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Biomedical subjects

Y Yang

Publications and source records attributed to Y Yang.

At least 1,207 records · Page 67Linked to original sources
PubMed1994

Mapping the human lung using Delaunay tessellation.

A computer protocol is (1) developed and (2) applied to the human body for medical research. Delaunay tessellation is used to derive an algorithm to describe the structure of the lung. This may be the first application of that mathematical concept to a physiological system. The lung is a complex yet systematic network of pathways described herein with cited dimensions and angles. Its terminal points are the most distal airways, alveolar sacs, defined by their (x, y, z) coordinates. We have addressed that spatial array as a set of points in 3-D space, and, visualized the physical boundary of a lung as the surface of the convex hull of that set in R3. As documented, the enveloping surface of the computer lung closely describes the outer contours of human lungs depicted in clinical studies. Therefore, the model has immediate and salient implications to problems in medicine where respiratory function and morphology have integral roles, specifically, thoracic surgery and aerosol therapy. Examples include the removal of lobes damaged by respiratory diseases such as cystic fibrosis and cancer, and the definition of lung boundaries for gamma camera, PET, and SPECT images. Importantly, the model can be varied to simulate the intersubject differences that physicians experience among a patient population. The mathematical simulations performed in this work are intended to be complementary to laboratory investigations in the medical arena. By providing accurate 3-D, quantitative descriptions of human lungs the supercomputer can be actively integrated into the clinical environment.

Algorithms↗
PubMed1994

IS204: an insertion sequence from Nocardia asteroides (mexicana) YP21.

An insertion sequence was found in Nocardia asteroides YP21. The element, designated IS204, is 1452 bp long and has 19/23 bp imperfect inverted repeats at its ends. The sequences of IS204 terminal inverted repeats have high homology with those of IS1096 from Mycobacterium smegmatis. An 8-bp duplication of target sequence was found at the insertion site. Sequence analysis revealed that IS204 contains an open reading frame of 1134 bp, which encodes a putative transposase similar to those found in IS1096 and in Tn4652 from Pseudomonas sp. EST1001. At least nine copies of IS204 are present in the genome of N asteroides YP21. The plasmid pCY 104::IS204 could be inserted with another copy of IS204 at a different site. The possible mechanisms are discussed.

Amino Acid Sequence↗
PubMed1994

The cells of the dorsal iris involved in lens regeneration are myoepithelial cells whose cytoskeleton changes during cell type conversion.

During newt lens regeneration, the pigmented epithelial cells (PECs) of the dorsal iris dedifferentiate and give rise to a new lens. We have studied the cytoskeleton of the PECs using iris flat mounts and sections. In flat-mount iris preparations stained by labelled phalloidin three main regions can be recognized: the pupillary (P) ring, the middle (M) ring, and the more external junctional (J) ring. The cells of the P ring that give rise to the lens have an elongated spindle shape and exhibit an elaborate cytoskeleton of actin filament bundles oriented along the long axis of the cells, reminiscent of myoepithelial or smooth muscle cells. These cells express smooth muscle-specific alpha actin, muscle gamma actin and cytokeratin II, and adhere to each other through the cell adhesion molecule A-CAM. During dedifferentiation, actin staining increases considerably as the actin filament bundles thicken and shorten and then accumulate preferentially in the apical and basel regions of the elongating lens fibres. Cytokeratin II, which is also organized as fibrils along the long axis of the normal iris PECs, increases progressively during dedifferentiation, when it is organized as a thick band surrounding the nucleus. The expression of this protein is repressed during lens fibre differentiation, but is retained in mitotic cells. The data suggest that during cell type conversion some cytoskeletal proteins increase and reorganize, while others disappear during lens fibre differentiation.

Actins↗
PubMed1994

Tumor necrosis factor-alpha mRNA and protein in endometrial tumors: analysis by in situ hybridization and immunocytochemistry.

