bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associational resistance mediated by natural enemies
Authors: Stiling Peter , Rossi Anthony M. , Cattell Maria V. 
Published: September 2003

Abstract. 1. Associational resistance theory suggests that the association of herbivore‐susceptible plant species with herbivore‐resistant plant species can reduce herbivore density on the susceptible plant species. Several casual mechanisms are possible but none has so far invoked natural enemies. Associational resistance mediated by natural enemies was tested for by examining densities of a gall fly,Asphondylia borrichiae(Diptera: Cecidomyiidae), and levels of parasitism on two closely related seaside plants,Borrichia frutescensandIva frutescens, when alone and when co‐occurring.2. BothBorrichiaandIvagrow alone or together on small offshore islands in Florida. Each host plant species has its own associated race of fly, but both races of fly are attacked by the same four species of parasitoids.Borrichianormally has a higher density of galls thanIva, and galls are larger onBorrichiathan onIva.3. Gall size, gall abundance, parasitism levels, and parasitoid community composition were quantified on bothBorrichiaandIvaon islands where each species grew alone or together. Some islands were then manipulated by addingBorrichiato islands supporting onlyIva, and by addingIvato islands supporting onlyBorrichia. Subsequent gall densities and gall parasitism levels on the original native species were then examined.4. On both natural and experimentally manipulated islands, gall densities onIvawere significantly lowered by the presence ofBorrichia. This is because bigger parasitoid species that were common onBorrichiagalls, which are bigger, spilled over and attacked the smallerIvagalls. Thus, parasitism rates onIvawere higher on islands whereBorrichiaco‐occurred than on islands whereBorrichiawere absent. Most parasitoids fromIvawere too small to successfully attack the largeBorrichiagalls and so gall density onBorrichiawas unaffected by the presence ofIva.
Immature dendritic cell/tumor cell fusions induce potent antitumour immunity
Authors: Takeda A. , Homma S. , Okamoto T. , Kufe D. , Ohno T. 
Published: September 2003

AbstractBackground  Maturation of dendritic cells (DCs) is important to induce antigen‐specific antitumour immunity in cancer immunotherapy with antigen‐loaded DCs. However, DCs from tumour‐bearing hosts are immature and functionally defective for antigen presentation. We examined whether DCs from tumour‐bearing mice could be an effective part of a DC/tumour cell fusion vaccine.Materials and methods  Dendritic cells from healthy (DC‐Hs) or MC38 tumour‐bearing mice (DC‐TBs) were examined for endocytotic capacity of FITC‐labelled dextran, antigen‐presenting capacity in allogeneic mixed leucocyte reaction (allo‐MLR) and expression of I‐Ab, CD80, and CD86. Fusion cells (FCs) of DC‐Hs or DC‐TBs and MC38 cells (FC‐Hs or FC‐TBs) were generated by treatment with polyethylene glycol (PEG). Mice vaccinated with FC‐Hs or FC‐TBs were studied for cytolytic activity of splenocytes and suppressive activity against established MC38 pulmonary metastases.Results  Dendritic cell‐TBs showed higher endocytotic capacity and lower antigen‐presenting capacity than did DC‐Hs, results indicating that DC‐TBs are more immature and functionally defective for antigen presentation than are DC‐Hs. Expression of surface molecules, however, was almost same between DC‐Hs and DC‐TBs. Splenocytes from mice immunized with FC‐Hs or FC‐TBs induced the same high cytolytic activity against MC38 cells. Vaccination of mice with FC‐Hs or FC‐TBs resulted in the same significant suppressive effect against established pulmonary metastases of MC38.Conclusion  Dendritic cells from tumour‐bearing mice, despite being functionally defective, are effective vehicles for immunotherapy using DC/tumour cell fusion vaccines.
Insulin therapy improves insulin actions on glucose metabolism and aortic wave reflection in type 2 diabetic patients
Authors: Tamminen M. K. , Westerbacka J. , Vehkavaara S. , Yki‐Järvinen H. 
Published: September 2003

