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Terms modified by Marked Selected AbstractsContesting "Corporate Value" Through Takeover Bids in JapanCORPORATE GOVERNANCE, Issue 1 2007D. Hugh Whittaker Livedoor's attempted takeover of Nippon Broadcasting System in February 2005 marked a watershed in the history of mergers and acquisitions in Japan. The drama was played out in public, changing popular perceptions, influencing policy makers and sending managers scurrying to debate and erect legitimate defence measures in case they themselves should be targeted. Tensions on the investor relations interface were not subsequently reversed by Livedoor's equally dramatic demise. The article considers the rise of takeover bids in Japan, responses to it, and their significance for corporate control and governance, as well as for the "community firm". [source] Increased gyrification in Williams syndrome: evidence using 3D MRI methodsDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 5 2002J Eric Schmitt BABS Understanding patterns of gyrification in neurogenetic disorders helps to uncover the neurodevelopmental etiology underlying behavioral phenotypes. This is particularly true in Williams syndrome (WS), a condition caused by de novo deletion of approximately 1 to 2Mb in the 7q11.23 region. Individuals with WS characteristically possess an unusual dissociation between deficits in visual-spatial ability and relative preservations in language, music, and social drive. A preliminary postmortem study reported anomalous gyri and sulci in individuals with WS. The present study examined gyrification patterns in 17 participants with WS (10 females, 7 males; mean age 28 years 11 months, SD 8 years 6 months) and 17 age- and sex-matched typically developing control participants (mean age 29 years 1 month, SD 8 years 1 month) using new automated techniques in MRI. Significantly increased cortical gyrification was found globally with abnormalities being more marked in the right parietal (p=0.0227), right occipital (p=0.0249), and left frontal (p=0.0086) regions. These results suggest that one or more genes in the 7q11.23 region are involved during the critical period when cortical folding occurs, and may be related to the hypothesized dorsal/ventral dissociation in this condition. [source] Blockade of the central generator of locomotor rhythm by noncompetitive NMDA receptor antagonists in Drosophila larvaeDEVELOPMENTAL NEUROBIOLOGY, Issue 1 2001Daniel Cattaert Abstract The noncompetitive antagonists of the vertebrate N -methyl- D -aspartate (NMDA) receptor dizocilpine (MK 801) and phencyclidine (PCP), delivered in food, were found to induce a marked and reversible inhibition of locomotor activity in Drosophilamelanogaster larvae. To determine the site of action of these antagonists, we used an in vitro preparation of the Drosophila third-instar larva, preserving the central nervous system and segmental nerves with their connections to muscle fibers of the body wall. Intracellular recordings were made from ventral muscle fibers 6 and 7 in the abdominal segments. In most larvae, long-lasting (>1 h) spontaneous rhythmic motor activities were recorded in the absence of pharmacological activation. After sectioning of the connections between the brain and abdominal ganglia, the rhythm disappeared, but it could be partially restored by perfusing the muscarinic agonist oxotremorine, indicating that the activity was generated in the ventral nerve cord. MK 801 and PCP rapidly and efficiently inhibited the locomotor rhythm in a dose-dependent manner, the rhythm being totally blocked in 2 min with doses over 0.1 mg/mL. In contrast, more hydrophilic competitive NMDA antagonists had no effect on the motor rhythm in this preparation. MK 801 did not affect neuromuscular glutamatergic transmission at similar doses, as demonstrated by monitoring the responses elicited by electrical stimulation of the motor nerve or pressure applied glutamate. The presence of oxotremorine did not prevent the blocking effect of MK 801. These results show that MK 801 and PCP specifically inhibit centrally generated rhythmic activity in Drosophila, and suggest a possible role for NMDA-like receptors in locomotor rhythm control in the insect CNS. © 2001 John Wiley & Sons, Inc. J Neurobiol 48: 58,73, 2001 [source] Moxonidine improves glycaemic control in mildly hypertensive, overweight patients: a comparison with metforminDIABETES OBESITY & METABOLISM, Issue 4 2006Irina Chazova Aim:, To compare the effects of moxonidine and metformin on glycaemic control in patients with impaired glucose tolerance and signs of the metabolic syndrome. Methods:, A multicentre, prospective, randomized, open-label study design was adopted with blinded endpoint evaluation. Patients ,40 years old, with impaired glucose tolerance (or diabetes mellitus treated with diet alone) and a body mass index (BMI) of at least 27 kg/m2 were treated twice daily with moxonidine 0.2 mg or metformin 500 mg for 16 weeks. Oral glucose tolerance test (OGTT) was performed at baseline and end-of-study; plasma insulin and plasma glucose levels were measured at 0, 60, 120 and 180 min after administration. Results:, With regard to effects on insulin [mean area under the curve (AUC) for insulin], the primary efficacy endpoint of the study, both drugs did not show equivalence. On the contrary, in the per protocol (PP) population, moxonidine statistically significantly (p = 0.025) decreased the AUC for insulin from baseline in the PP population; for metformin, the treatment effect on insulin was a small, net increase resulting in a statistically significant between-group difference of 16.2% (95% CI = 0.1,35.0). The change in mean insulin AUC was most marked in the subgroup of patients with higher sympathetic activity (heart rate >80 bpm). Mean fasting plasma glucose (FPG) levels and HbA1c levels were largely unchanged by moxonidine treatment but significantly decreased by metformin treatment. The difference between the groups was 14.7% (p = 0.0523) in the intent-to-treat (ITT) sample. By study end, both treatments had significantly increased the Matsuda Insulin Sensitivity Index (ISI) from baseline to a comparable extent: moxonidine by reducing plasma insulin after a glucose challenge, metformin by reducing FPG. BMI fell significantly in both groups and blood pressure normalized; both drugs were well tolerated. Conclusions:, Moxonidine improved insulin sensitivity in response to glucose challenge in patients with evidence of metabolic syndrome. This improvement resulted from a reduction in plasma insulin levels and was most marked in patients with high sympathetic drive at