Abnormal expression of polypeptide growth factors and their receptors is closely associated with tumorigenic transformation. In this study tumor necrosis factor-alpha (TNF-alpha) mRNA and protein were analyzed in polyps and proliferative lesions of endometrium as well as in low and high grade endometrial tumors by using in situ hybridization and immunocytochemistry. All samples contained products of the TNF-alpha gene. Histochemical scores (HS), which reflect the proportion of cells positive for TNF-alpha message or protein and the intensities of the signals, were higher for epithelial than for stromal cells. Benign lesions (endometrial polyps) contained little TNF-alpha mRNA or protein, whereas specific message was abundant in proliferative lesions (hyperplasia, adenofibroma). Although neoplastic cells in both low and high grade endometrial tumors contained TNF-alpha mRNA, two major differences were observed: HS for TNF-alpha mRNA were significantly less in low grade than in high grade neoplasms, and TNF-alpha message was restricted to the nucleus in low grade adenocarcinoma cells but was abundant in the cytoplasm of high grade tumor cells. In contrast to cells in benign and proliferative lesions, TNF-alpha protein scores in endometrial tumor cells were inversely rather than positively correlated with TNF-alpha mRNA scores. Collectively, the findings in this study are consistent with the postulate that TNF-alpha is useful to endometrial tumor cells and suggest that production may increase as cells diverge from normal.

Adenocarcinoma↗
PubMed1994

Human colon carcinoma cells (CaCo-2) synthesize IGF-II and express IGF-I receptors and IGF-II/M6P receptors.

The IGFs have been implicated in the development of the intestinal tract. We have studied the human colon carcinoma cell line CaCo-2 to gain more insight into the function of the IGFs in the gut. [125I]IGF-I and -II bound specifically to CaCo-2 cells as measured in competitive binding experiments. The existence of IGF-I receptors was further demonstrated by affinity crosslinking studies using DSS as the crosslinking agent. Western blotting of CaCo-2 cell extracts using an anti IGF-II/M6P receptor antiserum provided additional evidence for the expression of the IGF-II/M6P receptor. In addition, Northern blotting experiments showed specific IGF-I receptor and IGF-II/M6P receptor gene expression in CaCo-2 cells. An 11 kb band was visualized with a 614 bp PstI IGF-I receptor probe on autoradiographs. Hybridization with a 663 bp IGF-II/M6P receptor probe yielded a 9 kb RNA species. Analysis of CaCo-2 cell RNA using solution hybridization/RNase protection assays yielded two protected fragments, approximately 379 bases in length, with a 394 base IGF-I receptor riboprobe and a 250 base protected fragment with a 260 base IGF-II/M6P receptor riboprobe. In a subset of experiments a PstI 700 base fragment of the IGF-I cDNA and a 554 base SalI fragment of the IGF-II cDNA were used for hybridization: no hybridization was detected with the IGF-I probe. However, using the [32P]IGF-II probe bands at 6.0 and 5.0 kb were labeled in Northern blotting experiments. Analysis of CaCo-2 cell RNA using solution hybridization/RNase protection assays yielded a 289 base protected fragment and a faint 534 base species with a 556 base human IGF-II riboprobe. In addition, IGF-II immunoreactivity was measured in CaCo-2 cell-conditioned medium using an IGF-binding protein blocked radioimmunoassay. CaCo-2 cell-conditioned medium contained 5-15 ng/ml IGF-II immunoreactivity. In conclusion, (1) CaCo-2 cells express both IGF-I receptor mRNA and IGF-II/M6P receptor mRNA and contain functional IGF-I receptor and IGF-II/M6P receptor protein. (2) CaCo-2 cells express IGF-II mRNA and secrete IGF-II immunoreactivity. We hypothesize that in human colon carcinoma cells IGF-II could act as an autocrine growth factor or alternatively could serve as a regulatory factor during differentiation.

Autocrine Communication↗
PubMed1994

MHC class I-restricted cytotoxic T lymphocytes to viral antigens destroy hepatocytes in mice infected with E1-deleted recombinant adenoviruses.

The use of E1-deleted recombinant adenoviruses in gene therapy has consistently been associated with transient gene expression and inflammation due to immune-based destruction of the infected cells. We have used murine models of adenovirus-mediated gene transfer to liver to investigate these immunologic mechanisms. Adoptive transfer experiments, as well as studies involving genetic knockout mice, confirmed the original hypothesis that cell-mediated immunity induced by E1-deleted adenovirus destroyed trans-gene-expressing hepatocytes and defined MHC class I-restricted CD8+ cytolytic lymphocytes as the primary immune effectors for hepatocyte destruction. Responses mediated by CD4+ cells per se were insufficient to mediate destruction of hepatocytes in vivo, despite the activation of virus-specific T helper cells of Th1 subsets. A better understanding of the response of the host to in vivo gene therapy is important in evaluating its usefulness in humans.

