bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Chronic Stress and Mifepristone Treatment on Voltage‐Dependent Ca2+ Currents in Rat Hippocampal Dentate Gyrus
Authors: Van Gemert N. G. , Joëls M.
Published: August 2006

Chronic unpredictable stress affects many properties in rat brain. In the dentate gyrus, among other things, increased mRNA expression of the Ca2+ channel α1C subunit has been found after 21 days of unpredictable stress in combination with acute corticosterone application (100 nM). In the present study, we examined: (i) whether these changes in expression are accompanied by altered Ca2+ currents in rat dentate granule cells recorded on day 22 and (ii) whether treatment with the glucocorticoid receptor antagonist mifepristone during the last 4 days of the stress protocol normalises the putative stress‐induced effects. Three weeks of unpredictable stress did not affect Ca2+ current amplitude in dentate granule cells under basal conditions (i.e. after incubation with vehicle solution). However, the sustained Ca2+ current component (which largely depends on the α1C subunit) was significantly increased in amplitude after chronic stress when slices had been treated with corticosterone 1–4 h before recording. These findings suggest that dentate granule cells are exposed to an increased calcium load after exposure to an acute stressor when they have a history of chronic stress, potentially leading to increased vulnerability of the cells. The present results are in line with the molecular data on Ca2+ channel α1C subunit expression. A significant three‐way interaction between chronic stress, corticosterone application and mifepristone treatment was found, indicating that the combined effect of stress and corticosterone depends on mifepristone cotreatment. Interestingly, current density (defined as total current divided by capacitance) did not differ between the groups. This indicates that the observed changes in Ca2+ current amplitude could be attributable to changes in cell size.
Exaggerated Response of Arginine Vasopressin‐Enhanced Green Fluorescent Protein Fusion Gene to Salt Loading without Disturbance of Body Fluid Homeostasis in Rats
Authors: Fujio T. , Fujihara H. , Shibata M. , Yamada S. , Onaka T. , Tanaka K. , Morita H. , Dayanithi G. , Kawata M. , Murphy D. , Ueta Y.
Published: August 2006

We examined the effects of chronic salt loading on the hypothalamic expressions of the enhanced green fluorescent protein (eGFP), arginine vasopressin (AVP) and oxytocin (OXT) genes in AVP‐eGFP transgenic rats that expressed eGFP in the hypothalamic AVP‐containing neurones. In these rats, salt loading for 5 days caused a marked increase of the eGFP fluorescence in the magnocellular divisions of the paraventricular nucleus (PVN), the supraoptic nucleus (SON) and the internal layer of the median eminence. Expression of the eGFP gene was increased seven‐ to eight‐fold in the PVN and SON of salt‐loaded rats in comparison with euhydrated rats. By contrast, none of these changes were observed in the suprachiasmatic nucleus. The expression of the AVP and OXT genes was increased 1.5‐ to two‐fold in the PVN and SON of salt‐loaded nontransgenic (control) and transgenic rats. There were no differences in the expression levels of the AVP and OXT genes in the PVN and SON between nontransgenic (control) and transgenic animals under normal conditions and after salt loading. In the posterior pituitary gland, the intensity of the eGFP fluorescence did not change after salt loading for 5 days, but increased after 10 days of salt loading. Upon salt loading, significant increases in the plasma AVP concentrations, plasma osmolality and plasma Na+ were observed. Furthermore, there were no significant differences in changes of water intake, food intake, urine volume, urine osmolality, urine Na+ concentrations, and the body weights in both models under normal or salt‐loaded conditions. Our results show that the response of the AVP‐eGFP fusion gene to chronic salt loading is exaggerated, and humoral responses such as AVP and OXT and the body fluid homeostasis are maintained in AVP‐eGFP transgenic rats. The AVP‐eGFP transgenic rat gives us a new opportunity to study the dynamics of the AVP system in vivo.
Plasmacytoid Dendritic Cells Induce a Distinct Cytokine Pattern in Virus‐Specific CD4+ Memory T Cells that is Modulated by CpG Oligodeoxynucleotides
Authors: Farkas L. , Kvale E. O. , Lund‐Johansen F. , Jahnsen F. L.
Published: August 2006

Inherent properties of dendritic cell (DC) subsets are important in the regulation of naïve T‐cell differentiation (e.g. Th1 versus Th2 cells), whereas effector memory T cells are believed to produce a fixed cytokine repertoire independent of the type of antigen presenting cell. Here we show that two distinct human DC subsets, plasmacytoid DC (PDC) and myeloid CD11c+ DC, induced autologous mumps virus‐specific memory CD4+ T cells to produce markedly different cytokine patterns upon antigen stimulation. PDC stimulated the T cells to produce γ‐interferon (IFN‐γ) and interleukin‐(IL)‐10, whereas CD11c+ DC induced lower levels of IFN‐γ, virtually no IL‐10, but significant levels of IL‐5. Analysis of intracellular cytokine production showed simultaneous production of IL‐10 and IFN‐γ in mumps‐specific T cells activated by PDC, a cytokine pattern similar to that described for Th1‐like regulatory cells. Introduction of CpG oligodeoxynucleotides in PDC/T‐cell co‐cultures had synergistic effect on virus‐dependent IFN‐γ production, whereas the other cytokines remained unchanged. Together, our results show that the type of DC involved in reactivation of previously primed T cells may have significant impact on the resulting cytokine response and suggest that targeting of viral antigens and adjuvant to specific DC subsets should be considered in the design of therapeutic antiviral vaccines.
Immunomodulation of Japanese Encephalitis Vaccine Through CpG Oligodeoxynucleotides in Mice
Authors: Sidhapuriwala J. N. , Sivalingam S. P. , Lu J. , Moochhala S. M.
Published: August 2006