AbstractBackground  Normal insulin action in vivo involves a decrease in aortic systolic blood pressure as a result of an insulin‐induced decrease in the amplitude of the second systolic (reflected) pressure wave. This action of insulin and insulin action on glucose metabolism is impaired in insulin‐resistant and type 2 diabetic subjects. We determined whether 6 months of insulin therapy affects insulin actions on glucose metabolism and vascular function.Materials and methods  Thirteen type 2 diabetic patients (age 53 ± 2 years, body mass index 30·8 ± 1·2 kg m−2, HbA1C 8·8 ± 0·2%) were studied before and after insulin therapy. Central aortic pressure waveforms were reconstructed from those recorded in the periphery using applanation tonometry every 30 min. This allowed determination of augmentation, i.e. the pressure difference between the second and first systolic pressure peaks and the augmentation index (AgI, augmentation divided by pulse pressure). The measurements were performed basally and during euglycaemic hyperinsulinaemic conditions.Results  Insulin therapy increased whole body glucose disposal by 35% from 5·1 ± 0·7 to 6·8 ± 0·6 mg kg ffm−1 min−1 (P < 0·001 for 0 vs. 60 months). 6 months of insulin therapy decreased basal AgI from 26·2 ± 1·8 to 22·7 ± 2·3% (P < 0·05). The change in AgI by insulin infusion was similar before and after insulin therapy at all time points. Peripheral blood flow, heart rate and blood pressures remained unchanged.Conclusions  Insulin therapy improves insulin action on glucose metabolism and decreases basal AgI. These data support the idea that insulin therapy has beneficial effects on vascular function.
Basic fibrobrast growth factor induces the secretion of vascular endothelial growth factor by human aortic smooth muscle cells but not by endothelial cells
Authors: Belgore F. , Lip G. Y. H. , Blann A. D. 
Published: September 2003

AbstractBackground  Endothelial cell dysfunction and smooth muscle cell (SMC) proliferation are major events in atherogenesis. Both cells are a source of growth factors that mediate cellular proliferation and chemotaxis. Inappropriate production of, and/or response to, these growth factors (such as vascular endothelial growth factor, VEGF, and basic fibroblast growth factor (bFGF)) may contribute to atherogenesis and therefore to disease progression.Methods  Production of VEGF and its soluble receptor (sFlt‐1) by human SMCs and human umbilical endothelial cells (HUVECs) after stimulation with bFGF were examined by ELISA of cell culture media and by Western blotting.Results  Smooth muscle cells produced significantly more VEGF than HUVECs (P < 0·05) after 24 h of culture with bFGF levels ≥ 0·001 µg mL−1. bFGF induced dose‐dependent production of VEGF by SMCs, where maximum production was present in 1 µg mL−1 of bFGF. Conversely, the SMCs produced less sFlt‐1 than HUVECs (P < 0·05). However, bFGF induced dose‐dependent phosphorylation of Flt1 and another VEGF receptor, KDR, in HUVECs but not SMCs. There was no VEGF or sFLT‐1 after 6 h of culture in any dose of bFGF in either type of cell.Conclusions  Differences in the production of VEGF and sFlt‐1 by SMCs and HUVECs are consistent with the role of these cells in angiogenesis. Induction of VEGF production and expression by bFGF in these cells indicates that this growth factor may participate in angiogenesis indirectly by the induction of VEGF. The production of sFlt‐1 by both cell types is in agreement with the notion that sFlt‐1 may be involved in the regulation of VEGF activity. Additionally, the ability of bFGF to induce dose‐dependent phosphorylation of KDR in HUVECs highlights the important role of bFGF in VEGF‐mediated angiogenic processes.
Quantification of Bax and Bcl2 in polymorphonuclear leukocytes from haemodialysis patients: relation to hydrogen peroxide
Authors: Perianayagam M. C. , Balakrishnan V. S. , Guo D. , Pereira B. J. G. , Jaber B. L. 
Published: September 2003