Adenoviridae Infections↗
PubMed1994

Propositional reasoning by mental models? Simple to refute in principle and in practice.

Two experiments compared the predictions of mental-models theory with a mental-logic theory. Results show that people do not make fallacious inferences predicted by mental-models theory but not predicted by mental-logic theory and that people routinely make many valid inferences predicted by mental-logic theory that should be too difficult on mental-models theory. Thus, the mental-logic theory accounts better for the data. A difference between the two theories concerning predictions about the order in which inferences are made was also investigated. The data clearly favor the mental-logic theory. It is argued that the mental-logic theory provides the more plausible description of the actual psychological processes in propositional reasoning.

Cognition↗
PubMed1994

Inactivation of E2a in recombinant adenoviruses improves the prospect for gene therapy in cystic fibrosis.

Although first generation recombinant adenoviruses, deleted of sequences spanning E1a and E1b, have been useful for in vivo applications of gene therapy, expression of the recombinant gene has been transient and often associated with the development of inflammation. We show that with first generation adenovirus-mediated gene transfer to the mouse lung, viral proteins are expressed leading to destructive cellular immune responses and repopulation of the lung with nontransgene containing cells. Second generation E1 deleted viruses further crippled by a temperature sensitive mutation in the E2a gene were associated with substantially longer recombinant gene expression and less inflammation. Stable expression of human CF transmembrane conductance regulator has been achieved in lungs of CF mice instilled with a second generation virus.

Adenoviridae Infections↗
PubMed1994

Binocular rivalry disrupts stereopsis.

Does the shift from binocular rivalry to fusion or stereopsis take time? We measured stereoacuity after rivalry suppression of one half-image of a stereoacuity line target. After the observer signalled that the single stereo half-image had been suppressed, the other half-image was presented for a variable duration. Stereoacuity thresholds were elevated for 150-200 ms. A control experiment demonstrated that the threshold elevation was due to rivalry suppression per se, rather than masking effects associated with the rivalry-inducing target. Monocular Vernier thresholds, measured as the smallest identifiable abrupt shift in the upper line of an aligned Vernier target that had previously been suppressed by rivalry, were elevated for a much longer duration. This result shows that an appropriately matched stereo pair can break rivalry suppression more easily than can monocular changes in position. With the aid of a similar paradigm, we also measured the duration needed to detect a disparate feature in a random-dot stereogram after rivalry suppression of one half-image of the stereogram. Observers could correctly identify the location of the disparate feature (upper or lower visual field) when the other half-image was presented for a duration ranging from 150-650 ms. In the absence of the matching half-image, the first half-image was suppressed by the rival target for a far longer duration (a few seconds). These findings show that although stereopsis and fusion terminate rivalry, both are initially disrupted for a few hundred milliseconds by rivalry suppression.

Depth Perception↗
PubMed1994

Biofiltration control of hydrogen sulfide. 2. Kinetics, biofilter performance, and maintenance.

The kinetics of H2S oxidation in a biofilter were evaluated and the reaction rates determined to be first-order at low concentrations (< 200 ppm), zero-order at high concentrations (> 400 ppm), and fractional-order in the intermediate concentration range for H2S in the inlet waste gas. The overall performance of the biofilter system and changes in compost properties were investigated for 200 days of operation. The compost biofilter showed good buffering capacities to variations in gas flow rate and pollutant (H2S) loading impacts. Hydrogen sulfide removal efficiencies exceeding 99.9% were consistently observed. System acidification and sulfate accumulation were identified as inhibitors of required biological activity. Routine washing of the compost effectively mitigated these deficiencies. System upset was determined to be caused by compost dry-out or system overloading. Methods were developed to provide for recovery of contaminated filter material.

Air Pollutants↗
PubMed1994

Members of the fatty acid binding protein family are differentiation factors for the mammary gland.

