bluuebunny/crossref_metadata_2025_split huggingface dataset:
VEGF and Angiopoietin‐1 Stimulate Different Angiogenic Phenotypes That Combine to Enhance Functional Neovascularization in Adult Tissue
Authors: BENEST ANDREW V. , SALMON ANDREW H. , WANG WENYING , GLOVER COLIN P. , UNEY JAMES , HARPER STEVEN J. , BATES DAVID O. 
Published: July 2007

ABSTRACTObjective: Therapeutic angiogenesis requires an understanding of how growth factors such as vascular endothelial growth factor (VEGF) and angiopoietin‐1 (Ang‐1) result in physiological neovascularization. This study determined the physiological mechanism by which adenoviral delivery of growth factor combinations alter vascular phenotype and functionality.Methods: Adenovirus‐mediated gene transfer into the adjacent fat pad of the rat mesentery was used to characterize induction of angiogenesis by VEGF and Ang‐1, in a model that permitted a detailed examination of the neovessel phenotype.Results: Ang‐1 combined with VEGF resulted in a distinct vascular phenotype from either factor alone. Microvascular perfusion was significantly enhanced in all groups, but VEGF produced short, narrow, highly branched and sprouting vessels, with normal pericyte coverage. Ang‐1 induced broader, longer neovessels, with no increase in branching or sprouting, yet a significantly higher pericyte ensheathment. Combination of Ang‐1 and VEGF generated a significantly higher degree of functionally perfused, larger, less branched, and more mature microvessels, resulting from increased efficiency of sprout to vessel formation. Ang‐1 and VEGF also caused differential effects on larger compared with smaller blood vessels, a finding reproduced in vitro.Conclusions: Ang‐1 and VEGF use different physiological mechanisms to enhance neovascularization of relatively avascular tissue. Administration of both growth factors combines these physiological mechanisms to give greater enhancement of neovascularization than either growth factor alone. These results suggest that effective revascularization therapy may require combination growth factor treatment.
The p110δ Isoform of PI3K Differentially Regulates β1 and β2 Integrin‐Mediated Monocyte Adhesion and Spreading and Modulates Diapedesis
Authors: FERREIRA ALEXANDER M. , ISAACS HAROLD , HAYFLICK JOEL S. , ROGERS KEM A. , SANDIG MARTIN 
Published: July 2007

ABSTRACTObjective: Leukocyte diapedesis is misregulated in inflammatory disease and depends on the binding of monocytic LFA‐1 and VLA‐4 to endothelial ICAM‐1 and VCAM‐1, respectively. The authors hypothesized that these different molecular interactions elicit specific signaling cascades within monocytes regulating specific steps in adhesion, motility, and diapedesis.Methods: The authors employed the PI3K p110δ catalytic subunit specific inhibitor IC87114 (2 μ M) and the broad‐spectrum PI3K inhibitory agents LY294002 (50 μ M) and wortmannin (100 nM), to examine the role of PI3Kδ in monocyte diapedesis through endothelial monolayers and its role in monocyte adhesion and spreading upon carpets of ICAM‐1 or VCAM‐1. They further explored the effects of PI3Kδ inhibition on the activation state of β 1 and β 2 integrins with immunocytochemistry and flow cytometry.Results: In human peripheral blood monocytes IC87114 was as effective as wortmannin and LY294002 at inhibiting diapedesis, however, in THP‐1 cells LY294002 and wortmannin caused a 5‐fold reduction in diapedesis, while IC87114 only decreased diapedesis 2‐fold. PI3Kδ activity was specifically required for THP‐1 cell adhesion and spreading on VCAM‐1, but not on ICAM‐1 protein substrates. Flow cytometric analysis demonstrated that PI3Kδ inhibition decreased the amount of conformationally active β 1‐integrins, while having no effect on the prevalence of conformationally active β 2‐integrins expressed on the cell surface. In addition, PI3Kδ inhibition resulted in a 4‐fold decrease in the activation state of Rac‐1 and Cdc42.Conclusions: These results demonstrate the specific necessity of PI3Kδ in regulating monocytic integrin activation and the general role of PI3K signaling during diapedesis, implicating PI3K as a target for therapeutic intervention.
Putney Auditory Single Word Yes/No Assessment (PASWORD). Development of a reliable test of yes/no at a single word level in patients unable to participate in assessments requiring a specific motor response: an exploratory study
Authors: MacKenzie Sophie , Gale Emma , Munday Ros 
Published: July 2007

