bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated level of interleukin‐6 predicts organ failure and severe disease in patients with acute pancreatitis
Authors: Sathyanarayan Garipati , Garg Pramod Kumar , Prasad HK , Tandon Rakesh Kumar
Published: October 2006

Background and Aim:  Cytokines play an important role in the pathogenesis of acute pancreatitis (AP). The aim of the present paper was to study the profile of anti‐ and proinflammatory cytokines in AP and to determine their predictive value for severity of AP, organ failure and mortality.

Methods:  Consecutive patients with AP were included in the study. Cytokines were measured in those patients who presented within the first 72 h of the onset of AP. Plasma levels of proinflammatory cytokines tumor necrosis factor (TNF)‐α, interleukin (IL)‐Iβ, IL‐6 and anti‐inflammatory cytokine IL‐10 were measured on days 1, 3, 7 and 14 of AP.

Results:  Of 108 patients, 30 presented within 72 h of the onset (mean age 40.27 ± 13.89 years; 22 males). Of the 30 patients, 13 (43.3%) had severe and 17 (56.7%) had mild pancreatitis. Eleven (36.7%) patients developed organ failure and three died. The level of IL‐6 on day 3 was significantly higher in severe pancreatitis than in mild pancreatitis (146.29 ± 57.53 pg/mL vs 91.42 ± 71.65 pg/mL; P = 0.04) and was significantly higher in patients who developed organ failure compared with those who did not (161.59 ± 53.46 pg/mL vs 88.16 ± 65.50 pg/mL; P = 0.004). At a cut‐off value of 122 pg/mL on day 3, IL‐6 predicted organ failure and severe pancreatitis with a sensitivity and specificity of 81.8% and 77.7%, respectively. TNF‐α and IL‐10 were detectable only in one‐third of patients and were not related to the severity of pancreatitis, while Il‐1β was not detectable.

Conclusion:  Elevated levels of IL‐6 predicted organ failure and severe pancreatitis and suggested its pathophysiological significance in AP.
The bacterial storage compound poly‐β‐hydroxybutyrate protects Artemia franciscana from pathogenic Vibrio campbellii
Authors: Defoirdt Tom , Halet Dirk , Vervaeren Han , Boon Nico , Van de Wiele Tom , Sorgeloos Patrick , Bossier Peter , Verstraete Willy
Published: October 2006

Infections caused by antibiotic‐resistant luminescent Vibrios can cause dramatic losses in aquaculture. In this study, the short‐chain fatty acid β‐hydroxybutyrate and its polymer poly‐β‐hydroxybutyrate were investigated as possible new biocontrol agents. β‐Hydroxybutyrate was shown to completely inhibit the growth of pathogenic Vibrio campbelli at 100 mM. Moreover, the addition of 100 mM of this fatty acid to the culture water of Artemia nauplii infected with the V. campbelli strain significantly increased the survival of the nauplii. As Artemia is a non‐selective and particle filter feeder, we also investigated whether poly‐β‐hydroxybutyrate particles could be used to protect Artemia from the pathogenic V. campbellii. The addition of 100 mg l−1 poly‐β‐hydroxybutyrate or more to the Artemia culture water offered a preventive and curative protection from the pathogen as a significantly enhanced survival was noticed. If added as a preventive treatment, a complete protection of infected nauplii (no significant mortality compared with uninfected nauplii) was observed at 1000 mg l−1 poly‐β‐hydroxybutyrate. Our data indicate that the use of poly‐β‐hydroxybutyrate might constitute an ecologically and economically sustainable alternative strategy to fight infections in aquaculture.
Plant–microbe association for rhizoremediation of chloronitroaromatic pollutants with Comamonas sp. strain CNB‐1
Authors: Liu Lei , Jiang Cheng‐Ying , Liu Xing‐Yu , Wu Jian‐Feng , Han Ji‐Gang , Liu Shuang‐Jiang
Published: October 2006

Comamonas sp. strain CNB‐1, isolated from activated sludge and having a strong ability to degrade 4‐chloronitrobenzene (4CNB), was applied for rhizoremediation of 4CNB‐polluted soil through association with alfalfa. Confocal laser scanning microscopy revealed that strain CNB‐1 successfully colonized alfalfa roots. Determination of strain CNB‐1 populations by cultivation method and by quantitative competitive PCR technique targeting the chloronitrobenzene nitroreductase gene showed that the population of strain CNB‐1 in the rhizosphere was about 10–100 times higher than that in the bulk soil. Gnotobiotic and outdoor experiments showed that pollutant 4CNB was completely removed within 1 or 2 days after 4CNB application into soil, and that its phytotoxicity to alfalfa was eliminated by inoculation of strain CNB‐1. Results from PCR‐denaturing gradient gel electrophoresis and analysis of 16S rRNA gene libraries revealed that the indigenous soil microbial community mainly consisted of alphaproteobacteria, betaproteobacteria, gammaproteobacteria, the CFB bacteria (Cytophaga‐Flavabacterium‐Bacteriodes), and Acidobacteria. This microbial community was not significantly influenced by inoculation of strain CNB‐1. Thus, this study has developed a Comamonas‐alfalfa system for rhizoremediation of 4CNB.
Spatial variation of active microbiota in the rice rhizosphere revealed by in situ stable isotope probing of phospholipid fatty acids
Authors: Lu Yahai , Abraham Wolf‐Rainer , Conrad Ralf
Published: October 2006