Mammary gland development is controlled by systemic hormones and by growth factors that might complement or mediate hormonal action. Peptides that locally signal growth cessation and stimulate differentiation of the developing epithelium have not been described. Here, we report that recombinant and wild-type forms of mammary-derived growth inhibitor (MDGI) and heart-fatty acid binding protein (FABP), which belong to the FABP family, specifically inhibit growth of normal mouse mammary epithelial cells (MEC), while growth of stromal cells is not suppressed. In mammary gland organ culture, inhibition of ductal growth is associated with the appearance of bulbous alveolar end buds and formation of fully developed lobuloalveolar structures. In parallel, MDGI stimulates its own expression and promotes milk protein synthesis. Selective inhibition of endogenous MDGI expression in MEC by antisense phosphorothioate oligonucleotides suppresses appearance of alveolar end buds and lowers the beta-casein level in organ cultures. Furthermore, MDGI suppresses the mitogenic effects of epidermal growth factor, and epidermal growth factor antagonizes the activities of MDGI. Finally, the regulatory properties of MDGI can be fully mimicked by an 11-amino acid sequence, represented in the COOH terminus of MDGI and a subfamily of structurally related FABPs. This peptide does not bind fatty acids. To our knowledge, this is the first report about a growth inhibitor promoting mammary gland differentiation.

Amino Acid Sequence↗
PubMed1994

Gene therapy for cystic fibrosis using E1-deleted adenovirus: a phase I trial in the nasal cavity. The University of North Carolina at Chapel Hill.

Cystic fibrosis (CF) is an autosomal recessive disease that reflects mutations in the CFTR gene. Multiple mutations in this gene have been detected that lead to a protein (CFTR) that is abnormally metabolized, dysfunction, or both. The full spectrum of the activities of the gene product have not been defined, but it is clear that CFTR can act as a cAMP-regulated Cl- channel. This type of defect is consistent with the physiologic characterization of CF epithelia, which has revealed abnormalities in salt and water transport. In the lung, abnormalities in epithelial salt and water metabolism lead to abnormal mucociliary clearance. This defect in clerance represents a major failure of lung defense and leads ultimately to infection of the lung with Staphylococcus aureus, Pseudomonas aeruginosa, and other bacterial organisms. The chronic inflammatory response to this persistent intraluminal bacterial infection leads to protease-induced destruction of airway walls and finally, lung failure. More than 95% of CF patients die of lung disease. The clinical therapy of CF lung disease is limited to agents designed to promote clearance of secretions from the lung and antibiotics to treat the chronic bacterial infection. Recent laboratory demonstrations that introduction of the normal CFTR cDNA into CF cells corrects the ion transport defects of these cells has led to the hypothesis that gene therapy in the lung can be an effective, novel mode of therapy for this lung disease. The classic gene transfer vectors, e.g., retroviruses, appear to be not well suited for therapy of lung disease because of the low proliferation rate of airway epithelia in vivo. Recently, adenoviruses, which have a natural tropism for airway epithelia, have been genetically modified (E1-deleted) in an attempt to reduce potential toxicity of this virus and provide space for the CFTR cDNA. A series of in vitro studies have shown that this vector is highly efficient for transferring CFTR into airway epithelial cells in culture and correcting the CF defect. Further, studies in whole animals appear to indicate that this mode of gene transfer is associated with a low degree of toxicity. The present study is a dose-effect study designed to test for the safety and efficacy of E1-deleted recombinant adenovirus containing the CFTR cDNA under a CMV-beta-actin promoter in CF nasal epithelia.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenoviridae↗
PubMed1994

Accuracy of single concentration estimations of platelet angiotensin II receptor number. Its usefulness in screening for pregnancy-induced hypertension.

Platelet angiotensin II (AngII) receptor number has been suggested as a screening test for pregnancy-induced hypertension. However, markedly different false-positive rates have been reported, perhaps the result of differing methods used. We sought therefore to compare the two methods. Platelet AngII receptor number was determined by saturation analysis with computerized curve fitting and specific binding at a single radioligand concentration. The two methods were compared by correlation and by plotting their differences v their means, to determine their limits of agreement. There were significant correlations between the value obtained by saturation analysis and each of the three single ligand concentrations studied (1 nmol/L, P < .001; 500 pmol/L, P < .001; and 250 pmol/L, P < .01). However, for none of the three did the regression line approach the line of equality. Assessment of agreement by comparing differences and means for each subject showed increasing scatter with increasing receptor number and 95% confidence intervals too large to be clinically relevant. We conclude that the receptor number estimated from specific binding at one ligand concentration differs significantly from that obtained by saturation analysis. The limits of agreement of the two methods are wide and we urge caution in the use of single ligand concentration methods for estimating binding site densities.

