[C-type natriuretic peptide and cardiovascular disease].
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Arteriosclerosis↗
Biomedical subjects
J J Yang
Publications and source records attributed to J J Yang.
[Multi-slice CT scanners].
Some basic specifications of four commercial multi-slice CT scanners are compared with each other. The new technologies under the development of multi-slice CT are described and the image quality performance of multi-slice is discussed in this paper.
Algorithms↗
Cloning and expression of ZAK, a mixed lineage kinase-like protein containing a leucine-zipper and a sterile-alpha motif.
A novel mixed lineage kinase-like protein ZAK, containing a leucine-zipper (LZ) and a sterile-alpha motif (SAM), was cloned. This cDNA has 2456 bp and encodes a protein of 800 amino acids that contains a kinase catalytic domain, a leucine-zipper and a SAM. The molecular weight of this protein is 91kDa. Northern blot analysis revealed that the expression of this ZAK gene is found in various parts of human tissues. We also found that ZAK proteins might form homodimers or oligomers in mammalian cells. MLKs have been proposed to function as mitogen-activated protein kinase kinase kinase in pathways leading to MAPK cascade. The expression of ZAK in mammalian cells specifically leads to the activation of the JNK/SAPK pathway as well as the activation of transcription factor, NF-kappaB. Overexpression of the ZAK gene induces the apoptosis of a hepatoma cell line.
Amino Acid Sequence↗
Meeting future challenges in topical ocular drug delivery: development of an air-interfaced primary culture of rabbit conjunctival epithelial cells on a permeable support for drug transport studies.
The purpose of this study was to develop and characterize a functional air-interfaced primary culture of rabbit conjunctival epithelial cells grown on a permeable support for drug transport studies. Conjunctival epithelial cells from the pigmented rabbit were isolated, seeded at 1.2 x 10(6) cells cm(-2) on permeable Transwell filters, and cultured at the air interface using a modified PC-1 medium. Conjunctival epithelial cell layers showed a transepithelial resistance of 1.1+/-0.1 kOmega cm(2), a potential difference of 17.0+/-0.5 mV, and an equivalent short-circuit current (I(eq)) of 16.1+/-0.4 microA cm(-2). The I(eq) was reduced by 35% using 0.01 mM bumetanide, 66% using 0.1 mM ouabain, 46% using 2 mM barium chloride (all three in the basolateral fluid), and 63% using 0.3 mM NPAA in the apical fluid, consistent with active Cl(-)-secretion across the conjunctival epithelial barrier. Amiloride-sensitive Na(+) channels were absent. The permeability of the cell layers to polar solutes decreased with increased solute size, and the calculated equivalent pore size was about 8.0 nm. The Papp of beta-blockers varied with lipophilicity in a sigmoidal fashion. Uridine transport showed temperature sensitivity and directionality, favoring transport in the apical-to-basolateral direction. Apical L-carnosine uptake was reduced by 46% in the absence of an inwardly directed proton gradient, and lowering the temperature to 4 degrees C abolished direction-dependent L-carnosine uptake. Furthermore, uptake was inhibited by 73% using apical 10 mM glycyl sarcosine (a dipeptide transporter substrate) and by 60% using 1 mM L-valacyclovir (a dipeptide prodrug). In conclusion, a functional air-interfaced primary culture of rabbit conjunctival epithelial cell layers was established. This air-interfaced primary culture model may be useful for studying passive and active transport processes for ion and solute translocation in the mammalian conjunctival epithelial barrier in a defined experimental setting.
Adrenergic beta-Antagonists↗
Fine-mapping of the type 1 diabetes locus (IDDM4) on chromosome 11q and evaluation of two candidate genes (FADD and GALN) by affected sibpair and linkage-disequilibrium analyses.
Previous studies have identified a susceptibility region for insulin-dependent (type 1) diabetes mellitus on chromosome 11q13 (IDDM4). In this study, 15 polymorphic markers were analyzed for 382 affected sibpair (ASP) families with type 1 diabetes. Our analyses provided additional evidence for linkage for IDDM4 (a peak LOD score of 3.4 at D11S913). The markers with strong linkage evidence are located within an interval of approximately 6 cM between D11S4205 and GALN. We also identified polymorphisms in two candidate genes, Fas-associated death domain protein (FADD) and galanin (GALN). Analyses of the data by transmission/disequilibrium test (TDT) and extended TDT (ETDT) did not provide any evidence for association/linkage with these candidate genes. However, ETDT did reveal significant association/linkage with the marker D11S987 (P=0.0004) within the IDDM4 interval defined by ASP analyses, suggesting that IDDM4 may be in the close proximity of D11S987.
