bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular characterization of neurohybrid cell death induced by Alzheimer's amyloid‐β peptides via p75NTR/PLAIDD
Authors: Hashimoto Yuichi , Kaneko Yuka , Tsukamoto Emi , Frankowski Harald , Kouyama Keisuke , Kita Yoshiko , Niikura Takako , Aiso Sadakazu , Bredesen Dale E. , Matsuoka Masaaki , Nishimoto Ikuo
Published: July 2004

One of the most important pathological features of Alzheimer's disease (AD) is extracellular senile plaques, whose major component is amyloid‐β peptides (Aβ). Aβ binds to the extracellular domain of p75NTR (p75 neurotrophin receptor) and induces neuronal cell death. We investigated the molecular mechanism of Aβ‐induced neurotoxicity in detail from the standpoint of interaction between p75NTR and its recently identified relative, PLAIDD (p75‐like apoptosis‐inducing death domain). Using F11 neuronal hybrid cells, we demonstrate that there are two distinct pathways for Aβ‐induced toxicity mediated by p75NTR. One pathway that has been previously elucidated, is mediated by p75NTR, Go, JNK, NADPH oxidase and caspase3‐related caspases. We found that PLAIDD and Gi proteins, heterotrimeric G proteins, are involved in the alternative Aβ‐induced neurotoxicity mediated by p75NTR. The alternative pathway triggered by Aβ is thus mediated by p75NTR, PLAIDD, Gi, JNK, NADPH oxidase and caspase3‐related caspases. In addition, we found that HN, ADNF, IGF‐I, or bFGF inhibits both pathways of Aβ‐induced neurotoxicity mediated by p75NTR.
In vivo activation of insulin receptor tyrosine kinase by melatonin in the rat hypothalamus
Authors: Anhê Gabriel F. , Caperuto Luciana C. , Pereira‐Da‐Silva Marcio , Souza Lilian C. , Hirata A. Emiko , Velloso Lício A. , Cipolla‐Neto José , Carvalho Carla R. O.
Published: July 2004

Melatonin is the pineal hormone that acts via a pertussis toxin‐sensitive G‐protein to inhibit adenylate cyclase. However, the intracellular signalling effects of melatonin are not completely understood. Melatonin receptors are mainly present in the suprachiasmatic nucleus (SCN) and pars tuberalis of both humans and rats. The SCN directly controls, amongst other mechanisms, the circadian rhythm of plasma glucose concentration. In this study, using immunoprecipitation and immunoblotting, we show that melatonin induces rapid tyrosine phosphorylation and activation of the insulin receptor β‐subunit tyrosine kinase (IR) in the rat hypothalamic suprachiasmatic region. Upon IR activation, tyrosine phosphorylation of IRS‐1 was detected. In addition, melatonin induced IRS‐1/PI(3)‐kinase and IRS‐1/SHP‐2 associations and downstream AKT serine phosphorylation and MAPK (mitogen‐activated protein kinase) phosphorylation, respectively. These results not only indicate a new signal transduction pathway for melatonin, but also a potential cross‐talk between melatonin and insulin.
Inhibition of the E2F‐1/p53/Bax pathway by tauroursodeoxycholic acid in amyloid β‐peptide‐induced apoptosis of PC12 Cells
Authors: Ramalho Rita M. , Ribeiro Paulo S. , Solá Susana , Castro Rui E. , Steer Clifford J. , Rodrigues Cecília M. P.
Published: July 2004

Amyloid β‐peptide (Aβ)‐induced cell death may involve activation of the E2F‐1 transcription factor and other cell cycle‐related proteins. In previous studies, we have shown that tauroursodeoxycholic acid (TUDCA), an endogenous bile acid, modulates Aβ‐induced apoptosis by interfering with crucial events of the mitochondrial pathway. In this study, we examined the role of E2F and p53 activation in the induction of apoptosis by Aβ, and investigated novel molecular targets for TUDCA. The results showed that despite Bcl‐2 up‐regulation, PC12 neuronal cells underwent significant apoptosis after incubation with the active fragment Aβ (25–35), as assessed by DNA fragmentation, nuclear morphology and caspase‐3‐like activation. In addition, transcription through the E2F‐1 promoter was significantly induced and associated with loss of the retinoblastoma protein. In contrast, levels of E2F‐1, p53 and Bax proteins were markedly increased. Overexpression of E2F‐1 in PC12 cells was sufficient to induce p53 and Bax proteins, as well as nuclear fragmentation. Notably, TUDCA modulated Aβ‐induced apoptosis, E2F‐1 induction, p53 stabilization and Bax expression. Further, TUDCA protected PC12 cells against p53‐ and Bax‐dependent apoptosis induced by E2F‐1 and p53 overexpression, respectively. In conclusion, the results demonstrate that Aβ‐induced apoptosis of PC12 cells proceeds through an E2F‐1/p53/Bax pathway, which, in turn, can be specifically inhibited by TUDCA, thus underscoring its potential therapeutic use.
Metabotropic glutamate and dopamine receptors co‐regulate AMPA receptor activity through PKA in cultured chick retinal neurones: effect on GluR4 phosphorylation and surface expression
Authors: Gomes André R. , Cunha Paulo , Nuriya Mutsuo , Faro Carlos J. , Huganir Richard L. , Pires Euclides V. , Carvalho Ana Luísa , Duarte Carlos B.
Published: July 2004

