bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term follow‐up of patients following negative colposcopy: a new gold standard and its implications for cervical screening
Authors: Da Forno P. D. , Holbrook M. R. , Nunns D. , Shaw P. A. V.
Published: September 2003

From 1189 colposcopy referrals in 1997 at a single cervical screening centre, 88 women who had no biopsy taken at colposcopy (negative colposcopy) were identified. We followed up these women for a maximum of 4 years and calculated the positive predictive value (PPV) of a single smear before and after follow‐up. Using slide review we attempted to correlate the grade of smear leading to colposcopy referral with final outcome. Our results showed that long‐term follow‐up alters the PPV of cervical cytology. Analysis showed a strong correlation between the review grade of the referring smear and the final outcome after follow‐up. From these results we suggest an evidence‐based protocol for cervical screening follow‐up after negative colposcopy.
Host shifting by Operophtera brumata into novel environments leads to population differentiation in life‐history traits
Authors: Vanbergen Adam J. , Raymond Ben , Pearce Imogen S. K. , Watt Allan D. , Hails Rosie S. , Hartley Susan E.
Published: September 2003

Abstract.  1. Operophtera brumata L. (Lepidoptera: Geometridae), a polyphagous herbivore usually associated with deciduous trees such as oak Quercus robur L., has expanded its host range to include the evergreen species heather Calluna vulgaris (L.) Hull and, most recently, Sitka spruce Picea sitchensis (Bong.) Carrière.

2. Phenology, morphology, and survival of O. brumata were measured at several life‐history stages in populations from the three different host plant communities sampled from a range of geographical locations. The data were used to test for population differences, reflecting the marked differences in host‐plant secondary chemistry, growth form, and site factors such as climate. The hypothesis that spruce‐feeding populations originated from populations feeding on moorland, commonly sites of coniferous afforestation, was also tested.

3. Altitude, not host plant species, was the major influence on the timing of adult emergence. An effect of insect population independent of altitude was found, implying that additional unidentified factors contribute to this phenological variation. Larval survival and adult size varied between populations reared on different host plant species. Survival of larvae was affected negatively when reared on the novel host plant, Sitka spruce, versus the natal plant (oak or heather) but oak and heather‐sourced insects did not differ in survivorship on Sitka spruce.

4. Host range extension into novel environments has resulted in population differentiation to the local climate, demonstrating that host shifts pose challenges to the herbivore population greater than those offered by the host plant alone. The hypothesis that Sitka spruce feeding populations have arisen predominantly from moorland feeding populations was not supported.
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

Background  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

Background  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

Background  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

Background  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

Background  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

Background  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

Background  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

Background  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

Background  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

Background  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.
Clonidine improves postprandial baroreflex control in familial dysautonomia
Authors: Marthol H. , Tutaj M. , Brys M. , Brown C. M. , Hecht M. J. , Berlin D. , Axelrod F. B. , Hilz M. J.
Published: September 2003

Background  Patients with familial dysautonomia (FD) frequently experience hypertensive crises after gastrostomy feeding. The central α2‐agonist clonidine attenuates feeding‐induced crises. The aim of this study was to assess the effect of clonidine on cardiovascular autonomic modulation and particularly baroreflex sensitivity in familial dysautonomia after gastrostomy feeding.

Material and methods  In nine patients, we monitored the RR‐interval and systolic blood pressure at supine rest before (baseline 1) and after gastrostomy feeding (GF1). One day later, recordings were repeated after clonidine intake (baseline 2, GF2). We determined spectral powers of RR‐interval and systolic blood pressure in the low‐ (LF) and high‐frequency range (HF). Sympathovagal balance was determined from the LF/HF ratio of RR‐interval. Baroreflex sensitivity was assessed from the α‐index of systolic blood pressure and RR‐interval.

Results  Gastrostomy feeding decreased RR‐interval, while systolic blood pressure remained stable. Clonidine induced higher RR‐intervals before and after gastrostomy feeding but decreased systolic blood pressure at baseline only. Gastrostomy feeding decreased HF‐power of RR‐interval significantly without clonidine, but only slightly after premedication. Clonidine increased the HF‐power of RR‐interval slightly at baseline and significantly after gastrostomy feeding. Gastrostomy feeding increased the LF/HF ratio without clonidine only. Clonidine decreased the LF/HF ratio at baseline and after gastrostomy feeding. Gastrostomy feeding did not change baroreflex sensitivity, but baroreflex sensitivity was higher at visit 2 than visit 1.

