SEARCH · Search PubMed

Results for “HS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 487 records · Page 27Linked to original sources

PubMed1992

Metabolic pathways of heparan sulfate proteoglycans in a rat parathyroid cell line.

The distribution of heparan sulfate (HS) proteoglycans in clonal rat parathyroid cells is regulated by the extracellular Ca2+ concentration, which is a principal factor for parathyroid cell function (Takeuchi, Y., Sakaguchi, K., Yanagishita, M., Aurbach, G. D., and Hascall, V. C. (1990) J. Biol. Chem. 265, 13661-13668). Increasing the concentration of extracellular Ca2+ in the physiological range redistributes HS proteoglycans from the cell surface to an intracellular compartment. We have now examined effects of the extracellular Ca2+ concentration on the metabolism of the HS proteoglycans in detail using [35S]sulfate metabolic labeling-chase experiments. Two distinct metabolic pathways were demonstrated: (i) the intracellular generation of HS chains from HS proteoglycans in prelysosomal compartments followed by their release into the medium (pathway 1), and (ii) intracellular generation of HS oligosaccharides from HS chains in prelysosomal compartments, which are eventually degraded into free sulfate in lysosomes (pathway 2). The HS oligosaccharides were exclusively present within the cells, whereas HS chains were found primarily in the medium. The cells do not internalize either HS proteoglycans or HS chains from the medium. These observations indicate that these two degradation pathways are independent. In addition to these pathways, approximately 15% of the HS proteoglycans were released into the medium as a proteoglycan form. Treatment of cells with chloroquine, a lysosomotropic agent, did not affect generation of HS chains but inhibited conversion of HS chains to HS oligosaccharides or to free sulfate and resulted in the release of HS chains from the cells. The drug did not affect metabolic pathway 1. The extracellular Ca2+ concentration did not alter these intracellular degradation pathways for HS proteoglycans in the parathyroid cells. Thus, extracellular Ca2+ appears to regulate only the distribution of HS proteoglycans between the cell surface and intracellular compartments, and the process of cycling between these compartments when extracellular Ca2+ is low.

Animals↗

PubMed1997

Biosynthesis of the peptide bond in the coenzyme N-(7-mercaptoheptanoyl)-L-threonine phosphate.

The biochemical mechanism for the formation of the amide bond in N-(7-mercaptoheptanoyl)-L-threonine phosphate (HS-HTP) has been studied by measuring the incorporation of L-[3-(3)H]threonine into N-(7-mercaptoheptanoyl)-L-threonine (HS-HT) by cell extracts (CE) of Methanosarcina thermophila incubated with different precursors. Synthesis of HS-HT was observed from L-[3-(3)H]threonine and 7-mercaptoheptanoic acid (HS-H) when the incubations were conducted with either crude CE or Sephadex column-purified CE. In the presence of CE, the synthesis of HS-HT was found to be inhibited 66% by preincubation of the extract with ATPase, indicating that ATP was involved in the biosynthesis. In spite of this indication of ATP involvement in the coupling reaction, incubation of the crude CE with L-[3-(3)H]threonine, HS-H, and ATP was found to inhibit the formation of HS-HT. In contrast, the synthesis of HS-HT in the presence of Sephadex column-purified CE was found to be stimulated by the addition of ATP. Incubation of the crude CE with the CoA thioester of 7-mercaptoheptanoic acid (HS-HCoA) or the mixed disulfide formed between coenzyme M and 7-mercaptoheptanoic acid did not stimulate the biosynthesis. The biosynthesis of HS-HT was found to be strongly inhibited by an ethanol extract of the crude CE. This inhibition was found to be attributed to the HS-HTP present in the extract. Stimulation of HS-HT biosynthesis 300-fold was observed when the Sephadex column-purified CE was incubated with L-[3-(3)H]threonine and 7-mercaptoheptanoyl phosphate (HS-H-P). Data indicate that HS-HT is produced by the phosphorylation of HS-H to HS-H-P with ATP, which then reacts with L-threonine to produce HS-HT.

Adenosine Triphosphate↗

PubMed2007

The effect of heat shock on paclitaxel production in Taxus yunnanensis cell suspension cultures: role of abscisic acid pretreatment.