This report is part of a serial study applying stable isotope labelling to rice microcosms to track the utilization of recently photosynthesized carbon by active microbiota in the rhizosphere. The objective of the present study was to apply phospholipid fatty acid‐based stable isotope probing (PLFA‐SIP) to detect the spatial variation of active microorganisms associated with rhizosphere carbon flow. In total, 49 pulses of 13CO2 were applied to rice plants in a microcosm over a period of 7 days. Rhizosphere soil was separated from bulk soil by a root bag. Soil samples were taken from rhizosphere and bulk soil, and the bulk soil samples were further partitioned both vertically (up layer and down layer) and horizontally with increasing distance to the root bag. Incorporation of 13C into PLFAs sharply decreased with distance to the roots. The labelling of 16:1ω9, 18:1ω7, 18:1ω9, 18:2ω6,9 and i14:0 PLFAs was relatively stronger in the rhizosphere while that of i15:0 and i17:0 increased in the bulk soil. The microorganisms associated with 16:1ω9 were active in both up‐ and down‐layer soils. The microorganisms represented by i14:0, 18:1ω7 and 18:2ω6,9 exhibited a relatively higher activity in up‐layer soil, whereas those represented by i15:0 and i17:0 were more active in down‐layer soil. These results suggest that in the rhizosphere Gram‐negative and eukaryotic microorganisms were most actively assimilating root‐derived C, whereas Gram‐positive microorganisms became relatively more important in the bulk soil. The active populations apparently differed between up‐ and down‐layer soil and in particular changed with distance to the roots, demonstrating systematic changes in the activity of the soil microbiota surrounding roots.
Combination of IFNβ‐1a (Avonex®) and mycophenolate mofetil (Cellcept®) in multiple sclerosis
Authors: Vermersch P. , Waucquier N. , Michelin E. , Bourteel H. , Stojkovic T. , Ferriby D. , De Seze J. ,   on behalf of the G‐SEP (Groupe septentrional d’études et de prise en charge de la sclérose en plaques)
Published: October 2006

To determine the safety of a combination of mycophenolate mofetil (Cellcept®, MMF) and IFNβ‐1a (Avonex®) in relapsing‐remitting multiple sclerosis (RRMS) and to evaluate the effects of the combination on clinical and magnetic resonance imaging (MRI) measures of disease activity. Secondary objectives were clinical and MRI data. An open‐label, single‐centre study including 30 RRMS patients was performed. Inclusion criteria were patients expanded disability status scale (EDSS) score <6.0, treated by Avonex® for at least 6 months, with at least two relapses during the previous 2 years and at least one during the previous 6 months. MMF at a progressive dose of 2 g per day orally was added to Avonex® for a duration of 6 months. MRI data were obtained at baseline and at the end of the study. The pre‐study annual relapse rate was 2.0 ± 0.7 and the EDSS score at baseline was 2.9 ± 1.3. Eleven patients had gadolinium (Gd)‐enhanced lesions at baseline for a total number of 35 lesions. Two patients interrupted the combination, one after the first dose for personal reasons unrelated to the study and the other due to diarrhoea. A few of the patients also reported nausea and abdominal pains. Adverse events included benign infectious diseases, insomnia and dizziness. No significant biological abnormalities were noted. The annualized relapse rate was 0.57 ± 0.3 at the end of the study (P < 0.001). The mean EDSS score was 2.6 ± 1.5 and no Gd‐enhanced lesions were detected on MRI at the end of the study. MMF and IFNβ‐1a (Avonex®) combined therapy is safe and very well‐tolerated. Clinical and MRI data suggest that this combination may be beneficial.
Filling the gap: a fossil frogfish, genus Antennarius (Teleostei, Lophiiformes, Antennariidae), from the Miocene of Algeria
Authors: Carnevale G. , Pietsch T. W.
Published: October 2006

A new species of frogfish, Antennarius monodi sp. nov., is described from the Upper Miocene (Messinian) of Raz‐el‐Aïn, near Oran, north‐east Algeria. The type and only specimen of this taxon is the first articulated skeleton belonging to the family Antennariidae ever recorded as a fossil. The morphological and meristic characters observed support the inclusion of this species in the Antennarius ocellatus group, where it shares several features with the extant Antennarius senegalensis. Morphological features, sedimentary characters and faunal association concur to suggest that A. monodi sp. nov. possibly was a tropical, continental species that lived on muddy bottoms and turbid waters at depths less than 90–100 m. From a biogeographic point of view, the presence of an antennariid closely related to A. senegalensis in the Late Miocene of the Mediterranean suggests that this area had strong biotic relationships with the eastern tropical Atlantic at that time. The integrative analysis of phylogenetic interrelationships and fossil record of the entire order Lophiiformes reveals that all the lophiiform lineages were already in existence in the Eocene. Moreover, the existence of a derived species of the genus Antennarius in the Late Miocene at last fills a large gap that exists in the fossil record of the Teleostei, suggesting that the modern antennariid body plan originated well before that period.
Dual regulation of translation initiation and peptide chain elongation during BDNF‐induced LTP in vivo: evidence for compartment‐specific translation control
Authors: Kanhema Tambudzai , Dagestad Grethe , Panja Debabrata , Tiron Adrian , Messaoudi Elhoucine , Håvik Bjarte , Ying Shui‐Wang , Nairn Angus C. , Sonenberg Nahum , Bramham Clive R.
Published: October 2006

