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Biomedical subjects

B Zheng

Publications and source records attributed to B Zheng.

At least 145 records · Page 8Linked to original sources
PubMed1996

On the reporting of mass contrast in CAD research.

As research efforts for developing computer-aided diagnosis (CAD) schemes of digitized mammograms increase and interscheme results are compared, the desire to establish an acceptable consistent reporting protocol of the distribution of abnormal characteristic is becoming an issue. "Mass contrast" is very important and frequently reported in current CAD studies. In this report, 100 verified mass regions were analyzed systemically using 6 different definitions of "mass contrast." Measured variability in mass contrast was demonstrated by the distribution shift in this group masses. The need for universally accepted and largely standardized descriptors of objects of interest is clearly demonstrated.

Biophysical Phenomena↗
PubMed1996

Mass detection in digitized mammograms using two independent computer-assisted diagnosis schemes.

OBJECTIVE: Using two independent computer-assisted diagnosis (CAD) schemes, we investigated the potential to improve the sensitivity of mass detection by applying a logical "or" operation and to improve the specificity using a logical "and" operation. MATERIALS AND METHODS: Two independent mass detectors, one with Gaussian bandpass filtering and multilayer topographic feature analysis and the other with a five-stage search for a single suspicious region, were applied to a large image database that included 428 digitized mammograms with 220 verified masses. The performance of the two schemes and a combination of them in the form of either logical "or" or logical "and" operations were compared. RESULTS: In this preliminary study, a multilayer topographic feature analysis CAD scheme (CAD-1) achieved a sensitivity of 96% and had a false-positive detection rate of 0.79 per image. A five-stage search method scheme (CAD-2) achieved a sensitivity of 94% and had a false-positive detection rate of 1.69 per image. With an "or" operation, the combined results yielded 100% sensitivity with a false-positive detection rate of 2.07 per image. A logical "and" operation produced a reduction of the false-positive detection rate to 0.4 per image, but sensitivity also decreased to 90%. CONCLUSION: Similar to an independent double-reading approach and depending upon the relevant clinical question, sensitivity or specificity can be improved by combining the results of several independent CAD schemes.

Breast Neoplasms↗
PubMed1996

[Extraction of humic acid from drinking water in area with arsenosis in inner Mongolia and Taiwan and comparison of its spectrometry].

In order to study etiology of blackfoot disease in Taiwan and to explore whether it can occur in the area with arsenosis in Inner Mongolia in the future, chemical components of specimens of drinking water from Taiwan and Inner Mongolia were determined and compared with infrared (IR), ultra-violet (UV) spectrometry and fluorescence spectrometry. Humic acid was extracted from the water samples by XAD-7 ion-exchange resin and Sephadex G-25 gel filtration chromatography, respectively, yielding the same results. Studies showed arsenic and humic acid levels in water samples both from Taiwan and Inner Mongolia all were higher, and their fluorescence and UV-spectra were similar, except a small difference in their IR spectra. Their effects on environment are under further studies.

Arsenic↗
PubMed1995

In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. IV. Affinity-dependent, antigen-driven B cell apoptosis in germinal centers as a mechanism for maintaining self-tolerance.

Germinal centers (GCs) are the sites of antigen-driven V(D)J gene hypermutation and selection necessary for the generation of high affinity memory B lymphocytes. Despite the antigen dependence of this reaction, injection of soluble antigen during an established primary immune response induces massive apoptotic death in GC B cells, but not in clonally related populations of nonfollicular B lymphoblasts and plasmacytes. Cell death in GCs occurs predominantly among light zone centrocytes, is antigen specific, and peaks within 4-8 h after injection. Antigen-induced programmed death does not involve cellular interactions mediated by CD40 ligand (CD40L) or Fas; disruption of GCs by antibody specific for CD40L was not driven by apoptosis and C57BL/6.lpr mice, though unable to express the Fas death trigger, remained fully susceptible to soluble antigen. Single injections of antigen did not significantly decrease GC numbers or average size, but repeated injections during an 18-h period resulted in fewer and substantially smaller GCs. As cell loss appeared most extensive in the light zone, decreased GC cellularity after prolonged exposure to soluble antigen implies that the Ig- centroblasts of the dark zone may require replenishment from light zone cells that have survived antigenic selection. GC cell death is avidity-dependent; oligovalent antigen induced relatively little apoptosis and GC B cells that survived long exposures to multivalent antigen expressed atypical VDJ rearrangements unlikely to encode high affinity antibody. Antigen-induced apoptotic death in GCs may represent a mechanism for the peripheral deletion of autoreactive B cell mutants much as the combinatorial repertoire of immature B lymphocytes is censored in the bone marrow.