The heat shock (HS) response is a conserved cellular defense mechanism to elevated temperatures, observed in cells from bacteria to human. It is characterized by the increased accumulation of HS proteins. This work examines the effect of HS on the secondary metabolite biosynthesis of cultured plant cells. Suspension cultures of Taxus yunnanensis cells, which produce the anticancer diterpenoid paclitaxel (Taxol), were heat shocked at 35-50 degrees C for 30-60 min. The results show that HS reduced cell viability and growth but significantly induced paclitaxel production. The HS-induced paclitaxel production depended on the intensity of HS and the physiological state of the cells. Abscisic acid (ABA)-pretreatment not only increased cell viability and growth upon HS but also improved HS-induced paclitaxel yield. The best culture phase to apply the HS was the late-exponential growth phase. Under the optimized condition, HS enhanced paclitaxel yield by sixfold to 6.8 mg/L. In addition, a prior mild-HS treatment also significantly increased HS-induced paclitaxel production. Furthermore, HS induced oxidative burst, the early event of plant defense response to pathogen attack and other stress challenge; the addition of putative inhibitors of lipoxygenase, a key enzyme for jasmonic acid biosynthesis, significantly inhibited HS-induced pacliatxel accumulation. The stimulation of secondary metabolite production by HS may be a result of HS-induced plant cell defense response.

Abscisic Acid↗

PubMed1994

Autoantibodies to vascular heparan sulfate proteoglycan in systemic lupus erythematosus react with endothelial cells and inhibit the formation of thrombin-antithrombin III complexes.

Vascular heparan sulfate proteoglycan (vHSPG) is an important functional component of the microvasculature. Previous studies have demonstrated autoimmunity to vHSPG in systemic lupus erythematosus (SLE). In the current studies, we further investigated the immunospecificity of anti-vHSPG antibodies in SLE sera by enzyme-linked immunoassay (ELISA). In direct binding assays, SLE sera contained IgG antibodies reactive with native vHSPG and with heparan sulfate (HS) glycosaminoglycan in significantly higher titers than controls. Employing purified SLE IgG in liquid-phase competitive immunoinhibition ELISAs, SLE IgG anti-HS antibodies cross-reacted with heparin and DNA, but not with other glycosaminoglycans or anionic phospholipid antigens. Immunochemical studies demonstrated that the immunodominant site on HS recognized by SLE IgG contained 2-O-sulfated uronic acid. Removal of N-sulfated and 6-O-sulfated residues primarily on N-acetyl-glucosamine had no effect on antigenicity, further demonstrating that nonspecific charge interactions which are the result of sulfation do not solely account for the antigenicity of HS. SLE IgG from patients with active SLE was further affinity purified on DNA-cellulose and HS-Sepharose columns for immunospecificity studies. After affinity purification of both anti-DNA and anti-HS antibodies, significant enhancement of direct binding reactivity with HS was noted. In addition, anti-DNA and anti-HS IgG antibody reacted with the cell surface of endothelial cells by a cellular ELISA (CELISA). Immunoinhibition studies of CELISA reactivity confirmed that affinity-purified SLE IgG anti-DNA anti-HS antibody were reactive with endothelial cell surface HS antigens. Furthermore, SLE IgG anti-DNA antibody reactivity with endothelial cells was not reduced by DNase treatment of the cells, but was significantly reduced by heparitinase digestion. Since HS plays an important role in the maintenance of normal anticoagulation on the endothelial cell surface by binding antithrombin III, we investigated the inhibition of heparin-accelerated thrombin-antithrombin III complex formation by SLE IgG. Purified IgG from patients with active SLE, but not from normal controls, inhibited heparin-accelerated formation of TAT complexes. These studies demonstrate the presence of IgG autoantibodies to HS in patients with SLE. Anti-HS antibodies recognize an antigenic site also present in heparin, but not other glycosaminoglycans, bind to the endothelial cell surface, and inhibit the formation of TAT complexes. SLE IgG anti-HS antibodies recognize a sulfated uronic acid epitope containing 2-O-sulfate which is important in certain functions of HS, including antithrombin III binding. Thus, anti-HS antibodies may promote a procoagulant state at the endothelial cell surface.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1994

Multivalent ligand-receptor binding interactions in the fibroblast growth factor system produce a cooperative growth factor and heparin mechanism for receptor dimerization.

