bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of Isocitrate Dehydrogenase Catalytic Activity by Protein Phosphorylation in Escherichia coli
Authors: Cozzone Alain J. , El-Mansi Mansi
Published: January 2006

During aerobic growth of Escherichia coli on acetate as sole source of carbon and energy, the organism requires the operation of the glyoxylate bypass enzymes, namely isocitrate lyase (ICL) and the anaplerotic enzyme malate synthase (MS). Under these conditions, the glyoxylate bypass enzyme ICL is in direct competition with the Krebs cycle enzyme isocitrate dehydrogenase (ICDH) for their common substrate and although ICDH has a much higher affinity for isocitrate, flux of carbon through ICL is assured by virtue of high intracellular level of isocitrate and the reversible phosphorylation/inactivation of a large fraction of ICDH. Reversible inactivation is due to reversible phosphorylation catalysed by ICDH kinase/phosphatase, which harbours both catalytic activities on the same polypeptide. The catalytic activities of ICDH kinase/phosphatase constitute a moiety conserved cycle, require ATP and exhibit ‘zero-order ultrasensitivity’. The structural gene encoding ICDH kinase/phosphatase (aceK) together with those encoding ICL (aceA) and MS (aceB) form an operon (aceBAK; otherwise known as the ace operon) the expression of which is intricately regulated at the transcriptional level by IclR, FadR, FruR and IHF. Although ICDH, an NADP+-dependent, non-allosteric dimer, can be phosphorylated at multiple sites, it is the phosphorylation of the Ser-113 residue that renders the enzyme catalytically inactive as it prevents isocitrate from binding to the active site, which is a consequence of the negative charge carried on phosphoserine 113 and the conformational change associated with it. The ICDH molecule readily undergo domain shifts and/or induced-fit conformational changes to accommodate the binding of ICDH kinase/phosphatase, the function of which has now been shown to be central to successful adaptation and growth of E. coli and related genera on acetate and fatty acids.
Protein Phosphorylation on Ser, Thr and Tyr Residues in Cyanobacteria
Authors: Zhang Cheng-Cai , Jang Jichan , Sakr Samer , Wang Li
Published: January 2006

Cyanobacteria belong to an extremely diverse group of gram-negative prokaryotes. They are all able to perform oxygen-evolving photosynthesis, but differ in morphology, ecological habitats, and physiology. This diversity is also reflected in the complexity of regulatory proteins involved in protein phosphorylation on Ser, Thr and Tyr residues. For those strains whose genomes are completely sequenced, for example, the number of genes identified so far that encode Ser/Thr and Tyr kinases range from none to 52. Genetic, molecular as well as functional genomic analyses demonstrate that Ser/Thr and Tyr kinases and phosphatases are involved in the regulation of a variety of activities according to changes in growth conditions or cell metabolism, such as cell motility, carbon and nitrogen metabolism, photosynthesis and stress response. The major challenge in the near future is to integrate these components into signaling pathways and identify their targets. Some of the Ser/Thr and Tyr kinases and phosphatases are expected to interact with classical two-component signaling pathways.
Structure/Function Studies of Ser/Thr and Tyr Protein Phosphorylation in Mycobacterium tuberculosis
Authors: Greenstein Andrew E. , Grundner Christoph , Echols Nathaniel , Gay Laurie M. , Lombana T. Noelle , Miecskowski Carl A. , Pullen Kristi E. , Sung Pei-yi , Alber Tom
Published: January 2006

Many bacterial species express ‘eukaryotic-like’ Ser/Thr or Tyr protein kinases and phosphatases that are candidate mediators of developmental changes and host/pathogen interactions. The biological functions of these systems are largely unknown. Recent genetic, biochemical and structural studies have begun to establish a framework for understanding the systems for Ser/Thr and Tyr protein phosphorylation in Mycobacterium tuberculosis (Mtb). Ser/Thr protein kinases (STPKs) appear to regulate diverse processes including cell division and molecular transport. Proposed protein substrates of the STPKs include putative regulatory proteins, as well as six proteins containing Forkhead-associated domains. Structures of domains of receptor STPKs and all three Mtb Ser/Thr or Tyr phosphatases afford an initial description of the principal modules that mediate bacterial STPK signaling. These studies revealed that universal mechanisms of regulation and substrate recognition govern the functions of prokaryotic and eukaryotic STPKs. Several structures also support novel mechanisms of regulation, including dimerization of STPKs, metal-ion binding to PstP and substrate mimicry in PtpB.
A Re-Evaluation of the Role of Vision in the Activity and Communication of Nocturnal Primates
Authors: Bearder S.K. , Nekaris K.A.I. , Curtis D.J.
Published: January 2006

