bluuebunny/crossref_metadata_2025 huggingface dataset:
Rho-Kinase Mediates Hyperglycemia-Induced Plasminogen Activator Inhibitor-1 Expression in Vascular Endothelial Cells
Authors: Rikitake Yoshiyuki , Liao James K.
Published: June 2005

Background—

Elevated levels of plasminogen activator inhibitor-1 (PAI-1) are associated with myocardial infarction and stroke, especially in patients with diabetes. The induction of PAI-1 expression by hyperglycemia involves oxidative stress and protein kinase C (PKC). However, the mechanism by which hyperglycemia increases PAI-1 expression is unknown.

Methods and Results—

Compared with normoglycemia, exposure of human endothelial cells to hyperglycemia, but not mannitol, increased Rho-kinase activity in a time- and concentration-dependent manner. This increase was inhibited by a PKC inhibitor, GF109203X, and antioxidants
N
-acetylcysteine (NAC) and reduced form of glutathione (GSH). This correlated with inhibition of hyperglycemia-induced PAI-1 expression by GF109203X, NAC, and GSH. Hyperglycemia-increased PAI-1 mRNA and protein levels were inhibited by Rho-kinase inhibitors hydroxyfasudil and Y27632 and by a dominant-negative mutant of Rho-kinase. The mechanism for this inhibition occurs at the level of gene transcription because Rho-kinase inhibitors repress hyperglycemia-stimulated PAI-1 promoter activity without affecting mRNA stability. Hyperglycemia failed to stimulate Rho-kinase activity and PAI-1 expression in heterozygous ROCK I–knockout murine endothelial cells.

Conclusions—

Hyperglycemia stimulates Rho-kinase activity via PKC- and oxidative stress–dependent pathways, leading to increased PAI-1 gene transcription. These results suggest that inhibition of ROCK I may be a novel therapeutic target for preventing thromboembolic complications of diabetes and cardiovascular disease.
Deciphering the Message in Japanese Deflation Dynamics
Authors: McNelis Paul D. , Yoshino Naoyuki
Published: June 2005

This paper uses linear and nonlinear neural network regime-switching (NNRS) models to decipher the message in Japanese deflation dynamics and thus identify the channels through which Japan's economy can escape its deflationary spiral. The NNRS model is superior to a linear model with respect to in-sample specification tests and out-of-sample forecasting accuracy. The most important variables affecting inflation are interest rates and the output gap. Given the zero lower bound on interest rates, it will be most effective to end Japan's deflationary cycle with policies that reverse the output gap by stimulating investment.
Effect of chitin compost and broth on biological control of Meloidogyne incognita on tomato (Lycopersicon esculentum Mill.)
Authors: De Jin Rong , Suh Joo Won , Park Ro Dong , Kim Yong Woong , Krishnan Hari B. , Kim Kil Yong
Published: June 2005

Plant-parasitic nematodes are distributed worldwide and affect a broad range
of important agronomic plant species. Chitinolytic bacteria were evaluated
as potential biological control agents of the root-knot nematode,
Meloidogyne incognita, on tomato. After transplantation of seedlings into
pots containing soil amended with chitin compost, chitin broth, or
respective controls, soil was inoculated with nematode eggs and infective
second-stage juveniles (J2). Samples taken at 4, 6 and 8 weeks after
inoculation indicated that fresh weights of plants did not vary between
treatments or between treatments and controls. The gall index was lower in
the plants grown in the chitin-amended soil at each time point. Activities
of soil chitinase and β-1,3-glucanase were greater in those soils amended
with chitin compost and chitin broth. Gall index of tomato root was
negatively correlated with soil chitinase activity. Activities of tomato
root chitinase and β-1,3-glucanase were higher in plants growing in
non-chitin-amended soil at 6 and 8 weeks after nematode infestation.
Chitinase activity in tomato root was positively correlated with the gall
index of tomato root. The results indicate the potential of chitinase
producing bacteria to alleviate nematode parasitism in important vegetable
crops.
Response of Pratylenchus spp. in tall fescue infected with different strains of the fungal endophyte Neotyphodium coenophialum
Authors: Timper Patricia , Gates Roger N. , Bouton Joe H.
Published: June 2005