Protein synthesis underlying activity‐dependent synaptic plasticity is controlled at the level of mRNA translation. We examined the dynamics and spatial regulation of two key translation factors, eukaryotic initiation factor 4E (eIF4E) and elongation factor‐2 (eEF2), during long‐term potentiation (LTP) induced by local infusion of brain‐derived neurotrophic factor (BDNF) into the dentate gyrus of anesthetized rats. BDNF‐induced LTP led to rapid, transient phosphorylation of eIF4E and eEF2, and enhanced expression of eIF4E protein in dentate gyrus homogenates. Infusion of the extracellular signal‐regulated kinase (ERK) inhibitor U0126 blocked BDNF‐LTP and modulation of the translation factor activity and expression. Quantitative immunohistochemical analysis revealed enhanced staining of phospho‐eIF4E and total eIF4E in dentate granule cells. The in vitro synaptodendrosome preparation was used to isolate the synaptic effects of BDNF in the dentate gyrus. BDNF treatment of synaptodendrosomes elicited rapid, transient phosphorylation of eIF4E paralleled by enhanced expression of α‐calcium/calmodulin‐dependent protein kinase II. In contrast, BDNF had no effect on eEF2 phosphorylation state in synaptodendrosomes. The results demonstrate rapid ERK‐dependent regulation of the initiation and elongation steps of protein synthesis during BDNF‐LTP in vivo. Furthermore, the results suggest a compartment‐specific regulation in which initiation is selectively enhanced by BDNF at synapses, while both initiation and elongation are modulated at non‐synaptic sites.
Functional down‐regulation of volume‐regulated anion channels in AQP4 knockdown cultured rat cortical astrocytes
Authors: Benfenati Valentina , Nicchia Grazia Paola , Svelto Maria , Rapisarda Carmela , Frigeri Antonio , Ferroni Stefano
Published: October 2006

In the brain, the astroglial syncytium is crucially involved in the regulation of water homeostasis. Accumulating evidence indicates that a dysregulation of the astrocytic processes controlling water homeostasis has a pathogenetic role in several brain injuries. Here, we have analysed by RNA interference technology the functional interactions occurring between the most abundant water channel in the brain, aquaporin‐4 (AQP4), and the swelling‐activated Cl– current expressed by cultured rat cortical astrocytes. We show that in primary cultured rat cortical astrocytes transfected with control small interfering RNA (siRNA), hypotonic shock promotes an increase in cellular volume accompanied by augmented membrane conductance mediated by volume‐regulated anion channels (VRAC). Conversely, astroglia in which AQP4 was knocked down (AQP4 KD) by transfection with AQP4 siRNA changed their morphology from polygonal to process‐bearing, and displayed normal cell swelling but reduced VRAC activity. Pharmacological manipulations of actin cytoskeleton in rat astrocytes, and functional analysis in mouse astroglial cells, which retain their morphology upon knockdown of AQP4, suggest that stellation of AQP4 KD rat cortical astrocytes was not causally linked to reduction of VRAC current. Molecular analysis of possible candidates of swelling‐activated Cl– current provided evidence that in AQP4 KD astrocytes, there was a down‐regulation of chloride channel‐2 (CIC‐2), which, however, was not involved in VRAC conductance. Inclusion of ATP in the intracellular saline restored VRAC activity upon hypotonicity. Collectively, these results support the view that in cultured astroglial cells, plasma membrane proteins involved in cell volume homeostasis are assembled in a functional platform.
Regulation of glial development by cystatin C
Authors: Hasegawa Akiko , Naruse Masae , Hitoshi Seiji , Iwasaki Yasuno , Takebayashi Hirohide , Ikenaka Kazuhiro
Published: October 2006

Cystatin C (CysC) is an endogenous cysteine proteases inhibitor produced by mature astrocytes in the adult brain. Previously we isolated CysC as a factor activating the glial fibrillary acidic protein (GFAP) promoter, and showed that CysC is expressed in astrocyte progenitors during development. Here we show that protease inhibitor activity increased daily in conditioned medium, and that this activity was mainly a result of CysC released from primary cultured cells. Human CysC added to the culture medium of primary brain cells increased the number of GFAP‐positive and nestin‐positive cells. Human CysC also increased the number of neurospheres formed from embryonic brain, and thus it increases the number of neural stem/precursor cells in a manner similar to glycosylated rat CysC. The addition of a neutralizing antibody, on the other hand, greatly decreased the number of GFAP and glutamate aspartate transporter (GLAST)‐positive astrocytes. This decrease was reversed by the addition of CysC but not by another cysteine protease inhibitor. Thus, the promotion of astrocyte development by CysC appears to be independent of its protease inhibitor activity. The antibody increased the number of oligodendrocytes and their precursors. Therefore, CysC modifies glial development in addition to its activity against neural stem/precursor cells.
A role for the transcriptional repressor REST in maintaining the phenotype of neurosecretory‐deficient PC12 cells
Authors: Pance Alena , Livesey Frederick J. , Jackson Antony P.
Published: October 2006

