bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Implications of Changing Census Output Geographies for the Measurement of Residential Segregation: The Example of Northern Ireland 1991–2001
Authors: Shuttleworth I. G. , Lloyd C. D. , Martin D. J.
Published: July 2010

One problem in analysing social and demographic change through time by using census data arises from differences in the size and shape of the geographical units that are used to output data between different years. Failure to correct for changing output geographies may lead to unknown and possibly large biases when comparing results through time between different censuses. The paper addresses this issue by using the example of residential segregation in Northern Ireland. It has two main objectives. Firstly, by compiling 2001 Northern Ireland census data on 1991 census output geographies it assesses the sensitivity of indices of residential segregation to these changes in geographical units. Secondly, it suggests a method by which census analysts can assess how sensitive their results are to changing output geographies when they cannot correct for these changes and must work with the data ‘as they are’. A subsidiary aim is to contribute to the evidence base on residential segregation in Northern Ireland. The paper finds that indices of residential segregation are insensitive to changes in output geographies between 1991 and 2001. The reason suggested for this is that the units in each zonal geography are smaller than the spatial scale over which population counts are positively auto-correlated. The use of spatially weighted segregation indices is advanced as a generalizable means of learning about the geographical patterning of population in different censuses. It is argued that these insights combined with knowledge of the size of geographical units used in each census can help researchers elsewhere to judge how sensitive their results might be to changing census output geographies through time.
Modelling Bias in Combining Small Area Prevalence Estimates from Multiple Surveys
Authors: Manzi Giancarlo , Spiegelhalter David J. , Turner Rebecca M. , Flowers Julian , Thompson Simon G.
Published: July 2010

Combining information from multiple surveys can improve the quality of small area estimates. Customary approaches, such as the multiple-frame and statistical matching methods, require individual level data, whereas in practice often only multiple aggregate estimates are available. Commercial surveys usually produce such estimates without clear description of the methodology that is used. In this context, bias modelling is crucial, and we propose a series of Bayesian hierarchical models which allow for additive biases. Some of these models can also be fitted in a classical context, by using a mixed effects framework. We apply these methods to obtain estimates of smoking prevalence in local authorities across the east of England from seven surveys. All the surveys provide smoking prevalence estimates and confidence intervals at the local authority level, but they vary by time, sample size and transparency of methodology. Our models adjust for the biases in commercial surveys but incorporate information from all the sources to provide more accurate and precise estimates.
THE UPTAKE OF LOW CONCENTRATIONS OF LITHIUM IONS INTO RAT CEREBRAL CORTEX SLICES AND ITS DEPENDENCE ON CATIONS
Authors: Wraae O. , Hillman H. , Round Elizabeth
Published: July 2010

—Rat cerebral slices were incubated in oxygenated Krebs‐Ringer bicarbonate glucose saline, and the uptake of Li+ was measured after periods of 15 s to 5 min. Saturation was not seen within the concentrations of Li+ employed (0·5‐2·0 mm). The half‐time of the uptake was 7·9 min. At steady state, after 1 h incubation, the concentration of Li+ in the tissue was linearly related to that of the medium (0·5‐1·5 mm Li+) with a concentration ratio of 1·29–1·66. The concentrations of K+ and Na+ in the slices incubated without Li+ were found to be (μmol/g incubated wt, mean ±s.d.) 63·8 ± 9·6 and 96·2 ± 7·8 respectively (n = 28). In the presence of media with 1·5 mm ‐Li+, the K+ and Na+ in the slices were 56·2 ± 8·8 and 101·0 ± 7·7 respectively (n = 37). The concentration of Li+ in the slices, after 1 h incubation, increased in a non linear way as the concentration of K+ in the medium was decreased within a range of 0·10 mm‐K+. In the absence of K+ in the medium the uptake of Li+ was approx 50% higher than in the presence of 4·9 mm‐K+. There was an inverse linear relationship between the concentration of Li+ in the slices and that of Ca2+ in the medium within the range of 0‐5·2 mm (‐0·13 mm‐Li+/mm Ca2+). The concentration of Li+ in the slices increased by approx 10% when the Mg2+ in the medium was increased from 1·3 mm to 2·6 mm. Changes of the concentration of Na+ between 120 mm and 170 mm in the medium had no significant effect on the Li+ uptake.
Cerebral Phosphoinositide, Triacylglycerol, and Energy Metabolism in Reversible Ischemia: Origin and Fate of Free Fatty Acids
Authors: Yoshida Shinichi , Ikeda Masuhiro , Busto Raul , Santiso Mercedes , Martinez Elena , Ginsberg Myron D.
Published: July 2010