Glutamate receptor phosphorylation has been implicated in several forms of modulation of synaptic transmission. It has been reported that protein kinase A (PKA) can phosphorylate the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA) receptor subunit GluR4 on Ser842, both in vitro and in vivo. Here, we studied the regulation of GluR4 phosphorylation and intracellular trafficking by PKA and by metabotropic receptors coupled to adenylyl cyclase (AC), in cultured chick retinal amacrine‐like neurones, which are enriched in GluR4. The regulation of AMPA receptor activity by PKA and by metabotropic AC‐coupled receptors was also investigated by measuring the [Ca2+]i response to kainate in Na+‐free medium. Stimulation of AC with forskolin (FSK), or using the selective agonist of dopamine D1 receptors (±)‐1‐phenyl‐2,3,4,5‐tetrahydro‐(1H)‐3‐benzazepine‐7,8‐diol (SKF38393), increased the [Ca2+]i response to kainate, GluR4 phosphorylation at Ser842 and GluR4 surface expression. Pre‐incubation of the cells with (2S,2′R,3′R)‐2‐(2′,3′‐dicarboxycyclopropyl)glycine (DCG‐IV), an agonist of group II metabotropic glutamate receptors (mGluR), which are coupled to inhibition of AC, inhibited the effect of FSK and of SKF38393 on AMPA receptor activity, GluR4 phosphorylation and expression at the plasma membrane. These results indicate that there is a functional cross‐talk between dopamine D1 receptors and group II mGluR in the regulation of GluR4 phosphorylation and AMPA receptor activity. Our data show that GluR4 phosphorylation at Ser842 by PKA, and its recruitment to the plasma membrane upon phosphorylation, is regulated by metabotropic receptors.
Insulin receptor substrate of 53 kDa links postsynaptic shank to PSD‐95
Authors: Soltau Michaela , Berhörster Kerstin , Kindler Stefan , Buck Fritz , Richter Dietmar , Kreienkamp Hans‐Jürgen
Published: July 2004

The insulin receptor substrate of 53 kDa (IRSp53) is a target of the small GTPase cdc42 which is strongly enriched in the postsynaptic density of excitatory synapses. IRSp53 interacts with the postsynaptic shank1 scaffolding molecule in a cdc42 regulated manner. The functional significance of the cdc42/IRSp53 pathway in postsynaptic sites is however, unclear. Here we identify PSD‐95 as a second synaptic interaction partner of IRSp53. Interaction is mediated by a C‐terminal PDZ binding motif in IRSp53 and the second PDZ domain of PSD‐95. In HEK cells, overexpressed IRSp53 induces filopodia and targets PSD‐95 into these processes. Immunoprecipitation and immunocytochemistry experiments demonstrate that the interaction occurs at postsynaptic sites in the brain. By virtue of its PDZ‐binding and SH3 domains, IRSp53 is capable of inducing the formation of a triple complex (shank1/IRSp53/PSD‐95).
Neuronal expression of myeloperoxidase is increased in Alzheimer's disease
Authors: Green Pattie S. , Mendez Armando J. , Jacob Jason S. , Crowley Jan R. , Growdon Whit , Hyman Bradley T. , Heinecke Jay W.
Published: July 2004

Myeloperoxidase, a heme protein expressed by professional phagocytic cells, generates an array of oxidants which are proposed to contribute to tissue damage during inflammation. We now report that enzymatically active myeloperoxidase and its characteristic amino acid oxidation products are present in human brain. Further, expression of myeloperoxidase is increased in brain tissue showing Alzheimer's neuropathology. Consistent with expression in phagocytic cells, myeloperoxidase immunoreactivity was present in some activated microglia in Alzheimer brains. However, the majority of immunoreactive material in brain localized with amyloid plaques and, surprisingly, neurons including granule and pyramidal neurons of the hippocampus. Confirming neuronal localization of the enzyme, several neuronal cell lines as well as primary neuronal cultures expressed myeloperoxidase protein. Myeloperoxidase mRNA was also detected in neuronal cell lines. These results reveal the unexpected presence of myeloperoxidase in neurons. The increase in neuronal myeloperoxidase expression we observed in Alzheimer disease brains raises the possibility that the enzyme contributes to the oxidative stress implicated in the pathogenesis of the neurodegenerative disorder.
Frame‐shifted amyloid precursor protein found in Alzheimer's disease and Down's syndrome increases levels of secreted amyloid β40
Authors: Van Dijk R. , Fischer D. F. , Sluijs J. A. , Sonnemans M. A. F. , Hobo B. , Mercken L. , Mann D. M. A. , Hol E. M. , Van Leeuwen F. W.
Published: July 2004

Frame‐shifted amyloid precursor protein (APP+1), which has a truncated out‐of‐frame C‐terminus, accumulates in the neuropathological hallmarks of patients with Alzheimer's disease pathology. To study a possible involvement of APP+1 in the pathogenesis of Alzheimer's disease, we expressed APP695 and APP+1 in the HEK293 cell‐line and studied whether the processing of APP695 was affected. APP+1 is a secretory protein, but high expression of APP695 and APP+1 results in the formation of intracellular aggregate‐like structures containing both proteins and Fe65, an adaptor protein that interacts with APP695. APP+1 is shown to interact with APP695, suggesting that these structures consist of functional protein complexes. Such an interaction can also be anticipated in post‐mortem brains of young Down's syndrome patients without any sign of neuropathology. Here we observed APP+1 immunoreactivity in beaded fibres. Additional support for functional consequences on the processing of APP695 comes from a 1.4‐fold increase in levels of secreted amyloid β40 in cells co‐expressing APP695 and APP+1, although APP+1 itself does not contain the amyloid β sequence. Taken together, these data show that co‐expression of APP695 and APP+1 affects the processing of APP695 in a pro‐amyloidogenic way and this could gradually contribute to Alzheimer's disease pathology, as has been implicated in Down's syndrome patients.
Neuronal A1 receptors mediate increase in extracellular kynurenic acid after local intrastriatal adenosine infusion
Authors: Wu Hui‐Qiu , Fuxe Kjell , Schwarcz Robert
Published: July 2004