AbstractBackground  Bax and Bcl2 are two apoptosis‐related molecules that play an important role in determining cell fate following oxidative injury. In the present study, we explored the relation of hydrogen peroxide (H2O2) generation by polymorphonuclear cells (PMNs) to the cytosolic expression of Bax and Bcl2 proteins and apoptosis in haemodialysis (HD) patients.Methods  Cytosolic generation of H2O2 by PMNs from control subjects and HD patients was measured by flow cytometry using the dichlorofluorescin diacetate assay. Bax and Bcl2 expression was detected by flow cytometry using FITC‐conjugated antibodies. Apoptosis was quantified by flow cytometry using propidium iodide nuclear staining. To examine the effect of H2O2 on Bcl2 and Bax expression, PMNs from control subjects were briefly exposed to H2O2 (0·1–100 µM) for 10 min and then washed and cultured for 6 h, with or without catalase, a H2O2 detoxifying molecule. Bcl2 and Bax expression was determined by Western blot analysis.Results  Basal H2O2 generation by resting PMNs was significantly higher in HD patients compared with control subjects (211 ± 115 vs. 23 ± 5 MFI; P = 0·002). However, PMNs from HD patients did not undergo accelerated programmed cell death compared with control subjects (58 ± 7% vs. 46 ± 5; P = 0·14). Polymorphonuclear cells cytosolic Bcl2 was undetected in control subjects but detected in 25% of HD patients, and Bax was more frequently detected in PMNs from HD patients (75% vs. 67%; P = 0·04). In the HD patients with detectable cytosolic Bax and Bcl2 proteins, the Bax to Bcl2 ratio inversely correlated with H2O2 levels (P < 0·0001). Finally, brief exposure of PMNs to 0·1–100 µM of H2O2 resulted in a marked increase in Bcl2 expression (P = 0·001), which was prevented by catalase (P = 0·05). There was no apparent effect on Bax expression.Conclusions  This study demonstrates that in HD patients, high‐resting cytosolic H2O2 production by PMNs is not associated with accelerated in vitro apoptosis, and that the Bax/Bcl2 system may counter‐balance the deleterious effects of reactive oxygen species in human PMNs.
Effect of insulin upon protein degradation in cultured human myocytes
Authors: Roberts R. G. , Redfern C. P. F. , Goodship T. H. J. 
Published: September 2003

AbstractBackground  The anabolic effects of insulin are well recognized but the mechanism by which insulin decreases muscle protein degradation in human is unclear. However, in a variety of catabolic conditions it is believed to be changes in the activity of the ATP‐dependent ubiquitin proteolytic pathway that are responsible for changes in protein degradation in skeletal muscle. The aim of this study was to test the hypothesis that insulin regulates the ATP‐dependent ubiquitin proteolytic pathway in human muscle.Material and methods  The effects of insulin and acidosis on protein degradation were measured in human myocytes using L‐[14C]phenylalanine. The effect of insulin on the activity of the ATP‐dependent ubiquitin pathway was assessed from the mRNA expression of ubiquitin and the ubiquitin‐conjugating enzyme E214k in human myocytes.Results and conclusions  Coincubation of human myocytes with 100 nM of insulin was associated with a significant reduction in protein degradation. Metabolic acidosis is known to increase skeletal muscle protein degradation rates, and in our experiments protein degradation at a pH of 7·0 was significantly higher than pH 7·35. Eight‐hour exposure to 100 nM of insulin resulted in a significant reduction in the expression of E214k but no change in the expression of ubiquitin.Conclusions  In human muscle we have demonstrated regulation by insulin of the ATP‐dependent ubiquitin pathway at the level of ubiquitin conjugation.
Biochemical assessments of oxidative stress, erythrocyte membrane fluidity and antioxidant status in professional soccer players and sedentary controls
Authors: Cazzola R. , Russo‐Volpe S. , Cervato G. , Cestaro B. 
Published: September 2003