Abstract: Levels of phosphatidylinositol 4,5‐bisphosphate (PIP2), phosphatidylinositol 4‐phosphate (PIP), phosphatidylinositol (PI), phosphatidic acid, diacylglycerol (DAG), triacylglycerol (TAG), and free fatty acids (FFAs), as well as their fatty acid composition, were determined in rat forebrain during ischemia and postischemic recirculation. Cerebral energy state and electroencephalograms (EEGs) were also studied. Fifteen minutes of ischemia resulted in a decrease in PIP2 and PIP contents but not in PI content, concurrent with an enlargement of the FFA and DAG pools. The latter were enriched in stearate and arachidonate. Prolongation of ischemia did not produce further changes in content of any of the inositol phosphalipids, but the increase in levels of FFAs and DAG continued. At the end of 45 min of ischemia, levels of both PIP2 and PIP decreased by 45–50%, and the total phosphoinositide content (PIP2+ PIP + PI) decreased by 21%, whereas levels of FFAs and DAG increased to 14– and 3.6‐fold of control levels, respectively. During ischemia, the TAG‐palmitate level decreased, but the TAG‐arachidonate level increased; the tissue energy state deteriorated severely; and the EEG was suppressed. A 30‐min recirculation period after 15 or 45 min of ischemia led to increases in PIP2, PIP, and total phosphoinositide contents, whereas levels of FFAs and DAG promptly decreased toward control values. The TAG‐arachidonate level peaked and the TAG‐palmitate level returned to a low control value during early recirculation. The ischemic changes in tissue lipids were completely reversed within 3 h of recirculation after both periods of ischemia. Adenylates were fully phosphorylated with as little as 30 min of reflow. The EEG activity partially recovered during reflow after 15 min of ischemia, whereas it remained depressed after prolonged ischemia. Thus, phosphodiesteric cleavage of PIP2 and PIP followed by deacylation of DAG is likely to contribute to the production of FFAs in early ischemia. Deacylation of undetermined lipids plays a role for the increment in levels of FFAs in the later period of ischemia. The rapid postischemic increase in levels of PIP2 and PIP indicates active synthesis not only from existing PI, but probably also by means of accumulated FFAs and DAG. These results indicate that the impaired resynthesis of inositol phospholipids cannot be a cause of the poor EEG activity after prolonged ischemia. Degradation and resynthesis of polyphosphoinositides and formation of TAG‐arachidonate may be important for modulation of free arachidonic acid levels in the brain during temporary ischemia.
A Comparison of Biochemical Indices of 5‐Hydroxytryptaminergic Neuronal Activity Following Electrical Stimulation of the Dorsal Raphe Nucleus
Authors: Shannon N. J. , Gunnet J. W. , Moore K. E.
Published: July 2010

Abstract:The activity of 5‐hydroxytryptaminergic neurons has been estimated from measurements of: (1) concentrations of 5‐hydroxyindoleacetic acid; (2) the ratio of the concentrations of 5‐hydroxyindoleacetic acid to 5‐hydroxytryptamine; (3) the rate of accumulation of 5‐hydroxytryptophan following the administration of an aromatic l‐amino acid decarboxylase inhibitor (e.g., NSD 1015); (4) the rate of accumulation of 5‐hydroxytryptamine, and the rate of decline of 5‐hydroxyindoleacetic acid following the administration of a monoamine oxidase inhibitor (e.g., pargyline). The purpose of the present study was to compare these different methods under conditions of changing neuronal impulse traffic produced by electrical stimulation of 5‐hydroxytryptaminergic neurons. Male rats anesthetized with chloral hydrate were killed following 0, 15, or 30 tain of electrical stimulation of the dorsal raphe nucleus at a frequency of 0, 5, or 10 Hz. The concentrations of 5‐hydroxytryptamine, 5‐hydroxyindoleacetic acid, and 5‐hydroxytryptophan in nucleus accumbens, amygdala, suprachiasmatic nucleus, and dorsomedial nucleus were measured using HPLC coupled to an electrochemical detector. In each brain region, stimulation elicited an increase in the concentration of 5‐hydroxyindoleacetic acid and the 5‐hydroxyindoleacetic acid/5‐hydroxytryptamine concentration ratio in saline‐treated animals and an increase in 5‐hydroxytryptophan accumulation in NSD 1015‐treated animals, but did not alter the concentration of 5‐hydroxytryptamine or 5‐hydroxyindoleacetic acid in pargyline‐treated rats. The results of this study indicate that although the first three methods serve as valid indices of 5‐hydroxytryptaminergic neuronal activity, the pargyline‐dependent techniques are not responsive to changes in the rate of 5‐hydroxytryptamine nerve firing.
Characterization of Xylamine Binding to Proteins of PC12 Pheochromocytoma Cells
Authors: Koide Mayumi , Cho Arthur K. , Howard Bruce D.
Published: July 2010

AbstractPC12 pheochromocytoma cells take up 3,4‐dihydroxyphenylethylamine (dopamine) and norepinephrine by a Na+‐dependent, cocaine‐sensitive system. The kinetics suggest that the same transporter functions for both substrates. Xylamine, a nitrogen mustard that blocks catecholamine uptake into neurons, irreversibly inhibited norepinephrine uptake into PC12 (IC50= 15 μM). Pretreatment with 10 μMxylamine did not inhibit norepinephrine transport if 10 μMcocaine or 100 μMnorepinephrine was also present during the pretreatment period or if Na+was absent. These results indicate that xylamine must interact with the norepinephrine transporter to inhibit norepinephrine uptake. PC12 accumulated [3H]xylamine; this uptake had Na+‐dependent and Na+‐independent components. The Na+‐dependent uptake was saturable (Km= 13 μM), and it was inhibited by cocaine (IC50= 0.6 μM), desipramine (IC50< 1 nM), and norepinephrine (IC50= 1 μM). Several proteins became prominently labeled when intact PC12 cells were incubated with [3H]xylamine; these proteins were enriched in a plasma membrane fraction and have molecular weights of 17,000, 24,000, 31,000, 33,000, 41,000, 42,000, 52,000, and 80,000. Other proteins were labeled less prominently. The labeling of all proteins was markedly decreased when the incubation with [3H]xylamine occurred in the presence of cocaine, desipramine, gramicidin D, or in a Na+‐free buffer. These results indicate that xylamine must be transported into the cells for covalent binding to proteins to occur. [3H] Xylamine labeled essentially the same proteins when incubated with cell homogenates, but competition experiments with bretylium, desipramine, and cocaine failed to reveal which of the [3H]xylamine‐labeled proteins is associated with the norepinephrine transporter.
Artifactual High‐Affinity and Saturable Binding of [3H]5‐Hydroxytryptamine Induced by Radioligand Oxidation
Authors: Peroutka Stephen J. , Ison Pamela J. , Liu David U. , Barrett Ronald W.
Published: July 2010