The naturally occurring purine nucleoside adenosine has pronounced anticonvulsant and neuroprotective properties and plays a neuromodulatory role in the CNS. Kynurenic acid (KYNA) is an astrocyte‐derived, endogenous neuroinhibitory compound, which shares several of adenosine's properties. In a first attempt to examine possible interactions between these two biologically active molecules, adenosine was focally applied into the striatum of freely moving rats by reverse microdialysis, and changes in extracellular KYNA were monitored over time. A 2‐h infusion of adenosine increased KYNA levels in a dose‐dependent manner, with 10 mm of adenosine causing a twofold elevation within 1 h. This effect was reversible and was effectively blocked by coinfusion of the specific A1 adenosine receptor antagonist 8‐cyclopentyltheophylline (100 µm). In contrast, coinfusion of adenosine with MSX‐3 (100 µm), an A2A receptor antagonist, did not affect the adenosine‐induced increase in KYNA levels. Local striatal perfusion with the A1 receptor agonist N6‐cyclopentyladenosine (100 µm) mimicked the effect of adenosine, whereas perfusion with the A2A receptor agonist CGS‐21680 (100 µm) was ineffective. Finally, we tested the effect of adenosine (10 mm) on extracellular KYNA in striata that had been injected with quinolinate (60 nmol/1 µL) 7 days earlier. In this neuron‐depleted tissue, perfusion with adenosine failed to affect extracellular KYNA levels. These data demonstrate that adenosine is capable of raising extracellular KYNA in the rat striatum by interacting with postsynaptic neuronal A1 receptors. This mechanism may result in a synergism between the neurobiological effects of adenosine and KYNA.
Oligomeric potential of the M2 muscarinic cholinergic receptor
Authors: Park Paul S.‐H. , Wells James W.
Published: July 2004

G protein‐coupled receptors are known to exist as oligomers. Although such aggregates often are referred to as dimers, there is little direct evidence regarding their oligomeric size. In the present investigation, c‐Myc‐, FLAG‐, and influenza hemagglutinin (HA)‐tagged forms of the M2 muscarinic receptor have been coexpressed in Sf9 cells to probe for aggregates larger than a dimer. Immunochromatography, immunoprecipitation, and immunoblotting were carried out with various combinations of antibodies directed against the different epitopes to demonstrate that all three tagged forms of the receptor can be immunopurified within a single complex. Extracts of the M2 muscarinic receptor from Sf9 cells therefore contain aggregates that are at least trimeric, and the levels detected point to the existence of larger complexes. The data also suggest that the oligomers coexist with a sizeable population of monomers.
Functional expression of rat ABCG2 on the luminal side of brain capillaries and its enhancement by astrocyte‐derived soluble factor(s)
Authors: Hori Satoko , Ohtsuki Sumio , Tachikawa Masanori , Kimura Norihisa , Kondo Tetsu , Watanabe Masahiko , Nakashima Emi , Terasaki Tetsuya
Published: July 2004

The purpose of the present study was to clarify the expression, transport properties and regulation of ATP‐binding cassette G2 (ABCG2) transporter at the rat blood–brain barrier (BBB). The rat homologue of ABCG2 (rABCG2) was cloned from rat brain capillary fraction. In rABCG2‐transfected HEK293 cells, rABCG2 was detected as a glycoprotein complex bridged by disulfide bonds, possibly a homodimer. The protein transported mitoxantrone and BODIPY‐prazosin. In rat brain capillary fraction, rABCG2 protein was also detected as a glycosylated and disulfide‐linked complex. Immunohistochemical analysis revealed that rABCG2 was localized mainly on the luminal side of rat brain capillaries, suggesting that rABCG2 is involved in brain‐to‐blood efflux transport. For the regulation study, conditionally immortalized rat brain capillary endothelial (TR‐BBB13), astrocyte (TR‐AST4) and pericyte (TR‐PCT1) cell lines were used as an in vitro BBB model. Following treatment of TR‐BBB13 cells with conditioned medium of TR‐AST4 cells, the Ko143 (an ABCG2‐specific inhibitor)‐sensitive transport activity and rABCG2 mRNA level were significantly increased, whereas conditioned medium of TR‐PCT1 cells had no effect. These results suggest that rat brain capillaries express functional rABCG2 protein and that the transport activity of the protein is up‐regulated by astrocyte‐derived soluble factor(s) concomitantly with the induction of rABCG2 mRNA.
UCN‐01 alters phosphorylation of Akt and GSK3β and induces apoptosis in six independent human neuroblastoma cell lines
Authors: Shankar Sai Latha , Krupski Melissa , Parashar Bhupesh , Okwuaka Chidi , O'Guin Kathy , Mani Sridhar , Shafit‐Zagardo Bridget
Published: July 2004

