 weeks into the peristenotic area. Lesion area, the number of SMC layers, and proliferating cell nuclear antigen positive cells were determined in a 1.2-mm segment of each artery. Lesion areas were 304 788+/-113 453 micron(2) (saline), compared with 149 799+/-35 456 micron(2) (SC-69000) (P<0.01). Lesion areas in arteries treated with SC-64258, a compound that does not bind to alphaVbeta3, were 310 284+/-160 467 micron(2), P=not significant. In a second experiment, lesion areas were 110 391+/-17 347 micron(2) (saline) and 59 533+/-17 568 micron(2) (SC-65811, P<0.001). Neointimal SMC layers were reduced by SC-65811 from 7.4+/-4.5 to 3.0+/-0.4 (P<0.001). To determine whether IGF-I action was altered, IGF binding protein-5, which is synthesized in response to IGF-I, was analyzed. IGF-I binding protein-5 mRNA abundance was reduced by 67+/-8% in the 6 lesions treated with SRL-69000 compared with saline controls (P<0.001). We conclude that alphaVbeta3 antagonists block the development of lesions in pigs that have been induced by a high-cholesterol diet and stenosis, and the effect of these compounds is associated with their ability to inhibit IGF-I-mediated signaling.

Aniline Compounds↗
PubMed1999

The mPer2 gene encodes a functional component of the mammalian circadian clock.

Circadian rhythms are driven by endogenous biological clocks that regulate many biochemical, physiological and behavioural processes in a wide range of life forms. In mammals, there is a master circadian clock in the suprachiasmatic nucleus of the anterior hypothalamus. Three putative mammalian homologues (mPer1, mPer2 and mPer3) of the Drosophila circadian clock gene period (per) have been identified. The mPer genes share a conserved PAS domain (a dimerization domain found in Per, Arnt and Sim) and show a circadian expression pattern in the suprachiasmatic nucleus. To assess the in vivo function of mPer2, we generated and characterized a deletion mutation in the PAS domain of the mouse mPer2 gene. Here we show that mice homozygous for this mutation display a shorter circadian period followed by a loss of circadian rhythmicity in constant darkness. The mutation also diminishes the oscillating expression of both mPer1 and mPer2 in the suprachiasmatic nucleus, indicating that mPer2 may regulate mPer1 in vivo. These data provide evidence that an mPer gene functions in the circadian clock, and define mPer2 as a component of the mammalian circadian oscillator.

Animals↗
PubMed1999

A system for rapid generation of coat color-tagged knockouts and defined chromosomal rearrangements in mice.

Gene targeting in mouse embryonic stem (ES) cells can be used to generate single gene mutations or defined multi-megabase chromosomal rearrangements when applied with the Cre- loxP recombination system. While single knockouts are essential for uncovering functions of cloned genes, chromosomal rearrangements are great genetic tools for mapping, mutagenesis screens and functional genomics. The conventional approach to generate mice with targeted alterations of the genome requires extensive molecular cloning to build targeting vectors and DNA-based genotyping for stock maintenance. Here we describe the design and construction of a two-library system to facilitate high throughput gene targeting and chromo-somal engineering. The unique feature of these libraries is that once a clone is isolated, it is essentially ready to be used for insertional targeting in ES cells. The two libraries each bear a complementary set of genetic markers tailored so that the vector can be used for Cre- loxP -based chromosome engineering as well as single knockouts. By incorporating mouse coat color markers into the vectors, we illustrate a widely applicable method for stock maintenance of ES cell-derived mice with single gene knockouts or more extensive chromosomal rearrangements.

Agouti Signaling Protein↗
PubMed1999

p63 is a p53 homologue required for limb and epidermal morphogenesis.

The p53 tumour suppressor is a transcription factor that regulates the progression of the cell through its cycle and cell death (apoptosis) in response to environmental stimuli such as DNA damage and hypoxia. Even though p53 modulates these critical cellular processes, mice that lack p53 are developmentally normal, suggesting that p53-related proteins might compensate for the functions of p53 during embryogenesis. Two p53 homologues, p63 and p73, are known and here we describe the function of p63 in vivo. Mice lacking p63 are born alive but have striking developmental defects. Their limbs are absent or truncated, defects that are caused by a failure of the apical ectodermal ridge to differentiate. The skin of p63-deficient mice does not progress past an early developmental stage: it lacks stratification and does not express differentiation markers. Structures dependent upon epidermal-mesenchymal interactions during embryonic development, such as hair follicles, teeth and mammary glands, are absent in p63-deficient mice. Thus, in contrast to p53, p63 is essential for several aspects of ectodermal differentiation during embryogenesis.