baseline. By enhancing insulin sensitivity, moxonidine treatment may help prevent the development of diabetes and thereby ameliorate the risk for cardiovascular disease. [source] Circulating insulin antibodies: influence of continuous subcutaneous or intraperitoneal insulin infusion, and impact on glucose controlDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 6 2009R. P. Radermecker Abstract The purification of animal insulin preparations and the use of human recombinant insulin have markedly reduced the incidence, but not completely suppressed, the development of anti-insulin antibodies (IAs). Advances in technologies concerning the mode of delivery of insulin, i.e. continuous subcutaneous insulin infusion (CSII), continuous peritoneal insulin infusion (CPII) and more recently inhaled insulin administration, appear to significantly increase circulating levels of immunoglobulin G (IgG) anti-IAs in diabetic patients. However, the increase is usually moderate and mostly transient as compared to previous observations with poorly purified animal insulin preparations. The clinical impact of these circulating anti-IAs remains unclear. Nevertheless, several studies have suggested that antibodies could retard insulin action, leading to a worsening of postprandial hyperglycaemia and/or serve as a carrier, thus leading to unexpected hypoglycaemia. CPII may be associated with more marked and sustained increase in IAs levels, possibly related to the use of an unstable insulin and the formation of immunogenic aggregates of insulin. The possible clinical consequences of these high levels of IAs remain to be evaluated because a low-glucose morning syndrome or severe insulin resistance with ketone bodies production have been reported in some cases. In conclusion, even if CSII and CPII may promote the development of circulating IAs, this increase does not lead to immunological insulin resistance, compared to that previously described with animal non-purified insulin preparations, and seems to have only marginal influence on blood glucose control or complications in most diabetic patients. Copyright © 2009 John Wiley & Sons, Ltd. [source] Factors predictive of nephropathy in DCCT Type 1 diabetic patients with good or poor metabolic controlDIABETIC MEDICINE, Issue 7 2003L. Zhang Abstract Aims The study aim was to assess the time-related risk of developing diabetic nephropathy [albumin excretion rate (AER) , 40 mg/24 h] from baseline covariates in Type 1 diabetic patients with either good or poor metabolic control (MC). Methods Based on material from the Diabetes Control and Complications Trial study (n = 1441), patients were considered as under good or poor MC if their HbA1c mean level up to last visit fell in the lowest (, 6.9%) or highest (, 9.5%) quintile of the overall HbA1c distribution, respectively. Prevalence cases of nephropathy were excluded from the study. Survival analysis and Cox regression were applied to the data. Results Among patients with good MC (n = 277), 15% had developed nephropathy at the end of the study. Conversely, among patients with poor MC (n = 268), the proportion without the complication was 52%. When adjusting for MC, time to diabetic nephropathy was related to age (P < 0.0001), AER (P < 0.001), duration of diabetes (P < 0.005), body mass index (BMI) (P < 0.005), all at baseline, and to gender (P < 0.01). Patients with upper normal range AER levels, longer duration of diabetes and lower BMI were at higher risk, regardless of MC. The adverse effect of younger age on diabetic nephropathy was more marked in good than in poor MC. Although women tended to develop the complication more often under good MC, they appeared to be better protected under poor MC. Conclusions This study confirms occurrence of diabetic nephropathy under good MC and non-occurrence of the complication despite poor MC. It also demonstrates that some baseline covariates can affect, in a differential manner, time to diabetic nephropathy depending on MC. Diabet. Med. 20, 580,585 (2003) [source] Comparison of Proximal Isovelocity Surface Area Method and Pressure Half Time Method for Evaluation of Mitral Valve Area in Patients Undergoing Balloon Mitral ValvotomyECHOCARDIOGRAPHY, Issue 9 2005Thottuvelil Narayanan Sunil Roy M.D. Background: The pressure half time (PHT) method is unreliable for measurement of mitral valve area (MVA) immediately after valvotomy. The proximal isovelocity surface area (PISA) method has been used to derive mitral valve area in patients with mitral stenosis. The aim of our study was to compare PISA method and PHT method in patients undergoing percutaneous balloon mitral valvotomy (BMV). Methods: The PISA was recorded from the apex and MVA was calculated using continuity equation by the formula 2,r2 Vr/Vm, where 2,r2 is the hemispheric isovelocity area, Vr is the velocity at the radial distance "r" from the orifice, and Vm is the peak velocity. A plain angle correction factor (,)/180 was used to correct the inlet angle subtended by leaflet tunnel as a result of leaflet doming. Results: MVA calculated using PISA method (r = 0.5217, P < 0.0001, SE = 0.016) and PHT (r = 0.6652, P < 0.0001, SE = 0.017) correlated well with 2D method in patients with mitral stenosis before BMV. After BMV, MVA by PISA method correlated well with 2D planimetry (r = 0.5803, P < 0.0001, SE = 0.053) but PHT showed poor correlation (r = 0.1334, P = 0.199, SE = 0.036). The variability of measurement of MVA was most marked with PHT method in the post-BMV period. Conclusion: The PISA method correlates well with 2D planimetry in patients with mitral stenosis before and after BMV and is superior to the PHT method in the post-BMV period where the latter may be unreliable. [source] English county populations in the later eighteenth century1ECONOMIC HISTORY REVIEW, Issue 1 2007E. A. WRIGLEY SUMMARY When directing the first English census John Rickman was intent not only on discovering the size of the population in 1801 but also on tracing past trends both nationally and for individual counties. He returned to the latter investigation on several later occasions, notably in the 1830s. There have been many subsequent attempts to improve upon his national estimates, but his estimates of county totals have continued to be used extensively, either unchanged or slightly modified. Rickman was aware that his estimates were subject to wide margins of error. For the later eighteenth century it is possible to produce new estimates which are probably substantially more accurate, taking advantage of the fact that after Hardwicke's Act (1753) the registration of marriages in Anglican parish registers, unlike that of