In this study we evaluated UCN‐01, a small molecule that inhibits protein kinases by interacting with the ATP‐binding site, as a potential anti‐cancer agent for neuroblastoma. UCN‐01 was effective at inducing apoptosis in six neuroblastoma cell lines with diverse cellular and genetic phenotypes. 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT), terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end‐labeling (TUNEL) assays, detection of active caspase‐3 and cleaved poly ADP‐ribose polymerase (PARP) confirmed that UCN‐01 induced apoptosis. Cell cycle analysis determined that the UCN‐01 treated cells accumulated in S phase by 16 h. Unlike vinblastine and docetaxel that increased survivin expression, UCN‐01 treatment did not increase X‐linked inhibitor of apoptosis protein (XIAP) and survivin levels. Analysis of specific phosphoepitopes on chk1/2, Akt, and GSK3β following UCN‐01 treatment determined that there was no significant change in phospho‐chk1/2. However, there was decreased immunoreactivity at Ser473 and Thr308 of Akt and Ser9 of GSK3β by 4 h indicating that the Akt survival pathway and downstream signalling was compromised. Thus, UCN‐01 was effective at inducing apoptosis in neuroblastoma cell lines.
Localization of organic anion transporting polypeptide 3 (oatp3) in mouse brain parenchymal and capillary endothelial cells
Authors: Ohtsuki Sumio , Takizawa Takuya , Takanaga Hitomi , Hori Satoko , Hosoya Ken‐ichi , Terasaki Tetsuya
Published: July 2004

Organic anion transporting polypeptide 3 (oatp3) transports various CNS‐acting endogenous compounds, including thyroid hormones and prostaglandin E2, between extra‐ and intracellular spaces, suggesting a possible role in CNS function. The purpose of this study was to clarify the expression and localization of oatp3 in the mouse brain. RT‐PCR analysis revealed that oatp3 mRNA is expressed in brain capillary‐rich fraction, conditionally immortalized brain capillary endothelial cells, choroid plexus, brain and lung, but not in liver or kidney, where oatp1, 2 and 5 mRNAs were detected. Immunohistochemical analysis with anti‐oatp3 antibody suggests that oatp3 protein is localized at the brush‐border membrane of mouse choroid plexus epithelial cells. Furthermore, intense immunoreactivity was detected in neural cells in the border region between hypothalamus and thalamus, and in the olfactory bulb. Immunoreactivity was also detected in brain capillary endothelial cells in the cerebral cortex. These localizations in the mouse brain suggest that oatp3 plays roles in blood–brainand –cerebrospinal fluid barrier transport of organic anions and signal mediators, and in hormone uptake by neural cells.
β‐Naphthoflavone disturbs astrocytic differentiation of C6 glioma cells by inhibiting autocrine interleukin‐6
Authors: Takanaga Hiromi , Yoshitake Tomoko , Yatabe Emi , Hara Shuntaro , Kunimoto Manabu
Published: July 2004

Regulation of astrocyte differentiation is a key process in the development of the central nervous system (CNS), and disturbance of the differentiation can lead to brain system dysfunction. Here we show that β‐naphthoflavone (βNF), an agonist of the aryl hydrocarbon receptor (AhR), disturbed the cAMP‐induced astrocytic differentiation of C6 glioma by inhibiting autocrine interleukin‐6 (IL‐6). Treatment of cells with βNF reduced the induction of an astrocyte marker glial fibrillary acidic protein (GFAP). This was caused by the inactivation of its upstream transcription factor signal transducer and activator of transcription 3 (STAT3) by βNF. In addition, βNF attenuated the induction of the IL‐6 gene, which leads to the activation of STAT3. Most importantly, the inhibitory effect of βNF on GFAP promoter activity was recovered by the addition of recombinant IL‐6. Taken together, these results indicate that the inhibitory effect of βNF on IL‐6 induction suppresses STAT3 activation. These processes subsequently lead to the attenuation of GFAP induction.
Prejunctional AT1 receptor subtype‐dependent modification of neurotransmitter releases in canine isolated splenic arteries
Authors: Komiyama J. , Yang X.‐P. , Chiba S.
Published: July 2004

1 The regulation by angiotensin II (Ang II) formed locally on nerve‐stimulated purinergic and adrenergic components of double‐peaked vasoconstrictions in the canine splenic artery and Ang II receptor subtypes involved were investigated.

2 The perfusion of the precursor angiotensin I (Ang I, 0.1–1 nm) did not affect the vasoconstrictor responses to noradrenaline (NA, 0.03–1 nmol) and adenosine 5′‐triphosphate (ATP, 0.03–1 μmol). The second component vasoconstrictor response to nerve stimulation was dose dependently potentiated by Ang I (0.1–1 nm). The first peaked constriction was slightly, but insignificantly increased. The potentiating effects of Ang I were abolished by KRH‐594 (10 nm), a selective AT1 receptor antagonist, but not by PD 123319 (1–10 nm), an AT2 receptor antagonist. KRH‐594 (10 nm) or PD 123319 (10 nm) never affected the vasoconstrictions to either NA or ATP.

3 The treatment with KRH‐594 (1–10 nm) produced a greater inhibition on the second peaked response than the first one, although both of them were dose dependently inhibited. PD 123319 (1–10 nm) did not affect the vasoconstrictor responses induced by nerve stimulation.

4 Inhibition of angiotensin‐converting enzyme with 10 nm enalaprilat reduced the second peaked response, having no significant inhibition on the first peaked response. A higher dose of enalaprilat (100 nm) produced a greater inhibition of the second peak than the first one. It reduced the second peak by approximately 65%, while the first peak was decreased approximately 35%. After treatment with enalaprilat, Ang I (1 nm) failed to enhance the neuronal vascular response. Enalaprilat at doses used did not affect the vasoconstrictions to either NA or ATP.

5 The present results indicate that endogenously generated Ang II may produce a more marked potentiation of adrenergic transmission than purinergic transmission via activation of prejunctional AT1 receptors.
Coronary and aortic vasoconstriction by cathinone, the active constituent of khat
Authors: Al‐Motarreb A. L. , Broadley K. J.
Published: July 2004

1 The psychostimulant constituent of khat leaves, S‐(−)‐cathinone, was examined for vascular activity on the coronary vasculature of guinea‐pig‐isolated perfused hearts and aortic ring preparations.