The rat PC12 variant cell line, A35C, lacks regulated secretory organelles due to a selective transcriptional block. Hence, A35C may provide clues about the mechanisms that underlie control of neurosecretion. We used mRNA microarray profiling to examine gene expression in A35C. Genes for regulated secretory proteins were down‐regulated, while other membrane trafficking pathways were unaffected. A subset of genes repressed in A35C contain binding sites for the neuronal transcriptional repressor, RE1‐silencing transcription factor (REST), and REST is expressed in A35C but not normal PC12 cells. Blocking the activity of REST in A35C using a dominant‐negative construct induced the reappearance of mRNAs for synaptophysin, chromogranin A, synaptotagmin IV and the β3 subunit of the voltage‐gated sodium channel (Scn3b), all of which contain RE1 sites in their genes. In the case of Scn3b, the corresponding protein was also re‐expressed. Granule and synaptic vesicle proteins were not re‐expressed at the protein level, despite reactivation of their mRNA, suggesting the existence of additional post‐transcriptional control for these proteins. Our work identifies one of the mechanisms underlying the phenotype of neurosecretory‐deficient neuroendocrine cells, and begins to define the critical components that determine a key aspect of the neuroendocrine phenotype.
Inhibition of MLK3‐MKK4/7‐JNK1/2 pathway by Akt1 in exogenous estrogen‐induced neuroprotection against transient global cerebral ischemia by a non‐genomic mechanism in male rats
Authors: Wang Ran , Zhang Quan‐Guang , Han Dong , Xu Jing , Lü Qian , Zhang Guang‐Yi
Published: October 2006

Numerous studies have demonstrated the neuroprotective effects of estrogen in experimental cerebral ischemia. To investigate molecular mechanisms of estrogen neuroprotection in global ischemia, immunoblotting, immunohistochemistry and Nissel‐staining analysis were used. Our results showed that chronic pretreatment with β‐estradiol 3‐benzoate (E2) enhanced Akt1 activation and reduced the activation of mixed‐lineage kinase 3 (MLK3), mitogen‐activated protein kinase kinase 4/7 (MKK4/7), and c‐Jun N‐terminal kinase 1/2 (JNK1/2) in the hippocampal CA1 subfield during reperfusion after 15 min of global ischemia. In addition, E2 reduced downstream JNK nuclear and non‐nuclear components, c‐Jun and Bcl‐2 phosphorylation and Fas ligand protein expression induced by ischemia/reperfusion. Administration of phosphoinositide 3‐kinase (PI3K) inhibitor LY 294,002 prevented both activation of Akt1 and inhibition of MLK3, MKK4/7 and JNK1/2. The interaction between ERα and the p85 subunit of PI3K was also examined. E2 and antiestrogen ICI 182,780 promoted and prevented this interaction, respectively. Furthermore, ICI 182,780 blocked both the activation of Akt1 and the inhibition of MLK3, MKK4/7 and JNK1/2. Photomicrographs of cresyl violet‐stained brain sections showed that E2 reduced CA1 neuron loss after 5 days of reperfusion, which was abolished by ICI 182,780 and LY 294,002. Our data indicate that in response to estrogen, ERα interacts with PI3K to activate Akt1, which may inhibit the MLK3‐MKK4/7‐JNK1/2 pathway to protect hippocampal CA1 neurons against global cerebral ischemia in male rats.
Expression of the Wnt inhibitor Dickkopf‐1 is required for the induction of neural markers in mouse embryonic stem cells differentiating in response to retinoic acid
Authors: Verani R. , Cappuccio I. , Spinsanti P. , Gradini R. , Caruso A. , Magnotti M. C. , Motolese M. , Nicoletti F. , Melchiorri D.
Published: October 2006

Cultured mouse D3 embryonic stem (ES) cells differentiating into embryoid bodies (EBs) expressed several Wnt isoforms, nearly all isotypes of the Wnt receptor Frizzled and the Wnt/Dickkopf (Dkk) co‐receptor low‐density lipoprotein receptor‐related protein (LRP) type 5. A 4‐day treatment with retinoic acid (RA), which promoted neural differentiation of EBs, substantially increased the expression of the Wnt antagonist Dkk‐1, and induced the synthesis of the Wnt/Dkk‐1 co‐receptor LRP6. Recombinant Dkk‐1 applied to EBs behaved like RA in inducing the expression of the neural markers nestin and distal‐less homeobox gene (Dlx‐2). Recombinant Dkk‐1 was able to inhibit the Wnt pathway, as shown by a reduction in nuclear β‐catenin levels. Remarkably, the antisense‐ or small interfering RNA‐induced knockdown of Dkk‐1 largely reduced the expression of Dlx‐2, and the neuronal marker β‐III tubulin in EBs exposed to RA. These data suggest that induction of Dkk‐1 and the ensuing inhibition of the canonical Wnt pathway is required for neural differentiation of ES cells.
Sustained phosphorylation of tyrosine hydroxylase at serine 40: a novel mechanism for maintenance of catecholamine synthesis
Authors: Bobrovskaya Larisa , Gilligan Conor , Bolster Ellen K. , Flaherty Jeffrey J. , Dickson Phillip W. , Dunkley Peter R.
Published: October 2006

Tyrosine hydroxylase (TH) is the rate‐limiting enzyme in catecholamine synthesis. Its activity is known to be controlled acutely (minutes) by phosphorylation and chronically (days) by protein synthesis. Using bovine adrenal chromaffin cells we found that nicotine, acting via nicotinic receptors, sustained the phosphorylation of TH at Ser40 for up to 48 h. Nicotine also induced sustained activation of TH, which for the first 24 h was completely independent of TH protein synthesis, and the phosphorylation of TH at Ser31. Imipramine did not inhibit the acute phosphorylation of TH at Ser40 or TH activation induced by nicotine, but did inhibit the sustained responses to nicotine seen at 24 h. The protein kinase(s) responsible for TH phosphorylation at Ser40 switched from being protein kinase C (PKC) independent in the acute phase to PKC dependent in the sustained phase. Sustained phosphorylation and activation of TH were also observed with histamine and angiotensin II. Sustained phosphorylation of TH at Ser40 provides a novel mechanism for increasing TH activity and this leads to increased catecholamine synthesis. Sustained phosphorylation of TH may be a selective target for drugs or pathology in neurons that contain TH and synthesize dopamine, noradrenaline or adrenaline.
Repeated stress alters the ability of nicotine to activate the hypothalamic–pituitary–adrenal axis
Authors: Lutfy Kabirullah , Brown Maria C. , Nerio Namiko , Aimiuwu Otaren , Tran Benjamin , Anghel Adrian , Friedman Theodore C.
Published: October 2006