baptisms and burials, was virtually complete. They show that the contrast between population growth rates in ,industrial' counties and those in which agriculture continued to predominate were significantly more marked than suggested by Rickman's estimates. The same exercise that produces county estimates also yields hundredal totals, which will in future allow a more refined account of relative growth and stagnation to be made. [source] UNCERTAINTY AND MONETARY POLICY RULES IN THE UNITED STATESECONOMIC INQUIRY, Issue 2 2009CHRISTOPHER MARTIN This article analyzes the impact of uncertainty about the true state of the economy on monetary policy rules in the United States since the early 1980s. Extending the Taylor rule to allow for this type of uncertainty, we find evidence that the predictions of the theoretical literature on responses to uncertainty are reflected in the behavior of policymakers, suggesting that policymakers are adhering to prescriptions for optimal policy. Our estimates suggest that the effect of uncertainty on interest rates was most marked in 1983, when uncertainty increased interest rates by up to 140 basis points, in 1990,1991, when uncertainty reduced interest rates by up to 80 basis points, and in 1996,2001, when uncertainty reduced interest rates by up to 70 basis points over 5 yr. (JEL C51, C52, E52, E58) [source] Emergency management of the morbidly obeseEMERGENCY MEDICINE AUSTRALASIA, Issue 4 2004Peter Grant Abstract Objectives: To identify the difficulties encountered with the emergency management of morbidly obese patients and formulate recommendations to streamline care. Methods: An English language literature search was undertaken using Medline (1966,2003) with key words ,morbid obesity',anaesthesia',imaging',obesity',emergency',transportation',retrieval',critical illness' and ,monitoring'. Potential articles were selected for content applicable to emergency medicine based on title and abstract and reviewed in detail. Reference lists were manually searched for further relevant articles. In view of the very limited systematic study in this area, all information deemed by the authors' to be of assistance to the emergency physician was included regardless of evidence level. Additional information was sought from standard critical care textbooks and their bibliographies and through personal communication with local ambulance and retrieval services. The authors' unpublished personal experience in providing emergency care to the morbidly obese was included for aspects of management not documented in medical literature. Results: Obesity levels and associated health problems are rapidly rising in Australia. Few studies were identified dealing with critical illness in the morbidly obese and none specifically addressing ED management. Problems identified included size related logistical issues, and limitations of physical assessment, monitoring and routine investigations. Invasive procedures, intubation and ventilation can be particularly problematic, and modified techniques may be required. Limited data indicates a poorer outcome from critical illness most marked in the case of blunt traumatic injury. Conclusion: Very obese patients present a variety of logistical and medical challenges for EDs. A series of recommendations are made based on available data. Further studies in this area would be desirable to more specifically address ED issues. [source] HEPATITIS C AND ADDICTION: Chronic viral hepatitis is a significant contributor to the immunosenescent phenotype of parenteral drug addictionADDICTION BIOLOGY, Issue 2 2009Albert S. Reece ABSTRACT Intravenous drug addiction is known to be associated with an inordinate morbidity and mortality. As our previous report had identified an immune phenotype consistent with accelerated ageing, we wished to investigate how much of this change may have been related to chronic viral hepatitis. A total of 12 409 clinical pathology results from the period 1995,2007 were reviewed. To control for the differences in age, only patients less than 48 years of age were considered. A total of 636 substance use disorder (SUD) and 6103 non-SUD (N-SUD) patients were studied. They had comparable ages (mean ± SD 31.32 ± 6.90 versus 31.57 ± 9.23, P -value not significant), but the SUD group had more males (74.37% versus 53.20%, P < 0.001). For most of the changes examined splitting the two SUD groups into hepatitis C positive (HCV+) and hepatitis C negative (HCV,) demonstrated that the majority of the described changes were most marked in the HCV+ group. The globulins were higher in the HCV+ group and the albumin was lower and fell more markedly with age than in N-SUD or HCV, (all P < 0.001). The globulin/albumin ratio was significantly higher in HCV+ than HCV, or N-SUD (both P < 0.0001) and rose more with age. These changes were paralleled by the ESR, elevations in the CRP and lymphocyte count. Transaminases were elevated in SUD and HCV+ groups compared with N-SUD (all P < 0.02). At multivariate analysis ESR, lymphocyte count, dual hepatitis B and C seropositivity, AST and HCVAb were significant predictors of the serum globulin level and accounted for 21% of the variance. These data extend our earlier report and show that much of the immunosenescent phenotype of SUD, encompassing the known immunosuppression and the observed immunostimulation, is statistically related to chronic viral hepatitis. Important theoretical and practical management (vaccination) implications ensue. [source] Imaging of acetylcholine esterase activity in brainstem nuclei involved in regulation of sleep and wakefulnessEUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2007C. Eggers Positron emission tomography with 11C- N -methyl-4-piperidyl-acetate (MP4A) was applied in eight healthy volunteers and two patients with mild Alzheimer's disease (AD) to assess acetylcholine esterase (AChE) activity in magnetic resonance imaging-identified brainstem nuclei. Uptake ratios in lateral dorsal tegmental and pedunculopontine nuclei relative to cerebellum yielded reproducible values for the AChE activity in controls and reduced values in AD, more marked in a patient with complaints of disturbed sleep. Cortical AChE activity was related to the extent of cognitive impairment which was more severe in the AD patient without sleep disturbance. This preliminary observational study demonstrates the feasibility to image and assess AChE activity in small nuclei of the brain stem. This approach may be helpful to investigate the interaction of various nuclei in the complex network regulating sleep and wakefulness in representative patient groups with documented sleep