bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying the impact of diabetes research
Authors: Hanney S. R. , Home P. D. , Frame I. , Grant J. , Green P. , Buxton M. J. 
Published: September 2005

AbstractAims  Assessment of the impact of health research is a growing but problematic field. We examined how a combination of approaches might together inform assessment of the impact of a body of diabetes research published in 1981 and help identify factors behind success.Methods  Three broad approaches were applied to the work of one team leader of acknowledged influence. Standard bibliographic analysis was complemented by a second approach which categorized the importance of the primary publications to the papers citing them, in four domains. In parallel, a third approach involved qualitative assessment using surveys, critical pathway analysis by, and interviews of, co‐authors and external experts. Extending the approach incorporated key additional publications from other years.Results  In 1981, the team leader published 29 papers. Citations to these 29 first generation papers varied from 1 to 76 and resulted in 799 second generation papers. Citations to these produced 12 891 third generation papers. Analysis of second generation papers suggested the cited first generation paper was thought to be of considerable or essential significance in only 9% of cases. While much research made little impact, qualitative analysis included a wealth of information, sometimes missed by standard bibliographic techniques, on where the identified research influenced important streams of clinical development. Analysis covered major research studies (such as the Diabetes Control and Complications Trial), insulin pump therapy, and career development of co‐authors.Conclusions  Understanding the impact of research requires multiple approaches. With refinement, these techniques could be employed more widely and potentially could inform research policy.
Long‐term treatment experience in a subject with Dunnigan‐type familial partial lipodystrophy: efficacy of rosiglitazone
Authors: Lüdtke A. , Heck K. , Genschel J. , Mehnert H. , Spuler S. , Worman H. J. , Schmidt H. H.‐J. 
Published: September 2005

AbstractDunnigan‐type familial partial lipodystrophy (FPLD) is caused by mutations in LMNA, the gene that encodes nuclear lamins A and C. FPLD is characterized by peripheral fat loss, excess central adiposity, insulin resistance, and hyperlipidaemia, which are difficult to treat. We present our 2 years’ experience of treatment with rosiglitazone in a subject with FPLD. Insulin requirement decreased significantly from 240 IU/day to 76 IU/day (range 20–240 IU/day) and serum triglyceride concentration was lowered from 13.7 ± 14.4 mmol/l to 4.5 ± 4.3 mmol/l and remained stable. Mean HbA1c prior to rosiglitazone therapy was 9.4 ± 1.32% and decreased to 7.4 ± 0.6% during therapy with rosiglitazone. This case demonstrates the benefits of PPARγ‐agonists on glycaemic control and dyslipidaemia in a patient with FPLD. This in turn implies that PPARγ may play a pathophysiological role in FPLD.
Prevalence and risk factors for asymptomatic bacteriuria in women with Type 2 diabetes mellitus
Authors: Ishay A. , Lavi I. , Luboshitzky R. 
Published: September 2005

AbstractAims  Asymptomatic bacteriuria (ASB) has been considered as a complication in diabetic women. The reported data on the prevalence and various risk factors for ASB appear to be conflicting. Consequently, we investigated the prevalence and major risk factors of ASB in women with Type 2 diabetes mellitus.Methods  A total of 411 non‐pregnant women (aged 59.6 ± 10.8 years) with Type 2 diabetes, and 160 women without diabetes (aged 53.3 ± 15.1 years) assigned as controls, attending an outpatient endocrine clinic in a university‐affiliated teaching hospital, were included. All participating women were interviewed and screened for the presence of ASB. In all participants, fasting blood glucose, HbA1c and renal function were measured. Complications of diabetes were also assessed.Results  Of the 411 diabetic women, 25 (6.1%) had ASB, compared with four of 160 (2.5%) in control women (P = 0.07). Independent risk factors for the presence of ASB were albuminuria > 150 mg/24 h [odds ratio (OR) 4.96 (95% CI 1.64–15.0, P = 0.005)] and serum creatinine [OR 3.5 (95% CI 1.4–8.8, P = 0.008)]. No significant association was evident with age, BMI, duration of disease, glycaemic control assessed by HbA1c or chronic complications of diabetes, namely macrovascular disease, neuropathy and retinopathy.Conclusions  Women with Type 2 diabetes are not at higher risk of developing ASB than non‐diabetic women. Independent and significant risk factors for ASB are macroalbuminuria and serum creatinine. The low prevalence of ASB found in this study may be as a result of the ethnic origin of these women and the circumcised state of their partners.
Regression Models with Data‐based Indicator Variables*
Authors: Hendry David F. , Santos Carlos 
Published: September 2005