This paper examines the importance of vision in the lives of nocturnal primates in comparison to diurnal and cathemeral species. Vision is the major sense in all primates and there is evidence that the eyesight of nocturnal species is more acute and variable than has previously been recognized. Case studies of the behaviour of a galago and a loris in open woodland habitats in relation to ambient light show thatGalago moholimales are more likely to travel between clumps of vegetation along the ground when the moon is up, and during periods of twilight, whereas they retreat to more continuous vegetation and travel less when the moon sets. This is interpreted as a strategy for avoiding predators that hunt on the ground when it is dark. The travel distances ofLoris lydekkerianusare not affected by moonlight but this species reduces its choice of food items from more mobile prey to mainly ants when the moon sets, indicating the importance of light when searching for high-energy supplements to its staple diet. Evidence is presented for the first time to indicate key aspects of nocturnal vision that would benefit from further research. It is suggested that the light and dark facial markings of many species convey information about species and individual identity when animals approach each other at night. Differences in the colour of the reflective eye-shine, and behavioural responses displayed when exposed to white torchlight, point to different kinds of nocturnal vision that are suited to each niche, including the possibility of some degree of colour discrimination. The ability of even specialist nocturnal species to see well in broad daylight demonstrates an inherent flexibility that would enable movement into diurnal niches. The major differences in the sensitivity and perceptual anatomy of diurnal lemurs compared to diurnal anthropoids, and the emergence of cathemerality in lemurs, is interpreted as a reflection of evolution from different ancestral stocks in very different ecosystems, and not a recent shift towards diurnality due to human disturbance.
Influence of Abiotic Factors on Cathemeral Activity: The Case of Eulemur fulvus collaris in the Littoral Forest of Madagascar
Authors: Donati Giuseppe , Borgognini-Tarli Silvana M.
Published: January 2006

The role environmental factors play in influencing circadian rhythms in natural habitats is still poorly described in primates, especially for those taxa with an activity cycle extended over the 24-hour cycle. In this paper, we elucidate the importance of abiotic factors in entraining the activity of cathemeral primates, focussing on results from a long-term study of Eulemur fulvus collaris (collared brown lemur) in south-eastern Malagasy littoral forest. Two groups of lemurs were followed for 60 whole-day and 59 whole-night observation periods over 14 months. Diurnal and nocturnal observations were equally distributed among moon phases and seasons. Temperature and humidity were recorded hourly by automatic data loggers. The littoral forest has a climatic environment where rainfall and humidity are uncorrelated with temperature and photoperiod. Diurnal and nocturnal activity varied seasonally, with the former increasing significantly with extended day length and the latter increasing significantly with shortened day length. Dusk seemed to act as a primary zeitgeber for these lemurs, coordinating the onset of evening activity throughout the entire year. Lunar phase and the nocturnal luminosity index correlated positively with the duration of nocturnal activity and negatively with the length of diurnal activity. Temperature was positively associated with diurnal activity but did not seem to influence lemur rhythms at night. Finally, lemur nocturnal activity significantly decreased when levels of humidity and rainfall were high. Cathemeral biorhythm is triggered by zeitgebers and influenced by masking factors. The activity of collared brown lemurs appears to be seasonally influenced by photoperiod and directly modulated by nocturnal ambient luminosity. These results are discussed by comparing data from other cathemeral species living in various climatic situations.
Cathemerality and Lunar Periodicity of Activity Rhythms in Owl Monkeys of the Argentinian Chaco
Authors: Fernandez-Duque Eduardo , Erkert Hans G.
Published: January 2006

Although most South American owl monkeys are mainly nocturnal,Aotus azarai azaraiof the Argentinean Chaco regularly shows diurnal activity. In this study we examined the strong influence of moonlight on its diurnal and nocturnal activity, as well as the interaction of moonlight effects with other exogenous factors. We analyzed long-term automated activity recordings obtained with accelerometer collars from 7 owl monkeys during 2003 and 2004. Our data show marked lunar periodic and seasonal modulations of the owl monkeys’ activity pattern. On full moon days they were active throughout the whole night and displayed reduced activity during the day. With a new moon, activity decreased during the dark portion of the night, peaked during dawn and dusk and extended over the bright morning hours. Waxing and waning moons induced a significant increase in activity during the first and the second half of the night, respectively. During the cold winter months the monkeys displayed twice as much activity throughout the warmer bright part of the day than during the rest of the year. These findings indicate thatA. a. azaraiis mainly a dark-active species, but is still able to shift a considerable portion of activity into the bright part of the day if unfavourable lighting and/or temperature conditions prevail during the night.
Cathemerality in the Mayotte Brown Lemur (Eulemur fulvus) :Seasonality and Food Quality
Authors: Tarnaud Laurent
Published: January 2006

In past decades, cathemerality – as defined by Tattersall [1987] – has been documented in two primate families: Cebidae and Lemuridae. In the Lemuridae, in particular the genusEulemur,cathemeral activity seems to be a regular behavioural trait. Nevertheless, ultimate and proximate determinants responsible for this behaviour remain unclear. In this study, in a dry and deciduous forest on Mayotte (Comoro Archipelago), activities of 4 female brown lemurs(Eulemur fulvus fulvus)were recorded by focal animal sampling during the daylight period and by scan sampling on their respective groups during the night. Horizontal distances travelled by females and groups were measured using GPS. During the daylight period, food intakes were estimated in grams by extrapolation of counting of mouthfuls after weighing a large sample of plant parts eaten. Crude protein, crude lipid, soluble sugar and crude fibre were analyzed for each seasonal reconstituted diet. Records of temperature and rainfall were supplied by a local meteorological station. Observations confirmed cathemerality in the Mayotte brown lemur as reported by Tattersall in 1977. During the dry season, the animals increased their nocturnal activity – substantially increasing the time devoted to feeding and moving overall, but especially at night – and were less active during the daylight period. The quality of their diet in the dry season was poorer than that in the wet season, with soluble sugar content and protein content decreasing and fibre content increasing slightly. As a result, Mayotte brown lemurs may need to extend their foraging activity over the 24-hour cycle to balance nutritional requirements.
Tonic Activation of Brain GnRH Immunoreactivity despite Reduction of Peripheral Reproductive Parameters in Opportunistically Breeding Zebra Finches
Authors: Perfito Nicole , Bentley George , Hau Michaela
Published: January 2006