Acute nicotine administration has been shown to activate the hypothalamic–pituitary–adrenal (HPA) axis and stimulate secretion of adrenocorticotrophic hormone (ACTH), corticosterone/cortisol and β‐endorphin (beta‐END) in both rodents and humans, raising the possibility that activation of the HPA axis by nicotine may mediate some of the effects of nicotine. Since stress can increase the risk of drug use and abuse, we hypothesized that repeated stress would increase the ability of nicotine to stimulate the secretion of HPA hormones. To test our hypothesis, mice were exposed to repeated stress (swimming in 15°C water for 3 min/day for 5 days) and killed 15 min after injection of saline or nicotine (0.1 mg/kg, s.c.). Repeated exposure to stress increased the ability of nicotine to stimulate plasma ACTH (p < 0.05) and beta‐END (p < 0.05), but not corticosterone secretion. In contrast, repeated exposure to stress increased the post‐saline injection levels of corticosterone (p < 0.05), but not ACTH and beta‐END. The present results suggest that chronic stress leads to an enhanced sensitivity of some components of the HPA axis to a subsequent nicotine challenge.
Alternative splicing of RGS8 gene changes the binding property to the M1 muscarinic receptor to confer receptor type‐specific Gq regulation
Authors: Itoh Masayuki , Nagatomo Katsuhiro , Kubo Yoshihiro , Saitoh Osamu
Published: October 2006

RGS proteins constitute a large family that modulates heterotrimeric G‐protein signaling. We previously showed that RGS8 suppressed Gq signaling in a receptor type‐specific manner. To elucidate molecular mechanisms underlying receptor‐specific attenuation by RGS8, we examined whether RGS8 can interact with certain G‐protein‐coupled receptors. By pull‐down assay, we showed that RGS8 directly binds to the third intracellular (i3) loop of M1 and M3 muscarinic acetylcholine receptors (mAChRs). The binding of RGS8S, a splice variant with a different N‐terminus, was weaker. RGS8 could bind specifically to the C‐terminal part of M1i3 (containing amino acids of 304–353 of i3 of human M1‐mAChR), but RGS8S could not. Moreover, deletion of the N‐terminal 9 amino acids and substitution of both Arg‐8 and Arg‐9 of RGS8 with Ala resulted in reduced binding to M1i3. BRET experiments revealed that RGS8 actually interacts with M1‐mAChR, but RGS8S does not interact in the living cells. The RGS8 mutant, which had less binding ability to M1i3, showed a reduced inhibitory function of Gq signaling through M1‐mAChR. These results demonstrated that RGS8 can directly interact with M1‐mAChR via its N‐terminus and the i3 loop of the receptor, and this binding must play an essential role in receptor‐specific suppression by RGS8.
The heat‐shock protein 90 inhibitor 17‐allylamino‐17‐demethoxygeldanamycin suppresses glial inflammatory responses and ameliorates experimental autoimmune encephalomyelitis
Authors: Russo Cinzia Dello , Polak Paul E. , Mercado Pilar R. , Spagnolo Alessandra , Sharp Anthony , Murphy Patricia , Kamal Adeela , Burrows Francis J. , Fritz Lawrence C. , Feinstein Douglas L.
Published: October 2006

The heat‐shock response (HSR), a highly conserved cellular response, is characterized by rapid expression of heat‐shock proteins (HSPs), and inhibition of other synthetic activities. The HSR can attenuate inflammatory responses, via suppression of transcription factor activation. A HSR can be induced pharmacologically by HSP90 inhibitors, through activation of the transcription factor Heat Shock Factor 1 (HSF1). In the present study we characterized the effects of 17‐allylamino‐17‐demethoxygeldanamycin (17‐AAG), a less toxic derivative of the naturally occurring HSP90 inhibitor geldanamycin, on glial inflammatory responses and the development of experimental autoimmune encephalomyelitis. In primary enriched glial cultures, 17‐AAG dose dependently reduced lipopolysaccharide‐dependent expression and activity of inducible nitric oxide synthase, attenuated interleukin (IL)‐1β expression and release, increased inhibitor of κB protein levels, and induced HSP70 expression. 17‐AAG administration to mice immunized with myelin oligodendrocyte glycoprotein peptide prevented disease onset when given at an early time, and reduced clinical symptoms when given during ongoing disease. T cells from treated mice showed a reduced response to immunogen re‐stimulation, and 17‐AAG reduced CD3‐ and CD28‐dependent IL‐2 production. Together, these data suggest that HSP90 inhibitors could represent a new approach for therapeutic intervention in autoimmune diseases such as multiple sclerosis.
Improving Quality Assessment through Multilevel Modeling: The Case of Nursing Home Compare
Authors: Arling Greg , Lewis Teresa , Kane Robert L. , Mueller Christine , Flood Shannon
Published: October 2006

Objective. To demonstrate how multilevel modeling and empirical Bayes (EB) estimates can improve Medicare's Nursing Home Compare quality measures (QMs).