The presence of the fungal endophyte Neotyphodium coenophialum in tall fescue
(Festuca arundinacea) confers resistance to some plant-parasitic nematodes
but also results in the production of ergot alkaloids. Recently, new strains
of N. coenophialum have been isolated from wild tall fescue and artificially
inoculated into elite tall fescue cultivars. These strains produce low to
nil levels of ergot alkaloids and are referred to as non-ergot strains. Our
objective was to determine whether non-ergot strains of the endophyte confer
the same level of resistance to Pratylenchus spp. as the endemic strain in
tall fescue. In a glasshouse experiment, nematode resistance was compared in
two fescue cultivars (Jesup and Georgia 5) infected with either the endemic
strain (E+), or two non-ergot strains, AR542 and AR584. An additional
non-ergot strain, AR514, was tested only in cv. Jesup. Cultivars Georgia 5
and Jesup without endophytes (E−) were used as controls. The endophtye
status of the plants was confirmed and then three plants per
cultivar/endophyte combination were transplanted into 10 cm square pots. The
pots were inoculated with a mixed culture of Pratylenchus zeae and P.
scribneri in the first trial and a pure culture of P. scribneri in the
second trial of the experiment. After 8 weeks, the number of nematodes
within the roots from each pot was determined. Numbers of Pratylenchus spp.
in either cv. Georgia 5 or cv. Jesup containing the non-ergot strain AR542
were not different from numbers in E− plants. AR514 also did not confer
resistance to the nematodes in cv. Jesup. By contrast, the non-ergot strain
AR584 appears to confer resistance to Pratylenchus spp. in cv. Georgia 5,
but not in cv. Jesup; however, the level of resistance in cv. Georgia 5 was
less than the resistance conferred by the endemic endophyte. Genetic
differences between the two tall fescue cultivars may affect growth of the
endophyte or production of a nematode toxin or deterrent by the endophyte.
As only a small subset of endophyte strains has been tested, we are
screening additional non-ergot strains for resistance to P. scribneri.
Body and Soul
Authors: Appelrouth Scott
Published: June 2005

This article examines the discursive framing of jazz as it entered the musical mainstream. Voices in the contest to define the music turned to a body-centered discourse that highlighted jazz’s alleged impact on the listener. In doing so, observers not only responded to music’s unique capacities among the arts but also engaged in a symbolic struggle to define the boundaries of the individual body and with it, the body politic—a struggle whose stakes were magnified by ongoing social and cultural transformations.
The Embodiment of Sound and Cohesion in Music
Authors: Winther Jennifer
Published: June 2005

Is musical cohesion a function of structure, an interactive achievement, a combination of both, or something else? The author uses ethnographic field data to discuss the process of learning for novice musicians to identify quality of sound as it corresponds to particular bodily configurations, arguing that individual performers use a sound-bodydynamicto identify cohesionin a groupas anembodiedsound.The author concentrates on the earliest stages of practice among amateur taiko drummers, a Japanese style prominent in Japan and the United States, highlighting both individual learning and group interaction in ensemble performance.
Change Scores, Composites and Reliability Issues in Cross-National Development Research
Authors: Davis Byron L. , Kick Edward L. , Burns Thomas J.
Published: June 2005

While a number of researchers of world development examine social change using composite measures as indicators, there is a relative paucity of research on the reliability of these change score composites over time. We construct two development composites based simply on factor analysis, one economic and one social, and then perform reliability analysis on these two development composites at two discrete points in time (i.e. 1970 and 1985) and their change over the 15-year period defined by their beginning and ending points. Despite evidence of reliable beginning and ending points, change in composites over time yield markedly different patterns of reliability. We conclude that if composite indicators of development are used in cross-national research to assess change, the reliabilities of their change should be addressed directly in addition to the reliabilities of their beginning and ending points. The risk of not doing so is faulty inferences with respect to theory.
Performance measurement: test the water before you dive in
Authors: Halachmi Arie
Published: June 2005

Performance measurement and reporting are promoted in various publications as a management concept that can help administrators and elected officials address the issues of productivity and accountability. This article challenges this general assertion for two reasons. First, because the cost of performance score cards is always significant while the benefits, in many instances, may be only tentative. Second, because of possible problems that result when measuring performance is used for two different and potentially competing functions: accountability versus productivity. The article concludes that while performance measurement has a potential, its use should be encouraged but not mandated by external bodies. The article asserts that a more prudent introduction and use of performance score cards may result from better understanding of two things: first, what can go wrong when compiling performance reports; and, second, that there might be a need for other corresponding changes, within and outside government agencies, in order to facilitate meaningful performance reports.
Administrative reform in Japan: past developments and future trends
Authors: Masujima Toshiyuki
Published: June 2005