Opportunistically breeding species offer the unique opportunity to understand mechanisms in reproductive physiology that allow for extreme flexibility in the regulation of reproduction. We studied a well-known opportunistic breeder, the zebra finch (Taeniopygia guttata) to test the hypothesis that the reproductive axis of opportunists is in a constant state of ‘near-readiness’. In wild zebra finches, reproduction is highly correlated with rainfall, and in the laboratory, water availability and humidity are the strongest cues to affect reproductive activation. We therefore subjected individuals to water restriction for eleven weeks followed by a two week period of ad libitum access to water. The control group had water freely available for the entire experiment. We measured the state of activation of the hypothalamo-pituitary gonad (HPG) axis at three levels: in the hypothalamus by measuring immunoreactive (ir) cGnRH-I and cGnRH-II; in the anterior pituitary gland by measuring plasma luteinizing hormone (LH); and in the gonads by measuring gonadal volume and function. We found that water restriction caused a reduction in circulating LH concentrations and that testis volume was more likely to decrease in water restricted than in control birds. Subsequent short-term return to ad libitum water availability caused LH to return to baseline in water restricted birds. These changes occurred without significant changes in ir-cGnRH-I, ir-cGnRH-II, or in testis function. These data suggest that in these opportunistic breeders, an inhibition of parts of the reproductive axis is not necessarily correlated with full inactivation of reproductive potential. GnRH-ir cells in the hypothalamus appear to remain active and able to respond to subsequent stimulation.
Distribution of Neuropeptide FF-Like Immunoreactivity in the Brain of Dermophis mexicanus (Amphibia; Gymnophiona): Comparison with FMRFamide Immunoreactivity
Authors: López Jesús M. , Moreno Nerea , Morona Ruth , González Agustín
Published: January 2006

Neuropeptide FF (NPFF) is an FMRFamide-related peptide widely distributed in the mammalian brain. NPFF immunohistochemistry labeled cell bodies in a few locations and dense fiber networks throughout the brain. Recently, the distribution of NPFF immunoreactive (NPFF-ir) cells and fibers in the brain of anuran and urodele amphibians was studied and, as in mammals, significant species differences were noted. To further assess general and derived features of the NPFF-containing neuron system in amphibians, we have investigated the distribution of NPFF-ir cell bodies and fibers in the brain of the gymnophionan Dermophis mexicanus by means of an antiserum against bovine NPFF. This distribution was compared to that of FMRFamide immunoreactivity. Major traits shared with anurans and urodeles were the abundant fiber labeling in the ventral telencephalon, hypothalamus, isthmus, ventrolateral medulla and dorsal spinal cord. In addition, in the three amphibian orders the majority of the NPFF-ir cells were located in the preoptic-hypothalamic region. However, distinct particular features were present in the gymnophionan such as the lack of NPFF-ir cells in the telencephalon, brainstem and spinal cord and the absence of NPFF-ir fibers in the hypophysis and the olfactory bulbs. This pattern was distinct from that observed for FMRFamide distribution. Striking differences were noted in the pallium, caudal hypothalamus and midbrain tegmentum where FMRFamide – containing cells were localized. The present results in Dermophis support the idea that data from gymnophionans must be included when stating the amphibian condition of a given system because important variations are obvious when gymnophionans are compared with anurans and urodeles.
Primary Squamous Cell Carcinoma of the Colon Associated with Hypercalcemia and Hyperleukocytosis
Authors: Yitta Silaja , Liang Mike K. , Berman Russell , Carter Joseph J. , Yee Herman T. , Marks Jenifer L.
Published: January 2006

Background/Aims: Squamous cell carcinoma of the colon is a rare entity. We report a case of a patient who presented with a perforated squamous cell carcinoma of the sigmoid colon. Results: A 45-year-old female presented with a 2-month history of worsening abdominal pain, bloody diarrhea, and vomiting. She underwent an exploratory laparotomy and was found to have keratinizing squamous cell carcinoma of the sigmoid colon that had perforated forming multiple abscess cavities. The postoperative course was complicated by hypercalcemia and persistent hyperleukocytosis, ultimately resulting in the patient’s death. Conclusions: We present the second reported case of squamous cell carcinoma of the colon associated with hypercalcemia and the first reported case of associated hyperleukocytosis.
Dialysis, Ultrafiltration, and Blood Pressure
Authors: Bergström J. , Asaba H. , Fürst P. , Oulès R.
Published: January 2006

The effect of ultrafiltration on blood pressure was compared in six patients with problems of overhydration during single-pass dialysis, ultrafiltration only (the fluid bypassing the dialyser) and recirculation dialysis (using the RP 6 dialyser and the 75 l Rodial system). Adequate ultrafiltration during single-pass dialysis was hampered by symptomatic hypotension. However, during recirculation dialysis as well as during ultrafiltration without dialysis much more rapid ultrafiltration was tolerated without a fall in blood pressure. A considerable fall in plasma osmolality occurred with single-pass dialysis, whereas only a small decrease occurred with recirculation dialysis and no change with ultrafiltration only. We conclude that a rapid fall in plasma osmolality interferes with blood pressure regulation and that ultrafiltration is far better tolerated provided that osmotic shifts are avoided or minimised.
The Mayo Clinic Cohort Study of Personality and Aging: Design and Sampling, Reliability and Validity of Instruments, and Baseline Description
Authors: Rocca Walter A. , Grossardt Brandon R. , Peterson Brett J. , Bower James H. , Trenerry Max R. , Ahlskog J. Eric , Sanft Kevin R. , de Andrade Mariza , Maraganore Demetrius M.
Published: January 2006