Amino Acid Sequence↗
PubMed1995

Therapeutic potentiation of the immune system by costimulatory Schiff-base-forming drugs.

Immune responses are orchestrated by CD4 T lymphocytes, which receive a cognitive signal when clonally distributed receptors are occupied by major histocompatibility complex (MHC) class II-bound peptides on antigen-presenting cells (APCs). The APCs provide costimulatory signals, through macromolecules such as CD80, that regulate outcomes in terms of T-cell activation or anergy. We have studied essential complementary chemical events in the form of Schiff base formation between carbonyls and amines that are constitutively expressed on presenting cell and T-cell surfaces and provide a new target for manipulation of immune responses. Here we show that small Schiff base-forming molecules can substitute for the physiological donor of carbonyl groups and provide a costimulatory signal to CD4 Th-cells through a mechanism that activates clofilium-sensitive K+ and Na+ transport. One such molecule, tucaresol, enhances CD4 Th-cell responses, selectively favouring a Th1-type profile of cytokine production. In vivo tucaresol potently enhances CD4 Th-cell priming and CD8 cytotoxic T-cell priming to viral antigens, and has substantial therapeutic activity in murine models of disease.

Adjuvants, Immunologic↗
PubMed1995

Cellular interaction in germinal centers. Roles of CD40 ligand and B7-2 in established germinal centers.

Costimulatory interactions between T and B lymphocytes are crucial for T cell activation and B cell proliferation and differentiation. We have compared the roles of CD40L and B7-2 in the initiation and maturation of humoral immunity by administering anti-CD40 ligand (L) or anti-B7-2 Ab during the early (days -1 to 3) or late (days 6-10) phases of primary responses to thymus-dependent (Td) and -independent (Ti) Ags. Germinal center (GC) formation in response to a Td Ag was inhibited completely by the early administration of anti-CD40L or anti-B7-2 Abs. Later in the response, established GCs remained sensitive to anti-CD40L but were resistant to treatment with anti-B7-2. However, Ig hypermutation was reduced dramatically in GCs of anti-B7-2-treated mice and humoral memory was impaired. Early administration of anti-CD40L reduced serum Ab levels to approximately 10% of controls, whereas early treatment with anti-B7-2 reduced Ab production by only 50%. Later treatments with either Ab had no effect on Ab production. Response to a type II Ti Ag was more resistant than Td responses to interruption of costimulatory interactions. Our findings suggest that the costimulatory roles of CD40:CD40L and B7-2:CD28/CTLA-4 differ in the GC; administration of anti-CD40L abrogates an established GC reaction, whereas Ab to B7-2 suppresses Ig hypermutation and entry into the B cell memory compartment. Once B cells have entered the differentiation pathway to Ab production, neither CD40L nor B7-2 is necessary for their continued differentiation and persistence.

Animals↗
PubMed1995

Galactose oxidation as a potent vaccine adjuvant strategy. Efficacy in murine models and in protection against a bovine parasitic infection.