Data Sources/Study Setting. Secondary data from July 1 to September 30, 2004. Facility‐level QMs were estimated from minimum data set (MDS) assessments for approximately 31,000 Minnesota nursing home residents in 393 facilities.

Study Design. Prevalence and incidence rates for 12 nursing facility QMs (e.g., use of physical restraints, pressure sores, and weight loss) were estimated with EB methods and risk adjustment using a hierarchical general linear model. Three sets of rates were developed: Nursing Home Compare's current method, unadjusted EB rates, and risk‐adjusted EB rates. Bayesian 90 percent credibility intervals (CIs) were constructed around EB rates, and these were used to flag facilities for potential quality of care problems.

Data Collection/Extraction Methods. MDS assessments were performed by nursing facility staff, transmitted electronically to the Minnesota Department of Health, and provided to the investigators.

Principal Findings. Facility rates and rankings for the 12 QMs differed substantially using the multilevel models compared with current methods. The EB estimated rates shrank considerably toward the population mean. Risk adjustment had a large impact on some QM rates and a more modest impact on others. When EB CIs were used to flag problem facilities, there was wide variation across QMs in the percentage of facilities flagged.

Conclusions. Multilevel modeling should be applied to Nursing Home Compare and more widely in other health care quality assessment systems.
Organizational Culture and Physician Satisfaction with Dimensions of Group Practice
Authors: Zazzali James L. , Alexander Jeffrey A. , Shortell Stephen M. , Burns Lawton R.
Published: October 2006

Research Objective.To assess the extent to which the organizational culture of physician group practices is associated with individual physician satisfaction with the managerial and organizational capabilities of the groups.

Study Design and Methods.Physician surveys from 1997 to 1998 assessing the culture of their medical groups and their satisfaction with six aspects of group practice. Organizational culture was conceptualized using the Competing Values framework, yielding four distinct cultural types. Physician‐level data were aggregated to the group level to attain measures of organizational culture. Using hierarchical linear modeling, individual physician satisfaction with six dimensions of group practice was predicted using physician‐level variables and group‐level variables. Separate models for each of the four cultural types were estimated for each of the six satisfaction measures, yielding a total of 24 models.

Sample Studied.Fifty‐two medical groups affiliated with 12 integrated health systems from across the U.S., involving 1,593 physician respondents (38.3 percent response rate). Larger medical groups and multispecialty groups were over‐represented compared with the U.S. as a whole.

Principal Findings.Our models explain up to 31 percent of the variance in individual physician satisfaction with group practice, with individual organizational culture scales explaining up to 5 percent of the variance. Group‐level predictors: group (i.e., participatory) culture was positively associated with satisfaction with staff and human resources, technological sophistication, and price competition. Hierarchical (i.e., bureaucratic) culture was negatively associated with satisfaction with managerial decision making, practice level competitiveness, price competition, and financial capabilities. Rational (i.e., task‐oriented) culture was negatively associated with satisfaction with staff and human resources, and price competition. Developmental (i.e., risk‐taking) culture was not significantly associated with any of the satisfaction measures. In some of the models, being a single‐specialty group (compared with a primary care group) and a group having a higher percent of male physicians were positively associated with satisfaction with financial capabilities. Physician‐level predictors: individual physicians' ratings of organizational culture were significantly related to many of the satisfaction measures. In general, older physicians were more satisfied than younger physicians with many of the satisfaction measures. Male physicians were less satisfied with data capabilities. Primary care physicians (versus specialists) were less satisfied with price competition.

Conclusion.Some dimensions of physician organizational culture are significantly associated with various aspects of individual physician satisfaction with group practice.
Do State Parity Laws Reduce the Financial Burden on Families of Children with Mental Health Care Needs?
Authors: Barry Colleen L. , Busch Susan H.
Published: October 2006

Objective. To study the financial impact of state parity laws on families of children in need of mental health services.

Data Source. Privately insured families in the 2000 State and Local Area Integrated Telephone Survey National Survey of Children with Special Health Care Needs (CSHCN) (N=38,856).

Study Design. We examine whether state parity laws reduce the financial burden on families of children with mental health conditions. We use instrumental variable estimation controlling for detailed information on a child's health and functional impairment. We compare those in parity and nonparity states and those needing mental health care with other CSHCN.

Principle Findings. Multivariate regression results indicate that living in a parity state significantly reduced the financial burden on families of children with mental health care needs. Specifically, the likelihood of a child's annual out‐of‐pocket (OOP) health care spending exceeding $1,000 was significantly lower among families of children needing mental health care living in parity states compared with those in nonparity states. Families with children needing mental health care in parity states were also more likely to view OOP spending as reasonable compared with those in nonparity states. Likewise, living in a parity state significantly lowered the likelihood of a family reporting that a child's health needs caused financial problems. The likelihood of reports that additional income was needed to finance a child's care was also lower among families with mentally ill children living in parity states. However, we detect no significant difference among residents of parity and nonparity states in receipt of needed mental health care.

Conclusion. These results indicate that state parity laws are providing important economic benefits to families of mentally ill children undetected in prior research.
Nurse Working Conditions, Organizational Climate, and Intent to Leave in ICUs: An Instrumental Variable Approach
Authors: Stone Patricia W. , Mooney‐Kane Cathy , Larson Elaine L. , Pastor Diane K. , Zwanziger Jack , Dick Andrew W.
Published: October 2006

Objective. To investigate causes of nurse intention to leave (ITL) while simultaneously considering organizational climate (OC) in intensive care units (ICUs) and identify policy implications.