AbstractBackground: There are very few formal language assessments aimed at the very severely neurologically impaired individual. These individuals often have multiple deficits on top of their communication impairment that demand a novel approach to assessment. The authors set out to devise a tool (PASWORD) to enable professionals in this field to screen their clients' ability to understand and respond to very simple, closed questions by using their preferred modality.Aims: PASWORD assessment was examined for its reliability as a tool for determining whether profoundly neurologically impaired individuals could indicate yes or no reliably to simple closed questions.Methods & Procedures: The assessment comprises 20 high‐frequency objects that can be presented visually, auditorily or in the tactile modality, depending on the subject's abilities. Subjects are then asked a one‐word level closed question related to the object and were asked to give a yes or no response. Seventy control subjects with no neurological impairment first underwent the PASWORD test to assess for ambiguities in the test items (group 1, n = 74). Neurologically impaired subjects at the Royal Hospital for Neuro‐disability in the two experimental groups were allocated according to the opinion of the experienced multidisciplinary team, which observed the subjects closely over a period of time, in different contexts. Those that the team agreed were reliably able to answer simple yes/no questions on observation (group 2, n = 9) and those the team agreed could not indicate yes/no reliably to closed questions (group 3, n = 7). The results of the PASWORD were then compared with the original opinion of the team. Groups 2 and 3 were studied on two occasions to examine test–retest reliability.Outcomes & Results: There were no real ambiguities in the test items and the results of the PASWORD reflected the opinion of the experienced multidisciplinary team. As there are no other tests of single‐word closed questions, which can be presented in any of three modalities and during which the subject can respond in any augmentative or alternative fashion, the opinion of the team at the Royal Hospital, a centre of excellence for neurorehabilitation, was used against which to measure reliability.Conclusions: The findings imply that PASWORD is a useful screening tool when assessing the basic language skills of neurologically impaired individuals, whose extensive physical, linguistic and cognitive deficits often render the administration of more traditional language assessments impossible.
Purification, characterization and tissue distribution of human class theta glutathione s‐transferase T1‐1
Authors: Juronen Erkki , Tasa Gunnar , Uusküla Mart , Pooga Margus , Mikelsaar Aavo‐Valdur 
Published: July 2007

AbstractA high activity glutathione S‐transferase T1‐1 (GSTT1‐1) towards dichloromethane was isolated from human liver cytosol and purified to homogenity in 18.5% yield with a purification factor of 4400‐fold. The GSTT1‐1 was also isolated from erythrocytes, but the enzyme activity decreased rapidly in the final stages of purification. The purified GSTT1‐1‐s were homo‐dimeric enzymes with a subunit Mt value 25,300 and pI 6.64, as confirmed by SDS‐PAGE, IEF and Western blot analysis. The N‐terminal amino acid sequences of GSTT1‐1 from liver and red blood cells, analyzed up to the 12th amino acid, were identical. Immunoblot analysis revealed that GSTT1‐1 was also present in lung, kidney, brain, skeletal muscle, heart, small intestine and spleen, but not in lymphocytes.
ATP‐diphosphophydrolase activity in rat heart tissue
Authors: Espinosa Victoria , Galleguillos Marco , Mancilla Marta , Garrido Jorge , Kettlun Ana M. , Collados Lucía , Chayet Liliana , García Lorena , Traverso‐Cori Aída , Valenzuela M. Antonieta 
Published: July 2007

AbstractExtracellular nucleotides interact with specific receptors on the cell surface and are locally metabolized by ecto‐nucleotidases. Biochemical characterization of the ATPase and ADPase activities detected in rat heart sarcolemma, under conditions where mitochondrial ATPase and adenylate kinase were blocked, supports our proposal that both activities correspond to a single enzyme, known as ATP‐diphosphohydrolase or apyrase. The physiological function of this enzyme could be dephosphorylation of the nucleotides present in the interstitial heart compartment acting together with 5′‐nucleotidase. Both hydrolytic activities have similarities in: sarcolemma localization, bivalent metal ion dependence, optimum pH, effect of several amino acid residue modifiers, competitive inhibition of nucleotide analogs, and broad nucleoside di‐and triphosphate specificity. The ATPase activity could not be separated from the ADPase either through isoelectrofocusing or electrophoresis under acid conditions.
A point mutation in the cytb gene of cardiac mtDNA associated with Complex III deficiency in ischemic cardiomyopathy
Authors: Marin‐Garcia Jose , Hu Yaping , Ananthakrishnan Radha , Pierpont Mary Ella , Pierpont Gordon L. , Goldenthal Michael J. 
Published: July 2007