Synthetic oligodeoxynucleotides (ODN) containing unmethylated cytosine guanine (CpG) dinucleotides motifs act as immune adjuvant and provide means of modulation to immune responses when co‐delivered with antigens. They stimulate both innate and adaptive immune responses and induce T helper 1 (Th1) immune responses. We investigated the immunomodulation of Japanese encephalitis (JE) vaccine using CpG ODN as an adjuvant. Mice were immunized with one dose of JE vaccine 0.1 ml with different concentrations (10, 25 and 100 μg) of CpG ODN. The serum antibody level and cytokines were evaluated and compared with mice immunized with two doses of JE vaccine alone. Our studies revealed that anti‐JE antibody level in mice immunized with single dose of 0.1 ml JE vaccine and 100 μg CpG ODN were almost equal to mice immunized with two doses of JE vaccine alone. Furthermore, CpG ODN enhanced the production of TNF‐α and Th1‐mediated cytokines, including IFN‐γ and IL‐2 compared with JE vaccine alone. In addition, absence of any significant changes in biochemical, haematological and histological studies suggest that CpG ODN are safe adjuvants for JE vaccine. Therefore, it is inferred that CpG ODN are effective and improve the efficacy of JE vaccine.
Increased Soluble 4‐1BB Ligand (4‐1BBL) Levels in Peripheral Blood of Patients with Multiple Sclerosis
Authors: Liu G.‐z. , Gomes A. C. , Putheti P. , Karrenbauer V. , Kostulas K. , Press R. , Hillert J. , Hjelmström P. , Gao X.‐G.
Published: August 2006

4‐1BB ligand (4‐1BBL; CD137L) is a member of the tumour necrosis factor superfamily expressed primarily on antigen presenting cells such as B cells, macrophages and dendritic cells. Its engagement with the receptor 4‐1BB (CD137) has been shown to promote T‐cell activation and regulate proliferation and survival of T cells. The role of the costimulatory molecule in multiple sclerosis (MS) remains unclear. In this study, the expression of 4‐1BBL and soluble 4‐1BBL (s4‐1BBL) protein levels were analysed in peripheral blood of MS patients. Compared with healthy controls, MS patients had an increase in both plasma s4‐1BBL protein levels and expression of 4‐1BBL in CD14+ monocytes. In contrast, myelin basic protein‐reactive T‐cell proliferation was not found to be inhibited by the use of an anti‐4‐1BBL antibody. The elevated s4‐1BBL protein levels in the MS patients may function as a self‐regulatory mechanism of 4‐1BB/4‐1BBL interaction and costimulation.
Increase in Adhesion Molecules in Cerebrospinal Fluid of Children with Mumps and Mumps Meningitis
Authors: Sulik A. , Wojtkowska M. , Rozkiewicz D. , Oldak E.
Published: August 2006

Adhesion molecules play a key role in leucocyte migration into the central nervous system (CNS). Concentrations of endothelial‐derived soluble intercellular adhesion molecule‐1 (sICAM‐1) and leucocyte‐originated soluble L‐selectin (sL‐selectin) in cerebrospinal fluid (CSF) of children with mumps meningitis (mononuclear pleocytosis, n = 33) and mumps (absence of pleocytosis, n = 9) were compared with values from age‐matched control group (n = 19). In 14 patients from the meningitis group, adhesion molecule levels together with albumin concentration were estimated in paired CSF/serum samples to calculate concentration quotients and determine molecule intrathecal release. Both sICAM‐1 (median 3.44 versus 0.86 ng/ml; P < 0.0001) and sL‐selectin (median 29.91 versus 8.52 ng/ml; P < 0.0001) concentrations in CSF were increased in mumps meningitis patients compared with controls. Increased levels of the selected adhesion molecules were also observed in mumps patients without CNS involvement when compared with controls (median sICAM‐1: 1.14 versus 0.86 ng/ml, sL‐selectin: 13.54 versus 8.52 ng/ml; P < 0.01). Additionally, the concentration of adhesion molecules was found to correlate with CSF leucocyte count. Considerable correlation of sICAM‐1 and sL‐selectin quotients and corresponding albumin quotients suggests that a majority of the soluble adhesion molecules originated from the bloodstream. Analysis of adhesion molecule levels demonstrated indirect evidence of brain‐derived fractions. Our results suggest the involvement of adhesion molecules during the early phase of mumps meningitis.
Resistance Against Natural Killer Cell Cytotoxicity: Analysis of Mechanisms
Authors: Hasenkamp J. , Borgerding A. , Wulf G. , Uhrberg M. , Jung W. , Dingeldein S. , Truemper L. , Glass B.
Published: August 2006