2 Cathinone caused coronary vasoconstriction, negative inotropy and negative chronotropy in isolated hearts. The major metabolite of cathinone after its ingestion, 1R.2S‐(−)‐norephedrine (norephedrine), also caused coronary vasoconstriction comparable with that by cathinone. Norephedrine, however, had no effect on force or rate of cardiac contractions.

3 Cocaine (10 μm) potentiated the coronary vasoconstriction and positive inotropy by noradrenaline indicating inhibition of neuronal uptake. The vasoconstriction and negative inotropy by cathinone, however, were not affected, indicating that its action was not via release of noradrenaline from sympathetic neurones.

4 The α1‐adrenoceptor antagonist, prazosin, blocked the vasoconstriction by noradrenaline, but not that produced by cathinone in the presence of cocaine. This indicates that the coronary vasoconstriction by cathinone was not due to an action on α1‐adrenoceptors either directly or indirectly through noradrenaline release.

5 Three repeated doses of cathinone displayed the same coronary vasoconstrictor responses, indicating a lack of tachyphylaxis and therefore confirming that the response was unlikely to be due to indirect sympathomimetic activity through release of noradrenaline.

6 In guinea‐pig aortic rings, the order of vasoconstrictor activity was: noradrenaline > norephedrine > cathinone, with each causing approximately equivalent maximum responses. The time to reach plateau contractions was shortest for noradrenaline (5.1 ± 0.5 min), then norephedrine (9.3 ± 1.5 min) and cathinone the longest (25.4 ± 3.2 min, 335 μm dose).

7 These results indicate that cathinone has vasoconstrictor activity which is not due to indirect or direct sympathomimetic activity. The precise mechanism for this vasoconstriction remains to be determined. The coronary vasoconstriction may explain the increased incidence of myocardial infarction in khat chewers, which may arise from coronary vasospasm.
The Judicial Theory of a Reasonable Public Servant
Authors: Lee Yong S.
Published: July 2004

Contemporary theory of the constitutionally reasonable public servant, established by the U.S. Supreme Court in 1982 in Harlow v. Fitzgerald, is measured in reference to clearly established constitutional or statutory rights that a reasonable person would have known. In this article, the author seeks to elucidate the evolving contours of the objective reasonableness standard and examines how federal courts have applied it. To gain a firsthand impression of how public officials challenged in federal courts are measuring up to the objective reasonableness standard, the author provides a snapshot of 449 recent court cases selected from two federal circuits, the Eighth and the District of Columbia circuits. He concludes that public officials in these two circuits have fared very well under the standard of objective reasonableness. The flip side is that aggrieved individual citizens must carry a heavy burden to protect their constitutional rights.
The Implementation of Welfare Reform Policy: The Role of Public Managers in Front‐Line Practices
Authors: Riccucci Norma M. , Meyers Marcia K. , Lurie Irene , Han Jun Seop
Published: July 2004

This study examines the extent to which staff in local welfare systems have embraced new welfare reform goals and, if so, the extent to which local management practices contribute to the alignment of staff priorities with policy objectives. It looks at agency structure and several aspects of public management from a microperspective that prior research has linked to agency performance including training, performance monitoring, staff resources, leadership characteristics, and personnel characteristics. The research indicates that front‐line workers in welfare offices continue to believe that traditional eligibility determination concerns are the most important goals at their agencies. It also finds that management practices and the structuring of agency responsibilities matter: To the extent that public managers want to redirect local staff to focus their attention on the new goals associated with welfare reform, they can create the conditions under which staff have clear signals about what is expected and could provide them with the resources and incentives to realign their priorities.
Toward the Self‐Evaluating Organization? An Empirical Test of the Wildavsky Model
Authors: Boyne George A. , Gould‐Williams Julian S. , Law Jennifer , Walker Richard M.
Published: July 2004

This article presents the first empirical test of Wildavsky's model of self‐evaluation by public organizations. We elucidate Wildavsky's arguments and identify six variables that have theoretical effects on self‐evaluation. A statistical model that incorporates these variables explains 46 percent of the variation in self‐evaluation. The evidence suggests that self‐evaluation is positively related to leadership support and employee involvement, and negatively related to the number of organizational sub‐units undertaking evaluation at the same time. Refinements to the Wildavsky model are proposed, and conclusions are drawn on the theory and practice of self‐evaluation by public organizations.
U.S.‐Style Leadership for English Local Government?
Authors: Hambleton Robin , Sweeting David
Published: July 2004

Significant changes in the political management of local authorities in the United Kingdom are now taking place as a result of legislation passed by the Labour government since 1997. The new political management models aim to modernize local governance by strengthening local leadership, streamlining decision making, and enhancing local accountability. These changes owe much to U.S. experience: They involve the introduction of a separation of powers between an executive and an assembly, and they allow local authorities to introduce directly elected mayors for the first time ever. Is U.K. local government beginning to adopt what might be described as U.S.‐style approaches to local governance? The evidence suggests the new institutional designs for U.K. local authorities represent a radical shift toward U.S.‐style local leadership and decision making. However, the U.K. central state remains heavily involved in the details of local decision making, to an extent that would be unthinkable in the United States.
Activist Lawyers Repent
Authors: Rohr John A.
Published: July 2004

Books reviewed in this article:

Ross Sandler and David Schoenbrod, Democracy By Decree: What Happens When Courts Run Government
Locally delivered doxycycline improves the healing following non‐surgical periodontal therapy in smokers
Authors: Tomasi Cristiano , Wennström Jan L.
Published: July 2004

Objective: The outcome of non‐surgical periodontal therapy is known to be inferior in smokers compared to non‐smokers. In the present study, the question was asked whether such a difference in healing response may be less evident following adjunctive use of locally delivered controlled‐release doxycycline.