Conclusions  In familial dysautonomia, clonidine augments baroreflex sensitivity and parasympathetic modulation. The resulting cardiovascular stabilization might attenuate feeding‐induced crises.
Plasma angiopoietin‐1, angiopoietin‐2 and Tie‐2 in breast and prostate cancer: a comparison with VEGF and Flt‐1
Authors: Caine G. J. , Blann A. D. , Stonelake P. S. , Ryan P. , Lip G. Y. H.
Published: September 2003

Background  Angiogenesis is essential for tumour growth and metastasis, and is coordinated by several classes of growth factors mediating their effect through receptors linked, in turn, to tyrosine kinase. These growth factors include angiopoietin‐1 (Ang‐1), angiopoietin‐2 (Ang‐2) and vascular endothelial growth factor (VEGF), which act through receptors Flt‐1 and Tie‐2.

Materials and methods  In order to further determine abnormalities in levels of Ang‐1, Ang‐2, Tie‐2, sFlt‐1 and VEGF in human cancer (and their interrelationships), these molecules were measured in plasma from 30 patients with breast cancer, 30 patients with prostate cancer and 12 healthy controls per cancer group.

Results  In breast cancer, levels of Ang‐1 (P = 0·0005), Ang‐2 (P = 0·0173), Tie‐2 (P = 0·0001), and VEGF (P = 0·0001) were all significantly raised, and plasma levels of sFlt‐1 (P = 0·045) were significantly reduced compared with controls. However, in prostate cancer, only levels of VEGF and Tie‐2 were significantly higher (both P= 0·001). There were no significant differences between levels of any molecule between the two groups of cancer. The only difference between the healthy control groups was lower Ang‐1 in the women compared with men. Significant correlations were found between levels of Ang‐1 and Tie‐2 both in breast (r = 0·498, P= 0·005) and prostate cancer (r = 0·643, P= < 0·001). Angiopoietin‐1 was also positively correlated with Ang‐2 in both breast (r = 0·422, P= 0·02) and prostate cancer (r = 0·543, P= 0·002).

Conclusions  Abnormal levels of Ang‐1, Ang‐2 and their receptor, Tie‐2, are present in breast and prostate cancer, and their interrelationships may be important in the pathophysiology of these conditions.
Impact of parturition on iron status in nonanaemic iron deficiency
Authors: Krafft A. , Huch R. , Breymann C.
Published: September 2003

Background  Iron‐deficient nonanaemic parturients risk underdiagnosis as a result of the reliance on postpartum ferritin and haemoglobin as markers of iron status. Ferritin is an acute‐phase protein whose levels increase during the inflammatory response, as occurs after delivery. Our aims were to evaluate the impact of parturition on iron status, erythropoiesis and the inflammatory response, and identify the optimal parameters and timing for diagnosing iron deficiency in the presence of postpartum inflammation.

Materials and methods  Conventional parameters of iron status, erythropoiesis and the inflammatory response (serum ferritin, serum iron, transferrin saturation, C‐reactive protein) were compared with more recent parameters [soluble transferrin receptors (sTfR), hypochromic red cells, reticulocyte indices] within 48 h either side of delivery in 64 iron‐deficient nonanaemic women (defined by a prepartum serum ferritin ≤ 15 µg L−1, and a pre‐ and postpartum haemoglobin of ≥ 11·0 g dL−1 and ≥ 10·0 g dL−1, respectively).

Results  Mean sTfR decreased pre to postpartum from 7·3 to 5·8 µg mL−1 (P < 0·01), while mean serum ferritin increased from 9·7 to 16·9 µg L−1 (P < 0·01). Serum ferritin did not correlate with haemoglobin pre or postpartum (r = 0·04, P = 0·7; r = 0·2, P = 0·09), but a correlation persisted postpartum between hypochromic red blood cells and haemoglobin (r = −0·26; P < 0·05). The percentage of hypochromic red cells remained virtually unchanged pre‐ and postpartum (4·0% vs. 3·8%; NS). Postpartum mean reticulocyte haemoglobin content (CHr) was 27·1 ± 1·6 pg.