The binding interactions for the three primary reactants of the fibroblast growth factor (FGF) system, basic FGF (bFGF), an FGF receptor, FGFR1, and the cofactor heparin/heparan sulfate (HS), were explored by isothermal titrating calorimetry, ultracentrifugation, and molecular modeling. The binding reactions were first dissected into three binary reactions: (1) FGFR1 + bFGF<==>FGFR1/bFGF, K1 = 41 (+/- 12) nM; (2) FGFR1 + HS<==>FGFR1/HS, K2 = 104 (+/- 17) microM; and (3) bFGF + HS<==>bFGF/HS, K3 = 470 (+/- 20) nM, where HS = low MW heparin, approximately 3 kDa. The first, binding of bFGF to FGFR1 in the absence of HS, was found to be a simple binary binding reaction that is enthalpy dominated and characterized by a single equilibrium constant, K1. The conditional reactions of bFGF and FGFR1 in the presence of heparin were then examined under conditions that saturate only the bFGF heparin site (1.5 equiv of HS/bFGF) or saturate the HS binding sites of both bFGF and FGFR1 (1.0 mM HS). Both 3-and 5-kDa low MW heparins increased the affinity for FGFR1 binding to bFGF by approximately 10-fold (Kd = 4.9 +/- 2.0 nM), relative to the reaction with no HS. In addition, HS, at a minimum of 1.5 equiv/bFGF, induced a second FGFR1 molecule to bind to another lower affinity secondary site on bFGF (K4 = 1.9 +/- 0.7 microM) in an entropy-dominated reaction to yield a quaternary complex containing two FGFR1, one bFGF, and at least one HS. Molecular weight estimates by analytical ultracentrifugation of such fully bound complexes were consistent with this proposed composition. To understand these binding reactions in terms of structural components of FGFR1, a three-dimensional model of FGFR1 was constructed using segment match modeling. Electrostatic potential calculations confirmed that an elongated cluster, approximately 15 x 35 A, of nine cationic residues focused positive potential (+2kBT) to the solvent-exposed beta-sheet A, B, E, C' surface of the D(II) domain model, strongly implicating this locus as the HS binding region of FGFR1. Structural models for HS binding to FGFR1, and HS binding to bFGF, were built individually and then assembled to juxtapose adjacent binding sites for receptor and HS on bFGF, against matching proposed growth factor and HS binding sites on FGFR1. The calorimetric binding results and the molecular modeling exercises suggest that bFGF and HS participate in a concerted bridge mechanism for the dimerization of FGFR1 in vitro and presumably for mitogenic signal transduction in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

PubMed2001

6-O-sulfotransferase-1 represents a critical enzyme in the anticoagulant heparan sulfate biosynthetic pathway.

Using recombinant retroviral transduction, we have introduced the heparin/heparan sulfate (HS) 3-O-sulfotransferase 1 (3-OST-1) gene into Chinese hamster ovary (CHO) cells. Expression of 3-OST-1 confers upon CHO cells the ability to produce anticoagulantly active HS (HS(act)). To understand how 6-OST and other proteins regulate HS(act) biosynthesis, a CHO cell clone with three copies of 3-OST-1 was chemically mutagenized. Resulting mutants that make HS but are defective in generating HS(act) were single-cell-cloned. One cell mutant makes fewer 6-O-sulfated residues. Modification of HS chains from the mutant with pure 6-OST-1 and 3'-phosphoadenosine 5'-phosphosulfate increased HS(act) from 7% to 51%. Transfection of this mutant with 6-OST-1 created a CHO cell line that makes HS, 50% of which is HS(act). We discovered in this study that (i) 6-OST-1 is a limiting enzyme in the HS(act) biosynthetic pathway in vivo when the limiting nature of 3-OST-1 is removed; (ii) HS chains from the mutant cells serve as an excellent substrate for demonstrating that 6-OST-1 is the limiting factor for HS(act) generation in vitro; (iii) in contradiction to the literature, 6-OST-1 can add 6-O-sulfate to GlcNAc residues, especially the critical 6-O-sulfate in the antithrombin binding motif; (iv) both 3-O- and 6-O-sulfation can be the final step in HS(act) biosynthesis in contrast to prior publications that concluded 3-O-sulfation is the final step in HS(act) biosynthesis; (v), in the presence of HS interacting protein peptide, 3-O-sulfate-containing sugars can be degraded into disaccharides by heparitinase digestion as demonstrated by capillary high performance liquid chromatography coupled with mass spectrometry.

Animals↗

PubMed2002

Role of seminal plasma in heat stress infertility of broiler breeder males.

The present research was undertaken to determine the role of seminal plasma in heat stress (HS) infertility. Males were exposed to HS at 32 C or maintained at 21 C as controls. Centrifugation and reconstitution of semen samples created four final treatments: control sperm + control plasma (CsCp), control sperm + HS plasma (CsHp), HS sperm + HS plasma (HsHp), and HS sperm + control plasma (HsCp). Semen samples with HS males' seminal plasma had lower sperm quality index values than those containing plasma from control males. Seminal plasma from HS males diminished fertility of control sperm, and control seminal plasma did not improve fertility of HS sperm. Therefore, regardless of seminal plasma source, HS sperm had a lower fertilization rate than control sperm. Also, seminal plasma from semen samples with HS sperm (HsHp and HsCp) contained lower Ca, Na+ and Cl- concentrations than seminal plasma from semen samples with control sperm (CSCp and CsHp). When HS seminal plasma was mixed with control sperm, plasma ion concentrations increased, indicating an efflux of ions from the control sperm to the HS seminal plasma. On the other hand, when control seminal plasma was mixed with HS sperm, plasma ion concentrations decreased, indicating an influx of ions from the control seminal plasma to the HS sperm. Therefore, control sperm appear to have higher intracellular ion concentrations than the sperm from HS males. In conclusion, high temperatures might decrease male fertility by decreasing seminal plasma and intracellular ion concentrations.