disturbance. [source] Neuronal disinhibition in the trigeminal nucleus caudalis in a model of chronic neuropathic painEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2010Yasmina B. Martin Abstract The mechanisms underlying neuropathic facial pain syndromes are incompletely understood. We used a unilateral chronic constriction injury of the rat infraorbital nerve (CCI-IoN) as a facial neuropathic model. Pain-related behavior of the CCI-IoN animals was tested at 8, 15 and 26 days after surgery (dps). The response threshold to mechanical stimulation with von Frey hairs on the injured side was reduced at 15 and 26 dps, indicating the presence of allodynia. We performed unitary recordings in the caudalis division of the spinal trigeminal nucleus (Sp5C) at 8 or 26 dps, and examined spontaneous activity and responses to mechanical and thermal stimulation of the vibrissal pad. Neurons were identified as wide dynamic range (WDR) or low-threshold mechanoreceptive (LTM) according to their response to tactile and/or noxious stimulation. Following CCI-IoN, WDR neurons, but not LTM neurons, increased their spontaneous activity at 8 and 26 dps, and both types of Sp5C neurons increased their responses to tactile stimuli. In addition, the on,off tactile response in neurons recorded after CCI-IoN was followed by afterdischarges that were not observed in control cases. Compared with controls, the response inhibition observed during paired-pulse stimulation was reduced after CCI-IoN. Immunohistochemical studies showed an overall decrease in GAD65 immunoreactivity in Sp5C at 26 dps, most marked in laminae I and II, suggesting that following CCI-IoN the inhibitory circuits in the sensory trigeminal nuclei are depressed. Consequently, our results strongly suggest that disinhibition of Sp5C neurons plays a relevant role in the appearance of allodynia after CCI-IoN. [source] PACAP inhibits delayed rectifier potassium current via a cAMP/PKA transduction pathway: evidence for the involvement of IK in the anti-apoptotic action of PACAPEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2004Y. A. Mei Abstract Activation of potassium (K+) currents plays a critical role in the control of programmed cell death. Because pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to inhibit the apoptotic cascade in the cerebellar cortex during development, we have investigated the effect of PACAP on K+ currents in cultured cerebellar granule cells using the patch-clamp technique in the whole-cell configuration. Two types of outward K+ currents, a transient K+ current (IA) and a delayed rectifier K+ current (IK) were characterized using two different voltage protocols and specific inhibitors of K+ channels. Application of PACAP induced a reversible reduction of the IK amplitude, but did not affect IA, while the PACAP-related peptide vasoactive intestinal polypeptide had no effect on either types of K+ currents. Repeated applications of PACAP induced gradual attenuation of the electrophysiological response. In the presence of guanosine 5,-[,thio]triphosphate (GTP,S), PACAP provoked a marked and irreversible IK depression, whereas cell dialysis with guanosine 5,-[,thio]diphosphate GDP,S totally abolished the effect of PACAP. Pre-treatment of the cells with pertussis toxin did not modify the effect of PACAP on IK. In contrast, cholera toxin suppressed the PACAP-induced inhibition of IK. Exposure of granule cells to dibutyryl cyclic adenosine monophosphate (dbcAMP) mimicked the inhibitory effect of PACAP on IK. Addition of the specific protein kinase A inhibitor H89 in the patch pipette solution prevented the reduction of IK induced by both PACAP and dbcAMP. PACAP provoked a sustained increase of the resting membrane potential in cerebellar granule cells cultured either in high or low KCl-containing medium, and this long-term depolarizing effect of PACAP was mimicked by the IK specific blocker tetraethylammonium chloride (TEA). In addition, pre-incubation of granule cells with TEA suppressed the effect of PACAP on resting membrane potential. TEA mimicked the neuroprotective effect of PACAP against ethanol-induced apoptotic cell death, and the increase of caspase-3 activity observed after exposure of granule cells to ethanol was also significantly inhibited by TEA. Taken together, the present results demonstrate that, in rat cerebellar granule cells, PACAP reduces the delayed outward rectifier K+ current by activating a type 1 PACAP (PAC1) receptor coupled to the adenylyl cyclase/protein kinase A pathway through a cholera toxin-sensitive Gs protein. Our data also show that PACAP and TEA induce long-term depolarization of the resting membrane potential, promote cell survival and inhibit caspase-3 activity, suggesting that PACAP-evoked inhibition of IK contributes to the anti-apoptotic effect of the peptide on cerebellar granule cells. [source] A study of the factors controlling the adsorption of Cr(III) on modified montmorillonitesEUROPEAN JOURNAL OF SOIL SCIENCE, Issue 4 2001A. Bakhti Summary We have examined the way that the metallic ion Cr(III) is held by Na-montmorillonite and alumina pillared clay. We used several physico-chemical methods of analysis (X-ray powder diffraction, infrared absorption spectrometry, thermal analysis and chemical composition) to determine the structural formula of the Na-montmorillonite, and to clarify the effect of the introduction of the Al13 polycations between the clay layers on its physico-chemical and structural properties. Our results show that the strength of chromium retention increases with pH. This effect is more marked in pillared than in unpillared clays. It seems that the mechanism of fixing of the metallic cations on pillared clays is more complex than a simple cationic exchange and involves the surface groups of the pillars. In other words, chromium adsorption on pillared montmorillonite is more like adsorption on an amphoteric oxide surface (such as Al2O3) than on a non-pillared clay. Etude des facteurs contrôlant l'adsorption de Cr(III) sur des montmorillonites modifiées Résumé Nous avons examiné les possibilités de fixation de l'ion métallique Cr(III) sur une montmorillonite sodique et pontée. Les différentes analyses physico-chimiques (Rayons-X, Spectroscopie Infrarouge, Analyse Thermique Différentielle et composition chimique) ont permis d'une part, d'établir la formule structurale de l'argile sodique et d'autre part de mettre en évidence l'effet du pontage de l'argile par des polycations hydroxyaluminiques sur ses propriétés physico-chimiques et structurales. Nos résultats montrent que le pouvoir de rétention du chrome augmente avec le pH. Ce paramètre affecte davantage