Conclusion  Iron status should be tested prepartum, in the absence of an inflammatory response, rather than in the early postpartum. A valuable additional parameter, where available, might be the hypochromic red cell percentage, which is virtually uninfluenced by the inflammatory response. Furthermore, hypochromic red cell percentage, CHr and sTfR can be helpful to differentiate between functional iron deficiency and depleted iron stores.
Erythropoietin as an angiogenic factor
Authors: Ribatti D. , Vacca A. , Roccaro A. M. , Crivellato E. , Presta M.
Published: September 2003

Erythropoietin (Epo) is produced by the fetal liver and adult kidney and is an essential stimulator of erythropoiesis. It has, however, been shown to modulate host cellular signal transduction pathway to perform many other functions. New sites of Epo production have been found, such as the female reproductive organs and central nervous system. This review summarizes the involvement of Epo in the regulation of angiogenesis in both normal and pathological conditions.
From particles to individuals: modelling the early stages of anchovy (Engraulis capensis/encrasicolus) in the southern Benguela
Authors: Mullon C. , Fréon P. , Parada C. , Van Der Lingen C. , Huggett J.
Published: September 2003

Several individual‐based models (IBMs) have recently been developed to improve understanding of factors impacting on recruitment variability of anchovy (Engraulis capensis/encrasicolus) in the southern Benguela. These IBMs have focused on early life history stages (eggs through to post‐larvae) as it is thought that variations in anchovy recruitment strength are primarily driven by biological and/or physical factors impacting on these stages. The pelagic zone of the Benguela system constitutes an ideal system for studying the coupling between biological and physical processes; in the IBMs this coupling is obtained by releasing particles endowed with biological properties in the virtual currents resulting from the output of a hydrodynamic model of the southwestern coast of South Africa. The particles are tracked through virtual time and space and their final locations are assessed in terms of previously defined criteria deemed to promote successful recruitment. The aim of this paper is to provide a synthesis of the results of IBMs of the early stages of anchovy in the southern Benguela constructed to date. Emphasis is placed on the methodological aspects of these studies and on the sequential link of several simulation experiments of increasing complexity. In addition to improving understanding, such an approach allows for effective interplay between modelling experiments and surveys or laboratory experiments. Details of individual IBM experiments and their results have been published elsewhere.
Potential changes in skipjack tuna (Katsuwonus pelamis) habitat from a global warming scenario: modelling approach and preliminary results
Authors: Loukos Harilaos , Monfray Patrick , Bopp Laurent , Lehodey Patrick
Published: September 2003

Recent studies suggest a reduction of primary production in the tropical oceans because of changes in oceanic circulation under global warming conditions caused by increasing atmospheric CO2 concentration. This might affect the productivity of medium and higher trophic levels with potential consequences on marine resources such as tropical tuna. Here we combine the projections of up‐to‐date climate and ocean biogeochemical models with recent concepts of representation of fish habitat based on prey abundance and ambient temperature to gain some insight into the impact of climate change on skipjack tuna (Katsuwonus pelamis), the species that dominates present‐day tuna catch. For a world with doubled atmospheric CO2 concentration, our results suggest significant large‐scale changes of skipjack habitat in the equatorial Pacific. East of the date line, conditions could be improved by an extension of the present favourable habitat zones of the western equatorial Pacific, a feature reminiscent of warming conditions associated with El Niño events. Despite its simplicity and the associated underlying hypothesis, this first simulation is used to stress future research directions and key issues for modelling developments associated to global change.
Investigating remote synchronous patterns in fisheries
Authors: Fréon P. , Mullon C. , Voisin B.
Published: September 2003

The hypothesis that the population dynamics of distant fish stocks may be synchronized by climate variations is largely based on a few major pelagic fisheries or stocks (called here ‘target series’). We broadened the study of synchrony to all available fisheries in the world by making use of all available data in the FAO catch database during the last 50 years. We investigated synchronous patterns in remote fisheries using two different approaches. The first approach consisted of simulating catch time‐series as random walk processes and comparing the synchronies found between these time‐series to the synchronies found in FAO data. In the second approach, we applied classification algorithms to analyse synchronies in the FAO catch database. We usedK‐means clustering and neural networks to answer the following four questions: (1) Do the target series appear in the same cluster? (2) Do the clusters regroup series from the same region (local synchrony) or from distant ones (remote synchrony)? (3) Are there any numerically dominant patterns (clusters) in the catch series? (4) Do the species displaying the same pattern share some common bio‐ecological features or ranges of abundance? Our results indicate some degree of local rather than remote synchrony. Nonetheless, it does not prove that such remote synchronies do not exist, but simply that further process studies are required before accepting them as a new paradigm.
Comparing productivity of North Atlantic cod (Gadus morhua) stocks and limits to growth production
Authors: Dutil Jean‐Denis , Brander Keith
Published: September 2003