Methods: One hundred and three patients (42 smokers, 61 non‐smokers), each having at least eight periodontal sites with PPD (probing pocket depth) 5 mm, were following stratification for smoking randomly assigned to two different treatment protocols; non‐surgical scaling/root planing (Control) or ultrasonic instrumentation+application of a 8.5% w/w doxycycline gel (Atridox™) (Test). Instructions in oral hygiene were given to all patients. Clinical examinations of plaque, PPD, clinical attachment level (CAL) and bleeding following pocket probing were performed at baseline and after 3 months. Primary efficacy endpoints were changes in PPD and CAL. Patient mean values were calculated as basis for statistical analysis (multiple regression analyses).

Results: The baseline examination revealed no significant difference in mean PPD between treatment groups or between smokers and non‐smokers (mean PPD 5.7–5.9 mm). The mean PPD reduction in the control group at 3‐month was 1.1 mm (SD=0.45) for smokers and 1.5 mm (0.67) for non‐smokers. In the test group the PPD reduction was 1.4 mm (0.60) and 1.6 mm (0.45) for smokers and non‐smokers, respectively. The mean CAL gain for smokers and non‐smokers amounted to 0.5 mm (0.56) and 0.8 mm (0.71), respectively, in the control group, and to 0.8 mm (0.72) and 0.9 mm (0.82), respectively, in the test group. Multiple regression analysis revealed that smoking and initial PPD negatively influenced the treatment outcome in terms of PPD reduction and CAL gain, while the use of doxycycline had a significant positive effect.

Conclusion: Locally applied controlled‐release doxycycline gel may partly counteract the negative effect of smoking on periodontal healing following non‐surgical therapy.
The short‐term effectiveness of non‐surgical treatment in reducing protease activity in gingival crevicular fluid from chronic periodontitis patients
Authors: Figueredo C. M. S. , Areas A. , Miranda L. A. , Fischer R. G. , Gustafsson A.
Published: July 2004

Objectives: The aim of this study was to evaluate the short‐term effect of non‐surgical periodontal treatment on protease activity in gingival crevicular fluid (GCF) of patients with chronic periodontitis.

Material and Methods: After clinical examination, in which pocket probing depth, probing attachment level, plaque and bleeding indices were recorded, gingival fluid samples from 21 chronic periodontitis patients were collected from gingivitis (GP) and periodontitis (PP) sites with an intracrevicular washing method. Samples were taken in the same way from a group of patients with gingivitis alone (GG). The periodontitis patients received non‐surgical periodontal treatment and were re‐evaluated 30 days later. We compared elastase and collagenase activities before and after treatment. The former activity was measured with a low‐weight substrate (S‐2484) and inhibited by α‐1‐antitrypsin. Matrix‐metalloproteinase‐8 (MMP‐8) was measured with an ELISA and collagenolytic activity with fluorescein‐conjugated collagen type I as substrate.

Results: All clinical parameters showed a significant improvement after treatment (p<0.05) which was accompanied by a significant reduction in the values of total elastase activity, free elastase, MPP‐8 and collagenolytic activity in both GP and PP sites (p<0.05). However, the latter sites continued to have higher levels of MMP‐8 and collagenolytic activity than the former ones after treatment. The free elastase activity and the proportion of free elastase in GP and PP samples after treatment remained higher than in untreated GG samples.

Conclusion: This study shows that the clinical improvements after non‐surgical treatment are accompanied by reductions in protease and neutrophil activities.
Association of periodontal disease to anxiety and depression symptoms, and psychosocial stress factors
Authors: Solis A. C. O. , Lotufo R. F. M. , Pannuti C. M. , Brunheiro E. C. , Marques A. H. , Lotufo‐Neto F.
Published: July 2004

Objective: A cross‐sectional study was conducted to investigate if anxiety, depression and hopelessness symptoms are associated with periodontal disease.

Method: A total of 160 subjects took part in this study. Probing depth and clinical attachment level were recorded at six sites per tooth and the gingival and plaque indices were also recorded. The instruments used to assess the psychological variables (anxiety, depression, stress, psychiatric symptoms and hopelessness) were: the State–Trait Anxiety Inventory, the Beck Depression Inventory, the Life Events Scale modified by Savoia, the Self‐Report Screening Questionnaire‐20 and the Beck Hopelessness Scale.

Results: There was no difference in scale score means between patients with and without established periodontitis. Results of the Ordinal Logistic Regression Analysis model that included age, plaque index, smoking and psychological factors showed that patients with psychiatric symptoms (odds ratio (OR) 1.24, 95% confidence interval (CI) 0.33–4.78), depression symptoms (OR 0.57, 95% CI 0.15–2.21) and with hopelessness (OR 0.70, 95% CI 0.13–3.84) were not at a greater risk of developing established periodontitis.

Conclusion: In this sample, no evidence was found for an association between depression, hopelessness, psychiatric symptoms and established periodontitis. The association of periodontal disease to depression, anxiety and stress should be investigated in psychiatric populations, especially in those with depression and anxiety disorders.
The association of periodontal disease parameters with systemic medical conditions and tobacco use
Authors: Molloy John , Wolff Larry F. , Lopez‐Guzman Angel , Hodges James S.
Published: July 2004

Objectives: The objective of this study was to determine if an association existed between periodontal disease and various systemic medical conditions and tobacco use.

