Factors affecting human islet of Langerhans isolation yields.
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Adenosine↗
Biomedical subjects
Y Hong
Publications and source records attributed to Y Hong.
Acute rise of circulating vascular endothelial growth factor-A in patients with coronary artery disease following cardiothoracic surgery.
AIMS: Vascular endothelial growth factor-A (VEGF-A) is an angiogenic and vasoprotective molecule whose expression is modulated by hypoxia and inflammatory mediators. Here we have tested the hypothesis that plasma levels of VEGF-A are influenced by pre-existing coronary artery disease and by changes in circulating interleukin-6 (IL-6). METHODS AND RESULTS: Plasma VEGF-A and IL-6 were measured prior to and at various time intervals following surgery in individuals with angiographically normal coronary arteries requiring cardiac valve replacement (N group) and in patients with coronary artery disease and stable angina undergoing coronary artery bypass grafting (CAD group). Baseline VEGF-A levels were not significantly different in CAD (22.3+/-2.6 pg x ml(-1)) compared to the N group (14.9+/-2.9 pg x ml(-1)). Following cardiac surgery there was a significant rise of VEGF-A in CAD (P<0.0005 vs baseline), but not in the N group, reaching a maximum (approximately 2 fold increase) after 24 h. Surgery caused a rapid increase of plasma IL-6 in both groups, but the rise was significantly larger in CAD patients (P<0.0005 vs N) where it preceded the increase in VEGF-A. Furthermore, in patients with CAD there was a significant correlation between the change in VEGF-A and the change in IL-6 (P<0.04). CONCLUSION: These findings demonstrate that in patients with coronary artery disease cardiothoracic surgery leads to an acute rise in VEGF-A. We suggest that this rise may result from an interaction between the pre-existing atheromatous process and a systemic increase of inflammatory mediators.
Aged↗
Drosophila Stardust interacts with Crumbs to control polarity of epithelia but not neuroblasts.
Establishing cellular polarity is critical for tissue organization and function. Initially discovered in the landmark genetic screen for Drosophila developmental mutants, bazooka, crumbs, shotgun and stardust mutants exhibit severe disruption in apicobasal polarity in embryonic epithelia, resulting in multilayered epithelia, tissue disintegration, and defects in cuticle formation. Here we report that stardust encodes single PDZ domain MAGUK (membrane-associated guanylate kinase) proteins that are expressed in all primary embryonic epithelia from the onset of gastrulation. Stardust colocalizes with Crumbs at the apicolateral boundary, although their expression patterns in sensory organs differ. Stardust binds to the carboxy terminus of Crumbs in vitro, and Stardust and Crumbs are mutually dependent in their stability, localization and function in controlling the apicobasal polarity of epithelial cells. However, for the subset of ectodermal cells that delaminate and form neuroblasts, their polarity requires the function of Bazooka, but not of Stardust or Crumbs.
Adherens Junctions↗
Tomato yellow leaf curl China virus: monopartite genome organization and agroinfection of plants.
The complete DNA sequence (2734 nucleotides) of the monopartite genome of tomato yellow leaf curl China virus (TYLCCNV), a begomovirus transmitted by the whitefly Bemisia tabaci, was determined. The circular genomic DNA contains six open reading frames (ORFs) encoding proteins of molecular weights >10 kDa, of which two (V1 and V2) are located on the virion-sense strand and four (C1, C2, C3 and C4) on the complementary-sense strand. The ORFs are comparable to those of other whitefly-transmitted begomoviruses with a monopartite genome and to those encoded by DNA-A of bipartite begomoviruses. Sequence comparisons with other geminiviruses showed that TYLCCNV belongs to Begomovirus from the Old World. No putative DNA-B genome was found. Nicotiana species and tomato plants agroinoculated with the TYLCCNV monopartite genome developed typical yellowing and leaf-curling symptoms. The cloned molecule carried all the information needed for virus replication and systemic infection of plants.
China↗
Identification of alkylidene hydrazides as glucagon receptor antagonists.