Animals↗
PubMed1999

Health impacts of domestic coal use in China.

Domestic coal combustion has had profound adverse effects on the health of millions of people worldwide. In China alone several hundred million people commonly burn raw coal in unvented stoves that permeate their homes with high levels of toxic metals and organic compounds. At least 3,000 people in Guizhou Province in southwest China are suffering from severe arsenic poisoning. The primary source of the arsenic appears to be consumption of chili peppers dried over fires fueled with high-arsenic coal. Coal samples in the region were found to contain up to 35,000 ppm arsenic. Chili peppers dried over high-arsenic coal fires adsorb 500 ppm arsenic on average. More than 10 million people in Guizhou Province and surrounding areas suffer from dental and skeletal fluorosis. The excess fluorine is caused by eating corn dried over burning briquettes made from high-fluorine coals and high-fluorine clay binders. Polycyclic aromatic hydrocarbons formed during coal combustion are believed to cause or contribute to the high incidence of esophageal and lung cancers in parts of China. Domestic coal combustion also has caused selenium poisoning and possibly mercury poisoning. Better knowledge of coal quality parameters may help to reduce some of these health problems. For example, information on concentrations and distributions of potentially toxic elements in coal may help delineate areas of a coal deposit to be avoided. Information on the modes of occurrence of these elements and the textural relations of the minerals and macerals in coal may help predict the behavior of the potentially toxic components during coal combustion.

Air Pollution, Indoor↗
PubMed1999

U1 snRNA is cleaved by RNase III and processed through an Sm site-dependent pathway.

Core snRNP proteins bind snRNA through the conserved Sm site, PuA(U)n>/=3GPu. While yeast U1 snRNA has three matches to the Sm consensus, the U1 3'-terminal Sm site was found to be both necessary and sufficient for U1 function. Mutation of this site inhibited pre-mRNA splicing, blocked cell division and resulted in the accumulation of two 3'-extended forms of the U1 snRNA. Cells which harbor the Sm site mutation lack mature U1 RNA (U1alpha) but have a minor polyadenylated species, U1gamma, and a prominent, non-polyadenylated species, U1beta. Metabolic depletion of the essential Sm core protein, Smd1p, also resulted in the increased accumulation of U1beta and U1gamma. In vitro, synthetic U1 precursors were cleaved by Rnt1p (RNase III) very near the U1beta 3'-end observed in vivo. We propose that U1beta is an Rnt1p-cleaved intermediate and that U1 maturation to the U1alpha form occurs through an Sm-sensitive step. Interestingly, both U1alpha and a second, much longer RNA, U1straightepsilon, were produced in an rnt1 mutant strain. These results suggest that yeast U1 snRNA processing may progress through Rnt1p-dependent and Rnt1p-independent pathways, both of which require a fun-ctional Sm site for final snRNA maturation.

Autoantigens↗
PubMed1999

The construction of Schistosoma japonicum vaccine BCG-Sj26GST and its identification.

The expression of foreign gene, Schistosoma Japonicum 26 ku antigen (Sj26GST), in Bacillus Calmette-Guerin (BCG), Mycobacterium (M. smegmatis) and Escherichia coli (E. coli) were studied. The cDNA fragment encoding Sj26GST was amplified by PCR using plasmid pGEX, which could express Sj26GST in E. coli as template. The Sj26GST cDNA was cloned into the down-stream of human M. tuberculosis heat shock protein (hsp) 70 promoter with correct reading frame, and then the DNA fragment containing hsp70 promoter and Sj26GST gene were subcloned together into E. coli-Mycobacteria shuttle plasmid pBCG-2000 to construct the expression shuttle plasmid pBCG-Sj26. The recombinant BCG and M. smegmatis mc(2)155, which were electroplated with pBCG-Sj26, could express Sj26GST and the recombinant Schistosoma Japonicum vaccine BCG-Sj26GST was made. The recombinant Sj26GST (rSj26GST) were soluble and could be observed on SDS-PAGE at molecular weight of 26 ku. The content of rSj26GST accounted for 15% and 10% of total bacterial protein in BCG and M. smegmatis respectively. The results of Western blot showed the combination of rSj26GST with antibody of GST.