Material and Methods: The study design was a case‐controlled, retrospective chart review. Patient charts (n=2006) were selected from more than 13,000 active patients attending the University of Minnesota dental clinics. These charts were examined to determine patient's self‐reported systemic condition and smoking history. In addition, the number of missing teeth and bone loss were recorded. Two examiners collected the data. One examiner abstracted patient's medical history from the standard clinic medical questionnaire. The second examiner assessed the radiographs and dental charts to determine bone loss and number of missing teeth. Each examiner was blind to the findings of the other.

Results: After adjusting for age, sex, diabetes and smoking (yes/no) status, seven conditions were significantly (p=0.0003–0.04) related to bone loss or number of missing teeth (vascular disease, heart surgery, vascular surgery, heart attack, thyroid problems, arthritis, stomach ulcers). From these conditions, thyroid problems and arthritis had a negative association with bone loss.

Conclusions: These findings support the results from previous investigators that a number of systemic conditions and smoking are closely associated with missing teeth or bone loss.
Effect of recombinant human bone morphogenetic protein‐12 (rhBMP‐12) on regeneration of periodontal attachment following tooth replantation in dogs
Authors: Sorensen Rachel G. , Polimeni Giuseppe , Kinoshita Atsuhiro , Wozney John M. , Wikesjö Ulf M. E.
Published: July 2004

Objectives: Subcutaneous and intramuscular implants of bone morphogenetic protein‐12 (BMP‐12) have been shown to induce formation of tendon and ligament tissue. BMP‐12 induced a new attachment with a distinct fibrocartilaginous zone at the tendon‐bone interface in the rat tendon‐bone attachment model. Surgical controls showed poor healing and failure to reform the appropriate tendon–bone attachment morphologically. Application of recombinant human BMP‐12 (rhBMP‐12) to periodontal defects suggests that rhBMP‐12 has the potential to support regeneration of the periodontal ligament (PDL). The objective of this pilot study was to evaluate this effect of rhBMP‐12 in a tooth replantation model.

Methods: Six, young adult, male Hound Labrador mongrel dogs were used. Maxillary and/or mandibular incisor and premolar teeth were extracted and the PDL was either left “intact” or removed by root planing. rhBMP‐12 (1.0 mg/ml) or a buffer control was topically applied to teeth with “intact” PDL in contralateral jaw quadrants in each of 3 animals. The teeth were immersed in 1.0 ml of the rhBMP‐12 or the buffer solution for 10 min and then replanted. The remaining three animals received rhBMP‐12 (1.0 mg/ml) and the buffer control in a similar fashion applied to teeth instrumented to remove the PDL and cementum, and surface demineralized with citric acid. The animals were euthanized at 8 weeks postsurgery and block sections were collected and processed for histopathologic analysis.

Results: No dramatic differences were found between teeth receiving topical rhBMP‐12 and the buffer control. Application of rhBMP‐12 did not have an apparent effect on new cementum and PDL formation in the tooth replantation model. Moreover, application of rhBMP‐12 did not increase nor did it decrease the apparent presence and extent of ankylosis along the root surface compared to the control.

Conclusions: The observations from this study do not support the use of topical rhBMP‐12 to support the reestablishment of the PDL including regeneration of cementum and functionally oriented fibers, and to prevent ankylosis and root resorption following replantation of teeth.
Baseline radiographic defect angle of the intrabony defect as a prognostic indicator in regenerative periodontal surgery with enamel matrix derivative
Authors: Tsitoura Effie , Tucker Richard , Suvan Jean , Laurell Lars , Cortellini Pierpaolo , Tonetti Maurizio
Published: July 2004

Introduction: The baseline radiographic defect angle has previously been correlated with the clinical outcomes of intrabony defects treated with access flap or guided tissue regeneration. The aim of this study was to investigate whether an association exists between baseline radiographic defect angle and treatment outcome when enamel matrix derivative (EMD) is used in periodontal regenerative surgery.

Materials and Methods: Baseline radiographs were collected from the test group of a previously published clinical trial using a population of 166 patients treated for chronic periodontitis. All intrabony defects were 3 mm for inclusion in the original study. Either modified or simplified papilla preservation technique was used to access the defect. The roots were conditioned with an EDTA gel and the primary outcome measure was clinical attachment level (CAL) change, 1 year after surgery.

Results: Sixty‐seven radiographs were measurable. The probability of obtaining CAL gain >3 mm was 2.46 times higher (95% confidence interval: 1.017–5.970) when the radiographic defect angle was 22° than when it was 36°.

Conclusions: This study showed that there was a significant association between baseline radiographic defect angle and CAL gain at 1 year. The observed increased odds ratio of obtaining CAL gain of 4 mm after regenerative surgery with EMD is used in narrow (22°) intrabony defects, suggests that the baseline radiographic defect angle might be used as a prognostic indicator of treatment outcome.
Oxidation of CoS1.023 grains at 823–983 K
Authors: Kowzan Anna , Szczepaniak Włodzimierz , Zabłocka–Malicka Monika , Dudziński Włodzimierz
Published: July 2004

According to literature, cobalt sulfide oxidizes at higher temperatures in air to dense or porous cobalt (II) oxide. It is in general agreement with predominance phase diagram, but it also may be concluded from the diagram that cobalt sulfate formation should follow oxidation. This paper presents results of an investigation of oxidation in air of CoS1.023 grains of 0.63–0.80 mm diameter, in the temperature range 823–983 K. It was found that intense emission of SO2—a main gaseous product of the process—proceeds only at the beginning during several minutes. Time of this stage increases with temperature and proportionally increases the degree of sulfide transformation. With electron microscopy, internal composition of oxidized grain was revealed. It was found that the grain in general contains unreacted sulfide core surrounded by a dense layer of CoO without sulfate admixture, then porous layers of Co3O4 with up to 20% of cobalt in sulfate form inside and up to several percent at the grain surface.
Structure and properties of an ultra low carbon HSLA forging
Authors: Das Samar , Ghosh A. , Chatterjee S. , Ramachandrarao P.
Published: July 2004