Bacterial Proteins↗
Induction of apoptosis in KB cells by pingyangmycin.
Pingyangmycin (PYM; Bleomycin A(5)), an antitumour antibiotic is currently used during anticancer therapy. Previous experiments demonstrated that the therapeutic efficiency of PYM for treatment of malignant tumours is considered to be related to its ability to cause DNA strand breaks in vitro. However, very little is known about the interaction of PYM with the target cells, and it is still unclear how PYM enters the cells. In this study, cell death induced by PYM was studied in a human squamous cell carcinoma cell line (KB cells). In order to determine if cell death occurred by necrosis (reproductive cell death) or apoptosis (programmed cell death), KB cells were exposed to different concentrations of PYM and evaluated by biochemical and morphological criteria. Our results indicate that KB cells displayed an arrest in the G(2)-M phase of the cell cycle and became enlarged and polynucleated before dying at the low concentrations of PYM. In contrast, when cells were exposed to high concentrations of PYM, morphological changes identical to those usually associated with apoptosis were observed as well as internucleosomal digestion of genomic DNA. In conclusion, we demonstrate that PYM is able to induce two distinct modes of cell death depending on the doses of PYM.
Antibiotics, Antineoplastic↗
Role of P-glycoprotein in restricting propranolol transport in cultured rabbit conjunctival epithelial cell layers.
PURPOSE: To determine the role of P-glycoprotein (P-gp) in propranolol transport in cultured rabbit conjunctival epithelial cell layers (RCEC). METHODS: The localization of P-gp in the cultured RCEC as well as in the excised conjunctiva was determined by immunofluorescence technique. The role of P-gp in transepithelial transport and uptake of propranolol in conjunctival epithelial cells cultured on Transwell filters was evaluated in the presence and absence of P-gp competing substrates, an anti-P-gp monoclonal antibody (4E3 mAb), or a metabolic inhibitor, 2,4-dinitrophenol (2,4-DNP). RESULTS: Immunofluorescence studies revealed positive staining in the apical membrane of cultured RCEC and in the apical surface of the superficial cell layers in the excised conjunctiva, but not the basolateral membrane of cultured RCEC. Transport of propranolol showed preference in the basolateral-to-apical direction. The net secretory flux was saturable with a Km of 71.5 +/- 24.0 nM and a Jmax of 1.45 +/- 0.17 pmol/cm2/hr. Cyclosporin A, progesterone, rhodamine 123, verapamil, 4E3 mAb and 2,4-DNP all increased apical 50 nM propranolol uptake by 43% to 66%. On the other hand, neither beta-blockers (atenolol, metoprolol, and alprenolol) nor organic cation transporter substrates (tetraethylammonium (TEA) and guanidine), affected apical 50 nM propranolol uptake. CONCLUSIONS: The energy-dependent efflux pump P-gp appears to be predominantly located on the apical plasma membrane of the conjunctival epithelium. It may play an important role in restricting the conjunctival absorption of some lipophilic drugs.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Peptide analogs from E-cadherin with different calcium-binding affinities.
Cadherins are a family of calcium-dependent cell-surface proteins that are fundamental in controlling the development and maintenance of tissues. Motif B of E-cadherin seems to be a crucial calcium-binding site as single point mutations (D134A and D134K) completely inactivate its adhesion activity. We analyzed peptide models corresponding to motif B (amino acids 128-144) as well as selected mutations of this motif. Our NMR studies showed that this motif B sequence is actually an active calcium-binding region, even in the absence of the rest of the cadherin molecule. We found that the binding affinity of this motif is very sensitive to mutations. For example, our peptide P128-144 with the native calcium-binding sequence has an affinity of Kd 0.4 mM, whereas the mutants P128-144/ D134A and P128-144/D134K containing the replacement of Asp134 by Ala and Lys, have Kd values of only 1.5 and 11 mM, respectively. Removing Asp at position 134, which correlates with the loss of adhesion activity, decreases calcium-binding affinity 20-fold. Ala132, along with residues Asp134, Asp136 and Asn143, is involved in calcium binding in solution. We also demonstrated that the calcium-binding affinity can be increased 3-fold when an additional Asp is introduced at position 132. In 50% organic solvent, this binding affinity of peptide P128-144/A132D (17-mer) from E-cadherin is similar to that of peptide P72-100/C73-77-91A (29-mer) from alpha-lactalbumin.
Amino Acid Sequence↗
Target antigens for anti-neutrophil cytoplasmic autoantibodies (ANCA) are on the surface of primed and apoptotic but not unstimulated neutrophils.