Animals↗
PubMed1999

Feature selection for computerized mass detection in digitized mammograms by using a genetic algorithm.

RATIONALE AND OBJECTIVES: To investigate optimization of feature selection for computerized mass detection in digitized mammograms, and to compare the effectiveness of a genetic algorithm (GA) in such optimization with that of an "exhaustive" search of all feature permutations. MATERIALS AND METHODS: A Bayesian belief network (BBN) was used to classify positive and negative regions for masses depicted in digitized mammograms; 20 features were computed for each of 592 positive and 3,790 negative regions in two databases. Conditional probabilities for the BBN were computed by using a "training" database of 288 positive and 2,204 negative regions. Performance was measured by the area under the receiver operating characteristic curve (A) by using the remainder database (304 positive and 1,586 negative regions). The optimal set was first found by using an "exhaustive" (complete permutation) searching method. A GA-based search for the optimal set then was applied, and the results of the two approaches were compared. RESULTS: As the number of features in the classifier increased, the A value increased until it reached a maximum performance for 11 features of 0.876 +/- 0.008. The A value then decreased monotonically as the number of features increased from 11 to 20. Using 100 random chromosomes (seeds) in the first generation, the GA identified the same optimal set of features but reduced the total computation time by a factor of 65. CONCLUSION: A GA-based search might be an efficient and effective approach to selecting an optimal feature set.

Algorithms↗
PubMed1999

Computer-assisted diagnosis of breast cancer using a data-driven Bayesian belief network.

This study investigates a simple Bayesian belief network for the diagnosis of breast cancer, and specifically addresses the question of whether integrating image and non-image based features into a single network can yield better performance than hybrid combinations of independent networks. From a dataset of 419 cases, including 92 malignancies, 13 features relating to mammographic findings, physical examinations and patients' clinical histories, were extracted to build three Bayesian belief networks. The scenarios tested included a network incorporating all features and two hybrids which combined the outputs of sub-networks corresponding to the image or non-image features. Average areas (Az) under the corresponding ROC curves were used as measures of performance. The network incorporating only image based features performed better (Az =0.81) than that using nonimage features (Az = 0.71). Both hybrid classifiers yielded better performance (Az =0.85 for averaging and Az = 0.87 for logistic regression), but neither hybrid was as accurate as the network incorporating all features (Az = 0.89). This preliminary study suggests that, like human observers who concurrently consider different types of information, a single classifier that simultaneously evaluates both image and non-image information can achieve better diagnostic performance than the hybrid combinations considered here.

Adult↗
PubMed1999

Engineering a mouse balancer chromosome.

Balancer chromosomes are genetic reagents that are used in Drosophila melanogaster for stock maintenance and mutagenesis screens. Despite their utility, balancer chromosomes are rarely used in mice because they are difficult to generate using conventional methods. Here we describe the engineering of a mouse balancer chromosome with the Cre-loxP recombination system. The chromosome features a 24-centiMorgan (cM) inversion between Trp53 (also known as p53) and Wnt3 on mouse chromosome 11 that is recessive lethal and dominantly marked with a K14-Agouti transgene. When allelic to a wild-type chromosome, the inversion suppresses crossing over in the inversion interval, accompanied by elevated recombination in the flanking regions. The inversion functions as a balancer chromosome because it can be used to maintain a lethal mutation in the inversion interval as a self-sustaining trans-heterozygous stock. This strategy can be used to generate similar genetic reagents throughout the mouse genome. Engineering of visibly marked inversions and deficiencies is an important step toward functional analyses of the mouse genome and will facilitate large-scale mutagenesis programs.

Animals↗
PubMed1999

Mouse ENU mutagenesis.