AbstractOrdinary least squares estimation of an impulse‐indicator coefficient is inconsistent, but its variance can be consistently estimated. Although the ratio of the inconsistent estimator to its standard error has a t‐distribution, that test is inconsistent: one solution is to form an index of indicators. We provide Monte Carlo evidence that including a plethora of indicators need not distort model selection, permitting the use of many dummies in a general‐to‐specific framework. Although White's (1980) heteroskedasticity test is incorrectly sized in that context, we suggest an easy alteration. Finally, a possible modification to impulse ‘intercept corrections’ is considered.
Leaning into the Wind: A Structural VAR Investigation of UK Monetary Policy*
Authors: Mountford Andrew 
Published: September 2005

AbstractThis paper adapts Uhlig's [Journal of Monetary Economics (2005) forthcoming] sign restriction identification methodology to investigate the effects of UK monetary policy using a structural vector autoregression (VAR). It shows that shocks which can reasonably be described as monetary policy shocks have played only a small role in the total variation of UK monetary and macroeconomic variables. Most of the variation in UK monetary variables has been due to their systematic reaction to other macroeconomic shocks, namely non‐monetary aggregate demand, aggregate supply, and oil price shocks. We also find, without imposing any long run identifying restrictions, that aggregate supply shocks have permanent effects on output.
Technology, Labour Characteristics and Wage‐productivity Gaps*
Authors: Ilmakunnas Pekka , Maliranta Mika 
Published: September 2005

AbstractWe use plant‐level employer–employee data in production functions and wage equations to examine whether wages are based on productivity. We use a stepwise procedure to find out how the results are influenced by the kind of data that is available. The models include shares of employee groups based on age, level and field of education, and sex. The gap between the age‐related wage and productivity effects increases with age. Education increases productivity, but wage under‐compensates productivity especially for those with the highest level of non‐technical education. For women the results depend greatly on the specification and method used.
Testing the Exogeneity of Argentine Devaluation and Default Risks in Retrospect*
Authors: Ahumada Hildegart A. , Garegnani Maria Lorena 
Published: September 2005

AbstractThis paper studies the relationship between devaluation and default risks during Argentina's convertibility regime. Before default and devaluation occurred, a harder variant of the currency regime was under discussion. An often‐suggested argument among the supporters of dollarization was that the probability of default could have been reduced by removing fears of devaluation. For this to be true, default risk must be dependent on the devaluation risk. Long‐run relationships and ‘exogeneity’ are examined using a ‘cointegrating vector’ system approach. The results show that only devaluation risk can be modelled on default risk. No empirical evidence is found in favour of dollarization. Moreover, these conclusions are maintained when the information set is expanded to include the Latin American risk and Argentine macroeconomic variables.
Practical Problems with Reduced‐rank ML Estimators for Cointegration Parameters and a Simple Alternative*
Authors: Brüggemann Ralf , Lütkepohl Helmut 
Published: September 2005

AbstractJohansen's reduced‐rank maximum likelihood (ML) estimator for cointegration parameters in vector error correction models is known to produce occasional extreme outliers. Using a small monetary system and German data we illustrate the practical importance of this problem. We also consider an alternative generalized least squares (GLS) system estimator which has better properties in this respect. The two estimators are compared in a small simulation study. It is found that the GLS estimator can indeed be an attractive alternative to ML estimation of cointegration parameters.
Regulation of expression of the novel IL‐1 receptor family members in the mouse brain
Authors: Andre Ralph , Lerouet Dominique , Kimber Ian , Pinteaux Emmanuel , Rothwell Nancy J. 
Published: September 2005