The reaction of ANCA with ANCA antigens on the surface of neutrophils may play a critical role in the pathogenesis of ANCA vasculitis. Therefore, an understanding of the circumstances that result in surface expression of these antigens is important for an understanding of pathogenic mechanisms. In this study we investigated the surface expression of ANCA antigens on quiescent, primed, and apoptotic neutrophils. ANCA antigens and other granule constituents were not detected on the surface of neutrophils in freshly heparinized blood. ANCA antigens were on the surface of neutrophils primed by in vitro incubation for 4 h and 8 h. These cells did not show evidence of apoptosis. After 24 h incubation, about 30% of the neutrophils were apoptotic, and ANCA antigens and other granule constituents were present on the surface of both apoptotic and non-apoptotic cells. Our data indicate that there are no ANCA antigens on the surface of quiescent neutrophils, but that they are on the surface of primed neutrophils before the cells become apoptotic, and remain on the surface of cells after they become apoptotic. Based on these observations, we hypothesize that ANCA can react in vivo with primed but not quiescent neutrophils. Previously published observations indicate that the interaction of ANCA with primed neutrophils results in neutrophil activation, which may be involved in the pathogenesis of ANCA vasculitis.
Animals↗
ANCA antigens, proteinase 3 and myeloperoxidase, are not expressed in endothelial cells.
BACKGROUND: One hypothesis for the pathogenesis of vasculitis associated with antineutrophil cytoplasmic autoantibodies (ANCAs) proposes that ANCAs bind to ANCA antigens, such as proteinase 3 (PR3) or myeloperoxidase (MPO), which are produced by endothelial cells and expressed on their surfaces. There are conflicting reports, however, on whether endothelial cells express the ANCA antigen PR3, and there are no reports on endothelial expression of MPO. The aim of this study was to determine the presence or absence of PR3 and MPO mRNA in both venous and arterial endothelial cells, employing standard reverse transcription-polymerase chain reaction (RT-PCR) techniques and also the quantitative and highly specific method, TaqMan PCR. METHODS: RT-PCR (with 3 primer sets) and TaqMan PCR, a method for detecting low copy transcripts, were used to probe for PR3 and MPO transcripts in human endothelial cells from umbilical vein (HUVEC) and artery (HUAEC) and from lung microvascular (HLMVEC). Cells were treated with interferon-gamma (200 units/mL) or tumor necrosis factor-alpha (3 or 10 ng/mL) or both. RESULTS: Transcripts for PR3 and/or MPO were not detected in HUVEC, HUAEC, and HLMVEC by standard RT-PCR. Analyses for PR3 protein confirmed that PR3 is not expressed in HUVEC. HUVEC and HUAEC were negative for PR3 and MPO by TaqMan PCR. CONCLUSIONS: PR3 and MPO are not expressed in HUVEC, HUAEC, or HLMVEC. Endothelial cell presentation of endogenous PR3 and MPO antigens is not involved in the pathogenesis of ANCA-associated vasculitis. Alternative explanations need to be explored to determine the pathogenic effect of ANCAs.
Antibodies, Antineutrophil Cytoplasmic↗
A new acylated flavonol glycoside and antioxidant effects of Hedyotis diffusa.
A study on the bioactive principles of Hedyotis diffusa Willd., led to the isolation of a new acyl flavonol di-glycoside which was characterized as kaempferol 3-O[2"-O-(E-6'"-O-feruloyl)-beta-D-glucopyranosyl]-beta-D-galactop yranoside by spectral and chemical methods from the methanolic extract. In addition, three known flavonol glycosides and six known iridoid glycosides were also obtained. The above-mentioned glycosides were tested for antioxidant effects on xanthine oxidase inhibition, xanthine-xanthine oxidase cytochrome c and TBA-MDA systems.
Acylation↗
Nonnative intermediate state of acid-stable beta-sheet protein.
Cell adhesion molecule, CD2, from the immunoglobulin superfamily, is comprised of antibodies and Ig-like domains and plays a fundamental role, not only in the immune system, but also in the interactions between cells, specifically in cell-cell adhesion. This study examines the N-terminal domain 1 of CD2 (CD2-1) at different pHs, and in 2,2,2-trifluoroethanol (TFE), using nears- and far-UV circular dichroism (CD), fluorescence, and 1H nuclear magnetic resonance to elucidate factors contributing to the Ig beta-structure. Contrary to the complete unfolding induced by guanidinehydrochloride, CD2-1 retains its native tertiary structure at pHs from 1.0 to 10.0. Like the effects of high temperatures that have previously been observed, TFE reduces the integrity of the tertiary structure, while reorganizing the secondary structure from a native all-beta-sheet to a significantly alpha-helical conformation. The induced helicity of CD2-1 correlates with the helicity inherent in its primary sequence. Our results suggest that electrostatic interactions are less important for the formation of the native secondary and tertiary structure of CD2-1, although they are crucial for CD2's adhesion function. Interference with the protein's hydrophobic interactions and hydrogen-bonding networks, however, causes significant changes in its conformation. Residues of CD2-1, with high conformational flexibility, may contribute for the formation of a metastable dimer by domain-swapping.