Potent immunological adjuvants are urgently required to complement subunit protein and peptide vaccines in prophylactic and therapeutic vaccination. Carbonyl-amino condensations, which are essential to the inductive interaction between antigen-presenting cells and T-helper cells, were tested as a target for the enhancement or immune responses to vaccine antigens. Enzymic oxidation of cell surface galactose by the novel adjuvant NAGO, to increase amine-reactive carbonyl groups on lymphocytes and antigen-presenting cells, provided a potent noninflammatory method of enhancing the immunogenicity of viral, bacterial, and protozoal subunit vaccines in mice. In pilot protection studies with a glutathione-S-transferase vaccine against bovine Fasciola hepatica, a formulation containing NAGO as sole adjuvant agent proved very effective in inducing protection. In terms of protection in individual animals, NAGO alone was better than Quil A emulsified in squalene Montanide (five of eight animals were protected better than 80% by NAGO; four of eight animals were protected better than 93% by NAGO; two of eight animals were protected better than 80% by QA/SM). QA/SM (69% mean protection) was, however, more consistent overall than NAGO (65% mean protection). NAGO proved more effective in murine models when combined with muramyl dipeptide, but this combination has yet to be tested in protection studies.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1995

Computer-aided detection of clustered microcalcifications in digitized mammograms.

RATIONALE AND OBJECTIVES: We investigated a computer-aided detection (CAD) scheme for clustered microcalcifications in digitized mammograms. METHODS: A multistage CAD scheme was developed and tested. To increase sensitivity, the scheme uses a Gaussian band-pass filter and nonlinear threshold. A multistage local minimum searching routine and a multilayer topographic feature analysis are used to reduce the false-positive detection rate. One hundred ten digitized mammograms were used in this preliminary test, with 55 images containing one or two verified microcalcification clusters. RESULTS: The CAD scheme achieved 100% sensitivity and had an average false-positive detection rate of 0.18 per image. CONCLUSION: The CAD scheme performs as well as many published schemes and has some unique advantages to further improve detection sensitivity and specificity of future CAD schemes.

Breast Diseases↗
PubMed1995

Computerized detection of masses from digitized mammograms: comparison of single-image segmentation and bilateral-image subtraction.

RATIONALE AND OBJECTIVES: Two methods--single-image segmentation and bilateral-image subtraction--have been used commonly as the first stage in computer-aided detection (CAD) schemes to detect masses on digitized mammograms. In the current study, we investigated and compared the advantages and disadvantages of the two methods in achieving a high sensitivity for mass detection. METHODS: Two CAD schemes were tested. One used Gaussian filtering based on single-image segmentation, and the other used bilateral-image subtraction based on left-right image pairs to identify suspicious mass regions. A clinical database that contained 152 verified mass cases was used to compare the two approaches. RESULTS: The single-image segmentation method yielded 100% sensitivity and had a somewhat higher number of initial suspicious regions. The bilateral-image subtraction method missed several true-positive regions at the initial phase. Each approach achieved more than 90% sensitivity at a false-positive rate of approximately 0.8 per image. CONCLUSION: Optimal initial image segmentation schemes may depend on the complete detection and classification method used. Single-image segmentation methods may perform comparably with bilateral-image segmentation schemes, and these techniques appear to be more versatile and easily adaptable to future clinical CAD applications.

Breast Neoplasms↗
PubMed1995

Computerized detection of masses in digitized mammograms using single-image segmentation and a multilayer topographic feature analysis.

RATIONALE AND OBJECTIVES: We developed and evaluated a computer-aided detection (CAD) scheme for masses in digitized mammograms. METHODS: A multistep CAD scheme was developed and tested. The method uses a technique of single-image segmentation with Gaussian bandpass filtering to yield a high sensitivity for mass detection. A rule-based multilayer topographic feature analysis method is then used to classify suspected regions. A set of 260 cases, including 162 verified masses, was divided into two subsets; one set was used to set the rule-based classification and one was used to test the performance of the scheme. RESULTS: In a preliminary clinical study, the implemented detection scheme yielded 98% sensitivity with a false-positive detection rate of less than one false-positive region per image. CONCLUSION: Single-image segmentation methods seem to have high sensitivity in selecting true-positive mass regions in the first stage of a CAD scheme. A multilayer topographic image feature analysis method in the second stage of a CAD scheme has the potential to significantly reduce the false-positive detection rate.

Algorithms↗
PubMed1995

Structurally related but functionally distinct yeast Sm D core small nuclear ribonucleoprotein particle proteins.