AbstractMembers of the interleukin‐1 (IL‐1) family of cytokines are key mediators in the regulation of host defence responses and the development of inflammation in response to acute and chronic injury to the brain. Two major agonists, IL‐1α and IL‐1β, bind to a membrane receptor complex composed of the type‐1 IL‐1 receptor (IL‐1RI) and the accessory protein (IL‐1RAcP). The discovery of new orphan members of the IL‐1 receptor superfamily (including ST2/T1, IL‐1Rrp2, TIGIRR1 and ‐2, SIGGIR, IL‐18Rα and IL‐18Rβ) has increased speculation that alternative IL‐1 ligands signalling pathways exist in the brain. We demonstrate here that all the IL‐1R‐like orphan receptors are expressed by many brain cell types including astrocytes, microglia, oligodendrocytic progenitor cells and neurons. IL‐18Rβ expression was significantly increased in response to treatment of mixed glia with bacterial lipopolysaccharide (LPS) in vitro, whereas expression of IL‐1Rrp2 and TIGIRR1 was reduced. Furthermore, IL‐18Rβ, IL‐1Rrp2, but not TIGIRR1 expression, was increased in the brain in vivo in response to peripheral administration of LPS or middle cerebral artery occlusion (MCA). These results suggest possible roles for newly identified members of the IL‐1 receptor family in CNS diseases.
Astrocytes as antigen‐presenting cells: expression of IL‐12/IL‐23
Authors: Constantinescu Cris S. , Tani Marie , Ransohoff Richard M. , Wysocka Maria , Hilliard Brendan , Fujioka Toshiki , Murphy Sean , Tighe Patrick J. , Sarma Jayasri Das , Trinchieri Giorgio , Rostami Abdolmohamad 
Published: September 2005

AbstractInterleukin‐12 (IL‐12, p70) a heterodimeric cytokine of p40 and p35 subunits, important for Th1‐type immune responses, has been attributed a prominent role in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Recently, the related heterodimeric cytokine, IL‐23, composed of the same p40 subunit as IL‐12 and a unique p19 subunit, was shown to be involved in Th1 responses and EAE. We investigated whether astrocytes and microglia, CNS cells with antigen‐presenting cell (APC) function can present antigen to myelin basic protein (MBP)‐reactive T cells, and whether this presentation is blocked with antibodies against IL‐12/IL‐23p40. Interferon (IFN)‐γ‐treated APC induced proliferation of MBP‐reactive T cells. Anti‐IL‐12/IL‐23p40 antibodies blocked this proliferation. These results support and extend our previous observation that astrocytes and microglia produce IL‐12/IL‐23p40. Moreover, we show that stimulated astrocytes and microglia produce biologically active IL‐12p70. Because IL‐12 and IL‐23 share p40, we wanted to determine whether astrocytes also express IL‐12p35 and IL‐23p19, as microglia were already shown to express them. Astrocytes expressed IL‐12p35 mRNA constitutively, and IL‐23 p19 after stimulation. Thus, astrocytes, under inflammatory conditions, express all subunits of IL‐12/IL‐23. Their ability to present antigen to encephalitogenic T cells can be blocked by neutralizing anti‐IL‐12/IL‐23p40 antibodies.
Identification, expression and functional characterization of the GRAL gene
Authors: Li Zhihua , Wang Bingwei , Wu Xuefei , Cheng Shi‐Yuan , Paraoan Luminita , Zhou Jiawei 
Published: September 2005

AbstractThe glial cell line‐derived neurotrophic factor (GDNF) family is a group of neurotrophic factors with diverse biological functions. Members of the GDNF family exert their functions by interacting with a specific GDNF family receptor α (GFRα) and activation of the cRET. Here we report the identification and characterization of GDNF receptor‐alpha‐like (GRAL) gene. Sequence analysis indicated that GRAL is a distant homolog of the GFRα family, with 30% of its amino acid sequence identical to that of GFRα‐3. There are two splice variants of GRAL: the full‐length form (GRAL‐A) represented by a 2080 bp mRNA and a short form (GRAL‐B) represented by a 1833 bp mRNA. In adult mouse, GRAL transcripts have been found primarily in the CNS. In the developing mouse brain, the mRNA level of GRAL in the cerebrocortex and hippocampus reached a maximum at birth and declined afterwards. GRAL‐A protein was localized predominantly in the plasma membrane. Overexpression of GRAL‐A protected PC12 cells and cultured hippocampal neurons from serum starvation‐induced cell apoptosis. The neuroprotective effect of GRAL was associated with marked inhibition of the Jun‐N‐terminal kinase signaling pathway. Our results suggest that GRAL belongs to a superfamily of GFRα and might take part in neuroprotection and brain development.
Induction of mitochondrial oxidative stress in astrocytes by nitric oxide precedes disruption of energy metabolism
Authors: Jacobson Jake , Duchen Michael R. , Hothersall John , Clark John B. , Heales Simon J. R. 
Published: September 2005