AbstractBackground  Physical exercise is characterized by an increase in oxygen consumption by the whole body. This leads to a decrease in antioxidant levels that could promote both an increase in the markers of lipoprotein peroxidation and damage to the erythrocyte membrane with consequent modification of membrane fluidity.Materials and methods  Different markers of oxidative stress, erythrocyte membrane fluidity and antioxidant status were determined in 20 professional soccer players and 20 sedentary controls. Plasma lipoperoxides and kinetics of Cu‐stimulated plasma peroxidation were measured together with hydrosoluble (albumin, uric acid and vitamin C), liposoluble (vitamin E and bilirubin) and enzymatic (superoxide dismutase and glutathione peroxidase) serum antioxidants. Erythrocyte membrane rigidity was determined by measuring fluorescence anisotropy (rs) of the fluorescent probe 1, 3, 5 diphenylexatriene.Results  The sportsmen showed higher levels of the following plasmatic antioxidants: ascorbic acid (P < 0·0001), uric acid (P < 0·0001), α‐tocopherol (P = 0·03) and superoxide dismutase activity (P = 0·0001). According to this evidence, the lipoperoxide levels (P = 0·0158), the duration of the latency phase of plasma peroxidation (P = 0·0123) and erythrocytes membrane fluidity (P = 0·0152) were found to be significantly higher in the soccer players.Discussion  Athletes undergoing regular and adequate training show improved antioxidant status together with a more fluid membrane status, which could contribute to improving both peripheral resistance to insulin and all the functional metabolic interchanges in the cellular membrane.
Successful treatment of renovascular hypertension has no effect on insulin sensitivity
Authors: Voiculescu A. , Hollenbeck M. , Kutkuhn B. , Grabensee B. , Plum J. 
Published: September 2003

AbstractBackground  The association of insulin resistance (IR) and essential hypertension is well known, but a causal relationship has not been proven. Patients with secondary hypertension as a result of renal artery stenosis (RAS) usually do not reveal IR, but no study has addressed the effect of blood pressure reduction after successful treatment of RAS on insulin sensitivity and glucose effectiveness.Patients and methods  The insulin sensitivity index (SI) and glucose effectiveness (SG) were measured before and after successful intervention of an angiographically proven significant RAS in 18 out of 23 patients (eight males/10 females; mean age 51·5 ± 13·1 years) in which improvement/cure of arterial hypertension was achieved. After a mean of 10·7 months, patients were reevaluated for 24‐h blood‐pressure measurement, kidney function, adrenaline, noradrenaline, plasma‐renin‐activity (PRA), aldosterone, atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP), and glucose metabolism parameters such as basal insulin, glucose disappearance constant (K‐value), SI and SG. For calculation of SI and SG, insulin and glucose data from the modified frequent sampling intravenous glucose tolerance test (FSIGT) were submitted to the MINMOD program.Results  After intervention, systolic 24‐h blood pressure had decreased from 156·1 ± 16·4 mmHg to 139·9 ± 15·1 mmHg, and diastolic 24‐h blood pressure from 97·1 ± 14·7 mmHg to 87·3 ± 13·4 mmHg. No significant change in SI (before 4·3 ± 2·0, after 4·8 ± 2·0 min−1 per µU mL−1) or SG (before 1·55 ± 0·42 × 10−2 min−1, after 1·8 ± 0·48 × 10−2 min−1) was observed. Aldosterone decreased from 246·7 ± 180·7 to 115 ± 61·4 (P = 0·009) as PRA decreased from 12·4 ± 11·4 to 4·2 ± 7·6 ng mL h−1 (P = 0·01). Creatinine clearance, and adrenaline and noradrenaline levels as well as ANP and cGMP did not change after treatment for RAS. Subsequent to the definition of IR (SI ≤ 3·2 × 10−4 min−1 per µU mL−1) some differences among these two subgroups (SI ≤ 3·2, or SI > 3·2) could be found. Patients with IR (n = 8) were characterized by a higher body mass index (BMI), higher basal insulin values and significantly lower cGMP values. Only the group without IR (n = 10) developed significant improvement of systolic blood pressure.Conclusion  We conclude that blood pressure reduction by treatment of RAS does not alter insulin action and that there is no link between the circulating concentrations of renin/aldosterone and glucose metabolism in renovascular hypertension (RVH). The results do not support the hypothesis of a direct link between blood pressure in RVH and the individual state of insulin sensitivity. However, patients with a normal SI are more likely to experience an almost normalization of arterial blood pressure after treatment for RAS.
D‐2‐Hydroxyglutaric acid inhibits creatine kinase activity from cardiac and skeletal muscle of young rats
Authors: Da Silva C. G. , Bueno A. R. F. , Schuck P. F. , Leipnitz G. , Ribeiro C. A. J. , Wannmacher C. M. D. , Wyse A. T. S. , Wajner M. 
Published: September 2003