Data Sources/Study Setting. Data were obtained from multiple sources including nurse surveys, hospital administrative data, public use, and Medicare files. Survey responses were analyzed from 837 nurses employed in 39 adult ICUs from 23 hospitals located in 20 separate metropolitan statistical areas.

Study Design. We used an instrumental variable technique to assess simultaneously the relationship between OC and ITL. We estimated ordinary least squares and reduced form regressions to determine the extent of simultaneity bias as well as the sensitivity of our results to the instrumental variable model specification.

Principal Findings. Fifteen percent of the nurses indicated their ITL in the coming year. Based on the structural model, we found that nurses' ITL contributed little if anything directly to OC, but that OC and the tightness of the labor market had significant roles in determining ITL (p values <.05). Furthermore, OC was affected by the average regionally adjusted ICU wages, hospital profitability, teaching, and Magnet status (p values <.05).

Conclusions. OC is an important determinant of ITL among ICU nurses. Because higher wages do not reduce ITL, increased pay alone without attention to OC is likely insufficient to reduce nurse turnover. Implementing interventions aimed at creating a positive OC, as found in Magnet hospitals, may be a more effective strategy.
Beyond Our Walls: Impact of Patient and Provider Coordination across the Continuum on Outcomes for Surgical Patients
Authors: Weinberg Dana Beth , Gittell Jody Hoffer , Lusenhop R. William , Kautz Cori M. , Wright John
Published: October 2006

Objectives.To investigate patients' experience with coordination of their postsurgical care across multiple settings and the effects on key outcomes.

Data Sources.Primary data collected over 18 months from 222 unilateral knee‐replacement patients at Brigham and Women's Hospital in Boston, MA.

Study Design.Patients were surveyed about the coordination of their postdischarge care during the 6‐week period postdischarge when they received care from rehabilitation facilities and/or home care agencies and follow‐up care from the surgeon.

Data Collection.Patients were surveyed before surgery and at 6 and 12 weeks postsurgery.

Principal Findings.Patient reports highlight problems with coordination across settings and between providers and themselves. These problems, measured at 6 weeks, were associated with greater joint pain, lower functioning, and lower patient satisfaction at 6 weeks after surgery. At 12 weeks after surgery, coordination problems were associated with greater joint pain, but were not associated with functional status.

Conclusion.Coordination across settings affects patients' clinical outcomes and satisfaction with their care. Although accountable for transfer to the next care setting, providers are neither accountable for nor supported to coordinate across the continuum. Addressing this system problem requires both introducing coordinating mechanisms and also supporting their use through changes in providers' incentives, resources, and time.
Recurrence rate of presumed thoracolumbar intervertebral disc disease in ambulatory dogs with spinal hyperpathia treated with anti‐inflammatory drugs: 78 cases (1997–2000)
Authors: Mann F. A. , Wagner‐Mann Colette C. , Dunphy Elizabeth D. , Ruben Dawn S. , Rochat Mark C. , Bartels Kenneth E.
Published: October 2006

Objective:To determine the recurrence rate of clinical signs in dogs with spinal hyperpathia and mild neurological deficits due to presumed Hansen Type 1 thoracolumbar intervertebral disc disease (IVDD) that were managed medically with anti‐inflammatory agents, and to compare the recurrence rates between dogs treated with corticosteroids and those treated with nonsteroidal anti‐inflammatory drugs (NSAIDs).

Design:Retrospective study.

Setting:Private veterinary emergency clinic in a large metropolitan area.

Animals, interventions, and measurements:Medical records were used to ascertain study eligibility, record patient signalment and condition severity, and document medical treatment regimen. Each dog was assigned a severity score: (1) spinal hyperpathia with no neurological deficits, (2) spinal hyperpathia with conscious proprioceptive deficits only, or (3) spinal hyperpathia with ataxia but still retaining ambulatory motor function. Owners of 78 dogs weighing less than 16 kg presented from 1997 through 2000 were sent a questionnaire to determine recurrence rate.

Main results:All dogs recovered from the initial episode; 39 experienced recurrence and 39 did not. There was no statistically significant relationship between gender, age, or severity score and recurrence rate. Dogs treated with NSAIDs or methylprednisolone sodium succinate (MPSS) were less likely to experience recurrence than dogs treated with corticosteroids other than MPSS.

Conclusion:A 50% recurrence of presumed IVDD occurred in this population of dogs after treatment with NSAIDs or corticosteroids. Those treated with NSAIDs or MPSS were less likely to experience a recurrence.
Enhanced Bone Regeneration by Electrical Polarization of Hydroxyapatite
Authors: Itoh Soichiro , Nakamura Satoshi , Nakamura Miho , Shinomiya Kenichi , Yamashita Kimihiro
Published: October 2006

Abstract:  We examined osteogenic cell responses and new bone formation on electrically polarized hydroxyapatite (HAp) plates implanted into calvarial bone defects in rats. In the first group of rats, test pieces were placed with their positively charged surfaces face down on the dura mater. In a second group, test pieces were placed with their negatively charged surfaces facedown on the dura mater. A third group received noncharged test pieces. Histological examination was carried out to characterize the newly formed bone as well as quantification. Enzyme histochemistry involving the detection of alkaline phosphatase and tartrate‐resistant acid phosphatase was performed to quantify osteogenic cell activity. Bone growth was enhanced in the groups that received polarized HAp plates, both at the negatively and positively charged surfaces. In addition to the electrostatic force that attracts Ca2+ to the negatively charged surfaces, the suppressive effects on osteoclasts proliferation on the positively charged surfaces may enhance bone formation.
Negotiated Nonmonogamy and Male Couples
Authors: SHERNOFF MICHAEL
Published: October 2006