The binding of [3H]5‐hydroxytryptamine (5‐HT, serotonin) to cerebellar membranes was examined after preincubation of [3H]5‐HT in the presence or absence of ascorbate. The tissue preparation was identical in all experiments and consisted of rat cerebellar homog‐enates in Tris‐HCl buffer with 0.1%ascorbate. Cerebellar membranes were used because of their low density of 5‐HT, binding sites. In the presence of ascorbate during a 4‐h preincubation period, minimal specific binding of 2 nM[3H]5‐HT is detected. Similar results are obtained with equimolar concentrations of other antioxidants (bu‐tylated hydroxytoluene, sodium dithionite, and sodium metabisulfite). Apparent specific binding increases 14‐fold following a 4‐h preincubation of [3H]5‐HT in the absence of ascorbate. The increase in apparent specific [3H]5‐HT binding is time‐dependent and plateaus after 4–6 h of preincubation. When ascorbate is present during the 4‐h preincubation, Scatchard analysis of [3H]5‐HT binding reveals aKDvalue of 3.0 ± 0.3nMand aBmaxvalue of 1.9 ± 0.2 pmol/g tissue. When ascorbate is absent during the preincubation, theKDis essentially un changed at 3.6 ± 0.1nMbut theBmaxis significantly increased to 36.5 ± 7 pmol/g tissue. Drug competition studies reveal that the apparent specific “[3H]5‐HT binding” in the absence of ascorbate appears to be displaced by nanomolar concentrations of hydroxylated tryptamines (5‐HT, bufotenine) but not by nonhydroxy‐lated tryptamines (5‐methoxytryptamine, tryptamine). HPLC analysis demonstrates that [3H]5‐HT is essentially destroyed by a 4‐h incubation at 22°C in the absence of ascorbate. We conclude that oxidation of [3H]5‐HT prior to the addition of membrane homogenates leads to the detection of an artifactual high‐affinity and saturable “[3H]5‐HT binding site” that appears to have a distinct pharmacological profile. The capacity of other ligands to compete for this binding site is related to their potential as antioxidants and not to their affinity for a novel membrane recognition site labeled by [3H]5‐HT.
Characterization of a Dopaminergic Receptor that Modulates Adrenomedullary Catecholamine Release
Authors: Gonzalez M. C. , Artalejo A. R. , Montiel C. , Hervás P. P. , García A. G.
Published: July 2010

Abstract:Nicotine evokes the release of catecholamines from bovine adrenal glands perfused with oxygenated Krebs‐bicarbonate solution. Two 2‐min pulses of 5 μMnicotine, at 40‐min intervals (S1and S2), gave net catecholamine outputs of 45.2 ± 3.6 and 29.1 ± 3.5 μg/8 min, respectively. Apomorphine (1 or 10 μM) markedly inhibited catecholamine release during S2to 9.1 ± 2.2 and 0.5 μg/8 min, respectively. Haloperidol (0.5 μM) reversed the inhibitory effects of apomorphine. Haloperidol alone enhanced catecholamine release induced by nicotine to 67.9 ± 7.9 μg/8 min. [3H]Spiperone binds to adrenomedullary membranes with aKDof 0.24 nMand aBmaxof 117 fmol/mg of protein. Whereas spiperone and haloperidol potently displaced such binding, 3,4‐dihydroxyphenylethylamine (dopamine) and sulpiride were poorer displacers, and SCH23390, prazosin, phenoxybenzamine, propranolol, BAY‐K‐8644, and nitrendipine did not displace [3H]spiperone bound. These data strongly suggest that, as in the cat, the bovine adrenal medulla chromaffin cell contains a dopaminergic receptor that modulates the catecholamine secretory process triggered by stimulation of the nicotinic cholinoceptor. Such a receptor seems to be of the D2type and might be involved in a sympatho‐adrenal cooperative mechanism contributing to the maintenance of cardiovascular homeostasis during stressful situations as well as to the pathogenesis of hypertension. If so, selective dopaminergic agonists might prove clinically useful in the treatment of hypertension.
Neuronal and Nonneuronal Contributions to Renal Catecholamine Content in the Dog
Authors: Petrovic T. , Anderson W. P. , Bell C.
Published: July 2010

Abstract: Endogenous noradrenaline and 3,4‐dihydroxyphenylethylamine (dopamine) levels were measured in different zones of the dog kidney following chronic unilateral renal denervation. In outer and inner renal cortex, and in outer medulla, >95% of the tissue content of both catecholamines was contributed by renal nerves, whereas in inner medulla only nonneuronal catecholamines were found. The amounts of neuronal dopamine present in outer renal cortex were greater than would be expected for a population of solely noradrenergic nerves.
Differential Phosphorylation of τ by Cyclic AMP‐Dependent Protein Kinase and Ca2+/Calmodulin‐Dependent Protein Kinase II: Metabolic and Functional Consequences
Authors: Johnson Gail V. W.
Published: July 2010

Abstract: The effects of cyclic AMP‐dependent protein kinase (cAMP‐PK) or Ca2+/calmodulin‐dependent protein kinase II (CaMKII) phosphorylation on the binding of bovine τ to tubulin and calpain‐mediated degradation of τ were studied. Both cAMP‐PK and CaMKII readily phosphorylated τ and slowed the migration of τ on sodium dodecyl sulfate‐containing polyacrylamide gels. However, cAMP‐PK phosphorylated τ to a significantly greater extent than CaMKII (1.5 and 0.9 mol of 32P/mol of τ, respectively), and phosphorylation of τ by cAMP‐PK resulted in a greater shift to a more acidic, less heterogeneous pattern on two‐dimensional nonequilibrium pH gradient gels compared with CaMKII phosphorylation. Two‐dimensional phosphopeptide maps indicate that cAMP‐PK phosphorylates a site or sites on τ that are phosphorylated by CaMKII, as well as a unique site or sites that are not phosphorylated by CaMKII. Phosphorylation of τ by cAMP‐PK significantly decreased tubulin binding and, as previously reported, also inhibited the calpain‐induced degradation of τ. CaMKII phosphorylation of τ did not alter either of these parameters. These results suggest that the phosphorylation of site(s) on the τ molecule uniquely accessible to cAMP‐PK contributed to the decreased τ‐tubulin binding and increased resistance to calpain hydrolysis.
Long‐Term GABA Treatment Elicits Supersensitivity of Quisqualate‐Preferring Metabotropic Glutamate Receptor in Cultured Rat Cerebellar Neurons
Authors: Yu Onnfoh , Chuang De‐Maw
Published: July 2010