AbstractBackground  Tissue accumulation of high amounts of D‐2‐hydroxyglutaric acid (DGA) is the biochemical hallmark of the inherited neurometabolic disorder D‐2‐hydroxyglutaric aciduria (DHGA). Patients affected by this disease usually present hypotonia, muscular weakness, hypothrophy and cardiomyopathy, besides severe neurological findings. However, the underlying mechanisms of muscle injury in this disorder are virtually unknown.Materials and methods  In the present study we have evaluated the in vitro role of DGA, at concentrations ranging from 0·25 to 5·0 mm, on total, cytosolic and mitochondrial creatine kinase activities from skeletal and cardiac muscle of 30‐day‐old Wistar rats. We also tested the effects of various antioxidants on the effects elicited by DGA.Results  We first verified that total creatine kinase (CK) activity from homogenates was significantly inhibited by DGA (22–24% inhibition) in skeletal and cardiac muscle, and that this activity was approximately threefold higher in skeletal muscle than in cardiac muscle. We also observed that CK activities from mitochondrial (Mi‐CK) and cytosolic (Cy‐CK) preparations from skeletal muscle and cardiac muscle were also inhibited (12–35% inhibition) by DGA at concentrations as low as 0·25 mm, with the effect being more pronounced in cardiac muscle preparations. Finally, we verified that the DGA‐inhibitory effect was fully prevented by preincubation of the homogenates with reduced glutathione and cysteine, suggesting that this effect is possibly mediated by modification of essential thiol groups of the enzyme. Furthermore, α‐tocopherol, melatonin and the inhibitor of nitric oxide synthase L‐NAME were unable to prevent this effect, indicating that the most common reactive oxygen and nitrogen species were not involved in the inhibition of CK provoked by DGA.Conclusion  Considering the importance of creatine kinase activity for cellular energy homeostasis, our results suggest that inhibition of this enzyme by increased levels of DGA might be an important mechanism involved in the myopathy and cardiomyopathy of patients affected by DHGA.
Structural and oxidative modifications of erythrocyte ghosts in patients with primary biliary cirrhosis: relation with the disease stage and effect of bile acid treatment
Authors: Grattagliano I. , Giudetti A. M. , Grattagliano V. , Palmieri V. O. , Gnoni G. V. , Lapadula G. , Palasciano G. , Vendemiale G. 
Published: September 2003