Adult↗
PubMed1994

Characterization of neutral metabolites of benzo[a]pyrene in urine from germfree rats.

[14C]Benzo[a]pyrene (BP) was administered to male germfree rats. Urinary metabolites, constituting 9% of the administered radioactivity, were fractionated by lipophilic ion exchange chromatography. More than 80% of the urinary metabolites were conjugated, while neutral metabolites constituted 13-18%. The latter group was characterized by reversed-phase HPLC, ultraviolet spectrometry (UV) and gas chromatography/mass spectrometry (GC/MS). Relative quantities of BP metabolites were estimated from the distribution of radioactivity upon HPLC fractionation. Some coeluted peaks were further quantitated from the total ion current chromatograms obtained in the GC/MS analysis. Two 7,8,9,10-tetrols which might be produced from the ultimate carcinogen r-7-t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydro-BP (anti-7,8-diol-9,10-epoxide) were detected at trace levels and indicated to be the r-7-t-8,9-c-10-(7,10/8,9-) and r-7-t-8,9,10-(7/8,9,10-) isomers. A trans-11,12-dihydrodiol was characterized as a major metabolite, while a trans-7,8-dihydrodiol was present at trace levels. Three additional quantitatively important metabolites were identified as isomeric trihydroxy-BPs. Two metabolites coeluting with BP quinones on HPLC were detected with relatively high abundance and tentatively identified as carboxylic methyl ester derivatives of BP quinones. Three quinones were detected with 1,6-, 3,6- and 6,12-substitutions. The 6,12- and 11,12-dihydroxy-BPs were also found at trace levels. A group of quinone-like metabolites were tentatively identified as trioxo-BPs. No monohydroxy-BP was detected in the neutral fraction of the urine extract. The time course of excretion was also studied and found to differ between individual metabolites.

Animals↗
PubMed1994

Mutations in calphotin, the gene encoding a Drosophila photoreceptor cell-specific calcium-binding protein, reveal roles in cellular morphogenesis and survival.

Calphotin is a Drosophila photoreceptor cell-specific protein expressed very early in eye development, at the time when cell-type decisions are being made. Calphotin is a very hydrophobic and proline-rich protein which lacks obvious transmembrane domains. The cDNA encoding Calphotin was mapped to a region removed by a set of existing chromosomal deletions. Mutations that alter photoreceptor cell structure and development were isolated that fail to complement these deletions. These mutations fall into two classes. Class I mutations alter the structure of the rhabdomere, a photoreceptor cell organelle specialized for phototransduction. Class II mutations have rough eyes, due to misorientation of the rhabdomeres and photoreceptor cell death. Transformation rescue of these phenotypes in transgenic flies bearing calphotin genomic DNA indicates that both classes of mutations are in the calphotin gene. Analysis of these mutations suggest that Calphotin plays important roles in both rhabdomere development and in photoreceptor cell survival.

Animals↗
PubMed1994

Definition of airway composition within gamma camera images.

The efficacies of inhaled pharmacologic drugs in the prophylaxis and treatment of airway diseases could be improved if particles were selectively directed to appropriate sites. In the medical arena, planar gamma scintillation cameras may be employed to study factors affecting such particle deposition patterns within the lung. The value and versatility of such instruments, however, are compromised by the limited resolution of their images. Specifically, it is not possible to determine the composition of their central (C) or large airway, intermediate (I), and peripheral (P) or small airway zones. We present an analytical model to assist the clinician in the systematic analysis and interpretation of gamma camera images. Using the Cray Y-MP supercomputer, a range of human lung morphologies has been mapped to function as templates that can be superimposed on scans. The model is intended to complement laboratory regimens by providing a previously unavailable method to define the C, I, and P zones of the human lung generation by generation. A quantitative value now can be assigned to the degree of overlapping that exists in the images. For example, for a "typical" lung morphology consisting of 16,777,215 airways (total), the C zone itself may contain 1,608,246 airways, of which 1,595,940, or 99.2%, are alveolated airways. By identifying composition, our intent is to integrate the model into future aerosol therapy protocols and thereby assist procedures that target delivery of airborne pharmaceuticals.

Administration, Inhalation↗