Target cell resistance against natural killer (NK) cell‐mediated cytotoxicity obstructs NK cell‐based immunotherapy of leukaemia. Several mechanisms of resistance have been described. Because of lack of simple assays for analysing these mechanisms, their relative impact on a given effector–target pair is mostly unknown. We here analysed the combination of the Granzyme B (GrB) enzyme‐linked immunospot assay (ELISPOT) for the assessment of NK cell reactivity and cytotoxicity assays to estimate target cell escape mechanisms. Target cell recognition failure leads to negative GrB ELISPOT results, whereas target cell resistance shows positive GrB ELISPOT results in the absence of cytotoxicity. We confronted NK cells with the sensitive target cell line K562, and with the resistant cell lines ML2, SupB15 and Raji. ML2 cells sufficiently activated GrB‐release whilst being resistant against cytotoxic granules of NK cells. Partial resistance of Raji results from the interaction of HLA class I with inhibitory killer immunglobulin‐like receptors (KIR) on the NK cells. Failure of target recognition by HLA class I–KIR interaction, lacking ligands to stimulatory NK cell receptors and partial resistance to cytotoxic granules all contributed to resistance of SupB15. In conclusion, revealing the mechanisms of resistance against NK cell‐mediated cytotoxicity may allow improving the results of NK‐based immunotherapy.
Discrepancy in CD3‐Transmembrane Peptide Activity between In Vitro and In Vivo T‐Cell Inhibition
Authors: Collier S. , Bolte A. , Manolios N.
Published: August 2006

Electrostatic amino acid interactions between receptor subunits within the T‐cell antigen receptor (TCR) transmembrane domain are critical for the formation of the TCR‐CD3 complex. Core peptide, a short peptide corresponding to the TCR‐α transmembrane region, containing two positively charged amino acids, is known to inhibit T‐cell function in vitro and in vivo. The aim of this study was to examine peptides corresponding to the syntactic transmembrane CD3 region binding to TCR‐α for their ability to inhibit T‐cell activation in vitro and in vivo. Three peptides matching the transmembrane sequence of CD3‐δ, ‐ɛ and ‐γ were synthesized and tested in different biological in vitro and in vivo systems for their effect on T‐cell activity. The CD3‐peptides had no impact on T‐cell function in vitro, but surprisingly, decreased signs of inflammation in the adjuvant arthritis rat model in vivo. Preliminary evidence suggests that peptides with CD3 transmembrane‐derived sequences can inhibit an immune response as assessed by adjuvant‐induced arthritis. The lack of in vitro activity may lead to a wasteful disregard of active compounds in the process of drug discovery and development.
Cutis laxa acquisita associated with cutaneous mastocytosis
Authors: Mahajan Vikram K. , Sharma Nand Lal , Garg Geeta
Published: August 2006

A female child, a product of a nonconsanguineous parentage and normal pregnancy, was seen first at the age of 4 years. She had suffered from recurrent episodes of multiple, erythematous, confluent plaques and a few bullous lesions all over the body since infancy. The child was irritable but had no history of flushing, dyspnea, wheezing, or frequent diarrhea. Darier's sign was strongly positive and systemic examination did not reveal any abnormality. Routine laboratory investigations were normal and a skin biopsy specimen revealed an unremarkable epidermis and dense proliferation of round to spindle‐shaped mast cells which stained positive for metachromatic granules (Fig. 1). With the diagnosis of urticaria pigmentosa, she was managed with antihistaminic drugs and the parents were advised to handle the child gently. She did not report for further follow‐up.

Photomicrograph of skin histology showing metachromatic granules (toluidine blue, ×40)

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Recently, the child, now 8 years of age, was brought again with finely wrinkled, lax, and redundant skin, especially of the face, giving her a senile appearance (Fig. 2). Systemic examination did not show any abnormality. History revealed that the child had been asymptomatic during the last 4 years even without treatment, but developed slowly progressive lax and pendulous skin. A repeat biopsy from the lax facial skin revealed sparse and fragmented elastic fibres, normal collagen, and a perivascular and intradermal cellular infiltrate composed of metachromatic mast cells. Her serum α1‐antitrypsin levels were 190.0 mg/dL (normal, 93–224 mg/dL) and a pulmonary function test showed no abnormality. Treatment with antihistaminic drugs was started again and she was advised to have a cosmetic facial uplift at a later stage.

Patient with urticaria pigmentosa seen at 8 years of age showing cutis laxa and a senile appearance

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Head louse infestations: the “no nit” policy and its consequences
Authors: Mumcuoglu Kosta Y. , Meinking Terri A. , Burkhart Craig N. , Burkhart Craig G.
Published: August 2006

Health authorities in the USA, Canada and Australia recommend a “no nit” policy, i.e. the immediate dismissal of all children who have head lice, eggs and/or nits on their hair from school, camp or child‐care settings. These children would be readmitted to the institution only when all head lice, eggs and nits have been removed. The “no nit” policy assumes that all nits seen when examining the scalp are viable and therefore the infested individual should be treated for lice, and all nits must be removed from the scalp. However, it has been repeatedly shown that only a small number of children who have nits on their scalp are also infested with living lice. Accordingly, in the USA alone 4–8 million children are treated unnecessarily for head lice annually, which amounts to 64% of all lice treatments. In addition, 12–24 million school days are lost annually. The annual economic loss owing to missed workdays by parents who have to stay home with their children adds US$4–8 billion to the country's economy. The policy also results in serious psychological problems for children and their parents. Therefore, the “no nit” policy should be abandoned and alternative ways of examination and treatment for head lice should be found.
Vascular involvement in Behçet's disease: a retrospective analysis of 2319 cases
Authors: Sarica‐Kucukoglu Rifkiye , Akdag‐Kose Afet , Kayabalı Murat , Yazganoglu Kurtulus Didem , Disci Rian , Erzengin Dilek , Azizlerli Gulsevim
Published: August 2006

Background  Vascular lesions can be the presenting sign of Behçet's disease (BD) preceding classical symptoms. The aim of this study was to evaluate the prevalence and types of vascular involvement in BD.