Spliceosome assembly during pre-mRNA splicing requires the correct positioning of the U1, U2, U4/U6, and U5 small nuclear ribonucleoprotein particles (snRNPs) on the precursor mRNA. The structure and integrity of these snRNPs are maintained in part by the association of the snRNAs with core snRNP (Sm) proteins. The Sm proteins also play a pivotal role in metazoan snRNP biogenesis. We have characterized a Saccharomyces cerevisiae gene, SMD3, that encodes the core snRNP protein Smd3. The Smd3 protein is required for pre-mRNA splicing in vivo. Depletion of this protein from yeast cells affects the levels of U snRNAs and their cap modification, indicating that Smd3 is required for snRNP biogenesis. Smd3 is structurally and functionally distinct from the previously described yeast core polypeptide Smd1. Although Smd3 and Smd1 are both associated with the spliceosomal snRNPs, overexpression of one cannot compensate for the loss of the other. Thus, these two proteins have distinct functions. A pool of Smd3 exists in the yeast cytoplasm. This is consistent with the possibility that snRNP assembly in S. cerevisiae, as in metazoans, is initiated in the cytoplasm from a pool of RNA-free core snRNP protein complexes.

Amino Acid Sequence↗
PubMed1995

Effect of cortisol on energy expenditure and amino acid metabolism in humans.

Hydrocortisone was infused overnight into nine normal healthy adults on three occasions at 0, 80, and 200 micrograms.kg-1.h-1, producing plasma cortisol concentrations of 10.6 +/- 1.2, 34.0 +/- 2.0, and 64.9 +/- 4.3 micrograms/dl, respectively. L-[1-13C]leucine, L-[phenyl-2H5]phenylalanine, and L-[2-15N]glutamine were infused during the last 7 h of hypercortisolemia to measure amino acid kinetics. During the last 3.5 h, somatostatin, glucagon, and insulin were infused to reduce the cortisol-induced elevation in plasma insulin to basal. Hypercortisolemia increased plasma glucose, free fatty acid (FFA), and insulin concentrations. Institution of the somatostatin clamp returned insulin to basal but increased glucose and FFA. Acute hypercortisolemia increased protein breakdown 5-20%, as measured by increases in leucine and phenylalanine appearance rates. Normalizing insulin during hypercortisolemia did not alter phenylalanine flux but enhanced leucine appearance rate, the latter result indicating that insulin was affecting leucine metabolism during hypercortisolemia. The fraction of the leucine flux that was oxidized was not significantly increased with hypercortisolemia, but disposal by the nonoxidative route of leucine uptake for protein synthesis was increased. Hypercortisolemia increased cycling of amino acids by increasing protein breakdown and synthesis, but the increase in this process could have increased resting energy expenditure (REE) only 1-2%. Hypercortisolemia increased glutamine flux in a dose-dependent fashion through an increase in de novo synthesis, which presumably reflects increased release from skeletal muscle. Hypercortisolemia increased REE 9-15% at the 80 and 200 micrograms.kg-1.h-1 infusion rates. Respiratory quotient did not rise with cortisol infusion but tended to decrease, suggesting that the increase in REE was fueled by increased oxidation of fat. These data demonstrate that hypercortisolemia increases metabolic rate and may be in part responsible for the hypermetabolic state in injury.

Adult↗
PubMed1995

Construction and high expression of retroviral vector with human clotting factor IX cDNA in vitro.

The construction of the high titer and highly expressed safety retroviral vector carrying human clotting factor IX cDNA is reported. Retroviral vectors LNCIX, LIXSN and LCIXSN, driven by hCMV, LTR and hCMV combined with LTR promoter respectively, were constructed, based on the retroviral vector LNL6, and transferred into packaging cell line PA317 with electroporation. Human clotting factor IX was detected in the cultured cells transduced with LNCIX and LIXSN but not in the cells transduced with LCIXSN. The viral titer of PA317/LNCIX was 800,000 CFU per mL. With ELISA detection, it was found that the cells transduced with this vector can express human clotting factor IX at the level of 3.3 micrograms per 10(6) cells in 24 h in human fibrosarcoma cells HT-1080 and 2.5 micrograms per 10(6) cells in 24 h in hemophilia B patients' skin fibroblast HSF cells, and more than 80% of them were biologically active. The viral titer and expression of human FIX were increased, and the construction of retroviral vector backbone was improved and the safety was guaranteed as compared to those vectors used previously. These vectors may produce a sufficient quantity of factor IX proteins to cause the phenotypic modification for hemophilia B patients.