Abstract:In primary cultures of rat cerebellar granule neurons, GABA treatment (50 μM, 7 days) caused a withdrawal supersensitivity selective for the metabotropic glutamate receptors that mainly preferl‐glutamate, quisqua‐ late and, to a lesser extent, kainate. The withdrawal supersensitivity was absent when 10 μMSR‐95531 was coadministered with GABA during the treatment period, an event that suggests the GABAAreceptors primarily produced the GABA treatment effect. This was supported further by the inability of baclofen treatment to mimic completely the treatment effect of GABA. Withdrawal from 7 days of baclofen treatment only produced a slight increase in the metabotropic effect ofl‐glutamate and carbachol. In addition, in untreated neurons, baclofen had no acute effect, whereas GABA inhibited the effect ofl‐glutamate and carbachol. The inhibitory effect of GABA was reversed by SR‐95531 and was absent in neurons treated with GABA. These observations suggest the involvement of GABAAreceptors and the apparent development of tolerance to GABA, respectively. Also, dependence on GABA may have occurred; the metabotropic effects of glutamate, kainate, and quisqualate were not altered in neurons maintained with GABA treatment.
β‐Amyloid regulates leptin expression and tau phosphorylation through the mTORC1 signaling pathway
Authors: Marwarha Gurdeep , Dasari Bhanu , Prabhakara Jaya Prasanthi Rantham , Schommer Jared , Ghribi Othman
Published: July 2010

J. Neurochem. (2010) 115, 373–384.

High levels of the adipocytokine leptin are associated with reduced risk of Alzheimer’s disease. Leptin treatment also reduces β‐amyloid (Aβ) levels in in vivo and in vitro models of Alzheimer’s disease. Aβ and leptin interact with the Akt/mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. Akt/mTORC1 activation reduces tau phosphorylation through the inhibition of the downstream enzyme GSK‐3β. mTORC1 also regulates translation of many proteins including leptin. While Aβ has been shown to inactivate Akt, inhibit mTORC1, and facilitate the phosphorylation of tau, leptin activates both Akt and mTORC1 and reduces tau phosphorylation. However, the extent to which Aβ may modulate leptin expression and increase tau phosphorylation involving Akt/mTORC1 has not been determined. In this study, we show that incubation of organotypic slices from rabbit hippocampus with Aβ down‐regulates leptin expression, inhibits Akt, activates GSK‐3β, increases tau phosphorylation, and inactivates mTORC1. Leptin treatment reverses Aβ effects by alleviating Akt inhibition, preventing GSK‐3β activation, reducing tau phosphorylation, and activating mTORC1. On the other hand, Rapamycin, an allosteric inhibitor of mTORC1, down‐regulates leptin expression, increases tau phosphorylation, and does not affect Akt and GSK‐3β. Our results demonstrate for the first time that Aβ regulates leptin expression and tau phosphorylation through mTORC1.
Salvage cytoreduction for chemorefractory ovarian cancer with peritoneal carcinomatosis: A last chance or futile efforts?
Authors: CHUA Terence C. , ROBERTSON Gregory , LIAUW Winston , MORRIS David L.
Published: July 2010

Background:  The role of secondary cytoreductive surgery in recurrent ovarian cancer in the presence of carcinomatosis is increasingly accepted as being an effective management strategy for selected patients. However, in patients with chemorefractory disease, the role of cytoreduction remains controversial. The objective of this study was to evaluate if cytoreduction of peritoneal carcinomatosis in patients with chemorefractory recurrent ovarian cancer as salvage treatment confers any survival benefits.

Methods:  A retrospective review was performed on patients with chemorefractory ovarian cancer with peritoneal carcinomatosis who underwent cytoreduction as a salvage treatment. Survival was calculated using the Kaplan–Meier method. Univariate analysis was performed to examine potential prognostic factors using the log‐rank test.

Results:  A total of 16 patients were identified, of which 15 patients (94%) had FIGO Stage III ovarian cancer at initial diagnosis. The initial surgical effort was optimal in one patient (6%), and 13 patients (62%) had been on at least two lines of chemotherapy. The median progression‐free and overall survival was 18 (95% CI 0–42) months and 36 (95% CI 14–58) months, respectively. The 1‐, 3‐year survival rate was 73% and 23%, respectively. ECOG status zero (P = 0.023) and younger patients (age <51) (P = 0.066) appeared to be associated with an improved overall survival.