son comportement dans les argiles pontées. Il apparaît que le mécanisme de fixation du Cr(III) sur les argiles à piliers est différent d'un simple échange cationique. L'adsorption dans ce cas met en jeu les groupements de la surface des piliers. En d'autres termes, le mécanisme d'adsorption des cations du chrome sur une montmorillonite pontée se rapproche de l'adsorption sur une surface d'oxyde amphotère (tel que Al2O3) plutôt que l'adsorption sur une argile non pontée. [source] Topical treatment with thiazolidinediones, activators of peroxisome proliferator-activated receptor-,, normalizes epidermal homeostasis in a murine hyperproliferative disease modelEXPERIMENTAL DERMATOLOGY, Issue 3 2006Marianne Demerjian Abstract:, In a murine model of epidermal hyperplasia reproducing some of the abnormalities of several common skin disorders, we previously demonstrated the antiproliferative and pro-differentiating effects of peroxisome proliferator-activated receptor (PPAR),, PPAR,/,, and liver X receptor activators. Unlike other subgroups of PPAR activators, thiazolidinediones (TZDs), a family of PPAR, ligands, did not inhibit keratinocyte proliferation in normal murine skin. Here, we studied the effects of two TZDs, namely ciglitazone (10 mM) and troglitazone (1 mM), in the same murine model where epidermal hyperproliferation was reproduced by repeated barrier abrogation with tape stripping. Topical treatment with ciglitazone and troglitazone resulted in a marked and significant decrease in epidermal thickness. Furthermore, in all TZD-treated groups, we observed a significant decrease in keratinocyte proliferation using proliferating cell nuclear antigen, 5-bromo-2,-deoxyuridine, and tritiated thymidine incorporation. However, using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, we found no difference in apoptosis between different treatments, emphasizing that it is the antiproliferative role of these activators that accounts for the decrease of epidermal thickness. Finally, using immunohistochemical methods, we determined the effects of ciglitazone on keratinocyte differentiation in this hyperproliferative model. We observed an increased expression of involucrin and filaggrin following ciglitazone treatment, suggesting a pro-differentiating action of TZDs in this model. In summary, topical TZDs significantly reduce epidermal keratinocyte proliferation while promoting differentiation in a murine model of hyperproliferative epidermis. Together, these results suggest that in addition to their metabolic effects currently in use in the treatment of type 2 diabetes, topical TZDs could be considered as potential alternative therapeutic agents in hyperproliferative skin diseases such as psoriasis. [source] Substrate specificity of a maize ribosome-inactivating protein differs across diverse taxaFEBS JOURNAL, Issue 7 2000Julie E. Krawetz The superfamily of ribosome-inactivating proteins (RIPs) consists of toxins that catalytically inactivate ribosomes at a universally conserved region of the large ribosomal RNA. RIPs carry out a single N-glycosidation event that alters the binding site of the translational elongational factor eEF1A and causes a cessation of protein synthesis that leads to subsequent cell death. Maize RIP1 is a kernel-specific RIP with the unusual property of being produced as a zymogen, proRIP1. ProRIP1 accumulates during seed development and becomes active during germination when cellular proteases remove acidic residues from a central domain and both termini. These deletions also result in RIP activation in vitro. However, the effectiveness of RIP1 activity against target ribosomes remains species-dependent. To determine the potential efficiency of maize RIP1 as a plant defense protein, we used quantitative RNA gel blots to detect products of RIP activity against intact ribosomal substrates from various species. We determined the enzyme specificity of recombinant maize proRIP1 (rproRIP1), papain-activated rproRIP1 and MOD1 (an active deletion mutant of rproRIP1) against ribosomal substrates with differing levels of RIP sensitivity. The rproRIP1 had no detectable enzymatic activity against ribosomes from any of the species assayed. The papain-activated rproRIP1 was more active than MOD1 against ribosomes from either rabbit or the corn pathogen, Aspergillus flavus, but the difference was much more marked when rabbit ribosomes were used as a substrate. The papain-activated rproRIP1 was much more active against rabbit ribosomes than homologous Zea mays ribosomes and had no detectable effect on Escherichia coli ribosomes. [source] The response of the yeast Saccharomyces cerevisiae to sudden vs. gradual changes in environmental stress monitored by expression of the stress response protein Hsp12pFEMS YEAST RESEARCH, Issue 6 2008Ildar Nisamedtinov Abstract The response of the yeast Saccharomyces cerevisiae to sudden vs. gradual changes in different environmental stress conditions during both respiratory growth and aerobic fermentative growth in the presence of excess glucose was investigated by monitoring the level and rate of expression of the stress response protein Hsp12p using the fluorescent fusion construct Hsp12p-Gfp2p. The initial expression level and the rate of Hsp12p synthesis was significantly greater under glucose-limited conditions in the chemostat (D<0.14 h,1) compared with when excess glucose was present in the auxostat. Decreasing the dilution rate and the glucose concentration further in the A-stat resulted in increased Hsp12p expression, which was more marked when a rapid rather than a gradual change was affected. Common stress factors such as NaCl, ethanol and elevated temperature caused stress responses in both D-stat and auxo-accelerostat culture. The magnitude of the stress response depended on the stress factor, cultivation conditions as well as the rate of change of the stress factor. The rate of Hsp12p synthesis increased due to all applied stresses, with the observed increase between 2 and 20 times lower when the stress was applied gradually rather than rapidly. The results suggested that the Hsp12p expression rate is a good indicator of applied stress in S. cerevisiae. [source] Forced depression of leaf hydraulic conductance in situ: effects on the leaf gas exchange of forest treesFUNCTIONAL ECOLOGY, Issue 4 2007T. J. BRODRIBB Summary 1Recent work on the hydraulic conductance of leaves suggests that maximum photosynthetic performance of a leaf is defined largely by its plumbing. Pursuing this idea, we tested how the diurnal course of gas exchange of trees in a dry tropical forest was affected by artificially depressing the hydraulic conductance of leaves (Kleaf). 