Cells, Cultured↗
PubMed1995

[Effects of SL-probiotic preparation on the body weight and phagocytosis of white mice].

Effects of SL-probiotic preparation on the body weight and the phagocytic functions in white mice were studied. Bioassay of its toxicity showed SL-P was non-toxic. Body weight of the treated mice increased significantly as compared with that of controls 10 days after treatment with SL-probiotic preparation. Phagocytic activity, acid phosphatase activity, lysozyme activity of the peritoneal macrophages of the tested mice were enhanced significantly as compared with those of normal controls. The same results were obtained with respect to serum lysozyme activity. These observations showed that SL-probiotic preparation could activate macrophage function in mice and hence enhancement of non-specific immunity.

Acid Phosphatase↗
PubMed1994

Locus-specific somatic hypermutation in germinal centre T cells.

Somatic hypermutation and affinity-driven selection of active immunoglobulin genes occur in germinal centres (GCs), resulting in the generation of high-affinity memory B cells. In contrast, T lymphocytes do not require the germinal centre microenvironment to establish memory and the T-cell antigen receptor (TCR) genes, though homologous to immunoglobulin genes, are believed to be incapable of hypermutation. Here we present direct evidence that the small population of antigen-specific T cells that are recruited into splenic GCs acquire mutations in the variable region of genes encoding TCR alpha-chains (V alpha) but not those of beta-chains. These locus-specific mutations reach frequencies comparable to mutated immunoglobulin VH exons recovered from the same site and exhibit similar substitution biases and DNA strand polarity. T cells bearing identical mutations appear in multiple GCs, raising the possibility that some cells bearing mutant TCRs may re-enter the peripheral lymphocyte pool.

Amino Acid Sequence↗
PubMed1994

Human leukemia K562 cell mutant (K562/OA200) selected for resistance to okadaic acid (protein phosphatase inhibitor) lacks protein kinase C-epsilon, exhibits multidrug resistance phenotype, and expresses drug pump P-glycoprotein.

A human leukemia K562 cell mutant (K562/OA200) selected for resistance to okadaic acid (OA), an inhibitor of protein phosphatases 1 and 2A (PP1/PP2A), has been established. In wild type cells, the cytotoxicity of OA was associated with mitotic arrest and concentration- and time-dependent DNA fragmentation, a hallmark of apoptosis. The mutant was 100-fold more resistant to OA in terms of effects on these parameters. Although the synthesis of several proteins was altered, enzyme assay and immunoblot analysis indicated that the levels of PP1 and PP2A were unchanged in the mutant. Protein kinase C (PKC) assays and immunoblot analysis of calcium-dependent (cPKC) and calcium-independent (nPKC) isoforms revealed that nPKC-epsilon was strikingly absent in the mutant, which otherwise expressed in comparable amounts all other isotypes (cPKC-alpha, cPKC-beta, and nPKC-zeta) also present in the wild type. Northern blot analysis confirmed an absence of PKC-epsilon mRNA in the mutant cells. The OA200 cells were cross-resistant not only to another PP1/PP2A inhibitor, calyculin A, but also to structurally unrelated anticancer drugs (such as vinblastine and taxol) and furthermore, overexpressed the verapamil-sensitive drug pump P-glycoprotein at both the protein and mRNA levels. The mutant, however, was not cross-resistant to several PKC inhibitors tested including cardiotoxin, mastoparan, staurosporine, and an alkylphospholipid. Cardiotoxin, at a subtoxic concentration, enhanced by 6-fold vinblastine cytotoxicity in OA200 cells. These findings indicate that the multidrug resistance phenotype can be induced by cytotoxic agents other than conventional anticancer drugs, show that the development of multidrug resistance is not necessarily associated with increased cPKC activity, and identify certain PKC inhibitors that have potential as resistance modulators.

ATP Binding Cassette Transporter, Subfamily B, Mem↗