One issue that has the potential to confound family or couples therapists working with male couples is the issue of nonmonogamy. For many therapists, sexual nonexclusivity challenges fundamental clinical assumptions that “affairs,” or extra‐relationship sex or romantic involvements, are symptoms of troubled relationships and are always a form of “sexual acting out.” This article explores the issue of sexual exclusivity and nonexclusivity within male couples. In order to achieve both clinical and cultural competency in work with male couples, therapists need to challenge their cultural biases regarding monogamy.
II. Genotype‐Environment Interaction in the Schizophrenia Spectrum: Qualitative Observations
Authors: WYNNE LYMAN C. , TIENARI PEKKA , SORRI ANNELI , LAHTI ILPO , MORING JUHA , WAHLBERG KARL‐ERIK
Published: October 2006

Previous reports from the Finnish Adoptive Family Study of Schizophrenia have documented significant interplay between genetics (G) and family rearing (E), leading to adoptee outcomes of schizophrenia spectrum disorders. Quantitative evidence for this interplay is significantly enhanced when both high genetic liability and severe environmental dysfunction are present. However, when either genetic liability is low or the rearing environment is healthy, the adoptees appear to be resiliently protected against a pathologic outcome. Nevertheless, exceptions to this pattern do occur. Six qualitative vignettes, together with quantitative measures and categorical diagnoses from the same families, illustrate how multiple methods partially confirm one another and also suggest where further exploration of gene‐environment interaction is needed.
Processes Linked to Contact Changes in Adoptive Kinship Networks
Authors: DUNBAR NORA , VAN DULMEN MANFRED H. M. , AYERS‐LOPEZ SUSAN , BERGE JERICA M. , CHRISTIAN CINDA , GOSSMAN GINGER , HENNEY SUSAN M. , MENDENHALL TAI J. , GROTEVANT HAROLD D. , McROY RUTH G.
Published: October 2006

The purpose of this study was to reveal underlying processes in adoptive kinship networks that experienced increases or decreases in levels of openness during the child's adolescent years. Intensive case study analyses were conducted for 8 adoptive kinship networks (each including an adoptive mother, adoptive father, adopted adolescent, and birth mother), half of whom had experienced an increase in openness from indirect (mediated) to direct (fully disclosed) contact and half of whom had ceased indirect contact between Waves 1 and 2 of a longitudinal study. Adoptive mothers tended to be more involved in contact with the birth mother than were adoptive fathers or adopted adolescents. Members of adoptive kinship networks in which a decrease in level of contact took place had incongruent perspectives about who initiated the stop in contact and why the stop took place. Birth mothers were less satisfied with their degree of contact than were adoptive parents. Adults' satisfaction with contact was related to feelings of control over type and amount of interactions and permeability of family boundaries. In all adoptive kinship networks, responsibility for contact had shifted toward the adopted adolescent regardless of whether the adolescent was aware of this change in responsibility.
Can Spouses Provide Knowledge of Each Other's Communication Patterns? A Study of Self‐Reports, Spouses' Reports, and Observational Coding
Authors: KLINE RHOADES GALENA , STOCKER CLARE M.
Published: October 2006

The purposes of this study were (1) to assess individuals' self‐reports of communication and their reports about their spouses' communication in order to examine the congruence of spousal views and (2) to investigate whether each report provided unique information about observed marital interactions. These associations were evaluated in a sample of 119 longtime married couples. The Verbal Aggression and Cooperation subscales from the Conflicts and Problem‐Solving Scales were used as measures of negative and positive aspects of communication. The findings indicated that self‐reports of both verbal aggression and cooperation were strongly associated with the same individual's report of his or her spouse's verbal aggression and cooperation. Conversely, self‐reports were only moderately associated with reports made by spouses (e.g., the husband's report of his wife's communication). Hence, within‐reporter agreement was higher than between‐reporter agreement about marital communication. When entered into regression models, reports made by spouses, but not self‐reports, explained unique variance in observations of marital hostility and affection. There was one exception: Wife self‐report of verbal aggression explained unique variance in coders' ratings of wife hostility, controlling for husband report of wife verbal aggression. Findings indicate the importance of assessing partners' views of one another's communication for the most accurate portrayal of marital interactions. Implications for research and clinical work are discussed.
Abnormalities of the HPA axis in affective disorders: clinical subtypes and potential treatments
Authors: Porter Richard J. , Gallagher Peter
Published: October 2006

Background:

New evidence is emerging regarding abnormalities of hypothalamic-pituitary-adrenal (HPA) axis function in subtypes of affective disorders. Adverse effects of HPA axis dysregulation may include dysfunction of monoaminergic transmitter systems, cognitive impairment and peripheral effects. Newer treatments specifically targeting the HPA axis are being developed.

Objective:

To review these developments focusing particularly on the glucocorticoid receptor (GR) antagonist mifepristone.

Method:

A selective review of the literature.

Results:

The function of GRs is increasingly being defined. The role of corticotrophin-releasing hormone (CRH) and dehydroepiandrosterone (DHEA) in the brain is also increasingly understood. HPA axis function is particularly likely to be abnormal in psychotic depression and bipolar disorder, and it is in these conditions that trials of the GR antagonist mifepristone are being focused. CRH antagonists and DHEA are also being investigated as potential treatments.

Conclusion:

Initial studies of mifepristone and other HPA-axis-targeting agents in psychotic depression and bipolar disorder are encouraging and confirmatory studies are awaited.