AbstractWe report a high incidence of reduced respiratory Complex III activity in heart muscle concomitant with the presence of a specific mutation in cytochrome b (cytb) in patients with ischemic cardiomyopathy. This C → A mutation at nt 15452 converts the 236th residue of cytb from a leucine to isoleucine, is heteroplasmic and was observed in only 2 of 43 controls. Complex III activity is reduced (>50%) in 5 of 6 patients with the C→A15452 mutation suggesting that the cytb mutation is responsible for decreased Complex III activity and may play a role in the pathophysiology of ischemic cardiomyopathy.
Inhibition studies of the carnitine acetyltransferase from skeletal muscle of the camel (Camelus dromedarius) by sulfhydryl reagents and metal ions
Authors: Alhomida AS 
Published: July 2007

AbstractThe effect of certain sulfhydryl reagents and metal ions were studied on the carnitine acetyltransferase (CAT) activity from the skeletal muscle of the Arabian camel (Camelus dromedarius). DTNB and iodoacetamide caused concentration and time dependent inhibition of CAT activity. The inhibition seen with these sulfhydryl reagents could be protected with prior incubation of the enzyme with acetyl‐Co A, suggesting that these reagents might interact with the same site. Among the various metal ions tested, Cu2+, Zn2+ and Hg2+ caused total inhibition at very low concentrations, while, Mn2+, Mo6+ and Co2+ caused between 32‐52% inhibition at 10 mM concentrations. Alkali earth divalent metals Mg2+ and Ca2+ caused less than 15% inhibition at this concentration. These metal ions are probably interacting at certain nucleophilic groups in the enzyme thus disrupting its tertiary structure.
Osteoblast cells (MG‐63 and HOS) have aromatase and 5α‐reductase activities
Authors: Shimodaira Kazuhisa , Fujikawa Hiroshi , Okura Fumiya , Shimizu Yukiko , Saito Hiroshi , Yanaihara Takumi 
Published: July 2007

AbstractBoth aromatase and 5α‐reductase activities were found by whole‐cell assay in osteoblast‐like cells, MG‐63 and HOS. Aromatase activity was measured by the [3H] water release method, and the formation of 5α‐androstanedione from androstenedione was expressed as 5α‐reductase activity. When CGS16949A, an inhibitor of aromatase, was added to the incubation medium at a concentration of 2 × 10‐9 M, sufficient to completely inhibit placental aromatase activity, only 63% to 68% inhibitions were observed. When progesterone, a competitive inhibitor of 5α‐reductase, was added at a concentration of 10‐5 M, 28% to 40% inhibitions were recorded. Because the release of [3H] from [1β‐3H] androstenedione into water by 5α‐reductase is reported, results from the present study suggest that the measurement of aromatase activity in osteoblasts by the [3H] water release method may overestimate aromatase activity owing to the inclusion of 5α‐reductase activity. The results also suggest that osteoblast cells may play an important role in bone metabolism by transforming androgens into estrogens and more biologically active androgen derivatives.
Identification of 137Cs‐ and 241Am‐binding sites in the oyster crassostrea gigas
Authors: Milcent M. C. , Goudard F. , Durand J. P. , Germain P. , Pieri J. , George S. G. 
Published: July 2007

AbstractThe subcellular distribution and binding of 241Am and 137Cs in the visceral mass of the oyster Crassostrea gigas were investigated following exposure to sea water contaminated with these radionuclides. 241 Am was predominantly sequestered by the lysosomal system. Approximately, 10% of 241Am was associated with soluble macromolecules. 241Am was bound to lipofuscin, ferritin and to unidentified ligands of 60 to 15 kdaltons mol. wt. No evidence was found for binding of 241Am to metallothionein synthesized de novo. In contrast, only small amounts of 137Cs were present in lysosomes and 137Cs was not associated with soluble cellular proteins. These results indicate that they enter complete separate metabolic pathways.
Subcellular localization of diacylglycerol kinase activity in stimulated and unstimulated human peripheral blood lymphocytes and neutrophils
Authors: Hurttia Helena , Leino Lasse 
Published: July 2007

AbstractThe diacylglycerol (DAG) kinase activity was determined in crude cytosol and membrane fractions in human peripheral blood lymphocytes and neutrophils. In neutrophils the basal lipid kinase activity was indentical in the two subcellular fractions whereas in lymphocytes the basal enzyme activity was 1.6‐fold higher in the membrane fraction. In general, the DAG kinase activity in lymphocyte fractions was 10‐ to 20‐fold higher than in neutrophil fractions. When lymphocytes were stimulated with phytohaemagglutinin for 4 hours, a significant decrease in the DAG kinase activity in the membrane fraction was detected. By contrast, a 30‐min activation with N‐formyl‐methionyl‐leucyl‐phenylalanine markedly increased the lipid kinase activity in both subcellular fractions in neutrophils. This activity was partially inhibited by the compound R59022. These results suggest that the DAG kinase is widely distributed in human leukocytes, but the enzyme's activity and regulation may vary in different leukocyte types.
Studies on the lipid metabolism of Walker 256 tumour‐bearing rats during the development of cancer cachexia
Authors: Seelaender M. C. L. , Nascimento C.M. Oller Do , Curi R. , Williams J. F. 
Published: July 2007