Conclusions:  Salvage cytoreduction may be considered a last chance effort to prolong survival in this group of patients with chemorefractory ovarian cancer who have a ‘poor prognosis’ and would otherwise not have been candidates for any proven or effective therapy.
Searching the Soil: Forensic Importance of Edaphic Fauna After the Removal of a Corpse
Authors: Saloña Marta I. , Moraza M. Lourdes , Carles‐Tolrá Miguel , Iraola Victor , Bahillo Pablo , Yélamos Tomás , Outerelo Raimundo , Alcaraz Rafael
Published: July 2010

Abstract:  Arthropods at different stages of development collected from human remains in an advanced stage of decomposition (following autopsy) and from the soil at the scene are reported. The corpse was found in a mixed deciduous forest of Biscay (northern Spain). Soil fauna was extracted by sieving the soil where the corpse lay and placing the remains in Berlese–Tullgren funnels. Necrophagous fauna on the human remains was dominated by the fly Piophilidae: Stearibia nigriceps (Meigen, 1826), mites Ascidae: Proctolaelaps epuraeae (Hirschmann, 1963), Laelapidae: Hypoaspis (Gaeolaelaps) aculeifer (Canestrini, 1884), and the beetle Cleridae: Necrobia rufipes (de Geer, 1775). We confirm the importance of edaphic fauna, especially if the deceased is discovered in natural environs. Related fauna may remain for days after corpse removal and reveal information related to the circumstances of death. The species Nitidulidae: Omosita depressa (Linnaeus, 1758), Acaridae: Sancassania berlesei (Michael, 1903), Ascidae: Zerconopsis remiger (Kramer, 1876) and P. epuraeae, Urodinychidae: Uroobovella pulchella (Berlese, 1904), and Macrochelidae: Glyptholaspis americana (Berlese, 1888) were recorded for the first time in the Iberian Peninsula.
Melatonin reduces hyperalgesia associated with inflammation
Authors: Esposito Emanuela , Paterniti Irene , Mazzon Emanuela , Bramanti Placido , Cuzzocrea Salvatore
Published: July 2010

Abstract:  The perception of pain is altered by inflammatory processes. Anti‐inflammatory drugs block this by raising the pain threshold and by reducing the inflammatory process. Melatonin is claimed to have anti‐inflammatory activity in animal models of acute and chronic inflammation. However, little is known whether melatonin can reverse the hyperalgesia that is secondary to the inflammation. This study assessed the effect of melatonin on in a well‐established model of hyperalgesia associated with inflammation in rats. Peroxynitrite, as generated by the interaction between superoxide anion radical exogenously supplied (O2˙−) and endogenous nitric oxide (NO), led to the development of hyperalgesia. This subplantar injection of O2˙− into the right hindpaw evoked potent thermal hyperalgesia measured by changes in withdrawal latency. Melatonin (25–100 mg/kg, given ip 30 min prior to O2˙−) dose dependently attenuated the hyperalgesic responses to O2˙−. Moreover, melatonin (100 mg/kg) significantly improved tissue damage and inflammation, blocked protein nitration affecting cyclooxygenase‐2 and inducible nitric oxide synthase expression in paw tissue. To investigate the antinociceptive activity of melatonin and characterize the underlying mechanisms involved in this action, mitogen‐activated protein kinase and NF‐κB pathways were explored. Moreover, antihyperalgesic effect of melatonin derived partly from the inhibition of superoxide‐driven PARP activation. These results suggest that melatonin has ameliorative potential in attenuating the hyperalgesia associated with inflammation.
Direct interaction between CD91 and C1q
Authors: Duus Karen , Hansen Erik W. , Tacnet Pascale , Frachet Philippe , Arlaud Gerard J. , Thielens Nicole M. , Houen Gunnar
Published: July 2010

C1q‐mediated removal of immune complexes and apoptotic cells plays an important role in tissue homeostasis and the prevention of autoimmune conditions. It has been suggested that C1q mediates phagocytosis of apoptotic cells through a receptor complex assembled from CD91 (α‐2‐ macroglobulin receptor, or low‐density lipoprotein receptor‐related protein) and calreticulin, with CD91 being the transmembrane part and calreticulin acting as the C1q‐binding molecule. In the present study, we observe that C1q binds cells from a CD91 expressing monocytic cell line as well as monocytes from human blood. C1q binding to monocytes was shown to be correlated with CD91 expression and could be inhibited by the CD91 chaperone, receptor‐associated protein. We also report data showing a direct interaction between CD91 and C1q. The interaction was investigated using various protein interaction assays. A direct interaction between purified C1q and CD91 was observed both by ELISA and a surface plasmon resonance assay, with either C1q or CD91 immobilized. The interaction showed characteristics of specificity because it was time‐dependent, saturable and could be inhibited by known ligands of both CD91 and C1q. The results obtained show for the first time that CD91 recognizes C1q directly. On the basis of these findings, we propose that CD91 is a receptor for C1q and that this multifunctional scavenger receptor uses a subset of its ligand‐binding sites for clearance of C1q and C1q bound material.
Effect of endoscopic injection therapy with combined cyanoacrylate and lipiodol for bleeding gastric varices: A single center experience
Authors: KURT Mevlut , AKDOGAN Meral , SAYILIR Abdurrahim , KURAN Sedef , OZDERIN Yasemin O , ARHAN Mehmet , ONAL Ibrahim K , KEKILLI Murat , BEYAZIT Yavuz , HAYRAN Mutlu
Published: July 2010

OBJECTIVE:  To evaluate the safety and efficacy of the endoscopic injection therapy with combined cyanoacrylate and lipiodol for bleeding gastric fundal varices.

METHODS:  The medical records of cirrhotic and non‐cirrhotic patients who underwent at least one episode of endoscopic application of N‐butyl‐2‐cyanoacrylate‐lipiodol mixture for gastric varices at our gastroenterology clinic between October 2004 and January 2010 were reviewed. The technique comprised the dilution of 0.5 mL of cyanoacrylate with 0.5 mL of lipiodol and repeating intravariceal injections of 1.0 mL each until hemostasis was achieved.

RESULTS:  A total of 66 patients (41 male and 25 female) with gastric varices underwent 86 endoscopic injections of cyanoacrylate for hemostasis. Overall 38 patients (57.6%) had active bleeding during the endoscopic procedure, while the remaining 28 (42.4%) underwent cyanoacrylate under elective conditions. In one patient (1.5%) hemostasis could not be achieved, prompting referral for emergency surgery. The median number of sessions was one (range 1–3). Eleven patients (16.6%) rebled during a median follow‐up period of 6.02 months (0.1–62.4 months). There was no bleeding‐related death. One patient developed splenic infarction a day after N‐butyl‐2‐cyanoacrylate injection.