Data from stock assessments were used to compare stock biomass, annual growth (Gs) and surplus production per capita (TSPc) and per unit biomass (TSPb) among 15 cod (Gadus morhua) stocks in the North Atlantic. TSPc ranged from 99 to 1012 g per fish among stocks and averaged 448 g per fish. TSPb ranged from 140 to 469 g kg−1 among stocks and averaged 294 g kg−1. Gs varied considerably with low growth production associated with low surplus production. On average, cod produced 724 g per fish in growth annually with cod in the least productive stock producing 7.2 times less than in the most productive stock. The stocks divided into four clusters reflecting four levels of production. Celtic Sea, Irish Sea and West Scotland cod showed the highest levels of production whereas Eastern Scotian Shelf, Northeast Arctic, Northern Grand Bank, Northern and Southern Gulf of St Lawrence showed the lowest levels. Surface and bottom salinity and temperature differed significantly among clusters in a canonical discriminant analysis. Temperature and salinity correlated with the first and second canonical variates, respectively. The most productive stocks were associated with higher bottom salinity and temperature. None of the stocks, including stocks with a fast growth rate and living at higher temperatures, had a specific growth rate (SGR) close to the maximum rate observed in laboratory experiments. The difference between observed and maximum SGR decreased at temperatures above 6°C. Very cold temperatures resulted in smaller cod also achieving SGR values closer to the maximum. Temperature is a major determinant of stock production.
Modelling climate‐related variability of tuna populations from a coupled ocean–biogeochemical‐populations dynamics model
Authors: Lehodey Patrick , Chai Fei , Hampton John
Published: September 2003

In the last five decades for which tuna fishing data are available, the interannual ENSO signal (SOI) and the related Pacific Decadal Oscillation (PDO) suggest two different regimes characterized by higher intensity and frequency of either El Niño or La Niña events. Recent estimates from a statistical population dynamics model (MULTIFAN‐CL) suggest that recruitment of three tuna species in the Pacific are correlated with these climate indices. While tropical tuna species like skipjack (Katsuwonus pelamis) and yellowfin (Thunnus albacares) had higher recruitments during El Niño events, the subtropical albacore species (Thunnus alalunga) showed the opposite pattern with low recruitment during El Niño and high recruitment during La Niña. The potential explanatory mechanisms for such relationships between recruitment and climate are investigated with a spatial environmental population model (SEPODYM). The model is a two‐dimensional coupled physical–biological interaction model at the ocean basin scale, and contains environmental and spatial components used to constrain the movement and the recruitment of tuna. Input datasets for the model are sea surface temperature, oceanic currents and new primary production that are simulated fields from a three‐dimensional coupled physical–biogeochemical model. The hypothesis that the spatial dynamics of temperature, currents (advection), food availability and predation constrain tuna recruitment is evaluated with an application of SEPODYM to skipjack. Simulation results showed that this hypothesis can reproduce fluctuations in the population that are similar to those estimated from the statistical model.
The selection process from larval to juvenile stages of anchovy (Engraulis encrasicolus) in the Bay of Biscay investigated by Lagrangian simulations and comparative otolith growth
Authors: Allain Gwenhael , Petitgas Pierre , Grellier Patrick , Lazure Pascal
Published: September 2003