High throughput screening of our small molecule combinatorial library identified a class of benzoylnaphthalenehydrazones with modest affinity for the human glucagon receptor. Optimization of this initial hit through a series of targeted libraries and traditional medicinal chemistry led to ligands with nanomolar affinities. Pharmacological evaluation demonstrated that these ligands were competitive glucagon receptor antagonists. Intravenous administration of a representative benzoylnaphthalenehydrazone into rats attenuated glucagon-stimulated glucose levels.
Animals↗
[Lumbar structural observation of children with cerebral palsy after selective posterior rhizotomy].
OBJECTIVE: To investigate the stability of lumbar column after selective posterior rhizotomy and to observe the healing of exscinded laminae. METHODS: One hundred and seventy nine children with spastic cerebral palsy were divided into four groups (A, B, C, D) according to the age (< 10 years or > or = 10 years) and walking ability (ambulatory or unable to walk) and were operated on by selective posterior rhizotomy (SPR). Lumbar X-ray films, both standing and lying position, and orthotopic and lateral dynamic lumbar films were taken pre- and postoperatively. Lumbosacral angle, Cobb's angle in lateral position, and AO/W, RO/W of dynamic films were recorded and analyzed according to Posner's definition. Regeneration of exscinded laminae was observed. RESULTS: (1) The lumbosacral angle, Cobb's angle, and other indicators in the ambulatory group (A + C) were not significantly varied pre- and postoperatively; (2) The lumbo-sacral angle, Cobb's angle, and other indicators in the groups unable to walk independently (B + D groups) were varied significantly. (3) Nine cases of scoliosis (with the Cobb's angle of 18 degrees-35 degrees) were found in the group of 10 years younger (9.38%); (4) Six cases of spondylolysis (7.23%, with Cobb's angle of 15 degrees-25 degrees) and 5 cases of spondylolisthesis (6.58%) were found in the group of 10 years older. (5) Osteous healing of sectioned laminae was found in the group of age younger than 10 years, especially in the young children. (6) Stability of lumbar vertebrae were not significantly varied pre- and post-operatively among all groups. CONCLUSION: The exscinded laminae of children after SPR have the healing ability. The stability of lumbar column was not significant varied pre- and postoperatively.
Adolescent↗
Regulation of heat shock transcription factor 1 by stress-induced SUMO-1 modification.
Heat shock transcription factor 1 (HSF1) mediates the induction of heat shock protein gene expression in cells exposed to elevated temperature and other stress conditions. In response to stress HSF1 acquires DNA binding ability and localizes to nuclear stress granules, but the molecular mechanisms that mediate these events are not understood. We report that HSF1 undergoes stress-induced modification at lysine 298 by the small ubiquitin-related protein called SUMO-1. Antibodies against SUMO-1 supershift the HSF1 DNA-binding complex, and modification of HSF1 in a reconstituted SUMO-1 reaction system causes conversion of HSF1 to the DNA-binding form. HSF1 colocalizes with SUMO-1 in nuclear stress granules, which is prevented by mutation of lysine 298. Mutation of lysine 298 also results in a significant decrease in stress-induced transcriptional activity of HSF1 in vivo. This work implicates SUMO-1 modification as an important modulator of HSF1 function in response to stress.
Cell Compartmentation↗
Interaction between protein phosphatase 5 and the A subunit of protein phosphatase 2A: evidence for a heterotrimeric form of protein phosphatase 5.
Members of the phosphoprotein phosphatase family of serine/threonine phosphatases are thought to exist in different native oligomeric complexes. Protein phosphatase 2A (PP2A) is composed of a catalytic subunit (PP2Ac) that complexes with an A subunit, which in turn also interacts with one of many B subunits that regulate substrate specificity and/or (sub)cellular localization of the enzyme. Another family member, protein phosphatase 5 (PP5), contains a tetratricopeptide repeat domain at its N terminus, which has been suggested to mediate interactions with other proteins. PP5 was not thought to interact with partners homologous to the A or B subunits that exist within PP2A. However, our results indicate that this may not be the case. A yeast two-hybrid screen revealed an interaction between PP5 and the A subunit of PP2A. This interaction was confirmed for endogenous proteins in vivo using immunoprecipitation analysis and for recombinant proteins by in vitro binding experiments. Our results also indicate that the tetratricopeptide repeat domain of PP5 is required and sufficient for this interaction. In addition, immunoprecipitated PP5 contains associated B subunits. Thus, our results suggest that PP5 can exist in a PP2A-like heterotrimeric form containing both A and B subunits.