We established a historical cohort of 7,216 subjects who completed the Minnesota Multiphasic Personality Inventory (MMPI) at the Mayo Clinic from 1962 through 1965 for research (not clinical indication), and who resided within a 120-mile radius centered in Rochester, Minnesota. We describe here the overall cohort design and sampling, we report results concerning reliability and validity, and we describe age and sex patterns at baseline for four MMPI scores of primary interest (depression, anxiety, social introversion, and negativity). Subjects excluded from the cohort because of missing data had MMPI scores similar to subjects included (after appropriate rescaling). A cut-off specific for age and sex at the 75th percentile of the distribution of raw scores was valid compared with the traditional clinical cut-off (T scores plus one standard deviation). Baseline scores for all four scales were higher in women than in men at all ages (all p < 0.0001). Depression and social introversion scores showed an increasing trend with age in both sexes (Spearman rank correlation, rho = 0.05 and 0.08, respectively, p < 0.0001 for both). Baseline scores on the anxiety scale showed a decreasing trend with age in both sexes (rho = –0.06, p < 0.0001). Negativity scores remained relatively stable with age in both sexes (rho = 0.03, p = 0.01). We found a high correlation between the anxiety score and the negativity score (rho = 0.90, p < 0.0001) even after the exclusion of overlapping items (rho = 0.68, p < 0.0001). This newly established historical cohort study provides opportunities to test hypotheses regarding the link between personality and aging, aging-related diseases, and overall mortality.
Interaction of Nε(carboxymethyl)lysine- and methylglyoxalmodified albumin with endothelial cells and macrophages
Authors: Lieuw-a-Fa Mariska , Engelse Marten , van Hinsbergh Victor , Schalkwijk Casper
Published: January 2006

In diabetes mellitus an increased risk exists for vascular complications. A role for advanced glycation endproducts (AGEs) in the acceleration of vascular disease has been suggested. Nε(carboxymethyl)lysine (CML)- and methylglyoxal (MGO)-modified proteins have been identified as majorAGEs. The interaction of these AGEs with the human endothelial cells and macrophages was studied. Changes in adhesion molecule expression, i. e. vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin were determined by cell-bound Elisa on human endothelial cells after incubation with CML-modified albumin and MGO-modified albumin. The presence of the full-length receptor of AGEs (RAGE) and splice variants of RAGE was determined by specific RT-PCR. In addition, binding studies were performed with CML- and MGOmodified albumin to endothelial cells and P388D1 macrophages. We demonstrated that CML-albumin or MGO-albumin did not induce activation of endothelial cells as measured by the expression of adhesion molecules, while, under the same conditions, TNF-α did. No specific binding of CML-albumin and MGO-albumin on these cells was found. In contrast to endothelial cells, a specific binding of MGO-albumin to P388D1 macrophages was demonstrated, which could be competed by ligands of scavenger receptors. In human umbilical vein and microvascular endothelial cells we found the N-truncated and C-truncated splice variants of RAGE.

In conclusion, under our experimental conditions no CML- or MGO-albumin-induced increase in adhesion molecule expression was found on endothelial cells. In agreement with this, no binding of these AGEs was found to endothelial cells. The existence of splice variants of RAGE in endothelial cells might explain the lack of interaction of extracellular AGEs with these cells.
Potent low dose platelet inhibitory effects of clopidogrel and aspirin on coronary thrombus formation in an animal model of acute unstable angina
Authors: Berg Oliver , Heimann Axel , Münzel Thomas , Vahl Christian-Friedrich , Kempski Oliver , Darius Harald , Bierbach Benjamin , Horstick Georg
Published: January 2006

Application of clopidogrel before percutaneous coronary intervention in patients with acute coronary syndrome reduces the risk of cardiac events. Clopidogrel administration before surgery increases bleeding complications after CABG. Therefore, the antithrombotic effect of the low-dose combination of clopidogrel and aspirin was investigated in an in vivo pig model of coronary artery thrombus formation with cyclic flow reductions. The platelet inhibitory effect was determined by platelet aggregation and CFR, according to the methodology described by Folts. CFR were initiated by endothelial damage and placement of a constrictor around the LAD. 30 min after CFR were established, clopidogrel (0.1 mg/kg or5 mg/kg), aspirin (1 mg/kg or 7 mg/kg) or LDC (0.1 mg/kg clopidogrel and 1 mg/kg aspirin) were administered orally. CFR-frequency was determined for further 240 min. CFR-frequency (CFR/30 min) was significantly reduced at 60 min in response to aspirin (7 mg/kg, −48%, p<0.05), and at 120 min in response to clopidogrel (5 mg/kg, −65%, p<0.05) but not at low doses of either compound. In contrast, LDC of clopidogrel (0.1 mg/kg) plus aspirin (1 mg/kg) resulted in a complete and rapid abrogation of CFR at 90 min (−70%, p<0.05). Furthermore, LDC led to reduction of platelet aggregation when CFR-frequency was already significantly decreased. In contrast, high dose groups presented a significant reduction of platelet aggregation prior to CFR-frequency decrease. Low dose combination of clopidogrel plus aspirin demonstrates a potent over additive anti-thrombotic effect in vivo with a significant reduction in thrombus formation early after drug application. The effect occurs before inhibition of platelet aggregation is detectable.
Two sibling cases of hydrops fetalis due to alloimmune anti-CD36 (Naka) antibody
Authors: Cho Kazutoshi , Chiba Hitoshi , Azuma Hiroshi , Mochizuki Toshiko , Yamaguchi Miki , Sato Shin-ichiro , Ikeda Hisami , Yamada Hideto , Minakami Hisanori , Ariga Tadashi , Kobayashi Kunihiko , Okajima Satoru
Published: January 2006