Methods  Among 2319 patients diagnosed with BD according to the criteria of the International Study Group for BD, 332 patients (279 male, 53 female) with vascular involvement were included in this study.

Results  Prevalence of vascular involvement was 14.3%. Vascular involvement was found to be more common in males (P < 0.001, male : female ratio 5.26 : 1). Mean age at onset of vascular involvement was 30.58 ± 7.88. Vascular lesion was the presenting sign of BD in 50 patients (2.1%), whereas in 109 patients (4.7%) it started together with other clinical symptoms at the age of diagnosis. Superficial vein thrombophlebitis (SVT) was the most common vascular symptom (53.3%) followed by deep vein thrombosis (DVT) (29.8%). Arterial lesions were rare (3.6%). Of the patients 13.3% had more than one type of vascular involvement. Lower extremities were the most frequent localization in patients with SVT, whereas the femoral vein was mainly involved in patients with DVT and the pulmonary artery was mainly involved in the patients with arterial lesions.

Conclusion  In countries like Turkey where BD is more frequent, young male patients presenting with vascular involvement should be evaluated for BD.
Under‐expression of VHL and over‐expression of HDAC‐1, HIF‐1α, LL‐37, and IAP‐2 in affected skin biopsies of patients with psoriasis
Authors: Tovar‐Castillo Laura E. , Cancino‐Díaz Juan C. , García‐Vázquez Francisco , Cancino‐Gómez Francisco G. , León‐Dorantes Gladys , Blancas‐González Fernando , Jiménez‐Zamudio Luis , García‐Latorre Ethel , Cancino‐Díaz Mario E.
Published: August 2006

Background  A feature of psoriasis is the rapid proliferation of keratinocytes, during which apoptosis is blocked and angiogenesis starts. It is known that tumor hypoxic cells produce histone deacetylase‐1 (HDAC‐1), which up‐regulates hypoxia‐inducible factor‐1α (HIF‐1α) and down‐regulates von Hippel–Lindau (VHL) protein by up‐regulating vascular endothelial growth factor (VEGF) expression. It has been reported recently that the porcine peptide PR39 (homologous to human LL‐37) has angiogenic and antiapoptotic activity. Thus, LL‐37, induced by insulin‐like growth factor‐1 (IGF‐1), could help in the production of VEGF. PR39 also induces the expression of inhibitor of apoptosis protein‐2 (IAP‐2), which blocks apoptosis. The purpose of this work was to analyze whether these genes and their proteins are expressed in psoriatic biopsies.

Methods  Using semiquantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR) messenger RNA (mRNA) expression and immunohistochemical staining, we studied VHL, IAP‐2, and related genes in skin biopsies from psoriatic patients and healthy subjects.

Results  An over‐expression of the mRNA for HDAC‐1, HIF‐1α, LL‐37, and IGF‐1 in psoriatic skin, in comparison with skin from healthy subjects, was found. The antiangiogenic VHL mRNA and protein were under‐expressed in psoriatic skin and highly expressed in healthy skin. The antiapoptotic IAP‐2 was over‐expressed in dermal endothelial cells from psoriatic skin. The pro‐apoptotic Bax, Fas, and FasL mRNAs were expressed.

Conclusions  These findings suggest that there could be an association of HDAC‐1, HIF‐1α, LL‐37, VHL, and IAP‐2 with angiogenic and apoptotic mechanisms in psoriasis.
Crack resistance of austenitic stainless steel pipe and pipe welds with a circumferential crack under monotonic loading
Authors: SINGH P. K. , VAZE K. K. , GHOSH A. K. , KUSHWAHA H. S. , PUKAZHENDI D. M. , MURTHY D. S. R.
Published: August 2006

This paper describes the experimental studies carried out on cracked austenitic stainless steel pipe and pipe welds under bending loads. Pipe welds were produced by gas tungsten arc welding (GTAW) and shielded metal arc welding (SMAW). Fracture resistance curves for pipe and pipe welds were compared. Results indicate that the fracture resistance of pipe and pipe weld (GTAW) is comparable but that of pipe weld (GTAW+SMAW) is inferior. Cracks do not deviate from their original plane during propagation as observed in the cases of carbon steel pipe and pipe welds. The fracture resistance of pipe welds does not depend on the loading histories to which it has been subjected prior to fracture test. Initiation and crack propagation were observed prior to the maximum moment. An existing limit load expression is applicable for the pipe base material but gives non‐conservative results for the pipe welds. Multiplication factors have been suggested for the pipe welds for evaluation of limit loads using the existing expression. Fracture resistance for the pipe and compact tension specimens have also been compared for base material and welds.
Some comments on surface cracks in rails
Authors: FISCHER F. D. , DAVES W. , PIPPAN R. , POINTNER P.
Published: August 2006

The present work considers the problem of whether a shallow angle surface crack on a rail may propagate either parallel or perpendicular to the surface. After referring to a classification of crack‐like defects, a distinct surface crack with a typical length of 1 mm and more, inclined to the surface by an angle of approx. 30°, is introduced. Then various strain and stress states are discussed (eigenstress, residual and load stress state) which may control the crack growth. Stress intensity factor equations are provided for the internal and load stress states. In particular, the deformation process due to a single pass (overrolling) by a wheel is investigated. Recommendations are presented on how to relate the stress intensity factor ranges to the actual deformation process. For a typical loading condition, the positive part of the mode I stress intensity factor range is near to the effective threshold value of a rail steel. The influence of the material and its strength on the crack propagation behaviour is discussed qualitatively.
Kleptoplasty in an Antarctic dinoflagellate: caught in evolutionary transition?
Authors: Gast Rebecca J. , Moran Dawn M. , Dennett Mark R. , Caron David A.
Published: August 2006