Amino Acid Sequence↗
Association of C-reactive protein with markers of prevalent atherosclerotic disease.
Recent prospective studies have demonstrated that elevated C-reactive protein (CRP) is a marker of increased risk of atherothrombotic clinical events. We examined in a large, cross-sectional family-based study (n = 875 men, 948 women) whether serum CRP was associated with prevalent coronary heart disease (CHD), the ankle/brachial blood pressure index, or carotid intima-media thickness, an indicator of subclinical atherosclerosis as assessed by B-mode ultrasound. CRP was associated with many other cardiovascular risk factors, particularly markers of obesity and insulin resistance, markers of inflammation and acute phase reaction, and hormone replacement therapy. Adjusted for age and family type, there was a weak positive association of CRP with carotid intima-media thickness in both genders and with prevalent CHD in women. However, adjustment for other risk factors completely eliminated the associations. For example, among women, the risk factor-adjusted mean values of intima-media thickness across quartiles of CRP were 0.76, 0.74, 0.75, and 0.76 mm (p >0.5). In men there was a weak inverse association between CRP and ankle/brachial blood pressure index, independent of other risk factors, but no such association in women. Our findings indicate that CRP is not strongly and independently associated with prevalent atherosclerosis. Because CRP has been associated with clinical events, it could be that elevated CRP may be a stronger marker of thrombotic risk than of the degree of atherosclerosis.
Age Factors↗
Spinal delta-opioid receptors mediate suppression of systemic SNC80 on excitability of the flexor reflex in normal and inflamed rat.
Due to low central nervous system (CNS) bioavailability of delta-opioid peptides, little is known about the effect of systemic administration of delta-opioid receptor ligands. The present study examined the effect of non-peptidergic delta-opioid receptor agonists, (+)-4-[(alphaR)-alpha-((2R,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80) and (-)dibenzoyl-L-tartaric acid salt (SNC86), on the activity of alpha-motoneurons in decerebrate-spinal rats. The flexor reflex was facilitated by C-afferent conditioning inputs, shown by a decrease in mechanical threshold and increase in touch- and pinch-evoked responses. Systemic administration of SNC80 (10 micromol/kg) prevented and reversed the neuronal hyperactivity. We further examined the effect of this agonist on the hypersensitivity of the flexor reflex induced by intraplantar injection of Freund's adjuvant. SNC80 dose-dependently (1, 3, 5 and 10 micromol/kg) increased the mechanical threshold and decreased touch-, pinch- and Abeta-afferent inputs-evoked responses. Similar effects were seen with SNC86 (5 micromol/kg). Pretreatment with either naloxone (20 micromol/kg, i.p.) or (Cyclopropylmethyl)-6,7-dehydro-4,5alpha-epoxy-14beta-ethoxy-5beta-methylindolo [2',3':6',7']morphinan-3-ol hydrochloride (SH378; 5 micromol/kg, intraarterially (i.a.)), a novel selective delta-opioid receptor antagonist, completely abolished the anti-hypersensitivity effect of SNC80. The effect of SNC80 remained following intrathecal administration of mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2) (CTOP; 1.5 nmol). These results indicate that systemic injection of SNC80 exerted antihypersensitivity in models of both acute and tonic nociception and these effects are mediated mainly through a spinal delta-opioid mechanism.
Afferent Pathways↗
Regional characteristics of sulfur and lead isotope ratios in the atmosphere at several Chinese urban sites.