Two female sibling cases, who were born to a CD36 deficient mother, were presented with Coombs’ test-negative hydrops. The alloimmune anti-CD36 (Naka) antibody was accidentally found in the mother’s serum after an episode of anaphylactic shock with thrombocytopenia, which occurred in an individual receiving fresh frozen plasma prepared from the mother’s donated blood. The mother was then diagnosed as having type II CD36 deficiency, lacking CD36 on both platelets and monocytes, while both of her daughters were CD36 positive. Analyses of the CD36 gene revealed that the mother was a compound heterozygote for the CD36 gene mutation with a novel C→T transition at nt 1366 in exon 12, corresponding to Arg386Trp, and a known 12bp deletion at nt 1438–1449 in exon 13. On the other hand, both patients, who showed half the normal level of CD36 on platelets and monocytes, were heterozygote with one mutation at Arg386Trp. The anti-CD36 antibody in the mother seemed to be responsible for the hydrops fetalis observed in her daughters, because the IgG isolated from the mother’s serum showed suppressive effects on the CFU-E colony formation of CD34+ cells from a control donor. This is the first case report of hydrops fetalis caused by an alloimmune anti-CD36 antibody.
Combined genetic profiles of components and regulators of the vitamin K-dependent γ-carboxylation system affect individual sensitivity to warfarin
Authors: Vecsler Manuela , Loebstein Ronen , Almog Shlomo , Kurnik Daniel , Goldman Boleslav , Halkin Hillel , Gak Eva
Published: January 2006

We examined the influence of combined genotypes on interindividual variability in warfarin dose-response. In 100 anticoagulated patients we quantified the effects of polymorphisms in: CYP2C9, VKORC1, calumenin (CALU), γ-glutamyl carboxylase (GGCX) and microsomal epoxide hydrolase (EPHX1) on warfarin dose requirements. The G1542C VKORC1 polymorphism was associated with decreased warfarin doses in the heteroand homozygous mutant patients (21% and 50% lower, respectively; p<0.0001). Warfarin daily dose was predominantly determined by VKORC1 and CYP2C9 genotypes (partial r2= 0.21; 0.20, respectively). Together with age and body weight, these two genotypes explained 63% of the dose variance. A single patient, homozygous for G11A CALU mutant allele, required an excep tionally high warfarin dose (20mg/day) and the prevalence of heterozygous 11A allele carriers in the upper 10th dose percentile was significantly higher (0.27 vs. 0.18, p<0.02). Combined genotype analysis revealed that CYP2C9 andVKORC1 wild type and CALU mutant patients required the highest warfarin doses (7. 8±1. 5mg/day; n=9) as compared to the CYP2C9 and VKORC1 mutant and CALU wild type genotypes (2. 8±0. 3mg/day; n=18; p<0.01). The odds ratio for doses <3mg/day was 5. 9 (1.9–18. 4) for this genotype. Compound genetic profiles comprising VKORC1, CALU and CYP2C9 improve categorization of individual warfarin dose requirements in more than 25% of patients at steady-state anticoagulation.
Endothelial cells express a matrix protein which binds activated factor XII in a zinc-independent manner
Authors: Schousboe Inger
Published: January 2006

Recent studies have shown that peptides identified as surface binding regions of high molecular mass kininogen (HK) and factor XII (FXII) inhibit the Zn2+-dependent binding of FXII to confluent layers of human umbilical vein endothelial cells (HUVEC). This indicates that negatively charged FXII binding surfaces, such as sulfatides and dextran sulfate, may interfere with the binding of FXII to confluent layer of HUVEC. Upon investigating this hypothesis it was unexpectedly found that sulfatides enhanced a specific binding of FXII to a matrix protein expressed during growth of the endothelial cells and that this binding was independent of the presence of Zn2+. The function of sulfatides was partly to minimize nonspecific electrostatic binding and partly to induce and enhance autoactivation of FXII generating αFXIIa. Western blot analysis of the extracts of the matrix incubated with FXII and sulfatides showed that the binding was specific for αFXIIa. The dissociation constant for binding αFXIIa was 12. 8 ± 0. 4 nM (n=4). The binding of αFXIIa to ECM was mapped to the heavy chain as no binding was observed of the light chain containing the catalytic domain. HK, which previously has been shown to completely abolish the Zn2+-dependent binding of FXII to confluent layers of HUVEC, did not inhibit the binding of αFXIIa to the matrix but sulfatides enhanced binding of FXII to ECM. This suggests that HK interferes with the binding of FXII to sulfatides and thereby the autoactivation of FXII. Trypsin treatment of the matrix protein completely abolished the binding, and fibronectin but not laminin was found to bea suitable target. The binding of activated FXII to the ECM suggests that FXIIa may bea modulator of cellular adhesion, migration and vascularization.
Long term influence of regular intake of high dose n-3 fatty acids on CD40-ligand, pregnancy-associated plasma protein A and matrix metalloproteinase-9 following acute myocardial infarction
Authors: Brügger-Andersen Trygve , Hetland Øyvind , Grundt Heidi , Nilsen Dennis , Aarsetøy Hildegunn
Published: January 2006