AbstractAspects of the lipid metabolism of Walker 256 carcinosarcoma‐bearing cachectic rats (TB) were investigated during a 14 day interval of tumour growth. Food intake and body weight of the TB rats were reduced by 18% and 13%, respectively, on day 14, as compared with non‐tumour‐bearing animals. The tumour burden then, corresponded to 19 % of total body weight. The total fat content was not different in the liver, heart, carcass, epididymal (EAT) and retroperitoneal (RPAT) adipose tissues of the two groups. The brown adipose tissue (BAT) and skeletal muscle (gastrocnemius‐SM) of the TB rats had increased levels of fat (23 % and 200 %, respectively). Enteral absorption of 14C‐triolein was decreased in the TB rats, but the liver, heart, and SM of these animals incorporated more radiolabelled lipid than the control animals, while the adipose tissues exhibited a decreased incorporation of radioactivity in relation to controls. More lipid was incorporated into the VLDL fraction secreted by the liver of TB rats, which exhibited a different distribution of the incorporated 14C‐oleate in the various lipid subfractions. Ultrastructural studies showed that the hepatocytes of the TB rats had a greater incidence of lipid droplets in the cytoplasm.
Antigenic similarities among biotin‐binding proteins
Authors: Subramanian N. , Subramanian Sarada , Adiga P. Radhakantha 
Published: July 2007

AbstractUsing polyclonal antisera to avidin, streptavidin, and biotin binding protein‐II (BBP‐II), the extents of immunological cross‐reactivities shared by this family of biotin‐binders were investigated. In Western blot analysis, varying degrees of cross‐reactivities among these proteins depending on the antisera used was observed. Using liquid phase radioimmunoassay, evidence for the existence of common antigenic determinants shared by all the biotin‐binders was deduced. Antibodies directed against such epitopes inhibited the binding of [3H]biotin to as well as displace the bound ligand from all the three high affinity biotin‐binders in a dose dependent manner.
Effects of Ara‐C on neutral sphingomyelinase and mitogen‐and stress‐activated protein kinases in T‐lymphocyte cell lines
Authors: Bradshaw Cynthia D. , Ella Krishna M. , Thomas Aydrian L. , Qi Chen , Meier Kathryn E. 
Published: July 2007

AbstractNeutral sphingomyelinase (SMase)1 can be activated by extracellular signals to produce ceramide, which may affect mitogen‐activated protein kinase (MAPK) activities. Neutral SMase activity was assessed in membranes from Jurkat, a human T‐cell line, and EL4, a murine T‐cell line. Ara‐C activated SMase within 10 minutes in both Jurkat and EL4 cells, while phorbol ester (PMA) had no effect. PMA, but not Ara‐C or ceramides, activated ERK MAPKs in Jurkat and EL4. PMA acted synergistically with ionomycin to activate JNK MAPKs in Jurkat and EL4 within 10 minutes. Ara‐C activated JNKs only after prolonged incubation (90‐120 minutes). Thus, ceramide is not a positive signal for ERK activation in T‐cell lines. The effects of Ara‐C on JNK activity may be mediated through secondary response pathways.
Gender specific alterations in antioxidant status of aging Zaprionus paravittiger fed on propyl gallate
Authors: Bains J. S. , Kakkar R. , Sharma S. P. 
Published: July 2007

AbstractZaprionus paravittiger fed on propyl gallate (PG) supplemented diet (2.5, 25 and 250 µg/ml) showed an increase in life span. Further increase in concentration (2500, 5000 and 7500 µg/ml) accelerated the mortality rate. Females exhibited longer life span as compared to males. Antioxidant enzymes (catalase, peroxidase and glutathione reductase) were measured in control and optimum concentration of PG (25 µg/ml) fed flies at various age intervals. Antioxidant enzyme activities showed an increase during reproductive phase. Catalase and glutathione reductase activities decreased with age however no significant change was observed in peroxidase activity. The females exhibited higher enzyme activities as compared to males in control and PG fed group at most of the age intervals. PG feeding caused a significant increase in catalase and glutathione reductase activities in both the sexes. These findings suggest the PG has dose dependent and sex specific influence on longevity of Z. paravittiger and support the view that longevity and activity of antioxidant enzymes are positively linked.
Expression of S‐adenosylmethionine synthetase isozyme genes in regenerating rat liver after partial hepatectomy
Authors: Horikawa Saburo , Ozasa Hisashi , Ito Koji , Katsuyama Iwao , Tsukada Kinji , Sugiyama Toshihiro 
Published: July 2007