Photosynthetic dinoflagellates contain a diverse collection of plastid types, a situation believed to have arisen from multiple endosymbiotic events. In addition, a number of heterotrophic (phagotrophic) dinoflagellates possess the ability to acquire chloroplasts temporarily by engulfing algae and retaining their chloroplasts in a functional state. These latter relationships typically last from a few days to weeks, at which point the chloroplasts lose function, are digested and replaced with newly acquired plastids. A novel and abundant dinoflagellate related to the icthyotoxic genera Karenia and Karlodinium was recently discovered by us in the Ross Sea, Antarctica. Sequencing of its plastid small subunit ribosomal gene indicated that it did not share evolutionary history with the plastids of Karenia or Karlodinium, but was closely related to the free‐living haptophyte Phaeocystis antarctica, a species that often dominates phytoplankton blooms in the Ross Sea. Chloroplast uptake was observed to occur rapidly (within 2 days), with retention in cultures being long‐lived (several months) but not permanent. The dinoflagellate was also incapable of growing indefinitely in continuous darkness with algae as prey. Our findings may indicate an emerging endosymbiotic event yielding a dinoflagellate that is presently neither purely phototrophic nor purely heterotrophic, but occupies a niche juxtaposed between these contrasting nutritional modes.
Nateglinide or gliclazide in combination with metformin for treatment of patients with type 2 diabetes mellitus inadequately controlled on maximum doses of metformin alone: 1‐year trial results
Authors: Ristic S. , Collober‐Maugeais C. , Cressier F. , Tang P. , Pecher E.
Published: August 2006

Aim:  To compare long‐term efficacy and safety of nateglinide plus metformin with those of gliclazide plus metformin in patients with type 2 diabetes not adequately controlled with metformin monotherapy.

Methods:  Double‐blind, double‐dummy, multicentre study extended to a total of 52 weeks. Patients with inadequate glucose control on maximal doses of metformin were randomized to nateglinide (N = 133) or gliclazide (N = 129) add‐on treatment. After the initial 6‐month study, the majority of patients in the nateglinide group [n = 112 (93.3%)] and in the gliclazide group [n = 101 (92.7%)] entered a 6‐month, double‐blind, extension study.

Results:  There was no significant difference between treatment regimens in haemoglobin Alc (HbA1c) change from baseline to 52 weeks (−0.14% for nateglinide vs. −0.27% for gliclazide; p = 0.396). Proportions of patients achieving an endpoint HbA1c of <7% were similar (40 vs. 47.4%) for nateglinide and gliclazide groups. There was no significant between‐treatment difference in fasting plasma glucose change from baseline to 52 weeks (nateglinide: −0.2 mmol/l and gliclazide: −0.7 mmol/l; p = 0.096). The decreases in prandial plasma glucose area under the curve0–4 h from baseline were −3.26 and −1.86 h × mmol/l in the nateglinide and the gliclazide groups respectively, and the change was statistically significant in the nateglinide group only (p = 0.006). Initial insulin response to a meal was augmented with nateglinide treatment only, without between‐treatment difference in 2‐h insulin response. The overall rate of hypoglycaemic events was similar with nateglinide and gliclazide combinations with metformin. Nateglinide plus metformin treatment was not associated with weight gain.

Conclusions:  No significant difference was seen between nateglinide plus metformin and gliclazide plus metformin in terms of HbA1c. Treatment with nateglinide plus metformin for up to 12 months was not associated with weight gain.
THE AUTOMOTIVE INDUSTRY IN THE ‘OLD PERIPHERY’ OF THE EUROPEAN UNION: REGIONAL INPUT LINKAGES OF VOLKSWAGEN NAVARRA SA
Authors: ALÁEZ‐ALLER RICARDO , ERRO‐GARCÉS AMAYA
Published: August 2006

The intended main output of this paper is a measurement of the dependence of the regional economy of Navarre (Northern Spain) on the Volkswagen plant producing the Polo model. Based on a field survey (qualitative interviews with 33 automotive suppliers) an exercise is developed to estimate the impact of the closure of the VW plant on regional employment. The degree of dependence on the Volkswagen plant found is lower than had been speculated: it is calculated that 7,222 direct and indirect jobs would be lost if the plant relocated. This study also casts doubt on the reliability of input‐output tables in estimations such as the one proposed here. Finally, a comparison with other automotive assembly plants in Spain could be construed as evidence of convergence in the organisational models of the assembly plants on the ‘old periphery’ of Europe.
THE SPATIAL DISTRIBUTION OF WELFARE IN THE EUROPEAN UNION
Authors: EZCURRA ROBERTO , PASCUAL PEDRO , RAPÚN MANUEL
Published: August 2006