2Individual leaves from four tropical tree species were exposed to a brief episode of forced evaporation by blowing warm air over leaves in situ. Despite humid soil and atmospheric conditions, this caused leaf water potential (,leaf) to fall sufficiently to induce a 50,74% drop in Kleaf. 3Two of the species sampled proved highly sensitive to artificially depressed Kleaf, leading to a marked and sustained decline in the instantaneous rate of CO2 uptake, stomatal conductance and transpiration. Leaves of these species showed a depression of hydraulic and photosynthetic capacity in response to the ,blow-dry' treatment similar to that observed when major veins in the leaf were severed. 4By contrast, the other two species sampled were relatively insensitive to Kleaf manipulation; photosynthetic rates were indistinguishable from control (untreated) leaves 4 h after treatment. These insensitive species demonstrate a linear decline of Kleaf with ,leaf, while Kleaf in the two sensitive species falls precipitously at a critical water deficit. 5We propose that a sigmoidal Kleaf vulnerability enables a high diurnal yield of CO2 at the cost of exposing leaves to the possibility of xylem cavitation. Linear Kleaf vulnerability leads to a relatively lower CO2 yield, while providing better protection against cavitation. [source] Climate change causes rapid changes in the distribution and site abundance of birds in winterGLOBAL CHANGE BIOLOGY, Issue 11 2008ILYA M. D. MACLEAN Abstract Detecting coherent signals of climate change is best achieved by conducting expansive, long-term studies. Here, using counts of waders (Charadrii) collected from ca. 3500 sites over 30 years and covering a major portion of western Europe, we present the largest-scale study to show that faunal abundance is influenced by climate in winter. We demonstrate that the ,weighted centroids' of populations of seven species of wader occurring in internationally important numbers have undergone substantial shifts of up to 115 km, generally in a northeasterly direction. To our knowledge, this shift is greater than that recorded in any other study, but closer to what would be expected as a result of the spatial distribution of ecological zones. We establish that year-to-year changes in site abundance have been positively correlated with concurrent changes in temperature, but that this relationship is most marked towards the colder extremities of the birds' range, suggesting that shifts have occurred as a result of range expansion and that responses to climate change are temperature dependent. Many attempts to model the future impacts of climate change on the distribution of organisms, assume uniform responses or shifts throughout a species' range or with temperature, but our results suggest that this may not be a valid approach. We propose that, with warming temperatures, hitherto unsuitable sites in northeastern Europe will host increasingly important wader numbers, but that this may not be matched by declines elsewhere within the study area. The need to establish that such changes are occurring is accentuated by the statutory importance of this taxon in the designation of protected areas. [source] Controlled Fabrication of Multitiered Three-Dimensional Nanostructures in Porous Alumina,ADVANCED FUNCTIONAL MATERIALS, Issue 14 2008Audrey Yoke Yee Ho Abstract We present the fabrication of multitiered branched porous anodic alumina (PAA) substrates consisting of an array of pores branching into smaller pores in succeeding tiers. The tiered three-dimensional structure is realized by sequentially stepping down the anodization potential while etching of the barrier layer is performed after each step. We establish the key processing parameters that define the tiered porous structure through systematically designed experiments. The characterization of the branched PAA structures reveals that, owing to constriction, the ratio of interpore distance to the anodization potential is smaller than that for pristine films. This ratio varies from 1.8 to 1.3,nm,V,1 depending on the size of the preceding pores and the succeeding tier anodization potential. Contact angle measurements show that the multitiered branched PAA structures exhibit a marked increased in hydrophilicity over two-dimensional PAA films. [source] Effect of Helicobacter pylori Infection on Gastric Acid Secretion and Meal-Stimulated Serum Gastrin in ChildrenHELICOBACTER, Issue 2 2004Seiichi Kato ABSTRACT Background., Comparative studies of gastric acid secretion in children related to Helicobacter pylori infection are lacking. The purpose of this study was to compare acid secretion and meal-stimulated gastrin in relation to H. pylori infection among pediatric patients. Materials and Methods., Thirty-six children aged 10,17 years (17 with H. pylori infection) undergoing diagnostic endoscopy participated in the study. Diagnoses included gastritis only (n = 23), duodenal ulcer (n = 5) and normal histology (n = 8). Gastric acid output was studied using the endoscopic gastric secretion test before and 2,3 months after H. pylori eradication. Meal-stimulated serum gastrin response was assessed before and 12 months after eradication. Results.,H. pylori gastritis was typically antrum-predominant. Acid secretion was greater in H. pylori- positive patients with duodenal ulcer than in gastritis-only patients or controls [mean ± standard error (SE): 6.56 ± 1.4, 3.11 ± 0.4 and 2.65 ± 0.2 mEq/10 minutes, respectively; p < .001]. Stimulated acid secretion was higher in H. pylori- positive boys than girls (5.0 ± 0.8 vs. 2.51 ± 0.4 mEq/10 minutes, respectively; p < .05). Stimulated acid secretion pre- and post- H. pylori eradication was similar (5.47 ± 0.8 vs. 4.67 ± 0.9 mEq/10 minutes, respectively; p = .21). Increased basal and meal-stimulated gastrin release reversed following H. pylori eradication (e.g. basal from 134 to 46 pg/ml, p < .001 and peak from 544 to 133 pg/ml, p < .05). Conclusions.,H. pylori infection in children is associated with a marked but reversible increase in meal-stimulated serum gastrin release. Gastric acid hypersecretion in duodenal ulcer remains after H. pylori eradication, suggesting that the host factor plays a critical role in outcome of the infection. [source] Are transient environmental agents involved in the cause of primary biliary cirrhosis?HEPATOLOGY, Issue 4 2009Evidence from space, time clustering analysis The cause of primary biliary cirrhosis (PBC) is unclear. Both genetic and environmental factors are likely to contribute. Some studies have suggested that one or more infectious agents may be involved. To examine whether