AbstractInhibition of the mitochondrial electron transport chain (ETC) ultimately limits ATP production and depletes cellular ATP. However, the individual complexes of the ETC in brain mitochondria need to be inhibited by ∼ 50% before causing significant depression of ATP synthesis. Moreover, the ETC is the key site for the production of intracellular reactive oxygen species (ROS) and inhibition of one or more of the complexes of the ETC may increase the rate of mitochondrial ROS generation. We asked whether partial inhibition of the ETC, to a degree insufficient to perturb oxidative phosphorylation, might nonetheless induce ROS production. Chronic increase in mitochondrial ROS might then cause oxidative damage to the ETC sufficient to produce prolonged changes in ETC function and so compound the defect. We show that the exposure of astrocytes in culture to low concentrations of nitric oxide (NO) induces an increased rate of O2·− generation that outlasts the presence of NO. No effect was seen on oxygen consumption, lactate or ATP content over the 4–6 h that the cells were exposed to NO. These data suggest that partial ETC inhibition by NO may initially cause oxidative stress rather than ATP depletion, and this may subsequently induce irreversible changes in ETC function providing the basis for a cycle of damage.
Leptin induces a novel form of NMDA receptor‐dependent long‐term depression
Authors: Durakoglugil Murat , Irving Andrew J. , Harvey Jenni 
Published: September 2005

AbstractIt is becoming apparent that the hormone leptin plays an important role in modulating hippocampal function. Indeed, leptin enhances NMDA receptor activation and promotes hippocampal long‐term potentiation (LTP). Furthermore, obese rodents with dysfunctional leptin receptors display impairments in hippocampal synaptic plasticity. Here we demonstrate that under conditions of enhanced excitability (evoked in Mg2+‐free medium or following blockade of GABAA receptors), leptin induces a novel form of long‐term depression (LTD) in area CA1 of the hippocampus. Leptin‐induced LTD was markedly attenuated in the presence of D‐(‐)‐2‐Amino‐5‐Phosphonopentanoic acid (D‐AP5), suggesting that it is dependent on the synaptic activation of NMDA receptors. In addition, low‐frequency stimulus‐evoked LTD occluded the effects of leptin. In contrast, metabotropic glutamate receptors (mGluRs) did not contribute to leptin‐induced LTD as mGluR antagonists failed to either prevent or reverse this process. The signalling mechanisms underlying leptin‐induced LTD were independent of the Ras‐Raf‐mitogen‐activated protein kinase signalling pathway, but were markedly enhanced following inhibition of either phosphoinositide 3‐kinase or protein phosphatases 1 and 2A. These data indicate that under conditions of enhanced excitability, leptin induces a novel form of homosynaptic LTD, which further underscores the proposed key role for this hormone in modulating NMDA receptor‐dependent hippocampal synaptic plasticity.
Increased nuclear factor‐erythroid 2 p45‐related factor 2 activity protects SH‐SY5Y cells against oxidative damage
Authors: Cao Tracy T. , Ma Lei , Kandpal Geeta , Warren Lee , Hess J. Fred , Seabrook Guy R. 
Published: September 2005

AbstractThe ability of cells to control the balance between the generation and quenching of reactive oxygen species is important in combating potentially damaging effects of oxidative stress. One mechanism that cells use to maintain redox homeostasis is the antioxidant response pathway. Antioxidant response elements (AREs) are cis‐acting elements located in regulatory regions of antioxidant and phase II detoxification genes. Nuclear factor‐erythroid 2 p45‐related factor 2 (Nrf2) is a member of the Cap ‘n’ Collar family of transcription factors that binds to the ARE and regulates the transcription of specific ARE‐containing genes such as NAD(P)H:quinone oxidoreductase 1, glutamylcysteine synthetase and heme oxygenase. Activation of Nrf2 results in release from its negative repressor, Kelch‐like ECH‐associated protein 1 (Keap1), and allows Nrf2 to translocate into the nucleus to induce gene expression. In this study, we demonstrate that increasing Nrf2 activity by various methods, including chemical induction, Nrf2 overexpression or Keap1 siRNA knockdown, protects cells against specific types of oxidative damage. Cells were protected against 6‐hydroxydopamine‐ and 3‐morpholinosydnonimine‐mediated toxicity but not against 1‐methyl‐1‐4‐phenylpyridinium toxicity. As oxidative stress is a hallmark of several neurodegenerative disorders, including Parkinson's disease, pharmacological agents that selectively target the Keap1‐Nrf2 pathway may provide a novel neuroprotective strategy for the treatment of these diseases.
Spatio‐temporal activation of cyclic AMP response element‐binding protein, activity‐regulated cytoskeletal‐associated protein and brain‐derived nerve growth factor: a mechanism for pontine‐wave generator activation‐dependent two‐way active‐avoidance memory processing in the rat
Authors: Ulloor Jagadish , Datta Subimal 
Published: September 2005