Pregnancy-associated plasma protein A (PAPP-A) and matrix metalloproteinase 9 (MMP-9), both zinc-binding endopeptidases, are abundantly expressed in ruptured and eroded plaques in patients with acute coronary syndromes (ACS).The adhesion molecule CD-40 ligand (CD40L), expressed on activated platelets and T-lymphocytes, can activate metalloproteinases and thereby promote plaque-rupture. N-3 fatty acids, through their anti-inflammatory and anti-thrombotic properties,might reduce the levels of these proatherosclerotic markers and thereby the development of ACS. 300 patients were randomized on day4 to 6 following an acute myocardial infarction (MI) to receive either 4g of n-3 fatty acids or a similar daily dose of corn oil for at least one year.We compared levels of PAPP-A, MMP-9 and sCD-40 L at baseline and 12 months in each group, and also looked for inter-group changes. In the omega-3 group, the median level of PAPP-A rose from 0.47 mU/l to 0.56 mU/l (p < 0.001). In the same group, sCD-40 L decreased froma mean baseline value of 5.19 ng/ml to 2.45 ng/ml (p < 0.001) and MMP-9 decreased nonsignificantly from 360.50 ng/ml to 308.00 ng/ml. Corresponding values for the corn oil group were 0.54 mU/l to 0.59 mU/l for PAPP-A (p= 0.007), 5.27 ng/ml to 2.84 ng/ml for sCD-40 L (p< 0.001) and 430.00 ng/ml to 324.00 ng/ml for MMP-9 (p=ns), respectively. In conclusion; both interventions resulted in a significant rise in PAPP-A, a significant decrease in sCD40L and a non-significant decrease in MMP-9 after 12 months of treatment in MI survivors. No inter-group differences were noted.
Differential expression of tissue factor mRNA and protein expression in murine sepsis
Authors: de Waard Vivian , Hansen Hjalmar , Spronk Henri , Timmerman Janneke , Pannekoek Hans , Florquin Sandrine , Reitsma Pieter , ten Cate Hugo
Published: January 2006

Tissue factor (TF) is a transmembrane protein, which is essential for initiation of the coagulation cascade. TF has been reported to play an important role in the progression of endotoxin (lipopolysaccharide, LPS)-mediated endotoxemia, being induced in numerous tissues, such as kidney, spleen and lung. We developed and validateda rabbit anti-murine TF peptide antiserum to localize TF protein in a murine sepsis model. TF protein distribution was compared to localization of TF mRNA and fibrin deposits, the ultimate resultant of procoagulant TF activity. Evident LPSmediated TF mRNA induction was observed in the tubular area at the cortico-medullar junction in the kidney, and TF activity was increased after 6 hours of endotoxemia. In the spleen, however, TF mRNA was induced in the interfollicular region upon LPS injection, corresponding to increased TF protein in the same area. The clusters of TF-protein positive cells in the spleen are predominantly granulocytes, but no TF mRNA expression was observed within these cells. Based on these observations and the presence of TF-protein positive granulocytes after splenectomy, we hypothesize that granulocytes take-up TF for transport to other locations in order to initiate fibrin formation or to induce pronflammatory gene expression upon interaction with factor VIIa.
Increased plasma prothrombin concentration in cirrhotic patients with portal vein thrombosis and prothrombin G20210A mutation
Authors: Guardascione Maria , Ames Paul , Margaglione Maurizio , Iannaccone Luigi , Brancaccio Vincenzo , Balzano Antonio , Amitrano Lucio
Published: January 2006

It was the aim of the present study to investigate factor II levels in liver cirrhosis (LC) patients with portal vein thrombosis (PVT) carrying the heterozygous G20210A prothrombin (PT) mutation. Plasma concentrations of factor II, VII, X, V, protein C (PC) total protein S (tPS) antithrombin (AT) and D-dimers (DD) were measured in 13 LC patients with PVT heterozygous for PT G20210A, in 13 LC patients with PVT without PT G20210A and in 13 LC controls matched by age, sex and Child-Pugh score. Crude factor II and factor II/DD ratio were highest in LC patients with PVT heterozygous for PT G20210A (p=0.03 and p=0.02 respectively). The factor II/PC ratio, expression of a procoagulant/anticoagulant imbalance was highest in the same group (p=0.0008). Plasma factor II levels are elevated in LC patients heterozygous for PT G20210A and may favour PVT.
The serpin proteinase inhibitor 8: An endogenous furin inhibitor released from human platelets
Authors: Leblond Julie , Laprise Marie-Hélène , Gaudreau Simon , Grondin Francine , Kisiel Walter , Dubois Claire
Published: January 2006

The cornerstone of hemostasis is the ability of the organism to limit the enzymatic processes involved, thereby avoiding thrombosis. For this, anticoagulant systems in place involve serpins, such as PAI-1 and antithrombin III, which bind to their targeted serine proteases and limit their period of activity. We have previously identified the serine protease furin as a platelet-derived enzyme with an intrinsic role in platelet functions. We now report that furin enzymatic activity decreased rapidly following platelet activation, corresponding with the increase in formation of a high 180 M
r SDS-stable complex composed of furin and the PI8 serpin. PI8 is shown to be a platelet-derived constituent, synthesized by megakaryocytes and stored in platelets prior to its release. Immunoprecipitation and purification of the PI8-furin complex confirmed their direct interaction and indicates that one of the roles of PI8 is to inhibit furin enzymatic activity. Furthermore, our findings demonstrate the inhibitory capacity of exogenous PI8 in platelet aggregation assays. The finding that PI8 is released by platelets and controls functional responses suggests a role for this serpin in platelet-regulated pathophysiological responses.
Niklas Luhmann's systems theoretical redescription of the inclusion/exclusion debate
Authors: Braeckman Antoon
Published: January 2006