Animals↗

PubMed2006

Bovine polymerized hemoglobin (hemoglobin-based oxygen carrier-201) resuscitation in three swine models of hemorrhagic shock with militarily relevant delayed evacuation--effects on histopathology and organ function.

OBJECTIVE: To test our hypothesis that hemoglobin-based oxygen carrier (HBOC)-201 resuscitation in hemorrhagic shock (HS) will not lead to increased organ injury and dysfunction. DESIGN: Three swine HS models simulating military-relevant delayed evacuation: a) moderate controlled HS, b) severe controlled HS, and c) severe uncontrolled HS. SETTING: Military research laboratory. SUBJECTS: Swine. INTERVENTIONS: Swine were anesthetized/intubated and instrumented. To induce HS, in two controlled hemorrhage experiments, 40% (moderate controlled HS) or 55% (severe controlled HS) of blood volume was withdrawn; in an uncontrolled HS experiment, the liver was crushed/lacerated. During a 4-hr "prehospital phase," pigs were resuscitated with HBOC-201 (HBOC) or Hextend (HEX) or were nonresuscitated (NON). Upon "hospital arrival," liver injury was repaired (severe uncontrolled HS), blood or saline was infused, hemodynamics were monitored, and blood was collected. Upon animal death and/or 72 hrs, necropsy was followed by histopathologic evaluation of organ injury (hematoxylin and eosin, electron microscopy) and immunohistochemistry of oxidative potential (3-nitrotyrosine). Significance (p < .05) was assessed by Kruskal-Wallis, analysis of variance/Bonferroni, and mixed procedure tests. MEASUREMENTS AND MAIN RESULTS: Survival was significantly higher with HBOC than HEX only with severe uncontrolled HS (p = .002). Myocardial necrosis/fibroplasia, fluid requirements, cardiac output, and cardiac enzymes were generally similar or lower in HBOC than HEX pigs, but creatine kinase-MB (but not creatine kinase-MB/creatine kinase ratio) was higher with HBOC in moderate controlled HS. Alveolar/interstitial pulmonary edema was similar with HBOC and HEX, but Po2 was higher with HBOC in severe uncontrolled HS. Jejunal villar epithelial and hepatocellular necrosis were similarly minimal to moderate in all groups. Minimal biliary changes occurred exclusively with HBOC. Aspartate aminotransferase, lactate dehydrogenase, and alkaline phosphatase were generally higher with HBOC than HEX. Mild renal papillary injury occurred more frequently with HBOC, but consistent patterns for urine output, blood urea nitrogen, and creatinine, were not seen. The 3-nitrotyrosine staining intensity was not different. CONCLUSIONS: In comparison with hetastarch, HBOC-201 resuscitation of swine with HS increased survival (with severe HS), did not increase evidence of oxidative potential, and had histopathologic and/or functional effects on organs that were clinically equivocal (myocardium, lungs, hepatic parenchyma, jejunum, and renal cortex/medulla) and potentially adverse (hepatobiliary and renal papilla). The effects of HBOC-201-resuscitation in HS should be corroborated in controlled clinical trials.

Analysis of Variance↗

PubMed2006

Vasoactivity of bovine polymerized hemoglobin (HBOC-201) in swine with traumatic hemorrhagic shock with and without brain injury.

BACKGROUND: We previously reported that bovine polymerized hemoglobin (HBOC- 201) improved outcome in swine with hemorrhagic shock (HS) with and without traumatic brain injury (TBI). Herein, we add analyses of blood pressure (BP) responses, associated physiologic data, and HS fluid infusion guidelines. METHODS: HBOC-201 versus standard fluid resuscitation was compared in four anesthetized invasively monitored swine models: moderate controlled HS, severe controlled HS, severe uncontrolled HS (liver injury), and severe uncontrolled HS/TBI (liver/parietal brain injuries). Pigs received fluid for hypotension and tachycardia, and were followed up to 6 (HS alone) or 72 hours (HS/TBI). The change in mean arterial pressure (DeltaMAP) response severity was stratified and analyzed based on infusion number and HS severity, using Student's t and Fisher's exact tests. RESULTS: HBOC-201 vasoactivity resulted in higher MAP in all studies. Among HBOC-201 pigs, DeltaMAP responses were significant for the first two infusions and inversely related to HS severity. Among controls, DeltaMAP responses remained significant through the fourth infusion in controlled HS models, and through the first in severe uncontrolled HS/TBI; none were significant in severe uncontrolled HS. DeltaMAP was higher with HBOC-201 through the first infusion in moderate controlled HS, the fifth in severe uncontrolled HS, and the second in severe uncontrolled HS/TBI; there were no group differences in severe controlled HS. No severe MAP responses occurred. Higher DeltaMAP severity did not impact outcome. Hypotension satisfied fluid reinfusion criteria less consistently than tachycardia. Overall, HBOC-201 improved physiologic parameters and survival without causing hypoperfusion; in severe HS, perfusion improved. CONCLUSIONS: In swine with HS +/- TBI, HBOC-201 had mild to moderate vasoactivity, resulting in significant DeltaMAP responses mainly after initial infusions, no severe/adverse responses, and improved outcome. Our data suggest that use of physiologic parameters (e.g., tachycardia), in addition to hypotension to guide fluid reinfusion during HS resuscitation with HBOC-201, will minimize hypoperfusion risk and maximize potential benefit.