The relation between growth and survival was investigated using the otolith growth data collected during repeated larval surveys (May–July) and a juvenile survey (September) undertaken in 1999 on anchovy spawning and nursery grounds in the Bay of Biscay (NE Atlantic). The paper describes the methodology for reading the larval and juvenile otoliths, for reconstructing the correspondence in space and time between juveniles and larvae using Lagrangian simulations, and for comparing the otolith growth rates among the reconstructed sub‐cohorts. Virtual buoys were released weekly on the grid of a three‐dimensional hydrodynamic model and their trajectories were tracked. The origin of an individual was determined by selecting the trajectory beginning on its hatching week and ending at the minimum distance of its sampling location on the sampling date. Larvae and juveniles with the same spatio‐temporal origin were selected and supposed to belong to the same sub‐cohorts. The surviving juveniles showed faster growth rates during their larval period than the pool of larvae they were estimated to originate from, which supports the idea of growth‐selective survival. Alternative interpretations (transport and gear selectivity) are discussed. Variations in otolith growth pattern also suggest a higher juvenile growth over the shelf break than in oceanic waters.
Dependency of larval fish survival on retention/dispersion in food limited environments: the Baltic Sea as a case study
Authors: Hinrichsen H.‐H. , Lehmann A. , Möllmann C. , Schmidt J.O.
Published: September 2003

A three‐dimensional hydrodynamic model has been used to analyse temporally and spatially resolved circulation patterns in the Baltic Sea with special emphasis on drifting particles representing larval fish. The main purpose of this study was (i) to investigate potential drift patterns of larval fish, (ii) to identify its intra‐ and inter‐annual variability for time periods based on the timing of spawning and (iii) to analyse its seasonal and spatial variability in dependence of the atmospheric forcing conditions. For the time period 1979–1998 temporally and spatially resolved simulated flow fields were used to describe the potential drift from the centre of main reproductive effort of Baltic cod (Gadus morhua). The results of the model runs demonstrate a general change in circulation pattern from retention during a first decade (1979–1988) to dispersion in the following decade (1989–1998). This increase in dispersion was related to an increase in the variability of the local wind forcing conditions over the Baltic. The more frequent occurrence of dispersion in spring of the recent decade was accompanied by a strong decay in biomass of one of the main larval fish feeding component in the central basin, the calanoid copepod Pseudocalanus elongatus. Larger dispersion of this prey organism may have affected the spatial overlap and thus the contact rates between predator and prey. Hence, this may have resulted in a food limitation for early life stages of Baltic cod and potentially contributed to the pronounced shift in cod peak spawning time from spring to late summer. Early life stages of cod originating from late spawning fish, benefited from a stronger dispersion in late summer and autumn, into shallow coastal areas with higher calanoid abundance.
Interannual variability of Calanus helgolandicus in the English Channel
Authors: Irigoien Xabier , Harris Roger P.
Published: September 2003

Seasonal and interannual variability in environmental variables, egg production rates and abundance of Calanus helgolandicus at a station in the English Channel have been analysed. The results show a mismatch between the timing of maximum egg production and timing of the abundance peaks. However, except for the year 1996, there was a significant relationship between the initiation of the thermocline and the timing of the maximum female abundance. We advance advection and egg mortality because of sinking as the main factors controlling the timing of the C. helgolandicus abundance peaks in the English Channel.
Long‐term changes in copepod abundance and diversity in the north‐east Atlantic in relation to fluctuations in the hydroclimatic environment
Authors: Beaugrand Gregory
Published: September 2003

This study investigates long‐term monthly changes in both the hydroclimatic (sea surface temperature and wind) and biological (calanoid copepod diversity, abundance of Calanus finmarchicus and Calanus helgolandicus) environment of the north‐east Atlantic. On the basis of the long‐term variability of the hydroclimatic environment, three regions are defined: the west European basin, the subarctic gyre and the North Sea. A numerical procedure, used in climatology and terrestrial ecology to detect stepwise changes, is presented and applied to both hydroclimatic and biological data. This method reveals that a regime shift in the North Sea occurred after a stepwise change in both regional hydroclimatic parameters (wind and temperature) and large‐scale hydroclimatic parameters (e.g. Northern Hemisphere Temperature anomalies). However, it is also suggested that ecological changes (e.g. calanoid copepod diversity, abundance of C. finmarchicus, C. helgolandicus) observed in the North Sea after the mid‐1980s also resulted from a major structural reorganization in calanoid copepod diversity in the north‐east Atlantic, which has been related to an increasing trend in sea surface temperature in the west European basin. Although from the present study it is difficult to quantify the respective influence of advective processes versus the impact of changes in the regional hydroclimatic environment on Calanus species, it seems likely that both processes can play a substantial role.