The progress of human genome sequencing is driving genetic approaches to define gene function. Strategies such as gene traps and chemical mutagenesis will soon generate a large mutant mouse resource. Point mutations induced by N -ethyl- N -nitrosourea (ENU) provide a unique mutant resource because they: (i) reflect the consequences of single gene change independent of position effects; (ii) provide a fine-structure dissection of protein function; (iii) display a range of mutant effects from complete or partial loss of function to exaggerated function; and (iv) discover gene functions in an unbiased manner. Phenotype-driven ENU screens in the mouse are emphasizing relevance to human clinical disease by targeting cardiology, physiology, neurology, immunity, hematopoiesis and mammalian development. Such approaches are extremely powerful in understanding complex human diseases and traits: the base-pair changes may accurately model base changes found in human diseases, and subtle mutant alleles in a standard genetic background provide the ability to analyze the consequences of compound genotypes. Ongoing mouse ENU mutagenesis experiments are generating a treasure trove of new mutations to allow an in-depth study of a single gene, a chromosomal region or a biological system.

Animals↗
PubMed1999

Computerized localization of breast lesions from two views. An experimental comparison of two methods.

RATIONALE AND OBJECTIVES: The authors compared two computerized methods, the arc and cartesian straight-line, for the localization of breast lesions in two mammographic views. METHODS: A total of 571 craniocaudal and 571 mediolateral oblique matched mammographic image pairs (or 1142 individual images) depicting 290 pathology-verified masses on both views were selected from our image database. Using a previously developed computer-aided detection scheme, all 290 masses and 3992 suspicious but negative regions were identified. After pairing all identified regions from both views, all masses (true-positive-true-positive matched pairs) and a total of 10330 false-positive pairs (including false-positive-false-positive, true-positive-false-positive, and false-positive-true positive pairs) were assessed as to their position in relation to the nipple using both the arc and the cartesian straight-line methods. Receiver operating characteristic methodology was used to evaluate the performance levels for each method in determining, based solely on location, whether a pair of suspicious regions represented a true mass or a false-positive combination. RESULTS: The areas under the receiver operating characteristic curves (Az) were 0.79 and 0.78 for the arc and cartesian straight-line methods, respectively. The difference between the two techniques (as measured by Az) was not statistically significant (P > 0.99). CONCLUSIONS: These preliminary results demonstrated that the two methods are comparable in identifying true masses from triangulated observations on two views. However, the arc method is somewhat favorable because only the nipple location is required for localization.

Biopsy↗
PubMed1999

[Diagnosis and analysis of cyclodialysis by ultrasound biomicroscopy].

OBJECTIVE: To determine the morphologic changes and their clinical significance of cyclodialysis. METHODS: 173 eyes of 173 patients with cyclodialysis were examined by ultrasound biomicroscopy (UBM) for the morphologic changes, and the measurements of relative parameters were analyzed statistically. RESULTS: The cyclodialysis in all the cases was 360 degree. The characteristic manifestations of cyclodialysis found by UBM were as follows: no echoes between sclera and ciliary body, anterior displacement and rotation of ciliary process and displacement of pars plana toward the centre of eyeball. Superciliary effusion could be observed in some cases. In some patients, the ciliary body may be completely disintegrated from the scleral spur, but the disintegration may be quadrantal instead of 360 degree, resulting in a fistula between anterior chamber and superciliary cavity. The anterior chamber depth of the affected eye (2,115 +/- 589) microm was markedly shallower than that of the normal eye (2,736 +/- 441) microm (t = 4.49, P < 0.001). The shallowing of anterior chamber was caused by the anterior displacement and rotation of ciliary processes and the resulting anterior bulging of the iris root. CONCLUSIONS: UBM can be used to make a correct diagnosis of cyclodialysis irrespective of optic media condition, and can provide evidences for treatment.

Adolescent↗
PubMed1999

[Histopathology studies on 8,673 cases of ocular adnexal hyperplastic lesions and tumors].