Animals↗

PubMed1984

Biological Activity of the Isomeric Forms of Helminthosporium sacchari Toxin and of Homologs Produced in Culture.

The effect of Helminthosporium sacchari (HS) toxin isomers and related, pathogen-produced compounds on dark CO(2) fixation in HS-susceptible sugar cane leaf slices was investigated. HS toxin consists of a mixture of three isomeric bis-5-O-(beta-galactofuranosyl)-beta-galactofuranosides (A, B, and C) differing in the position of one double bond in the sesquiterpene aglycone. Maximum inhibition of dark CO(2) fixation in susceptible sugar cane (CP52-68) occurred within 30 to 40 minutes, and amounts necessary to reach 50% inhibition values typically were approximately 1.7 micromolar for natural toxin mixture ( approximately 2:3:5 mixture of isomers A:B:C) and 4, 6, and 0.7 micromolar for isomers A, B, and C, respectively. Other fractions from cultures of the pathogen consist of comparable mixtures of sesquiterpene isomers but have only 1, 2, or 3 galactofuranose units (HS(1), HS(2), HS(3)) or two alpha-glucopyranose units as well as four beta-galactofuranose units (HS(6)). The lower toxin homologs were not toxic to clone CP52-68, but protected sugar cane from the effects of toxin. Minimum ratios of protectant: toxin giving 95% protection were approximately 50:1, 6:1, and 12:1 for HS(1), HS(2), and HS(3), respectively. HS(2) and HS(3) protected when added up to 12 minutes after toxin as well as when added with or before toxin. Some common plant galactopyranosides were not toxic and did not protect at 500:1 molar excess. The sample of HS(6) was toxic at 500 micromolar, and did not protect against HS toxin. With the availability of purified, homogeneous preparations of HS toxin, homologs, and chemically modified or synthetic analogs, the dark CO(2) fixation assay should prove to be a useful tool for understanding the mode of action of HS toxin.

Journal Article↗

PubMed1990

Anti-heparan sulphate reactivity in sera from patients with systemic lupus erythematosus with renal or non-renal manifestations.

Previously, we have shown that anti-DNA can bind to heparan sulphate (HS), a constituent of the glomerular basement membrane (GBM). We hypothesized that binding of anti-DNA to HS in the GBM plays a role in the onset of systemic lupus erythematosus (SLE) nephritis. To test this hypothesis we measured the anti-HS reactivity in cross-sectional and longitudinal studies of SLE patients with or without nephritis. In the transverse serum study single serum samples from 26 SLE patients were studied. We found no correlation between anti-HS reactivity and previously development of nephritis (anti-HS positive: seven out of 16 with history of nephritis, two out of 10 without nephritis). However, six of the seven anti-HS positive sera in the nephritis group were obtained within 1 month of the onset of nephritis, suggesting a temporal relationship between anti-HS reactivity and onset of nephritis. In the longitudinal serum study between six and 16 serum samples were studied from each of 10 SLE-patients. In five out of five episodes of nephritis we found anti-HS reactivity before the onset or exacerbation of the nephritis. In four non-renal manifestations anti-HS reactivity was found in only one episode; in none of the three patients who remained clinically stable did serum samples show anti-HS reactivity. Anti-HS reactivity was only found in sera positive for anti-DNA by Farr assay but the anti-HS titre was not a mere reflection of the reactivity measured in the Farr assay. This indicates that only a subpopulation of anti-DNA can bind to HS. We found a high correlation (r = 0.99) between anti-HS reactivities in plasma and serum and we conclude that anti-HS reactivity in serum samples from SLE patients is not due to in vitro complex formation during clotting. Although further prospective analysis is necessary, our data suggest that measurement of anti-HS reactivity in SLE patients might identify patients at risk for the development of nephritis.

Adult↗

PubMedDate not supplied

Mechanoenergetic alterations during the transition from cardiac hypertrophy to failure in Dahl salt-sensitive rats.