Sulfur and lead isotope ratios in the atmosphere were measured at several selected sites (Harbin, Changchun, Dalian, Waliguan, Shanghai, Nanjing, Guiyang) in China and Tsukuba (Japan), to reveal regional sources characteristics over Eastern Asia. Average S isotope ratios for SO2 and sulfate in the atmosphere in China were close to those of the coals used in each region, indicating a considerable contribution of coal combustion to the sulfur compounds in the atmosphere. Most northern cities had around 5% sulfur isotope ratio, while Guiyang, a southwestern city in China, showed a considerably lower sulfur isotope ratio (about -3%) because of the unusually light sulfur isotope ratio of coals in this region. These were considerably different from the value (-1.4%) for Tsukuba (Japan). Lead isotope ratios also suggested that coal combustion considerably contributed to atmospheric lead in some cases in China. At the same time, influences by the emission of Chinese lead ores were also observed in northern cities. Seasonal variations of both sulfur and lead isotope ratios indicated the existence of a certain amount of industrial sources other than coal combustion. In addition, fractionation effect between SO2 and sulfate showed a seasonal tendency (high in winter (0-6%) and low in summer (-1-3%)), suggesting the oxidation pathway of SO2 changed seasonally.
Air Pollution↗
Lack of ultraviolet-light inducibility of the medakafish (Oryzias latipes) tumor suppressor gene p53.
P53 is by far the most frequently altered gene in mammalian tumors. However, so far not a single p53 lesion has been reported in malignancies of cancer model systems in lower vertebrates. For analyzing the function of p53 in lower vertebrates, the gene was cloned from the medakafish (Oryzias latipes). Despite some differences in the genomic organization, the fish p53 amino acid sequence is highly conserved. Contrary to higher vertebrates, the level of p53 mRNA in medaka embryos gradually increases during embryogenesis. High expression of the p53 mRNA was detected in melanoma cells compared to undetectable expression of the gene in embryonic stem cells and fibroblasts. No effect of ultraviolet (UV) irradiation on the expression of p53 in cell cultures as well as in medaka fry was observed, indicating a possible difference in the function of p53 in lower vertebrates.
Amino Acid Sequence↗
Sumo-1 modification regulates the DNA binding activity of heat shock transcription factor 2, a promyelocytic leukemia nuclear body associated transcription factor.
Heat shock transcription factor 2 (HSF2) is a transcription factor that regulates heat shock protein gene expression, but the mechanisms regulating the function of this factor are unclear. Here we report that HSF2 is a substrate for modification by the ubiquitin-related protein SUMO-1 and that HSF2 colocalizes in cells with SUMO-1 in nuclear granules. Staining with anti-promyelocytic leukemia antibodies indicates that these HSF2-containing nuclear granules are PML bodies. Our results identify lysine 82 as the major site of SUMO-1 modification in HSF2, which is located in a "wing" within the DNA-binding domain of this protein. Interestingly, SUMO-1 modification of HSF2 results in conversion of this factor to the active DNA binding form. This is the first demonstration that SUMO-1 modification can directly alter the DNA binding ability of a transcription factor and reveals a new mechanism by which SUMO-1 modification can regulate protein function.
Biological Transport↗
Solution structure determination and mutational analysis of the papillomavirus E6 interacting peptide of E6AP.
E6AP is a cellular protein that binds cancer-related papillomaviral E6 proteins. The E6 binding domain, called E6ap, is located on an 18-amino acid segment of E6AP. The corresponding peptide was synthesized and its structure determined by nuclear magnetic resonance spectroscopy. The overall structure of the peptide is helical. A consensus E6-binding sequence among different E6 interacting proteins contains three conserved hydrophobic residues. In the structure of the E6AP peptide, the three conserved leucines (Leu 9, Leu 12, and Leu 13) form a hydrophobic patch on one face of the alpha-helix. Substitution of any of these leucines with alanine abolished binding to E6 protein, indicating that the entire hydrophobic patch is necessary. Mutation of a glutamate to proline, but not alanine, also disrupted the interaction between E6 and E6AP protein, suggesting that the E6-binding motif of the E6AP protein must be helical when bound to E6. Comparison of the E6ap structure and mutational results with those of another E6-binding protein (E6BP/ERC-55) indicates the existence of a general E6-binding motif.
Amino Acid Sequence↗
Its8, a fission yeast homolog of Mcd4 and Pig-n, is involved in GPI anchor synthesis and shares an essential function with calcineurin in cytokinesis.