Amino Acid Sequence↗
Genetic and physical mapping of a type 1 diabetes susceptibility gene (IDDM12) to a 100-kb phagemid artificial chromosome clone containing D2S72-CTLA4-D2S105 on chromosome 2q33.
Polymorphic markers within the CTLA4 gene on chromosome 2q33 have been shown to be associated with type 1 diabetes. Therefore, a gene responsible for the disease (IDDM12) most likely lies within a region of <1-2 cM of CTLA4. To define more precisely the IDDM12 interval, we genotyped a multiethnic (U.S. Caucasian, Mexican-American, French, Spanish, Korean, and Chinese) collection of 178 simplex and 350 multiplex families for 10 polymorphic markers within a genomic interval of approximately 300 kb, which contains the candidate genes CTLA4 and CD28. The order of these markers (D2S346, CD28, GGAA19E07, D2S307, D2S72, CTLA4, D2S105, and GATA52A04) was determined by sequence tagged site content mapping of bacterial artificial chromosome (BAC) and yeast artificial chromosome (YAC) clones. The transmission disequilibrium test (TDT) analyses of our data revealed significant association/linkage with three markers within CTLA4 and two immediate flanking markers (D2S72 and D2S105) on each side of CTLA4 but not with more distant markers including the candidate gene CD28. Tsp analyses revealed significant association only with the three polymorphic markers within the CTLA4 gene. The markers linked and associated with type 1 diabetes are contained within a phagemid artificial chromosome clone of 100 kb, suggesting that the IDDM12 locus is either CTLA4 or an unknown gene in very close proximity.
Abatacept↗
Left prefrontal cortex activation during semantic encoding accessed with functional near infrared imaging.
OBJECTIVE: To investigate the left prefrontal lobe activation during semantic and non-semantic encoding tasks with functional near-infrared imaging (fNIRI) technique. METHOD: 22 healthy subjects were assigned semantic encoding and non-semantic encoding tasks. During semantic encoding tasks, subjects were asked to make a meaningful sentence including two unrelated Chinese word pairs, while during non-semantic encoding task they were asked to judge whether the two Chinese word pairs had the same morphological structure or not. Light intensity of two wavelengths (760 nm and 850 nm) diffused through skull and left prefrontal lobe were real-time recorded and used to reconstruct the brain activation image during the experiment. RESULT: With the fNIRI, significant activations were observed in the left inferior prefrontal cortex (Brodmann' areas 45 and 47) during the two tasks, but the evoked activations were more significant for semantic than non-semantic task. These observations were consistent with the results reported by others with functional megnetic resonance imaging (fMRI) and positron-emission tomography PET. CONCLUSION: The results suggest that fNIRI provides an important, non-invasive way to map the prefrontal activation during cognitive tasks.
Adolescent↗
[Intranasal endoscopic treatment of chronic sinusitis in children].
OBJECTIVE: To explore the curative effect of endoscopic sinus surgery (ESS) and the factors associated with surgery effect for treating children with chronic sinusitis. METHOD: Thirty-one children with a median age of 10 years (range 5-14 years) who suffered from chronic sinusitis or/and nasal polyps and were operated via ESS from May 1996 to January 1999 were retrospectively analyzed. RESULT: According to the therapeutic evaluation standard (ESS-1997, Haikou), twelve cases (38.7%) were completely cured, fifteen cases (48.4%) were improved and four children (12.9%) showed no change with a general effective rate of 87.1% without any severe operative complication. CONCLUSION: The results suggested ESS is a safe and effective method in the treatment of children with chronic sinusitis or/and nasal polyps. Furthermore, meticulous postoperative endoscopic care and medication are also important for securing optimal long-term results.
Adolescent↗
Effects of diesel exhaust particles (DEP), carbon black, and silica on macrophage responses to lipopolysaccharide: evidence of DEP suppression of macrophage activity.