BACKGROUND: The time course and mechanisms of altered mechanoenergetics and depressed cross-bridge cycling in hypertrophied and failing myocardium are uncertain. METHODS AND RESULTS: We studied mechanoenergetics in Dahl salt-sensitive (DS) rats fed high-salt diet (HS) for 6 (HS-6) and 12 (HS-12) weeks to produce compensated hypertrophy and failure. The slope of the end-systolic pressure-volume relation (E'max) was similar in HS-6 and low-salt controls (LS-6), but reduced in HS-12 compared with controls (LS-12). Efficiency [1/slope of oxygen consumption (&f1;O2)-pressure-volume area (PVA) relation] was similar in HS-6 and LS-6 but higher in HS-12 versus LS-12 (59+/-16% versus 44+/-7%, P<0.05). Economy [1/slope of the force-time integral (FTI)-&f1;O2 relation] was similar in HS-6 and LS-6 but higher in HS-12 versus LS-12 (218+/-123 versus 74+/-39x10(3) g. s. mL O2-1. g; P<0.05). Compared with controls, myofibrillar ATPase activity was reduced by 24% in HS-6 and 44% in HS-12. V3 Isomyosin was increased in HS-6 (40+/-12% versus 9+/-8%; P<0.05) and further increased in HS-12 (76+/-10% versus 22+/-18%; P<0.05). Hypothyroid LS-12 rats had 100% V3 isomyosin, yet efficiency, economy, and ATPase values were intermediate between LS-12 and HS-12. HS-12 rats demonstrated increased troponin T3 isoform (17+/-2 versus 23+/-2%, P<0.05). There were no changes in troponin I or tropomyosin isoforms. However, the proportion of phosphorylated troponin T was reduced in HS-12 versus LS-12 hearts (P<.001). CONCLUSIONS: In DS rats, the transition to failure is associated with depressed E'max and increased efficiency and economy. These findings are linked to myofibrillar ATPase activity and suggest that mechanisms other than isomyosin switching are important determinants of ventricular energetics. A troponin T isoform switch is one potential mechanism.

Adenosine Triphosphatases↗

PubMed2003

Enhancement of intrarenal angiotensinogen in Dahl salt-sensitive rats on high salt diet.

This study was performed to examine whether there is an inappropriate regulation of intrarenal angiotensinogen in Dahl-salt sensitive rats (DS) fed a high salt diet (HS). Dahl salt-resistant rats (DR) and DS were maintained on HS (8% NaCl) or low salt diet (LS, 0.3% NaCl) for 4 weeks. Systolic blood pressure (SBP), measured by tail-cuff plethysmography, was unaltered in DR (DR+HS, 127+/-3 mm Hg, n=5; DR+LS, 126+/-3, n=5); however, SBP was significantly increased in DS+HS (208+/-7, n=9) compared with DS+LS (134+/-2, n=5). HS suppressed plasma renin activity in both strains (0.7+/-0.2 ng of angiotensin I/mL per hour in DS+HS, 3.1+/-0.5 in DS+LS, 0.8+/-0.2 in DR+HS, 5.1+/-0.7 in DR+LS). Plasma angiotensinogen levels, measured by Western blot analysis, were also suppressed by HS in both strains (36 919+/-2170 integrated densitometric unit in DS+HS, 53 028+/-2752 in DS+LS, 44 722+/-1721 in DR+HS, 55782+/-3785 in DR+LS). However, kidney angiotensinogen levels were significantly increased in DS+HS (75 850+/-4171, integrated densitometric unit) compared with DS+LS (47 232+/-3470), DR+HS (44 748+/-8236), and DR+LS (42 504+/-4052). Urinary excretion of angiotensinogen, measured by radioimmunoassay of angiotensin I after incubation with excess renin, had a similar profile. Urinary excretion of angiotensinogen was significantly increased in DS+HS (2958+/-531 pmol/d) compared with DS+LS (56+/-4), DR+HS (31+/-12), and DR+LS (21+/-7). These data indicate that intrarenal angiotensinogen is enhanced in DS+HS, which is reflected by the increased urinary excretion of angiotensinogen. The results suggest that DS on HS have an inappropriate augmentation of intrarenal angiotensinogen, which may contribute to impaired sodium excretion during a high salt diet and the development of hypertension in this strain.

Angiotensinogen↗

PubMed2005

Incidence of puberty in beef heifers fed high- or low-starch diets for different periods before breeding.