This article examines the place that the reform of central government ministries — the ‘Hashimoto reforms’ — has occupied within the context of administrative reform in the last half of the 20th century. The first part traces the administrative reforms attempted by successive governments, with particular reference to the Hashimoto reforms in comparison with the earlier highly productive ‘Rinchô’ reforms. The article also identifies the controversial points inherent in the Hashimoto reforms and considers the implications of these reforms for Japanese government in the 21st century. Brief reference is also made to the administrative reforms being pursued by the government as of 2004.
Public administration in Latin America: promises, frustrations and new examinations
Authors: Kliksberg Bernardo
Published: June 2005

Public administration faces great challenges in Latin America, a continent with great economic potential, but with 44 percent of the population in poverty. One of the causes is inequality: whereas 10 percent of the richest possess 48 percent of the national income, 10 percent of the poorest possess only 1.6 percent. There is disillusionment with the rigid orthodox policies applied in the 1980s and 1990s, one of whose objectives was the downsizing of the state; such policies worsened poverty and inequality. Today, according to surveys, the citizenry demands that public administration return to fulfilling an important role associated with civil society: implement active, transparent and well-managed public policies with a strong social emphasis. The article analyzes state reforms made in the past decades, their uncertain results, new social demands and the great challenge that is raised in the region: how to build an intelligent and equitable state that serves to recover the social cohesion that has deteriorated.
Neural Network Modeling as a Tool for Forecasting Regional Employment Patterns
Authors: Longhi Simonetta , Nijkamp Peter , Reggianni Aura , Maierhofer Erich
Published: June 2005

This article analyzes artificial neural networks (ANNs) as a method to compute employment forecasts at a regional level. The empirical application is based on employment data collected for 327West German regionsover a periodof fourteenyears. First, the authors compare ANNs to models commonly used in panel data analysis. Second, they verify, in the case of panel data, whether the common practice of combining forecasts of the computed models is able to produce more reliable forecasts. The technique currently employed by the German authorities to compute such regional employment forecasts is comparable to a simple naïve no-change model. For this reason, ANNs are also compared to this undemanding technique.
Nonprofit and For-Profit Competition with Public Alternatives in an Urban Setting with Congestion
Authors: Brown H. Shelton
Published: June 2005

This theoretical analysis describes nonprofit-public and for-profit-public competition in an urban setting. The model resembles a Hotelling game with endogenous firm location, prices, and facility congestion. Because residents have free mobility, rent is also endogenous. The analysis identifies the optimal spatial and pricing configuration, against which nonprofit-public and for-profit-public competition are compared. If there is no congestion, both types of public-private competition are equivalent if profits are ignored. Neither type of public-private competition is optimal. However when congestion is present, nonprofit-public competition improves overall welfare in comparison to for-profit-public competition. The analysis identifies optimal subsidies and zoning rules that induce welfare-improving behavior on the part of either type of competition.
We hate it here, please let us stay! Irish social partnership and the community/voluntary sector’s conflicted experiences of recognition
Authors: Meade Rosie
Published: June 2005

This article critically assesses the outcomes of community and voluntary sector participation in the partnership processes that have dominated the Irish social policy scene for the last decade. As community organizations have embraced the state sponsored corporatist project in both its local and national manifestations, they have been given official recognition by government as de facto representatives of the socially excluded. State policy discourses have celebrated this development as evidence of its own enablement of civil society and as reflective of participatory democracy in action. However, because the state has taken such an instrumental role in the initiation, funding and direction of community organizations at the local level, the actual autonomy and independence of the community sector has been grievously undermined. At a national level, community and voluntary organizations have found that because they lack economic clout - the basis of political influence in Ireland’s neo-liberal climate - they have been granted only a marginal influence over the substance of policy decisions. The article concludes by urging that community organizations begin to cultivate alternative alliances outside the state controlled sphere of social partnership, in order to challenge neo-liberalism’s hegemony and to promote the political interests of those they claim to represent.
The friendships and play partners of lonely children
Authors: Qualter Pamela , Munn Penny
Published: June 2005

The research examines the play partners and friendship patterns of a sample of children (N= 409) from four separate clusters (lonely, rejected, lonely and rejected, and nonlonely/nonrejected controls). Controls were more likely than rejected, lonely and lonely/rejected children to have a best friend. Control and rejected children differ from lonely and lonely/rejected children by reporting significantly more support from a close friend. Observations of play showed that lonely, lonely/rejected and rejected children are not isolated and dyadic interactions between children in these three clusters were likely to be positive in nature, involving pro-social acts, and acts that were positively received by others. We note that there are discrepancies between children’s reports of friendships and observations of play partner choice and we consider why this might be the case.
The demonisation of pan-Arab nationalism
Authors: Coury Ralph M.
Published: June 2005