In fission yeast, calcineurin is required for cytokinesis and ion homeostasis; however, most of its physiological roles remain obscure. To identify genes that share an essential function with calcineurin, we screened for mutations that confer sensitivity to the calcineurin inhibitor FK506 and high temperature and isolated the mutant its8-1. its8(+) encodes a homolog of the budding yeast MCD4 and human Pig-n that are involved in glycosylphosphatidylinositol (GPI) anchor synthesis. Consistently, reduced inositol labeling of proteins suggested impaired GPI anchor synthesis in its8-1 mutants. The temperature upshift induced a further decrease in inositol labeling and caused dramatic increases in the frequency of septation in its8-1 mutants. BE49385A, an inhibitor of MCD4 and Pig-n, also increased the septation index of the wild-type cell. Osmotic stabilization suppressed these morphological defects, indicating that cell wall weakness caused by impaired GPI anchor synthesis resulted in abnormal cytokinesis. Furthermore, calcineurin-deleted cells exhibited hypersensitivity to BE49385A, and FK506 exacerbated the cytokinesis defects of the its8-1 mutant. Thus, calcineurin and Its8 may share an essential function in cytokinesis and cell viability through the regulation of cell wall integrity.
Amino Acid Sequence↗
PIG-M transfers the first mannose to glycosylphosphatidylinositol on the lumenal side of the ER.
Glycosylphosphatidylinositol (GPI) acts as a membrane anchor of many cell surface proteins. Its structure and biosynthetic pathway are generally conserved among eukaryotic organisms, with a number of differences. In particular, mammalian and protozoan mannosyltransferases needed for addition of the first mannose (GPI-MT-I) have different substrate specificities and are targets of species- specific inhibitors of GPI biosynthesis. GPI-MT-I, however, has not been molecularly characterized. Characterization of GPI-MT-I would also help to clarify the topology of GPI biosynthesis. Here, we report a human cell line defective in GPI-MT-I and the gene responsible, PIG-M. PIG-M encodes a new type of mannosyltransferase of 423 amino acids, bearing multiple transmembrane domains. PIG-M has a functionally important DXD motif, a characteristic of many glycosyltransferases, within a domain facing the lumen of the endoplasmic reticulum (ER), indicating that transfer of the first mannose to GPI occurs on the lumenal side of the ER membrane.
Amino Acid Sequence↗
Sibling correlation of left ventricular mass and geometry in hypertensive African Americans and whites: the HyperGEN study. Hypertension Genetic Epidemiology Network.
BACKGROUND: Evidence suggests that left ventricular (LV) mass is under genetic control, independently of risk factors known to influence LV size and geometry. METHODS: As part of the HyperGEN study, four field centers recruited African American and white hypertensive siblings (n = 1,664), aged 23 to 87 years. Two-dimensionally guided M-mode echocardiography was performed, and LV mass and relative wall thickness (RWT) were measured at a central reading center. Familial correlations were calculated separately for each ethnic group using maximum likelihood methods, adjusted for the potential confounding influences of age, gender, systolic blood pressure, and obesity. RESULTS: In African Americans, brother-sister, brother-brother, and sister-sister correlation coefficients and standard errors for LV mass were 0.29 (0.08), 0.44 (0.10), and 0.33 (0.05). In whites, the corresponding correlations were lower than in African Americans at 0.05 (0.08), 0.12 (0.11), and 0.22 (0.09), respectively. Sibling correlation of LV geometry, assessed by RWT, was less in African Americans than in whites: brother-sister, 0.04 (0.10) v 0.21 (0.10), brother-brother, 0.12 (0.22) v 0.28 (0.09), and sister-sister, 0.11 (0.07) v 0.19 (0.11). CONCLUSIONS: LV mass is strongly correlated in hypertensive African American siblings, and modestly correlated in their white counterparts, whereas RWT has stronger sibling correlation in whites. The patterns of familial correlation of echocardiographic LV mass and RWT suggest that the genetic underpinnings of LV hypertrophy and geometric remodeling may differ among ethnic groups.
Adult↗
Efficiency, efficacy and adverse effects of adenovirus versus liposome-mediated ex vivo immunosuppressive cytokine gene transfer on the functional cardiac allografts.
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Journal Article↗