Relying on Niklas Luhmann's systems theoretical redescription of modern society, this article aims at questioning the basic theoretical notions of the ongoing inclusion/exclusion debate. The most remarkable aspect of Luhmann's reassessment of the inclusion/exclusion relationship within functionally differentiated societies is that individuals are basically situated within the exclusiondomain of society, and thus cannot but partially be includedwithin society's function systems and organizations. This reassessment not only allows Luhmann to raise fundamental questions with respect to the implicit norm of full inclusion which still dominates the debate on inclusion and exclusion, but it also directs his attention to the different inclusion/exclusion conditions within function systems, organizations and interaction systems. Eventually Luhmann's position comes down to the idea that exclusion rather than inclusion is the rule, and, moreover, that inclusions differ from one another. The article closes off with a critical evaluation of Luhmann's redescription of the inclusion/exclusion debate. It is argued that systems theory might suffer from empirical deficiency, as it seems to have difficulties to detect and to depict the actual mechanisms of social exclusion without resorting to theories that are more geared to empirical reality and that are of help in observing it.
Technology and Terrorism in the Movie Brazil
Authors: Stivers Richard
Published: January 2006

The movie Brazil calls attention to the relationship between technology and terrorism. Terrorism appears to be a threat to the order that technology creates. But terrorism forces technology to adapt and change so that technology perfects itself as a system. In the movie, terrorism is equated with any form of bureaucratic deviance so that everyone is more or less under suspicion as a terrorist.
Democratic participation and Letters to the Editor in Britain and Italy
Authors: Pounds Gabrina
Published: January 2006

Both in Italy and Britain ‘Letters to the Editor’ can arguably be considered a means through which readers can express and debate opinions on current affairs and thereby contribute to and participate in the democratic process. Two main questions arise: first, to what extent can one talk about ‘democratic participation’ in either case, given the role of the ‘Letters' in the two cultural settings?; second, to what extent and at what levels does the discourse of the ‘Letters' encode ‘participation’? It is argued that the Italian and British ‘Letters' perform significantly different functions, reflecting the different roles played by the press in Britain and Italy. A model for the analysis of ‘participation’ in the discourse of the ‘Letters' is suggested and exemplified. The findings from its application to a corpus of British and Italian ‘Letters' are presented and assessed in the light of the preceeding cultural comparison.
The alchemy of the upwardly mobile: symbolic capital and the stylization of elites in frequent-flyer programmes
Authors: Thurlow Crispin , Jaworski Adam
Published: January 2006

From a sample of 51 major international airlines, we offer a critical discourse analysis of so-called loyalty or frequent-flyer programmes and their related business-class services. As examples of cultural capital par excellence, these seemingly innocuous discursive formations act as significant agents of, and channels for, globalist relations of power in the context of international travel and tourism. The principal logic of frequent-flyer programmes hinges on establishing a synthetically personalized (see Fairclough, 1989) framework by which ‘loyalty’ is defined and rewarded, and by which privilege is then awarded and regulated. However, what actually sustains this commodified interpersonal appeal is the airlines' skilful reworking of symbolic capital, their manipulation of the illusion of distinction, and the exploitation of social anxieties about status. This is all achieved through a series of discursive strategies that stylize(see Cameron, 2000a) ‘preferred’ passengers as elite. Our analysis of frequent-flyer programmes and business-class services exposes some of the ways social privilege and superiority are nowadays measured, as well as the normative production of luxury. We argue that, for the sake of global marketability and profit, the semiotic realization of super-elitism by the airline industry powerfully ‘re-organizes' anachronistic modes of tourism while also reformulating very traditional notions of class distinction.
Views of justice among survivors of historical child sexual abuse
Authors: Jülich Shirley
Published: January 2006

Restorative justice for adults in New Zealand has made a cautious start, although crimes of gendered violence are typically excluded. The findings reported in this article draw on interviews of adult survivors of child sexual abuse (eighteen women and three men), asking them to describe their experiences with the abuse and its impact, and to suggest changes to the criminal justice system, which would provide them with a sense of justice. Although the survivors spoke of justice in ways that reflected the goals of restorative justice, they were reluctant to endorse restorative justice as a paradigm within which they would pursue justice.
Correlates of Return to Work for Breast Cancer Survivors
Authors: Bouknight Reynard R. , Bradley Cathy J. , Luo Zhehui
Published: January 2006

Purpose

To identify correlates of return to work for employed breast cancer survivors.

Patients and Methods

Patients included 416 employed women with newly diagnosed breast cancer identified from the Metropolitan Detroit Cancer Surveillance System. Patients were interviewed by telephone 12 and 18 months after diagnosis. Correlates of return to work at 12 and 18 months were identified using multivariate logistic regression.

Results

More than 80% of patients returned to work during the study period, and 87% reported that their employer was accommodating to their cancer illness and treatment. After adjusting for demographic characteristics, health status, cancer stage, treatment, and job type, heavy lifting on the job (odds ratio = 0.42; 95% CI, 0.18 to 0.99), perceived employer accommodation for cancer illness and treatment (odds ratio = 2.2; 95% CI, 1.03 to 4.8), and perceived employer discrimination because of a cancer diagnosis (odds ratio = 0.27; 95% CI, 0.10 to 0.71) were independently associated with return to work at 12 months after breast cancer diagnosis, and perceived employer accommodation (odds ratio = 2.3; 95% CI, 1.06 to 5.1) was independently associated with return to work at 18 months after breast cancer diagnosis.