Although the denigration and misrepresentation of pan-Arab nationalism existed long before recent attempts to portray Saddam Hussein’s regime as exceptionally heinous, threatening and a major source of terrorism, the demonisation of this profoundly important and evolving political force has been given further impetus by the imperative to justify current US Middle Eastern policy. The fallacies that inform reductionist and hostile approaches to pan-Arabism, including the assumption that it is inherently racist and totalitarian, are here dissected and contextualised, and the evolution of pan-Arab nationalist thought is illuminated in the process.
Ben Okri and the freedom whose walls are closing in
Authors: Smith Andrew
Published: June 2005

Postcolonial models of culture tend to treat the relationship between reality and representation as arbitrary at best. This article argues, contrastingly, that the long-standing materialist assumption of a mappable relationship between cultural form, on the one hand, and the social conditions of cultural formation, on the other, remains absolutely relevant. Ben Okri’s celebrated Famished Road trilogy is taken as a noteworthy example in this regard. While Okri’s development of a disassociated or elevated narrative form can be seen to fit well with many of the critical propositions of postcolonial theory, it can itself be read as peculiarly expressive of its own social and historical context of production.
The Black middle class and the mulatto motion picture
Authors: Robinson Cedric J.
Published: June 2005

The growth of the early film industry in the US coincided with the institutionalisation of racial segregation at all levels of society. At the same time, an increasingly self-assertive Black middle class had begun to organise itself culturally, socially, politically and economically in ways that contradicted the virulent cultural racism underpinning ‘Jim Crow’. The importance of the new medium is often stressed for its role in cohering America’s new immigrant communities. However, it is its political function in the service of white supremacy and big business - a cultural instrument to cement racism and foreclose any potential alliance between Black and immigrant labour - that is explored for the first time here.
In defence of materialism: a critique of Afrocentric ontology
Authors: Williams Christopher J.
Published: June 2005

Over the last twenty-five years, Afrocentric thinkers have made notable contributions to the ongoing task of challenging Eurocentrism. In the course of so doing, however, some measure of over-reach has occurred. In particular, Afrocentrists have coupled their general critiques of Eurocentrism with specific rejections of its putatively constituent elements, one of which is materialism. Among other things, this rejection of materialism has led Afrocentrists to refrain from interrogating capitalism, downplay the structural dimensions of racial oppression and elevate the ontological status of culture to the point where it is posited as the dominant source of pressing problems affecting people of African descent in the US. Such an outlook undermines the potential of Afrocentricity to be a force for radical social change.
Chicano Lite
Authors: Campbell Howard
Published: June 2005

This article is an ethnography of working-class, Mexican-American consumer patterns on the US-Mexico border. Through a study of locally-owned grocery stores, family parties and fast-food restaurants in El Paso, Texas, I examine the double-edged nature of border consumerism. Minority consumers, such as Mexican-Americans, often modify mainstream consumer products and processes to suit their own needs and values. The resultant consumer styles embody a considerable degree of creativity, contradiction and hybridity, especially for immigrant minorities. I show how, despite their subordinated class and status positions in US society, Mexican-Americans create spaces of resistant cultural meaning within consumer spheres normally treated as generically (Anglo-) American. I conclude that US consumer culture is both a source of self-fulfilment and a means through which Mexican-Americans become further enmeshed in a system of vastly unequal political and economic power.
Latino Educational Outcomes and the Campus Climate
Authors: Hurtado Sylvia , Ponjuan Luis
Published: June 2005

The authors present a longitudinal study aimed at understanding the factors that affect educational outcomes for Latinos. They explore Latino students’ perceptions of the campus climate, their sense of belonging in college, their analytical skills and abilities, and their development of a pluralistic orientation necessary to function in a diverse workplace. They conclude with a discussion of implications for improving the climate of public, 4-year institutions.
Extraembryonic expression of EPCR is essential for embryonic viability
Authors: Li Weihong , Zheng Xunzhen , Gu Jian-Ming , Ferrell Gary L. , Brady Mingming , Esmon Naomi L. , Esmon Charles T.
Published: June 2005