AbstractBackground  Erythrocyte membrane modifications in patients with cholestasis are supposed to reflect those of hepatocytes.Methods  Erythrocyte membrane composition (cholesterol, phospholipids, fatty acids, protein sulphydrils and carbonyls) was assessed and related to the stage of liver disease in patients with primary biliary cirrhosis before and after 1 year of ursodeoxycholate treatment.Results  Compared with controls, patients showed lower levels of protein sulphydrils (28·9 ± 7·1 vs. 65·6 ± 1·8 nmol mg−1 prot) and accumulation of carbonyls (4·7 ± 1·7 vs. 1·4 ± 0·1 nmol mg−1 prot). Phosphatidylethanolamine level was lower in stage III–IV cirrhosis while phosphatidylcholine and cholesterol levels were higher; as a consequence the phosphatidylcholine/sphingomyelin ratio was higher than in controls (4·25 ± 0·55 in the I–II stage and 2·89 ± 0·44 in the stage III–IV vs. 1·61 ± 0·30). These changes were particularly evident in patients with more advanced stages of liver disease. Protein sulphydrils and carbonyls, phosphatidylethanolamine and cholesterol levels correlated (P < 0·05) with the histological stage of the liver disease, serum and membrane cholesterol levels were significantly related (r = 0·66, P < 0·05). One year of ursodeoxycholate administration was accompanied by major changes of the membrane lipid composition, partial reversal of protein oxidation, and improvement of serum parameters.Conclusions  This study indicates that major alterations in protein status and lipid composition occur in erythrocyte membrane of patients with primary biliary cirrhosis. These changes were more pronounced in patients with advanced liver disease. Ursodeoxycholate was able to revert in part serum and erythrocyte alterations, especially in patients with early stages of liver disease.
Activation of p53 signalling in acetylsalicylic acid‐induced apoptosis in OC2 human oral cancer cells
Authors: Ho C.‐C. , Yang X. W. , Lee T.‐L. , Liao P.‐H. , Yang S.‐H. , Tsai C.‐H. , Chou M.‐Y. 
Published: September 2003

AbstractBackground  Nonsteroidal anti‐inflammatory drugs (NSAIDs) such as acetylsalicylic acid (ASA, aspirin) are well known chemotherapeutic agents of cancers; however, the signalling molecules involved remain unclear. The aim of this study was to investigate the possible existence of a putative p53‐dependent pathway underlying the ASA‐induced apoptosis in OC2 cells, a human oral cancer cell line.Materials and methods  The methyl tetrazolium (MTT) assay was employed to quantify differences in cell viability. DNA ladder formation on agarose electrophoresis was used as apoptosis assay. The expression levels of several master regulatory molecules controlling various signal pathways were monitored using the immunoblotting techniques. Flow cytometry was used to confirm the effect of ASA on cell cycle. Patterns of changes in expression were scanned and analyzed using the NIH image 1·56 software (NIH, Bethesda, MD, USA). All the data were analyzed by anova.Results  Acetylsalicylic acid reduced cell viability and presence of internucleosomal DNA fragmentation. In the meanwhile, phosphorylation of p53 at serine 15, accumulation of p53 and increased the expression of its downstream target genes, p21 and Bax induced by ASA. The expression of cyclooxygenase‐2 was suppressed. Disruption of p53‐murine double minute‐2 (MDM2) complex formation resulted in increasing the expression of MDM2 60‐kDa cleavage fragment. Inhibited the activation of p42/p44 mitogen‐activated protein kinase (MAPK) by PD98059, a specific inhibitor of extracellular regulatory kinase (ERK), significantly decreased cell viability and enhanced the expression of p53 induced by ASA. The result of the cell‐cycle analysis showed that ASA and PD98059 induced the cell cycle arrested at the G0/G1 phase and resulted in apoptosis.Conclusion  Nonsteroidal anti‐inflammatory drug‐inhibited cyclooxygenase is not the only or even the most important mechanism of inhibition. Our study presents evidences that activation of p53 signalling involved in apoptosis induced by ASA. Furthermore, the apoptotic effect was enhanced by blocking the activation of p42/p44 MAPK in response to treatment with ASA, thus indicating a negative role for p42/p44 MAPK.