In this paper we examine the regional distribution of welfare in the European Union between 1993 and 2000. In order to achieve this aim, we use a set of econometric techniques proposed in the literature for dealing with spatial data. The results obtained reveal the presence of positive spatial dependence in the variable of interest. This means that spatially close regions register similar welfare levels in the European context. The empirical evidence presented also shows that high welfare regions tend to be those characterised by the presence of certain types of advanced services with elevated productivity and by a relatively important endowment of human capital. However, the regional unemployment rates, the size of the agricultural sector and the non‐market services are negatively correlated with the study variable. These results, moreover, are robust to the welfare measure considered in the analysis.
TOWARDS A THEORETICAL EXPLORATION OF THE DIFFERENTIAL URBANISATION MODEL IN SUB‐SAHARAN AFRICA: THE BOTSWANA CASE
Authors: GWEBU THANDO D.
Published: August 2006

This paper investigates the extent to which the differential urbanisation model is applicable to Botswana by using empirical data obtained from periodic censuses, supportive documentary information and observations from personal on‐going research on urbanisation and migration. Differential urbanisation refers to the cyclic spatio‐temporal growth trends that the elements of human settlement hierarchies undergo, in response to migration. Empirical studies have verified the validity of differential urbanisation in the United States, Europe, India and South Africa. These areas, unlike Botswana, have longer histories of urbanisation, larger population sizes, denser population distributions, and higher levels of economic development. Current research interest is focused on investigating the theoretical applicability of the differential urbanisation model to those countries at the lower end of the economic development spectrum. The rationale and thrust of this paper is to therefore investigate the relevance of differential urbanisation under unique environmental, demographic and socio‐economic conditions that pertain to Botswana. Evidence from the paper shows that urbanisation in Botswana has occurred in sequenced phases that, in general, resemble those suggested by the differential urbanisation model in the following ways. First, there has been concentration in the primate city due to mainstream migration. Secondly, there has been fission leading to the fast growth of the adjacent intermediate settlements, partly as a result of deglomeration economies at the primate core accompanied by substream migration. Third, the peripheral regional and rural centres appear to be now growing relatively rapidly, in response to the implementation of decentralisation policies.
CREATING PROFITABLE LIVELIHOODS: MOBILITY AS A ‘PRACTICAL’ AND ‘STRATEGIC’ GENDER NEED IN PORTO NOVO, BENIN
Authors: MANDEL JENNIFER L.
Published: August 2006

This paper examines the importance of spatial mobility to the creation of profitable livelihood strategies for women in Porto Novo, Benin. Drawing on 522 surveys and 15 life‐history interviews conducted with women who use a wide array of strategies, this paper demonstrates that under some circumstances mobility may be as important to increasing women's income‐generating opportunities as access to capital. Moreover, I argue that focusing on women's access to spatial mobility will not only increase the profitability of their livelihood strategies, but may also create spaces in which issues of autonomy and independence can also be addressed. In so doing, this research contributes to work on gender and development by demonstrating the importance of considering the spatial aspects of social and economic processes.
THE SPATIAL PREFERENCE MAP OF DUTCH ENTREPRENEURS: SUBJECTIVE RATING OF LOCATIONS, 1983, 1993 AND 2003
Authors: MEESTER WILHELM J. , PELLENBARG PIETER H.
Published: August 2006

Location decisions are often based on inaccurate information about potential locations. Decision‐makers seem to be guided by their subjective interpretation of reality, not so much by reality itself. Twenty years ago this fundamental idea was the starting point for a research programme of the Faculty of Spatial Sciences of the University of Groningen, focused on the subjective rating of locations by Dutch entrepreneurs. Three extensive and identical postal enquiries were held, in 1983, 1993 and 2003. On this basis a comparison can now be made of the changing ‘mental map’ of Dutch entrepreneurs during those twenty years. The paper analyses the three maps, preceded by a short introduction about the behavioural approach in economic geography, which inspired the research project. The survey data are used in a factor analysis, to establish the basic influences that form the entrepreneurial mental maps. The basic dome shape of the maps did not change much. During 1983 to 1993 we witness a decrease of appreciation of locations on its West flank (the ‘old’ Randstad) while in 1993 to 2003 this decrease extends to the Eastern Randstad. Factor analysis suggests that three fundamental dimensions determine entrepreneurs’ judgments: potency, activity and evaluation. Potency may be understood as centrality of location. Activity is correlated to agglomeration. It is hypothesised that landscape and culture determine the evaluative dimension.
THE GEOGRAPHY OF PRODUCTION LINKAGES IN THE IRISH AND SCOTTISH MICROCOMPUTER INDUSTRY: THE ROLE OF INFORMATION EXCHANGE
Authors: VAN EGERAAT CHRIS , JACOBSON DAVID
Published: August 2006

This paper considers the idea that technical information exchange in the context of time‐based‐competition encourages buyer‐supplier proximity and local production linkages. The relevance of this idea was tested in a study of 11 subsidiaries of multinational microcomputer assemblers operating in Ireland and Scotland. We show that the assembly plants sourced the vast majority of inputs from regions outside Ireland and Britain and where we find regional linkages, proximity was generally not driven by considerations related to information exchange. Part of the explanation lies in the fact that the European operations played a limited role in technological co‐ordination with suppliers. Another reason is that much of the technical information exchange in the industry is of a relatively limited intensity requiring low levels of face‐to‐face contact.
The Use of Radiolabelled Human Serum Albumin and SPECT/MRI Co-Registration to Study Inflammation in The Cavernous Sinus of Cluster Headache Patients
Authors: Schuh-Hofer S , Richter M , Israel H , Geworski L , Villringer A , Munz DL , Arnold G
Published: August 2006