CONCLUSION:  Endoscopic injection therapy combining cyanoacrylate and lipiodol is effective for bleeding gastric fundal varices.
CD66c expression in B‐cell acute lymphoblastic leukemia: strength and weakness
Authors: GUILLAUME N. , PENTHER D. , VAIDA I. , GRUSON B. , HARRIVEL V. , CLAISSE J .F. , CAPIOD J. C. , LEFRERE J. J. , DAMAJ G.
Published: July 2010

Introduction:  In B‐cell acute lymphoblastic leukemia (B‐ALL), testing at diagnosis for BCR/ABL1 gene rearrangements is mandatory for prognostic stratification and treatment decisions. Several diagnostic methods have been proposed using flow cytometry to identify BCR/ABL1+ B‐ALL.

Methods:  We evaluated expression of the myeloid antigen CD66c by flow cytometry in B‐ALL. We studied 94 patients with B‐ALL. The t(9;22)(q34;q11) or BCR/ABL1 rearrangement was detected by cytogenetic analysis or RT/PCR. Myeloid antigens CD66c, CD13, CD33, CD117, Myeloperoxidase, CD15 and CD65 were determined by flow cytometry.

Results:  Of these 94 cases, 17 (18%) cases displayed BCR/ABL1 gene rearrangements and 38 (40%) cases were CD66c positive. CD66c was the most common myeloid antigen expressed on malignant lymphoblasts. Its expression was correlated with BCR/ABL1 rearrangements (P = 0.0001): sensitivity 82%, specificity 69%, positive predictive value 37% and negative predictive value 95%. Co‐expression of CD66c+ CD13+ was more frequent in BCR/ABL1+ B‐ALL (29%) than BCR/ABL1− cases (4%) (P = 0.0044). Some BCR/ABL1− B‐ALL cases (including hyperdiploid or cases with normal karyotype) were CD66c positive (31%).

Conclusion:  CD66c expression is correlated, but not specifically, with BCR/ABL1 rearrangement. It would seem better to interpret the absence of CD66c expression with a lack of BCR/ABL1 rearrangement. This myeloid antigen could be interesting in the detection of minimal residual disease.
Probing and modeling of interfacial carrier motion in organic devices by optical second harmonic generation
Authors: Iwamoto Mitsumasa , Manaka Takaaki , Weis Martin , Taguchi Dai
Published: July 2010

Here the authors report a novel optical second harmonic generation (SHG) measurement that allows carrier motion in solids to be probed directly. By catching nonlinear polarization induced in the solids by coupling with incident electromagnetic waves (laser beam) and dc electric field from moving carriers, carrier motion is visualized. Experiments making use of time-resolved SHG technique has revealed dynamic changes of SHG intensity profiles arising from pentacene field effect transistors in accordance with the carrier transport in the channel. The observed SHG intensity profiles are strongly dependent on the physical condition of the organic field effect transistors channel and well accounts for the effect of carrier traps on gate insulator such as silicon dioxide (SiO2) and poly(methyl methacrylate). The authors anticipate that a technique using time-resolved SHG can be a powerful tool to characterize interface states of organic devices.
Brain over Muscle
Authors: Kiberstis Paula A.
Published: July 2010

Identification of the origin of muscle weakness that accompanies a form of neonatal diabetes may lead to safer therapies.
Staying in Place
Authors: Hurtley Stella M.
Published: July 2010

Signaling proteins are retained in the cilium by a diffusion barrier created by a member of the septin family.
HAND SURGERY ON ANTICOAGULATED PATIENTS: A PROSPECTIVE STUDY OF 121 OPERATIONS
Authors: Edmunds Ian , Avakian Zorik
Published: July 2010

The management of anticoagulated patients requiring surgery presents a challenge to hand surgeons. The risk of bleeding related complications needs to be weighed up against the increased risk of thrombotic events if anticoagulants are altered or ceased. There is literature reporting the safety of hand, skin, eye and dental surgery on patients taking anticoagulants, and there is literature highlighting the risks associated with altering regular anticoagulant medication. However, it is common practice to cease or alter patients' anticoagulants peri-operatively for hand surgery.

We report a prospective study of 107 patients taking anticoagulants who underwent 121 hand operations from December 2005 to August 2009. There was only one significant complication, that being a haematoma which occurred in a patient taking clopidogrel. We conclude that interruption to therapy with warfarin (provided the INR is not greater than 3.0), clopidogrel or clopidogrel with aspirin is unnecessary for patients undergoing hand surgery.
SURGICAL TREATMENT OF MUCOUS CYSTS ON FINGERS WITHOUT SKIN EXCISION
Authors: Hoshino Yuko , Saito Norio , Kuroda Hiroshi
Published: July 2010

Mucous cysts on the fingers are commonly treated by excision followed by a rotation flap or skin graft. However, such procedures require skin donors or large incisions. Therefore, a less invasive procedure is needed. Here, we report a surgical treatment method that does not require the excision of the cyst. A skin flap was made around the cyst and raised; the pedicle of the cyst was then electrodesiccated or ligated, and the contents of the cyst were evacuated. If the pedicle could not be clearly identified, the backside of the flap was electrodesiccated to break the connection between the cyst and the distal interphalangeal joint. The skin flap was replaced and sutured. The flaps became almost normal during the follow-up period. No complications or recurrences occurred in any of the six cases that were treated. Our procedure appears to be an effective and less-invasive treatment for mucous cysts of the fingers.
CURRENT MANAGEMENT OF JERSEY FINGER IN RUGBY PLAYERS: CASE SERIES AND LITERATURE REVIEW
Authors: Goodson A. , Morgan M. , Rajeswaran G. , Lee J. , Katsarma E.
Published: July 2010