An ultra low carbon HSLA steel was subjected to a two, stage‐forging operation followed by different post‐cooling techniques. The higher strength value, obtained at a faster cooling rate of 35°C/s, is due to a highly dislocated acicular ferrite structure along with fine precipitation of microalloying carbides and/or carbonitrides. At a slower cooling rate of 1.15°C/s, the strength value drops with an increase in ductility due to the larger volume fraction of less dislocated polygonal ferrite structure. The strength value remained almost unchanged with a further decrease in cooling rate to 0.68°C/s due to the formation of polygonal ferrite microstructure predominantly. At the slowest post‐cooling rate, a high impact toughness value was obtained at ambient and at −40°C testing temperature due to fine grained polygonal ferrite microstructure. At all post‐cooling conditions, the change in impact toughness value at ambient and at −40°C temperature was found to be negligible due to the ultra low carbon content of the steel.
Thermal decomposition of precipitated fine aluminium trihydroxide
Authors: Bhattacharya I. N. , Das S. C. , Mukherjee P. S. , Paul S. , Mitra P. K.
Published: July 2004

Fine (1.5 μm) aluminium trihydroxide (ATH), prepared from Bayer liquor, was subjected to dehydration at various temperatures up to 1400°C. The fine ATH was found to be gibbsitic in nature. XRD data indicated the formation of various transitional phases before becoming a stable α‐Al2O3 phase. Boehmite phase formation, that is unlikely at such a fine particle level, started at around 250°C and completed its transformation at 400°C. Formation of boehmite phase was also observed with 0.25 and 1 μm sized particles. Beyond 400°C, various transitional phases were formed. At 500°C, chi‐alumina formation was found; kappa‐alumina phase transformation started at 900°C and completed at 1000°C. Coarser particles (∼100 μm) also followed the similar trend. In the case of coarse ATH, α‐Al2O3 transformation was found at around 1200°C, whereas for fine particles, α‐Al2O3 transformation temperature was found to be 1400°C. FTIR spectra showed the presence of molecular water and Al–O bonds in gibbsitic material. Characteristic vibrations at 3098, 2099 and 1070 cm−1 were found for boehmite particles at 400°C. Lattice parameters and hkl values were calculated and reported. Determination of crystallite size, cell volume, number of atoms/unit cell and number of unit cell/crystallite were also undertaken and reported.
Glass‐ceramic from industrial waste materials
Authors: Francis A. A. , Youssef N. F.
Published: July 2004

The crystallization behavior of a vitrified sample prepared from a mixture of slag, glass cullet and dolomite was investigated using differential thermal analysis (DTA), X‐ray diffraction and scanning electron microscopy. Differential thermal analyses were performed on the glass at different heating rates up to 1150°C, which showed that the crystallization exotherm occurs in the temperature range 900–1100°C. X‐ray diffraction revealed the presence of diopside Ca(Mg,Al)(Si,Al)2O6 as the major crystalline phase. The microstructure was characterized by the presence of dendritic diopside crystals. The activation energy of crystallization was estimated using Kissinger equation and is equal to 360 kJ/mol. The Avrami parameter was found to be equal to 1.66, which is indicative of three‐dimensional diffusion controlled growth of diopside crystals.
Spielräume des auktorialen Diskurses bei Hermann Broch: Eine methodologische Novelle
Authors: Martens Gunther
Published: July 2004

Die moderne Narratologie hat ihr terminologisches Instrumentarium vorwiegend an Texten mit so genannten engeren Fokalisationen und Perspektivierungen (Virginia Woolf usw.) entwickelt. Das führt zu einer gewissen Verlegenheit, wenn man feststellt, dass z.B. in den modernistischen Texten Thomas Manns, Robert Musils und Hermann Brochs durchaus auktoriale Vermittlung von Bedeutung ist. Der folgende Beitrag hat sich zweierlei zum Ziel gesetzt: Zunächst erfolgt eine kritische Darstellung der einflussreichen normativen Poetiken, die die missverständliche Austreibung des auktorialen Erzählers aus der Literatur(wissenschaft) herbeigeführt haben, sowie eine Problematisierung der Art und Weise, wie Auktorialität mit Autor‐Intentionalität und Thesenroman gleichgesetzt wird. Anschließend wird ein kombiniertes Narrativik‐Modell, das einerseits im Sinne von Genette auf Informationsverteilung, andererseits auf grammatische Merkmale auktorialen Sprechens achtet, auf Brochs experimentelle Methodologische Novelle (1918) angewendet. Die Analyse versucht den Beweis zu erbringen, dass die Konvention des Allwissens und der Allmacht des Erzählers nicht unbedingt mit Dogmatik gleichgesetzt, sondern auch mit einem subversiven, dynamischen Akzent versehen werden kann.
Shakespeare's Skepticism Redefined
Authors: Weidhorn Manfred
Published: July 2004

Critics have been busy tracing Shakespeare's apparent skepticism in individual plays and groups of plays. Skepticism, however, pervades the entire canon, in the sense that various plays are in antithetical relationships with each other, often as comic and tragic versions of the same themes (Richard III and The Taming of the Shrew, Romeo and Juliet and A Midsummer Night's Dream, King Lear and As You Like It, Othello and Much Ado About Nothing, Antony and Cleopatra and Troilus and Cressida). Such pairings suggest an unwillingness to be pinned down to any one reading of reality.