infections may contribute to the cause of PBC, we have analyzed for space,time clustering using population-based data from northeast England over a defined period (1987,2003). Space,time clustering is observed when excess cases of a disease are found within limited geographical areas at limited periods of time. If present, it is suggestive of the involvement of one or more environmental components in the cause of a disease and is especially supportive of infections. A second-order procedure based on K -functions was used to test for global space,time clustering using residential addresses at the time of diagnosis. The Knox method determined the spatiotemporal range over which global clustering was strongest. K -function tests were repeated using nearest neighbor thresholds to adjust for variations in population density. Individual space,time clusters were identified using Kulldorff's scan statistic. Analysis of 1015 cases showed highly statistically significant space,time clustering (P < 0.001). Clustering was most marked for cases diagnosed within 1,4 months of one another. A number of specific space,time clusters were identified. In conclusion, these novel results suggest that transient environmental agents may play a role in the cause of PBC. (HEPATOLOGY 2009.) [source] Functional significance of hepatic arterial flow reserve in patients with cirrhosisHEPATOLOGY, Issue 2 2003Alexander Zipprich In cirrhosis, hepatic arterial vasodilatation occurs in response to reduced portal venous blood flow. However, although the hepatic arterial flow reserve is high in patients with cirrhosis, its impact on hepatic function is unknown. This study investigated the effect of adenosine-induced hepatic arterial vasodilatation on different markers of liver function. In 20 patients with cirrhosis (Child-Pugh class A/B/C: n = 2/7/11) adenosine (2-30 ,g · min,1 · kg body wt,1) was infused into the hepatic artery and hepatic arterial average peak flow velocities (APV), pulsatility indices (PI), and blood flow volumes (HABF) were measured using digital angiography and intravascular Doppler sonography. Indocyanine green (ICG), lidocaine, and galactose were administered intravenously in doses of 0.5, 1.0, and 500 mg/kg body weight in the presence of adenosine-induced hepatic arterial vasodilatation and, on a separate study day, without adenosine. ICG disappearance, galactose elimination capacity (GEC), and formation of the lidocaine metabolite monoethylglycinxylidide (MEGX) were assessed. Adenosine markedly increased APV and HABF and markedly decreased PI. Serum MEGX concentrations were 63.7 ± 18.2 (median, 62; range, 36-107) and 99.0 ± 46.3 (82.5; 49-198) ng/mL in the absence and presence of adenosine infusion, respectively (P = .001). Adenosine-induced changes in MEGX concentrations were correlated inversely to changes in APV (r = ,0.5, P = .02) and PI (r = ,0.55, P = .01) and were more marked in Child-Pugh class C compared with Child-Pugh class A patients (57.4 ± 49.9 [44; ,14 to 140] vs. 8.4 ± 16.5 [13; ,11 to 35] ng/mL, P < .01). In conclusion, hepatic arterial vasodilatation provides substantial functional benefit in patients with cirrhosis. The effect does not depend directly on hepatic arterial macroperfusion and is observed preferentially in patients with decompensated disease. [source] Long-term trend analysis for precipitation in Asian Pacific FRIEND river basinsHYDROLOGICAL PROCESSES, Issue 18 2005Z. X. Xu Abstract In order to analyse the long-term trend of precipitation in the Asian Pacific FRIEND region, records from 30 river basins to represent the large range of climatic and hydrological characteristics in the study area are selected. The long-term trend in precipitation time series and its association with the southern oscillation index (SOI) series are investigated. Application of the nonparametric Mann,Kendall test for 30 precipitation time series has shown that only four of these 30 time series have a long-term trend at the 5% level of significance. Nevertheless, most of the records tend to decrease over the last several decades. The dataset is further divided geographically into northern, middle, and southern zones, with 20°N and 20°S latitude as the dividing lines. The middle zone has the greatest variation and the southern zone the least variation over the past century. Also, the southern zone has greater variation during the past 30 years. The association between precipitation and SOI is investigated by dividing the precipitation records of each station into El Niño, La Niña, and neutral periods. The Wilcoxon rank-sum test showed that differences in precipitation for the three classes were most marked in the southern zone of the study area. The frequencies of below- and above-average precipitation for El Niño, La Niña, and neutral periods are estimated for the 30 precipitation time series as well. The results show that the frequencies of precipitation under each set of conditions, with lower precipitation generally associated with El Niño periods in the southern zone. Copyright © 2005 John Wiley & Sons, Ltd. [source] Breast cancer survival in England, Norway and Sweden: a population-based comparison,INTERNATIONAL JOURNAL OF CANCER, Issue 11 2010Henrik Møller Abstract Several international studies have found that survival from breast cancer is lower in the United Kingdom than in some other European countries. We have compared breast cancer survival between the national populations of England, Norway and Sweden, with a view to identifying subsets of patients with particularly good or adverse survival outcomes. We extracted cases of breast cancer in women diagnosed 1996,2004 from the national cancer registries of the 3 countries. The study comprised 303,657 English cases, 24,919 Norwegian cases and 57,512 cases from Sweden. Follow-up was in 2001,2004. The main outcome measures were 5-year cumulative relative survival and excess death rates, stratified by age and period of follow-up. In comparison with Norway and Sweden, the excess mortality in England was particularly pronounced in the first month and in the first year after diagnosis, and generally more marked in the oldest age groups. Compared with Norwegian patients, 81% of the excess deaths in the English patients occurred in the first 2 years after diagnosis. Our findings emphasise the importance of awareness of symptoms and early detection as the main strategy to improve breast cancer survival in the United Kingdom. [source] Impact of late-life self-reported emotional problems on Disability-Free Life Expectancy: results from the MRC Cognitive Function and Ageing StudyINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 6 