We discuss a combination of established and modern techniques in the investigation and management of traumatic flexor digitorum profundus rupture ('Rugger Jersey Finger') in seven cases (male rugby players ranging from 15 to 30 years of age; mean = 26). We discuss the use of X-ray and ultrasound investigation followed by various surgical repairs including intraosseous sutures, suture anchors, tendon lengthening and "pull-through suture over button" repairs. Functional outcome at outpatient follow-up is discussed in each case. Type I, II and Vb injuries were identified. Patients presenting early attained good functional outcome. Six patients received surgery within ten days of injury and attained satisfactory outcome at follow-up. One patient presented late and required a tendon lengthening procedure to manage myostatic contracture. Ultrasound imaging proved valuable in diagnosis and pre-operative planning. Numerous surgical repairs were used and all associated with a positive outcome providing there is adequate patient compliance.
Role of neural-cadherin in early osteoblastic differentiation of human bone marrow stromal cells cocultured with human umbilical vein endothelial cells
Authors: Li Haiyan , Daculsi Richard , Grellier Maritie , Bareille Reine , Bourget Chantal , Amedee Joelle
Published: July 2010

In our previous studies, roles of gap junction and vascular endothelial growth factor in the cross-talking of human bone marrow stromal cells (HBMSCs) and human umbilical vein endothelial cells (HUVECs) have been extensively studied. The present study focused on the investigation of the roles of neural (N)-cadherin in early differentiation of HBMSCs in direct-contact cocultures with HUVECs for 24 and 48 h. Quantitative real-time polymerase chain reaction, immunofluorescence, Western blot, as well as functional studies were applied to perform the studies at both protein and gene levels. Results showed that cocultured cells expressed much higher N-cadherin than monocultured cells after 24 and 48 h of culture. We observed that N-cadherin concentrated in the membrane of cocultured HBMSCs (co-HBMSCs) while distributed within the cytoplasm of monocultured HBMSCs, which indicated that the cell-cell adhesion was improved between cocultured cells. In addition, more β-catenin was found to translocate into the cocultured cells nuclei and more T cell factor-1 (TCF-1) were detected in cocultured cells than in the monocultured cells. Moreover, mRNA levels of early osteoblastic markers including alkaline phosphatase (ALP) and type I collagen (Col-I) of co-HBMSCs were significantly upregulated, whereas neutralization of N-cadherin led to a downregulation of ALP and Col-I in both of the HBMSCs and co-HBMSCs compared with untreated cells. Taking our findings together it can be concluded that cocultures of HBMSCs with HUVECs increased N-cadherin expression and improved cell-cell adhesion. Whether this applies only to osteoprogenitor cells or to all the cell types in the culture will need to be determined by further studies. Subsequently, signaling transduction might be induced with the participation of β-catenin and TCF-1. With the N-cadherin-mediated cell-cell adhesion and signaling transductions, the early osteoblastic differentiation of co-HBMSCs was significantly upregulated.
Adrenergic Signaling Polymorphisms and Their Impact on Cardiovascular Disease
Authors: Dorn Gerald W.
Published: July 2010

This review examines the impact of recent discoveries defining personal genetics of adrenergic signaling polymorphisms on scientific discovery and medical practice related to cardiovascular diseases. The adrenergic system is the major regulator of minute-by-minute cardiovascular function. Inhibition of adrenergic signaling with pharmacological β-adrenergic receptor antagonists (β-blockers) is first-line therapy for heart failure and hypertension. Advances in pharmacology, molecular biology, and genetics of adrenergic signaling pathways have brought us to the point where personal genetic differences in adrenergic signaling factors are being assessed as determinants of risk or progression of cardiovascular disease. For a few polymorphisms, functional data generated in cell-based systems, genetic mouse models, and pharmacological provocation of human subjects are concordant with population studies that suggest altered risk of cardiovascular disease or therapeutic response to β-blockers. For the majority of adrenergic pathway polymorphisms however, published data conflict, and the clinical relevance of individual genotyping remains uncertain. Here, the current state of laboratory and clinical evidence that adrenergic pathway polymorphisms can affect cardiovascular pathophysiology is comprehensively reviewed and compared, with a goal of placing these data in the broad context of potential clinical applicability.
Neurophysiological and Computational Principles of Cortical Rhythms in Cognition
Authors: Wang Xiao-Jing
Published: July 2010

Synchronous rhythms represent a core mechanism for sculpting temporal coordination of neural activity in the brain-wide network. This review focuses on oscillations in the cerebral cortex that occur during cognition, in alert behaving conditions. Over the last two decades, experimental and modeling work has made great strides in elucidating the detailed cellular and circuit basis of these rhythms, particularly gamma and theta rhythms. The underlying physiological mechanisms are diverse (ranging from resonance and pacemaker properties of single cells to multiple scenarios for population synchronization and wave propagation), but also exhibit unifying principles. A major conceptual advance was the realization that synaptic inhibition plays a fundamental role in rhythmogenesis, either in an interneuronal network or in a reciprocal excitatory-inhibitory loop. Computational functions of synchronous oscillations in cognition are still a matter of debate among systems neuroscientists, in part because the notion of regular oscillation seems to contradict the common observation that spiking discharges of individual neurons in the cortex are highly stochastic and far from being clocklike. However, recent findings have led to a framework that goes beyond the conventional theory of coupled oscillators and reconciles the apparent dichotomy between irregular single neuron activity and field potential oscillations. From this perspective, a plethora of studies will be reviewed on the involvement of long-distance neuronal coherence in cognitive functions such as multisensory integration, working memory, and selective attention. Finally, implications of abnormal neural synchronization are discussed as they relate to mental disorders like schizophrenia and autism.
Gut Microbiota in Health and Disease
Authors: Sekirov Inna , Russell Shannon L. , Antunes L. Caetano M. , Finlay B. Brett
Published: July 2010