A sterile inflammation in the cavernous sinus was hypothesized to underlie cluster headache (CH). Neurogenic inflammation is accompanied by the extravasation of plasma proteins in the surrounding tissue. We tested the hypothesis of an inflammatory process in the cavernous sinus in CH patients using 99mTc-human serum albumin (HSA) and single photon emission computed tomography (SPECT). Six patients with episodic CH were enrolled. After baseline imaging, CH attacks were induced by IV injection of nitroglycerin. The patients remained untreated for 20 min. A second SPECT was performed after successful treatment. Region of interest (ROI) analysis was performed on the basis of coregistered MRI/SPECT data. There was no statistical difference between the 99mTc-HSA uptake in the ipsilateral cavernous sinus before and after induction of an acute CH attack. There was no evidence for 99mTc-HSA extravasation in the cavernous sinus during the active episode as compared with the remission phase. Our results do not support the hypothesis of an inflammation in the cavernous sinus.
Motion Perception in Migraineurs: Abnormalities are Not Related to Attention
Authors: McKendrick AM , Badcock DR , Badcock JC , Gurgone M
Published: August 2006

Migraine groups have impaired ability to identify global motion direction in noisy random dot stimuli, an observation that has been used as evidence for cortical hyperexcitability. Several studies have also suggested abnormalities in cognitive processing, particularly in the domains of attention, visuo-spatial processing and memory. This study aimed to determine whether poor performance by migraineurs in motion coherence tasks could be explained by non-visual cognitive factors such as attention. Twenty-nine migraineurs and 27 non-headache controls participated. Global motion coherence thresholds were measured along with measures of neuropsychological function, using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The migraine group had significantly higher motion coherence thresholds than controls. No significant difference in attention or any other RBANS index score was found between groups. Index scores did not correlate with motion perception thresholds. This study does not support inattention or other cognitive abnormality as an explanation for motion perception anomalies in migraine.
Efficient Nonprofits?
Authors: Brooks Arthur C.
Published: August 2006

This article looks at efficiency as it relates to nonprofit activities. I argue that average return‐on‐investment measures are inadequate for nonprofit organizations, and that nonprofits should seek instead to measure marginal returns to investments in nonprogram areas, such as administration and fundraising. Using a national sample of approximately two hundred fifty thousand nonprofits from 2002, I find that some types of organizations spend their nonprogram funds efficiently, while other types do not. These findings have implications for nonprofit management.
Potential Focusing Projects and Policy Change
Authors: Lowry William
Published: August 2006

Why do policies change dramatically? Most prominent theories and many empirical studies of policy change address that question with attention to external shocks to policy systems or focusing events. These shocks or events are usually described as unplanned, unpredicted jolts such as global crises or natural disasters. I assert a role for focusing projects. These planned activities continue traditional priorities in an issue but do so to a degree perceived as excessive by enough people to shatter seemingly stable policy systems. I then propose a theoretical framework to explain the varying impacts from such projects. The framework uses two dimensions: one that accounts for the mobilization of pro‐change forces and one that assesses policy learning by members of pro‐status quocoalitions. I examine this framework in the context of changes to dam‐building policies in four diverse political settings: United States, Australia, Canada, and China. I find intriguing similarities between the focusing projects in these different contexts but also considerable variation in the extent to which they produce policy change.
Breathless: Schools, Air Toxics, and Environmental Justice in California
Authors: Pastor Manuel , Morello‐Frosch Rachel , Sadd James L.
Published: August 2006

The exposure of children to environmental disamenities has emerged as a key policy concern in recent years, with some analysts and activists suggesting that minority children are disproportionately impacted. Utilizing a dataset that combines air toxics at the census tract level with school‐based demographic and other information, this article indicates disparate exposures for students of color in California schools and suggests that there may be negative impacts on one measure of academic performance, even after controlling for other factors usually associated with test scores. Policy implications include a special focus on school remediation and strengthening overall efforts to reduce emissions “hot spots.”
Punctuated Equilibria and Budgets in the American States
Authors: Breunig Christian , Koski Chris
Published: August 2006

In this article, we examine long‐term state budget trends to find evidence of punctuated equilibrium. We use the American states as a broad set of institutional variation with which to examine the nature of policy change through the lens of incrementalism and punctuated equilibrium theories of policymaking. The strength of this article is its sensitivity of variations in policy outcomes across time (18 years), across space (50 state institutions), and across issue space (10 budget categories). This research advances the characterization of policy outcomes by employing a quantitative measure that is both less sensitive to outliers and one that characterizes budget distributions on a simple numeric scale. Our general findings are: (i) state budget categories are interdependent; (ii) state budgets are generally punctuated; but (iii) to varying degrees: Thus, considerable stability (indicated by tall peaks) and punctuations (represented by fat tails) are a central feature of policy outcomes in the American states. This result confirms the logic of punctuated equilibrium theory, but raises future questions about the impact specific variations in institutional costs have on policymaking across the 50 states.
Policy Coherence and Policy Domains
Authors: May Peter J. , Sapotichne Joshua , Workman Samuel
Published: August 2006

Policy scholars generally agree that greater coherence of policies is desirable, but the concept is under‐theorized and has received little empirical examination. This research examines the policy coherence of 18 policy domains and considers institutional factors that affect variation among them. There is considerable variation in coherence among substantive, regional, and identity‐based policy domains. Greater degrees of policy coherence exist for policy domains that have dominant congressional committees or have more involvement of lead federal agencies. These findings extend what policy scholars know about policy subsystems in American policymaking to consideration of the coherence of policy domains.
Punctuated Equilibrium in Limbo: The Tobacco Lobby and U.S. State Policymaking from 1990 to 2003
Authors: Givel Michael
Published: August 2006