AbstractThe present study explored possible physiological and molecular mechanisms of pontine‐wave (P‐wave) generator activation‐dependent memory processing in the rat using a two‐way active‐avoidance learning paradigm. The results show that learning training increased rapid eye movement sleep and activated brainstem cells in the P‐wave generator. During this period, there was a time‐dependent increase in phosphorylation of cAMP response element‐binding protein (CREB) in the dorsal hippocampus and amygdala and increased synthesis of activity‐regulated cytoskeletal‐associated protein (Arc) in the dorsal hippocampus, amygdala, frontal cortex and occipital cortex. Learning training also increased synthesis of brain‐derived nerve growth factor (BDNF) in the occipital cortex, amygdala and dorsal hippocampus at different time intervals. During this time, the levels of nerve growth factor did not change. The results also show that the increase in rapid eye movement sleep P‐wave density during the post‐training 3‐h recording session is positively correlated with the increased levels of phosphorylated CREB, BDNF and Arc in the dorsal hippocampus. These results suggest that memory processing of two‐way active‐avoidance learning may involve excitation of P‐wave‐generating cells in the brainstem and increased expression of phosphorylated CREB, Arc and BDNF in a time‐dependent manner in the forebrain. These dynamic changes in cellular and molecular features provide considerable insight into the mechanisms of the P‐wave generator activation‐dependent memory consolidation process.
Methamphetamine‐induced inhibition of mitochondrial complex II: roles of glutamate and peroxynitrite
Authors: Brown Jeffrey M. , Quinton Maria S. , Yamamoto Bryan K. 
Published: September 2005

AbstractHigh‐dose methamphetamine (METH) is associated with long‐term deficits in dopaminergic systems. Although the mechanism(s) which contributes to these deficits is not known, glutamate and peroxynitrite are likely to play a role. These factors are hypothesized to inhibit mitochondrial function, increasing the free radical burden and decreasing neuronal energy supplies. Previous studies suggest a role for the mitochondrial electron transport chain (ETC) in mediating toxicity of METH. The purpose of the present studies was to determine whether METH administration selectively inhibits complex II of the ETC in rats. High‐dose METH administration (10 mg/kg every 2 h × 4) rapidly (within 1 h) decreased complex II (succinate dehydrogenase) activity by ∼20–30%. In addition, decreased activity of complex II–III, but not complex I–III, of the mitochondrial ETC was also observed 24 h after METH. This inhibition was not due to direct inhibition by METH or METH‐induced hyperthermia and was specific to striatal brain regions. METH‐induced decreases in complex II–III were prevented by MK‐801 and the peroxynitrite scavenger 5,10,15,20‐tetrakis (2,4,6‐trimethyl‐3,5‐sulphonatophenyl) porphinato iron III. These findings provide the first evidence that METH administration, via glutamate receptor activation and peroxynitrite formation, selectively alters a specific site of the ETC.
Modulation of the cannabinoid CB2 receptor in microglial cells in response to inflammatory stimuli
Authors: Maresz Katarzyna , Carrier Erica J. , Ponomarev Eugene D. , Hillard Cecilia J. , Dittel Bonnie N. 
Published: September 2005

AbstractThe cannabinoid system is known to be important in neuronal regulation, but is also capable of modulating immune function. Although the CNS resident microglial cells have been shown to express the CB2 subtype of cannabinoid receptor during non‐immune‐mediated pathological conditions, little is known about the expression of the cannabinoid system during immune‐mediated CNS pathology. To examine this question, we measured CB2 receptor mRNA expression in the CNS of mice with experimental autoimmune encephalomyelitis (EAE) and, by real‐time PCR, found a 100‐fold increase in CB2 receptor mRNA expression during EAE onset. We next determined whether microglial cells specifically express the CB2 receptor during EAE, and found that activated microglial cells expressed 10‐fold more CB2 receptor than microglia in the resting state. To determine the signals required for the up‐regulation of the CB2 receptor, we cultured microglial cells with combinations of γ‐interferon (IFN‐γ) and granulocyte) macrophage‐colony stimulating factor (GM‐CSF), which both promote microglial cell activation and are expressed in the CNS during EAE, and found that they synergized, resulting in an eight to 10‐fold increase in the CB2 receptor. We found no difference in the amount of the CB2 receptor ligand, 2‐arachidonylglycerol (2‐AG), in the spinal cord during EAE. These data demonstrate that microglial cell activation is accompanied by CB2 receptor up‐regulation, suggesting that this receptor plays an important role in microglial cell function in the CNS during autoimmune‐induced inflammation.