2008Karine Pérès Abstract Objectives Depression in old age is a major public health problem though its relationship to onset of disability and death is not well understood. We aim to quantify the impact of late-life self-reported depression and emotional problems on both the length and quality of remaining life. Methods Longitudinal analysis of 11,022 individuals from the MRC Cognitive Function and Ageing Study (MRC CFAS), multi-centre longitudinal study on ageing in individuals age 65 years and older living in England and Wales. Individuals have been followed at intermittent time intervals over 10 years. Subjects reporting at baseline that they had consulted about emotional problems for the first time since the age of 60 years were considered, along with a subgroup where a GP suggested depression. Disability was defined as an IADL or ADL disability that required help at least once a week. Total and Disability-Free Life Expectancy (TLE and DFLE) were calculated using multi-state models, separately by gender, and with presence of emotional problems/depression and multimorbidity as covariates. Results Emotional problems had a greater impact on DFLE than TLE, reducing DFLE by 1.8 years, but TLE by only 0.5 years at age 65 with the effect increasing with age. The effect was most marked in older people reporting other co-morbidities where emotional problems in addition resulted in a reduction of 0.9 years in total and 2.6 years disability-free. Conclusions Although emotional problems were only self-reported, these results highlight the burden of late-life depression on the quality of remaining years of life. Copyright © 2007 John Wiley & Sons, Ltd. [source] The Increasing Political Power of Immigrants from the Former Soviet Union in Israel: From Passive Citizenship to Active CitizenshipINTERNATIONAL MIGRATION, Issue 1 2003Tamar Horowitz The immigrants in Israel from the Former Soviet Union (FSU) followed a different pattern of political growth than other immigrant groups. Their increased power began on the national level and moved down to the local level, rather than from the periphery toward the centre , the pattern followed by the Oriental Jewish immigrants. We can trace three stages in the development of their political power. The first stage was during the 1992 elections when the immigrants attempted to organize their own list. Though they failed, the results of the election strengthened them because they were given credit for the left's victory, giving them a sense of political effectiveness. The second stage came during the 1996 elections. It was a defining moment for the former Soviet immigrants' political power. In this stage external factors and internal factors reinforced each other. The change in the electoral system made it possible for the immigrants to vote for their community on the one hand and for a national figure on the other, thus resolving their identity dilemma. The local elections in 1998 marked the third stage in their political strength. They found the immigrant community better organized, with an improved understanding of its local interests, the capacity to put forward a strong local leadership, and a stronger link between the immigrant political centre and the local level. [source] The European Policy for the Development of an Information Society: the Right Path?,JCMS: JOURNAL OF COMMON MARKET STUDIES, Issue 4 2008JOSÉ LUIS GÓMEZ-BARROSO The end of 2005 marked the closure of one stage in the European strategy for the promotion of the information society (the eEurope programme) and the start of the next one (i2010). This seems to be a good time for assessing the results achieved to date by the community policy in this area and analysing whether the correct approach has been adopted. Despite the satisfaction shown in certain official appraisals, the picture resulting from consulting different classifications globally measuring the adaptation of countries to the information society is not that optimistic. Only the European Union leaders in this field (the Nordic countries) have improved their positions, broadening the gap with the rest: western European countries have lost ground (or at least have not improved) in the rankings, the southern countries do not seem to have corrected their deficiencies and the indices for the new Member States have not evolved as expected or have even deteriorated in some cases. Even though becoming one of the most competitive and dynamic knowledge-based economies in the world was the first Leitmotiv of the Lisbon strategy, the interpretation of the documents connected to the definition of the new stage in the strategy led to doubts over whether the European Union has a clear notion on the course of action to take in order to make progress on the information society a matter of priority. [source] Serum Carotenoids and Cerebral White Matter Lesions: The Rotterdam Scan StudyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 5 2001Tom Den Heijer MSc OBJECTIVES: To study the relation between serum levels of carotenoids and white matter lesions (WMLs) on magnetic resonance imaging (MRI). DESIGN: Evaluation of cross-sectional data from a cohort study. SETTING: The Rotterdam Scan Study. PARTICIPANTS: Two hundred and three nondemented older persons, age 60 to 90, from the Rotterdam Scan Study. MEASUREMENTS: Serum levels of carotenoids were determined. WMLs on MRIs were rated separately into periventricular and subcortical WMLs. Odds ratios (ORs) for the presence of severe WMLs (upper decile) were calculated per standard deviation (SD) increase in serum carotenoid level and per SD increase in overall carotenoid serum level. Effect modification by smoking status was studied through stratified analyses. RESULTS: Increasing levels of all the separate carotenoids were associated with less severe periventricular WMLs, which reached statistical significance for the overall carotenoid serum level (OR 0.4 per SD; 95% confidence interval (CI) = 0.2,0.9). We found no association between carotenoid levels and the presence of severe subcortical WMLs (OR 1.2 per SD; 95% CI = 0.7,2.0). The association of carotenoid levels with severe periventricular WMLs was more marked in those who ever smoked (OR 0.1 per SD; 95% CI = 0.0,0.9) than in those who had never smoked (OR 0.9 per SD; 95% CI = 0.4,2.1). CONCLUSIONS: These findings are compatible with the view that high levels of carotenoids may protect against WMLs in the periventricular region, in particular in smokers. Longitudinal studies with repeated measurements of both carotenoids and WMLs are necessary to explore this hypothesis further. [source] | |||||||||||||||||||||||||||||||||||||||||||