Gut microbiota is an assortment of microorganisms inhabiting the length and width of the mammalian gastrointestinal tract. The composition of this microbial community is host specific, evolving throughout an individual's lifetime and susceptible to both exogenous and endogenous modifications. Recent renewed interest in the structure and function of this “organ” has illuminated its central position in health and disease. The microbiota is intimately involved in numerous aspects of normal host physiology, from nutritional status to behavior and stress response. Additionally, they can be a central or a contributing cause of many diseases, affecting both near and far organ systems. The overall balance in the composition of the gut microbial community, as well as the presence or absence of key species capable of effecting specific responses, is important in ensuring homeostasis or lack thereof at the intestinal mucosa and beyond. The mechanisms through which microbiota exerts its beneficial or detrimental influences remain largely undefined, but include elaboration of signaling molecules and recognition of bacterial epitopes by both intestinal epithelial and mucosal immune cells. The advances in modeling and analysis of gut microbiota will further our knowledge of their role in health and disease, allowing customization of existing and future therapeutic and prophylactic modalities.
Heat Shock Protein 90 Inhibition Depletes TrkA Levels and Signaling in Human Acute Leukemia Cells
Authors: Rao Rekha , Nalluri Srilatha , Fiskus Warren , Balusu Ramesh , Joshi Atul , Mudunuru Uma , Buckley Kathleen M. , Robbins Kelly , Ustun Celalettin , Reuther Gary W. , Bhalla Kapil N.
Published: July 2010

Nerve growth factor (NGF) induces autophosphorylation and downstream progrowth and prosurvival signaling from the receptor tyrosine kinase TrkA. Overexpression or activating mutation of TrkA has been described in human acute myeloid leukemia cells. In the present study, we show the chaperone association of TrkA with heat shock protein 90 (hsp90) and the inhibitory effect of the hsp90 inhibitor, 17-DMAG, on TrkA levels and signaling in cultured and primary myeloid leukemia cells. Treatment with 17-DMAG disrupted the binding of TrkA with hsp90 and the cochaperone cdc37, resulting in polyubiquitylation, proteasomal degradation, and depletion of TrkA. Exposure to 17-DMAG inhibited NGF-induced p-TrkA, p-AKT, and p-ERK1/2 levels, as well as induced apoptosis of K562, 32D cells with ectopic expression of wild-type TrkA or the constitutively active mutant ΔTrkA, and of primary myeloid leukemia cells. Additionally, 17-DMAG treatment inhibited NGF-induced neurite formation in the rat pheochromocytoma PC-12 cells. Cotreatment with 17-DMAG and K-252a, an inhibitor of TrkA-mediated signaling, induced synergistic loss of viability of cultured and primary myeloid leukemia cells. These findings show that TrkA is an hsp90 client protein, and inhibition of hsp90 depletes TrkA and its progrowth and prosurvival signaling in myeloid leukemia cells. These findings also support further evaluation of the combined activity of an hsp90 inhibitor and TrkA antagonist against myeloid leukemia cells. Mol Cancer Ther; 9(8); 2232–42. ©2010 AACR.
Oxytocin Induces the Migration of Prostate Cancer Cells: Involvement of the Gi-Coupled Signaling Pathway
Authors: Zhong Miao , Boseman Maryam L. , Millena Ana C. , Khan Shafiq A.
Published: July 2010

Expression of genes that encode oxytocin (OXT) and vasopressin (AVP) and their cognate receptors in normal and diseased prostates are only partially characterized. Reverse transcription and PCR were used to examine the expression of these genes in normal prostate epithelial and stromal cell lines, k-ras–transformed prostate epithelial cell lines, and in four prostate cancer cell lines. Secreted and cell-associated OXT peptide was measured by an enzyme immunoassay. OXT and its receptor (OXTR) were expressed in all eight prostate cell lines. Cell-associated OXT peptide was also found in all prostate epithelial cell lines except in DU145 cells. Neither AVP nor its cognate receptors (V1a receptor and V2 receptor) were expressed in any prostate cell line examined. These data point to the OXTR as the primary target of OXT and AVP, and suggest that OXT might be an autocrine/paracrine regulator in human prostate. We found that OXT induces the migration of PC3 and PC3M, but not DU145 prostate cancer cells. The effect of OXT is distinct from the epidermal growth factor (EGF)–induced migration of prostate cancer cells, in which ERK1/2 and EGF receptor kinase activities were required. When cells were pretreated with pertussis toxin, the effect of OXT, but not EGF, on cell migration was abolished. Pretreatment with the cyclic AMP analogue, 8-Br-cAMP, did not affect OXT-induced cell migration, which eliminated the nonspecific effect of pertussis toxin. We conclude that a Gi-dependent mechanism is involved in OXTR-mediated migration of prostate cancer cells, and indicates a role for OXTR in prostate cancer metastasis. Mol Cancer Res; 8(8); 1164–72. ©2010 AACR.
Estrogen Receptors in Colorectal Cancer: Goalkeepers, Strikers, or Bystanders?
Authors: Hartman Johan , Gustafsson Jan-Åke
Published: July 2010

This perspective on Jin et al. (beginning on page 910 in this issue of the journal) discusses the importance of estrogen signaling in colorectal carcinogenesis, with a focus on estrogen receptor β (ERβ), which is the predominant ER in the colorectal epithelium. The importance of ERβ in breast cancer is well described in the literature, and recent studies reveal that ERβ functions similarly in colorectal cancer. The implications of this pathway include new possibilities to treat or prevent colorectal cancer with targeted endocrine drugs and the potential of ERβ as a novel diagnostic tool. Cancer Prev Res; 3(8); 897–9. ©2010 AACR.