The effects of diesel exhaust particle (DEP) exposure on alveolar macrophage (AM) response to ex vivo and in vivo lipopolysaccharide (LPS) challenge were determined by monitoring LPS-stimulated production of interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha). The roles of the insoluble particulate and the organic compounds of DEP in altering pulmonary responses were evaluated by comparing the DEP-induced pulmonary responses to those of carbon black (CB), a carbonaceous particle with few adsorbed organic compounds, or to silica, a known pneumotoxic dust. Male Sprague-Dawley rats were exposed to a single intratracheal dose (5 or 35 mg/kg body weight) of DEP, CB, or silica, or to saline vehicle. Rats were sacrificed 1, 3, or 7 d postexposure. To study the responsiveness to the bacterial product LPS, AM isolated from particle-exposed rats were challenged ex vivo with LPS (0.1 microg/10(6) AM) and LPS-stimulated cytokine release was monitored. In addition, rats were exposed intratracheally to a single dose of DEP (5 mg/kg) and 3 d later exposed in vivo to 1 mg/kg LPS for 3 h prior to measurement of cytokine production by AM. DEP exposure resulted in neutrophil infiltration and elevated levels of albumin and lactate dehydrogenase (LDH) activity in the bronchoalveolar lavage fluid; these responses were not substantially different from those elicited by CB or silica exposure. AM from DEP-exposed rats showed increased spontaneous production of IL-1, but not TNF-alpha, while the opposite was true for CB or silica. Upon ex vivo challenge with LPS, AM from DEP-exposed rats showed a significant decrease in the secretion of TNF-alpha and, to a lesser extent, IL-1, compared to the sum of the DEP and LPS effects. In contrast, AM from CB- or silica-exposed rats did not show this decreased responsiveness to subsequent LPS challenge. This inhibitory action of DEP on LPS-stimulated AM production of IL-1 and TNF-alpha was further confirmed by the results obtained from rats exposed to both DEP and LPS in vivo. In summary, these results indicate that while DEP, CB, and silica all induce pulmonary inflammatory responses due to particle stimulation, only DEP suppress AM cytokine release in response to LPS stimulation. The contrasting cellular response with respect to DEP and CB exposures may be due to the presence of adsorbed organic compounds on DEP, which may contribute to the increased susceptibility of hosts to pulmonary infections after DEP exposure.
Albumins↗
Difference in the effects of radioprotection between aerial and root parts of Lycium chinense.
Radiation protection from bone marrow death by consecutive injections of crude extracts from different parts of Lycium chinense (LC), root (LCR) and aerial part (LCA), before whole body X-irradiation was confirmed by tests with ICR strain mice. Both extracts were effective after intraperitoneal injection of a high dose, once a day, for seven consecutive days before irradiation. Based on the studies of endogenous hematopoietic spleen colony formation (CFUs), and the postirradiation behavior of hematograms and hematocrits, it was demonstrated that the LCR protects mice more effective when given in a dose of 500 mg/kg. Enhanced CFUs was found in the irradiation range of 4-8 Gy by various treatments. Recovery of leukocyte, erythrocyte and thrombocyte counts was significantly stimulated by the extract of LCR with 500 mg/kg administration. Stimulated recovery by the extract from the LCR was also observed in hematocrit. On the contrary, the extracts of both LCA and LCR did not markedly affect recovery of leukocyte, erythrocyte, thrombocyte counts and hematocrits by 250 mg/kg administration. It could be deduced that the uncertainly radioprotective action is induced by a possible process of enhanced regeneration of the hematopoietic stem cells due to either enhanced postirradiation repair or an increased proliferation of the hematopoietic stem cells under the suitable extract administration.
Animals↗
Evaluation of the antioxidant activities of Erycibe obtusifolia.
Free radicals may be involved in various pathogenesis processes. Tissue damage and cellular toxicity of some chemicals mediated by oxygen free radicals can be monitored by studying the levels of lipid peroxidation in the tissues. The study reported here is to investigate the MDA concentrations in different tissues after various doses of Erycibe obtusifolia (EO) treatments. EO given at doses of 10, 20 and 30 mg/kg body weight is experimentally tested through oral administration. The antioxidant effect of EO extract is assessed by the measurements of hepatic, renal and splenic lipid peroxides (measured as malondialdehyde; MDA) after treatments. The results show no significant time-related and dose-dependent increase or decrease of MDA concentrations in the liver, kidney and spleen after EO administrations, respectively. The peak of antioxidant activities is found on the first day and the 6 hrs after treatments for liver and kidney, respectively. In contrast, the MDA concentrations in spleen after EO administrations remained above the normal values. This result suggests that a high dose of EO administration may contribute a little antioxidant activity in both liver and kidney.
Animals↗