AbstractMammalian S‐adenosylmethionine (AdoMet) synthetase exists as two isozymes, liver‐type and non‐hepatic‐type enzymes. To investigate the possible role of AdoMet synthetase in proliferating cells, we have examined the expression of these two isozyme genes in regenerating rat liver after partial hepatectomy using Northern blot analysis. In normal adult rat liver the non‐hepatic‐type isozyme mRNA was not detectable, however, when partial hepatectomy was performed, there was an obvious appearance of the non‐hepatic‐type enzyme mRNA after operation. The levels of non‐hepatic‐type isozyme mRNA was peaked at 4 h and maintained the level at least till 8 h after operation, then decreased. In addition, the liver‐type AdoMet synthetase gene expression was also induced by partial hepatectomy with similar time course. These results indicate that these two AdoMet synthetase isozymes may play an important role during the prereplicative phase which precedes DNA synthesis.
Induction of apoptosis in primary culture of rat hepatocytes by protease inhibitors
Authors: Maeda Sumio , Lin Kong Hua , Inagaki Hidetoshi , Saito Takao 
Published: July 2007

AbstractThere is growing evidence that suggests the involvement of intracellular proteases in the process of apoptosis or programmed cell death. In this study, we have demonstrated that leupeptin, a cysteine protease inhibitor, can significantly increase the incidence of both apoptotic nuclear morphology change and internucleosomal DNA fragmentation in primary cultured hepatocytes in the absence of known apoptotic stimuli for hepatocytes. On the other hand, aspartic and serine protease inhibitors showed little or no effects on the apoptotic changes. In addition, we found that the apoptotic changes could be induced by chloroquine, an inhibitor of lysosomal proteolysis, but could not be induced by calpain inhibitors. These data suggest that inhibition of lysosomal cysteine proteases may induce apoptosis in primary cultured hepatocytes.
Phosphorylation of native and truncated isoforms of protein τ by the double‐stranded DNA‐dependent protein kinase (DNA‐PK) shows that the primary phosphorylation sites are localized between amino acid residues 212‐231 of the longest τ
Authors: Wu Joseph M. , Chen Yuping , Hsieh Tze‐chen , Brandt Roland , Lee Gloria 
Published: July 2007

AbstractAlzheimer's disease (AD) is pathologically characterized by the appearance of neurofibrillary tangles (NFT), senile plaques, and loss of subpopulation of neuronal cells. The NFT is composed of paired helical filaments (PHT) with extensively modified protein τ as its primary constituent.Previously we had reported on the hyperphosphorylation of τ by a double‐stranded‐DNA‐stimulated protein kinase (DNA‐PK). In this communication, we have compared the DNA‐PK mediated phosphorylation of native and truncated τs with that catalyzed by the cAMP‐dependent protein kinase (PKA). In addition, we have attempted to map the primary site(s) of phosphorylation of τ by DNA‐PK. Our results suggest that DNA‐PK phosphorylates τ at sites substantially different from those targeted by PKA. Furthermore, we show that the primary phosphorylation sites lie between amino acid residues 212‐231 (using numbering system for the longest τ, which is the isoform with four “repeats” and a 58 amino acid “insert” at the carboxyl‐ and amino‐termini, respectively, of the protein molecule).
Chemical conjugation of Gly‐Pro‐Arg‐Pro tetrapeptide to low molecular weight urokinase
Authors: Chen Xiao‐Chun , Hua Zi‐Chun , Zhu De‐Xu 
Published: July 2007

AbstractTwo low molecular weight urokinase derivatives were obtained by covalent coupling of a synthetic Gly‐Pro‐Arg‐Pro tetrapeptide to peptide A of low molecular weight urokinase and exchanging the native peptide A of low molecular weight urokinase with Gly‐Pro‐Arg‐Pro‐peptide A to obtain derivative I or direct conjugation of Gly‐Pro‐Arg‐Pro tetrapeptide to low molecular weight urokinase to obtain derivative II. In caseinolytic assay, fibrin can stimulate the two derivatives to activate plasminogen. But the two derivatives showed different kinetic behaviors. The derivative I displayed immediate onset of lysis and derivative II displayed a lag phase.