Spring-born Hereford x Angus heifers (n = 206) were used to determine effects of energy supplementation programs and amount of starch in the diet on incidence of puberty. In Exp. 1, heifers (205 +/- 5 kg; n = 68) grazing dormant native pasture were fed 0.9 kg/d (as-fed basis) of a 42% CP supplement from November until February 14. Heifers were stratified by weaning weight and allotted randomly to treatment before breeding (May to July). Treatments were 1) 0.9 kg (as-fed basis) of a 42% CP supplement/d and pasture (control); 2) a high-starch (HS) diet (73% corn; 53% starch) fed in a drylot for 60 d (HS-60); 3) a HS diet fed in drylot for 30 d (HS-30); or 4) a low-starch (LS) diet (49% corn; 37% starch) self-fed on pasture for 30 d (LS-30). The HS-60 and HS-30 heifers were limited-fed to gain 0.9 kg/d, and the LS-30 heifers had ad libitum access to the diet. High-starch-60 and LS-30 heifers were heavier (P < 0.05) than control and HS-30 heifers at the beginning of the breeding season. Thirty-one, 25, and 26% more HS-60 heifers were pubertal (P < 0.05) on May 1 compared with LS-30, HS-30, and control heifers, respectively. At puberty, HS-60 heifers were 24 and 22 d younger (P < 0.05) than LS-30 and control heifers, and 31 kg lighter (P < 0.01) than LS-30 heifers. In Exp. 2, heifers grazed dormant pasture and were fed 0.9 kg (as-fed basis) of a 42% CP supplement/d from weaning in October to late February; then heifers were assigned randomly to treatments for 60 d before the breeding season. In two years, control heifers (n = 46) grazed pasture and received 0.9 kg of SBM supplement/d; LS (n = 46) heifers were self-fed a distiller's grain and soybean hull-based diet in drylot; and HS heifers (n = 46) were limited-fed a corn-based diet in drylot. During treatment, HS and LS heifers had greater weight gains than control heifers. Pubertal BW (313 +/- 6 kg) was not influenced by treatment, but HS and LS heifers were younger (P < 0.03) than control heifers at puberty. During a 60-d breeding period, the incidence of puberty was greater (P < 0.05) for HS and LS heifers than for control heifers and was greater (P < 0.05) in HS than in LS heifers in Year 1. Feeding a LS or a HS diet for 30 d before breeding may be inadequate to stimulate puberty in beef heifers, but feeding a diet with a greater amount of starch for 60 d before breeding may increase the incidence of puberty during breeding of heifers that have inadequate yearling weight.

Animal Feed↗

PubMed2002

Clinical and neuropathological characteristics of hippocampal sclerosis: a community-based study.

BACKGROUND: Hippocampal sclerosis (HS) is a neuropathologic finding characterized by neuronal loss and gliosis in the CA-1 and subiculum of the hippocampus. Previous studies of HS have shown that this is a common postmortem finding in elderly subjects with dementia. However, these studies were from selected samples and therefore are not necessarily representative of patients seen in the general medical community. OBJECTIVES: To examine the clinical and pathologic characteristics of HS in a community-based case series of dementia and to compare these characteristics with those observed in subjects with Alzheimer disease (AD) from the same study sample. METHODS: One hundred thirty-four autopsy cases were available from a community-based registry of dementia. Sixteen cases (12%) had a postmortem diagnosis of HS. Thirty-two comparison control cases with a neuropathologic diagnosis of AD were selected from the same files. Each case of HS was reviewed for HS neuropathologic features, including severity, distribution, and additional pathologic processes. Blinded review of clinical characteristics for the HS and control groups was performed to assess risk factors. RESULTS: There was a wide range of severity and distribution of HS lesions between cases and substantial variability in lesion severity and age within individual cases. Serial neuropsychologic and behavioral assessments revealed similar clinical features and rates of dementia progression between HS and AD groups. Of all neuropsychologic tests performed at enrollment, only enhanced performance on Trails A differentiated the HS from the AD group (64 seconds, 0 errors vs 114 seconds, 0.6 errors; P< or = .05). The number of AD cases with at least 1 apolipoprotein epsilon 4 allele was significantly greater than the HS cases (61% vs 31%; chi(2) = 3.81, P< or = .05). Although medical record review indicated higher frequencies of clinical stroke and neuroradiologic white matter abnormalities in the HS group, risk factors for vascular disease and neuropathologic evidence of cerebrovascular disease did not differ between the groups. CONCLUSIONS: Our results suggest that HS is a frequent pathologic finding in community-based dementia. Individuals with HS have similar initial symptoms and rates of dementia progression to those with AD and therefore are frequently misclassified as having AD. Our clinical and pathologic findings suggest that HS has characteristics of a progressive disorder although the underlying cause remains elusive.

Age of Onset↗

PubMed1986

The functions of the heparan sulphate proteoglycans.