Since the mid‐1980s, U.S. tobacco policy has been an intense and acrimonious issue between antitobacco advocates and the tobacco industry. In the United States, the tobacco industry has responded to heightened state antitobacco litigation, adverse public opinion, and public health advocacy by aggressively mobilizing against tobacco taxes and regulations. This article examines whether these tobacco policy trends can be generalized to punctuated equilibrium theory ideas that policy monopolies are stable over long periods and usually change because of sharp and short‐term exogenous shocks to the policy system. From 1990 to 2003, there was a sharp mobilization by health advocates in all states and a significant rise in new legislation to control tobacco use. The tobacco industry, nevertheless, was able to generally keep state tobacco taxes low and counter significant regulatory threats to tobacco sales. From this, I conclude that the policy monopoly favoring the tobacco industry did not significantly change, despite the symbolic appearance of punctuation in the policy system.
Tobacco's Tipping Point: The Master Settlement Agreement as a Focusing Event
Authors: Wood Robert S.
Published: August 2006

Focusing events have been widely referenced in policy studies literature as important drivers of major policy change. In multiple streams theory, punctuated equilibrium theory, and the advocacy coalition framework, they play a prominent role in explaining how major changes occur. Nearly all existing research, however, has focused on the very large and catastrophic events that catapult otherwise obscure issues onto the agenda, to the neglect of focusing events that may perform other functions. This article examines one such event: the Master Settlement Agreement (MSA) between the tobacco industry and the states signed in 1998. I observe that although the MSA focused substantial attention on the topic of tobacco regulation, produced major policy change, and shifted the policy image of the domain, it was not a typical focusing event. Drawing from the tipping point theories of Sociology and Malcolm Gladwell's The Tipping Point, I expand a theoretical distinction articulated by Baumgartner and Jones between “triggering” events and “consolidating” or “tipping” events to resolve this discrepancy.
Up in Smoke: Mapping Subsystem Dynamics in Tobacco Policy
Authors: Worsham Jeffrey
Published: August 2006

This study develops and employs congressionally based indicators to track the evolution of the tobacco policy subsystem between 1945 and 2005. It concludes that far from disintegrating, the tobacco subsystem has proven resilient, weathering several punctuations over the course of the study. The subsystem has, however, undergone a significant transformation resulting in both the introduction of new ideas as well as changes in the policies affecting tobacco.
Tooth loss in well‐maintained patients with chronic periodontitis during long‐term supportive therapy in Brazil
Authors: Chambrone Luiz A. , Chambrone Leandro
Published: August 2006

Aim: The objective of this retrospective study was to assess the reasons for tooth loss in a sample of patients who underwent periodontal therapy and supportive periodontal therapy (SPT) in a Brazilian private periodontal practice.

Material and Methods: A sample of 120 subjects who had been treated and maintained for 10 years or longer was selected from patients attending a periodontal practice. All patients followed a similar treatment: basic procedures, re‐evaluation and periodontal surgery where indicated. Reasons for tooth loss were categorized as periodontal, caries, endodontal, root fractures and extraction of retained or partially erupted third molars.

Results: Of the 2927 teeth present at the completion of active periodontal treatment, 53 (1.8%) were lost due to periodontal disease, 16 (0.5%) for root fracture, six (0.2%) to caries, five (0.2%) for endodontic reasons and 31 (1.0%) were lost to extraction of retained or partially erupted third molars. Logistic regression analysis was performed to investigate the association between five independent variables with tooth loss due to periodontitis. Only age (>60 years) and smoking were statistically significant (p<0.05).

Conclusion: The findings of this survey were consistent with previous studies. Older subjects and smokers were more susceptible to periodontal tooth loss. In addition, patients with generalized chronic periodontitis were treated and maintained for long‐term periods with low rates of tooth loss.
Proportion of antibiotic resistance in subgingival plaque samples from Mexican subjects
Authors: Almaguer‐Flores Argelia , Moreno‐Borjas Jazmin‐Yunuen , Salgado‐Martinez Araceli , Sanchez‐Reyes Marco‐Antonio , Alcantara‐Maruri Eulalio , Ximenez‐Fyvie Laurie‐Ann
Published: August 2006

Aim: To determine the proportion of bacteria resistant to amoxicillin and doxycycline in subgingival plaque samples from Mexican subjects.

Materials and Methods: Two subgingival plaque samples were taken from 20 Mexican subjects. Samples were dispersed, diluted and plated on non‐antibiotic agar plates and on plates containing 0.5, 1, 2, 4, 8 and 16 μg/ml of either amoxicillin or doxycycline. The proportion of resistant bacteria was calculated based on the total number of colony‐forming units present in the non‐antibiotic containing plates.

Results: On average, 0.4–13.4% and 0.9–20.4% of the total cultivable subgingival microbiota was resistant to the concentrations tested of amoxicillin and doxycycline, respectively. The differences between antibiotics were statistically significant for the 0.5, 2 and 4 μg/ml concentrations (p<0.05, Wilcoxon's test).

Conclusions: Our findings revealed that a relatively small proportion of the total cultivable subgingival microbiota from Mexican subjects was resistant to amoxicillin and doxycycline.