OBJECTIVE: To study the histopathologic classification of ocular adnexal hyperplastic lesions and tumors according to the histogenesis and the anatomic sites. METHOD: To analyze retrospectively the pathologic specimens of 8,673 cases of ocular adnexal hyperplastic lesions and tumors between 1961 - 1997. RESULTS: There were 7,265 benign cases (83.77%), and 1,408 malignant cases (16.23%). Classification by anatomic sites: eye lid 5,313 cases (61.26%), orbit 1,484 cases (17.11%) and epibulbar 1,876 cases (21.63%). Classification by histogenesis: (1) Primary tumor 6,679 cases: epitheliogenic 2,481 cases (37.15%), mesenchymal 753 cases (11.27%), lympho-hematopoietic 102 cases (1.53%), neurogenic 1,542 cases (23.09%), congenital abnormal embryogenetic 1,767 cases (26.46%), uncertain resource tumor 34 cases (0.50%). (2) Secondary tumor 13 cases; (3) Metastatic tumor 9 cases; (4) Non-tumor lesion 1,972 cases. CONCLUSION: The classification is helpful to the histopathologic diagnosis and the study about the detailed distribution of common ocular adnexal hyperplastic lesions and rare tumors, and it also increases the pathologic diagnostic data in North China.

Eyelid Neoplasms↗
PubMed1999

[Effects of humic acid on lipid peroxidation in arsenosis prevalent areas].

OBJECTIVE: To explore the causes of blackfoot disease in Taiwan. METHODS: Experiments to induce lipid peroxidation by arsenic and humic acid were made in vitro. Arsenic was determined for the water sampled from the arsenosis prevalent areas in Inner Mongolia and blackfoot disease prevalent areas in Taiwan and humic acid determined for the extracts of the coal rich in arsenic sampled from Guizhou Province in China by MDA-TBA colorimetry. RESULTS: Experiments found that humic acid could induce lipid peroxidation caused by sodium salt of unsaturated fatty acids in vitro in a weak and unstable manner, which could be promoted by 0.05 mmol/L of Fe(+ +) and not by 1 mmol/L As(2)O(3). The extent of lipid peroxidation caused depended on the sources, constituents and structure of humic acid samples, those from Inner Mongolia ranked the highest, those from Guizhou and Taiwan the medium and the commercial humic acid (Aldrich Co. in the US) the lowest. The experiments also found that lipid peroxidation caused by commercial humic acid presented a dynamic process in the existence of trace amount of iron, and humic acid could decompose the products of lipid peroxidation. CONCLUSION: The experiments suggested the relations of humic acid and arsenic to iron and other transition elements in the blackfoot disease prevalent areas and areas with an environment rich in arsenic and humic acid.

Arsenic Poisoning↗
PubMed1998

GIPC, a PDZ domain containing protein, interacts specifically with the C terminus of RGS-GAIP.

We have identified a mammalian protein called GIPC (for GAIP interacting protein, C terminus), which has a central PDZ domain and a C-terminal acyl carrier protein (ACP) domain. The PDZ domain of GIPC specifically interacts with RGS-GAIP, a GTPase-activating protein (GAP) for Galphai subunits recently localized on clathrin-coated vesicles. Analysis of deletion mutants indicated that the PDZ domain of GIPC specifically interacts with the C terminus of GAIP (11 amino acids) in the yeast two-hybrid system and glutathione S-transferase (GST)-GIPC pull-down assays, but GIPC does not interact with other members of the RGS (regulators of G protein signaling) family tested. This finding is in keeping with the fact that the C terminus of GAIP is unique and possesses a modified C-terminal PDZ-binding motif (SEA). By immunoblotting of membrane fractions prepared from HeLa cells, we found that there are two pools of GIPC-a soluble or cytosolic pool (70%) and a membrane-associated pool (30%). By immunofluorescence, endogenous and GFP-tagged GIPC show both a diffuse and punctate cytoplasmic distribution in HeLa cells reflecting, respectively, the existence of soluble and membrane-associated pools. By immunoelectron microscopy the membrane pool of GIPC is associated with clusters of vesicles located near the plasma membrane. These data provide direct evidence that the C terminus of a RGS protein is involved in interactions specific for a given RGS protein and implicates GAIP in regulation of additional functions besides its GAP activity. The location of GIPC together with its binding to GAIP suggest that GAIP and GIPC may be components of a G protein-coupled signaling complex involved in the regulation of vesicular trafficking. The presence of an ACP domain suggests a putative function for GIPC in the acylation of vesicle-bound proteins.

Adaptor Proteins, Signal Transducing↗