Heparan sulphate (HS)-containing proteoglycans (HS-PGs) are present at the surface of nearly all adherent mammalian cells. The principal mode of attachment is by way of the protein core which is inserted into the plasma membrane. Other forms of HS-PG may be components of pericellular matrices, notably basement membranes. The core proteins of HS-PGs can be small (35K) as in hepatocytes, intermediate (50K) as in many mesenchymal cells, or very large (400K) as in basement membranes. A special case is the HS-PG synthesized by postconfluent fibroblasts. This proteoglycan has a core protein that closely resembles the transferrin receptor glycoprotein. It is possible that this HS-PG is a pro-form of the receptor. Low molecular weight, carbohydrate-rich HS-PG forms are probably derived from larger forms by partial degradation. The HS side-chains can contain 24 different disaccharides in an unknown number of arrangements. The biosynthetic machinery can impose considerable restrictions; for example, the extent of N-sulphation rarely exceeds 40-50%, whereas O-sulphation may range from 20% to 75% of potential sites. Nevertheless, the informational capacity of HS is formidable. By way of the HS chains, HS-PG at the surface of endothelial cells can interact specifically or selectively with a number of plasma proteins. HS-PG at the surface of matrix-producing cells is similarly in a position to interact with matrix proteins, notably collagen, fibronectin and laminin. As the cytoplasmic portion of the HS-PG core protein can bind actin, this proteoglycan can provide a connection between extracellular matrices and the cytoskeleton. A number of studies support a role for HS-PGs in the control of cell growth, and this could be one of their major functions. Whether the HS side-chains or the core protein or both are carrying out such a function remains to be determined.

Animals↗

PubMed1994

Insulin production following intravenous glucose, arginine, and valine: different pattern in patients with impaired glucose tolerance and non-insulin-dependent diabetes mellitus.

To better understand abnormal insulin production (IP) in states of carbohydrate intolerance, insulin release was quantified following equimolar (2.4 mmol/kg) infusions of glucose, arginine, and valine in healthy subjects ([HS] age, 45 +/- 3 years; body mass index [BMI, kg/m2], 26.3 +/- 2.4; means +/- SEM), obese subjects with impaired glucose tolerance ([IGT] age, 43 +/- 5 years; BMI, 35.4 +/- 2.4), and non-obese patients with chronic non-insulin-dependent diabetes mellitus ([NIDDM] age, 55 +/- 3 years; BMI, 26.4 +/- 1.4; duration of disease, 13 +/- 3 years). There were eight subjects per group. Incremental IP (metabolic clearance rate of C-peptide [MCRCP] x total incremental area under the curve of plasma C-peptide [AUCCP], pmol/kg) following substrate infusion was as follows: glucose: HS, 227 +/- 14; IGT, 1,050 +/- 184 (P < .001 v HS); NIDDM, 114 +/- 27 (P < .001 v HS); arginine: HS, 139 +/- 23; IGT, 488 +/- 106 (P < .01 v HS); NIDDM, 206 +/- 47; and valine: HS, 21 +/- 7; IGT, 32 +/- 10; NIDDM, 54 +/- 12 (P < .01 v HS). The fractional clearance rate ([FCR] k, %/min) was impaired in IGT and NIDDM for glucose (HS, 3.9 +/- 0.4; IGT, 2.3 +/- 0.3 [P < .01 v HS]; NIDDM, 1.4 +/- 0.1 [P < .001 v HS]), arginine (2.4 +/- 0.1; 1.9 +/- 0.2 [P < .01 v HS]; 1.9 +/- 0.2 [P < .01 v HS]), and valine (0.95 +/- 0.06; 0.65 +/- 0.09 [P < .05 v HS]; 0.74 +/- 0.1 [P < .05 v HS]).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2006

Comparison of mechanical and in vivo performance of new and reprocessed harmonic scalpels.

OBJECTIVES: To compare the mechanical and clinical performance of new and reprocessed harmonic scalpels (HS). METHODS: A total of 89 reprocessed and 90 new HS (laparoscopic coagulating shears with a curved blade and 5-mm-diameter shaft) were subjected to visual inspection, destructive testing, and nondestructive mechanical testing. Subsequently, new HS, randomly selected reprocessed HS, and selected reprocessed HS with known abnormalities were graded on clinical performance by 14 surgeons in a porcine model. RESULTS: Visual inspection of the HS discriminated between the new and reprocessed instruments in 11 of the 12 visual criteria (P < or = 0.02). In vitro mechanical testing revealed greater clamp arm dislodge forces for the new HS (P < 0.01) and greater midshaft temperatures for reprocessed HS (P < 0.01). Overall, 65 (73%) of 89 reprocessed and 7 (7.8%) of 90 new HS had gross abnormalities noted on inspection and mechanical evaluation (P < 0.01). The surgeons' evaluation of the instruments during in vivo testing demonstrated that the new instruments manifested significantly greater hemostatic control compared with randomly selected reprocessed HS (P = 0.01) and were significantly better for tissue sticking (P = 0.01), tissue transection (P = 0.02), tissue dissection (P < 0.01), grasping (P < 0.01), and hemostatic control (P = 0.04) compared with reprocessed HS with obvious defects. CONCLUSIONS: In vitro and in vivo data demonstrated significantly greater performance for new HS compared with reprocessed HS. Mechanical testing of reprocessed HS could not adequately distinguish which HS would result in decreased performance. These findings raise important issues of clinical safety in the contemporary quest for cost-effectiveness.

Disposable Equipment↗