Conclusion

A high percentage of employed breast cancer patients returned to work after treatment, and workplace accommodations played an important role in their return. In addition, perceived employer discrimination because of cancer was negatively associated with return to work for breast cancer survivors. Employers seem to have a pivotal role in breast cancer patients' successful return to work.
Risk of Selected Subsequent Carcinomas in Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study
Authors: Bassal Mylène , Mertens Ann C. , Taylor Leslie , Neglia Joseph P. , Greffe Brian S. , Hammond Sue , Ronckers Cécile M. , Friedman Debra L. , Stovall Marilyn , Yasui Yutaka Y. , Robison Leslie L. , Meadows Anna T. , Kadan-Lottick Nina S.
Published: January 2006

Purpose

To determine the risk of subsequent carcinomas other than breast, thyroid, and skin, and to identify factors that influence the risk among survivors of childhood cancer.

Patients and Methods

Subsequent malignant neoplasm history was determined in 13,136 participants (surviving ≥ 5 years postmalignancy, diagnosed from 1970 to 1986 at age < 21 years) of the Childhood Cancer Survivor Study to calculate standardized incidence ratios (SIRs), using Surveillance, Epidemiology, and End Results data.

Results

In 71 individuals, 71 carcinomas were diagnosed at a median age of 27 years and a median elapsed time of 15 years in the genitourinary system (35%), head and neck area (32%), gastrointestinal tract (23%), and other sites (10%). Fifty-nine patients (83%) had received radiotherapy, and 42 (59%) developed a second malignant neoplasm in a previous radiotherapy field. Risk was significantly elevated following all childhood diagnoses except CNS neoplasms, and was highest following neuroblastoma (SIR = 24.2) and soft tissue sarcoma (SIR = 6.2). Survivors of neuroblastoma had a 329-fold increased risk of renal cell carcinomas; survivors of Hodgkin's lymphoma had a 4.5-fold increased risk of gastrointestinal carcinomas. Significantly elevated risk of head and neck carcinoma occurred in survivors of soft tissue sarcoma (SIR = 22.6), neuroblastoma (SIR = 20.9), and leukemia (SIR = 20.9).

Conclusion

Young survivors of childhood cancers are at increased risk of developing subsequent carcinomas typical of later adulthood, underscoring the importance of long-term follow-up and risk-based screening. Follow-up of the cohort is ongoing to determine lifetime risk and delineate individual characteristics that contribute to risk.
OPTIMOX1: A Randomized Study of FOLFOX4 or FOLFOX7 With Oxaliplatin in a Stop-and-Go Fashion in Advanced Colorectal Cancer—A GERCOR Study
Authors: Tournigand Christophe , Cervantes Andres , Figer Arie , Lledo Gérard , Flesch Michel , Buyse Marc , Mineur Laurent , Carola Elisabeth , Etienne Pierre-Luc , Rivera Fernando , Chirivella Isabel , Perez-Staub Nathalie , Louvet Christophe , André Thierry , Tabah-Fisch Isabelle , de Gramont Aimery
Published: January 2006

Purpose

In metastatic colorectal cancer, a combination of leucovorin (LV) and fluorouracil (FU) with oxaliplatin (FOLFOX) 4 is a standard first-line regimen. The cumulative neurotoxicity of oxaliplatin often requires therapy to be stopped in patients who are still responding. This study evaluates a new strategy of intermittent oxaliplatin treatment that is based on FOLFOX7, a simplified leucovorin and fluorouracil regimen with high-dose oxaliplatin.

Patients and Methods

Previously untreated patients were randomly assigned to either FOLFOX4 administered every 2 weeks until progression (arm A) or FOLFOX7 for six cycles, maintenance without oxaliplatin for 12 cycles, and reintroduction of FOLFOX7 (arm B).

Results

Six hundred twenty patients were enrolled, including an exploratory cohort of 95 elderly or poor prognosis patients. Median progression-free survival and survival times were 9.0 and 19.3 months, respectively, in patients allocated to arm A compared with 8.7 and 21.2 months, respectively, in patients allocated to arm B (P = not significant). Response rates were 58.5% with arm A and 59.2% with arm B. National Cancer Institute Common Toxicity Criteria grade 3 or 4 toxicity was observed in 54.4% of the patients in arm A v 48.7% of patients in arm B. From cycle 7, fewer patients experienced grade 3 or 4 toxicity in arm B. Grade 3 sensory neuropathy was observed in 17.9% of the patients in arm A v 13.3% of patients in arm B (P = .12). In arm B, oxaliplatin was reintroduced in only 40.1% of the patients but achieved responses or stabilizations in 69.4% of these patients.

Conclusion

Oxaliplatin can be safely stopped after six cycles in a FOLFOX regimen. Further study is needed to fully evaluate oxaliplatin reintroduction.
Factors Predicting the Choice of an Online versus a Traditional Course
Authors: Robinson Ryan P. , Doverspike Dennis
Published: January 2006

Universities sometimes offer students the choice of an online course as an alternative to the traditional classroom. We employed the theory of planned behavior (Azjen, 1991) to examine an individual's intention to enroll in an online experimental psychology class versus a traditional class. General attitudes and subjective norms significantly predicted students' reported enrollment intentions. We discuss suggestions for increasing interest in online courses.