The endothelial cell protein C receptor (EPCR) augments protein C activation by the thrombin-thrombomodulin complex. Deletion of the EPCR gene (Procr) in mice leads to embryonic lethality before embryonic day 10 (E10.0). EPCR is detected in the giant trophoblast cells at the feto-maternal boundary from E7.5 and weakly in embryonic aortic endothelial cells from E13.5, suggesting that extraembryonic EPCR expression may be essential for embryonic viability. Using conditional knock-out strategies, we demonstrate that Procr-deficient embryos with EPCR expression on placenta giant trophoblasts can be carried to term and then develop normally. Conversely, EPCR expression in the embryo, without expression in the giant trophoblast cells, does not rescue the mice. In genetically modified mice with low tissue factor activity, Procr deficiency is not lethal to the embryo. As adults, Procr-deficient mice generate more thrombin and activate less protein C in response to procoagulant stimuli. Spontaneous thrombin formation in the deficient animals increases with age. These findings show that extraembryonic EPCR expression is critical for embryo development.
In vitro sensitivity to imatinib-induced inhibition of ABL kinase activity is predictive of molecular response in patients with de novo CML
Authors: White Deborah , Saunders Verity , Lyons A. Bruce , Branford Susan , Grigg Andrew , To L. Bik , Hughes Timothy
Published: June 2005

Most patients with de novo chronic myeloid leukemia (CML) achieve good responses to imatinib, but the rate and degree of molecular response is variable. We assessed the inhibitory concentration 50% for imatinib (IC50imatinib) in 62 patients with de novo chronic-phase CML as a predictor of molecular response. IC50imatinib was determined in pretherapy blood samples by measuring the in vitro imatinib-induced reduction of the phosphorylated form of the adaptor protein Crkl (CT10 regulator of kinase like). There was marked variability between patients, with IC50imatinib ranging from 0.375 to 1.8 μM (median, 0.6 μM). Patients with low IC50imatinib (IC50 ≤ 0.6 μM; n = 36) had a 36% probability of achieving 2-log reduction in BCR-ABL (breakpoint cluster region-abelson) by 3 months compared with 8% in patients with high IC50imatinib (n = 26) (P = .01). The IC50imatinib was also predictive of molecular response at 12 months, with 47% of patients in the low IC50imatinib group achieving 3-log reduction and 23% in the high IC50imatinib group (P = .03). The predictive power of IC50imatinib was particularly strong in patients with low Sokal scores. These data provide strong evidence that intrinsic sensitivity to imatinib is variable in previously untreated patients with CML, and the actual level of BCR-ABL kinase inhibition achieved is critical to imatinib response. The IC50imatinib potentially provides a new prognostic indicator for molecular response in patients treated with imatinib. (Blood. 2005; 106:2520-2526)
Thrombus formation induced by antibodies to β2-glycoprotein I is complement dependent and requires a priming factor
Authors: Fischetti Fabio , Durigutto Paolo , Pellis Valentina , Debeus Alessandra , Macor Paolo , Bulla Roberta , Bossi Fleur , Ziller Federica , Sblattero Daniele , Meroni Pierluigi , Tedesco Francesco
Published: June 2005

We monitored the number of intravascular platelet-leukocyte aggregates (PLAs) and thrombotic occlusions (TOs) by intravascular microscopy in the mesentery of rats receiving antiphospholipid (aPL) immunoglobulin G (IgG) purified from the sera of patients with antiphospholipid syndrome. aPL IgG had no procoagulant effect, but it caused rapid endothelial deposition of fibrinogen, followed by PLA and TO in rats receiving an intraperitoneal injection of bacterial lipopolysaccharide 3 hours before IgG infusion. Anti-β2-glycoprotein I-depleted aPL IgG failed to induce PLAs and TOs. C3 and C9 colocalized with aPL IgG on the mesenteric vessels. The number of PLAs and TOs was markedly reduced in C6-deficient rats and in animals treated with anti-C5 miniantibody, suggesting the contribution of the terminal complement (C) complex to the aPL antibody-mediated intravascular thrombosis. In conclusion, our data indicate that antibodies to β2-glycoprotein I trigger coagulation subsequent to a priming proinflammatory factor and that the terminal C complex is the main mediator of the coagulation process.
Alkahest NuclearBLAST : a user-friendly BLAST management and analysis system
Authors: Diener Stephen E , Houfek Thomas D , Kalat Sam E , Windham DE , Burke Mark , Opperman Charles , Dean Ralph A
Published: June 2005

Background -

Sequencing of EST and BAC end datasets is no longer limited to large research groups. Drops in per-base pricing have made high throughput sequencing accessible to individual investigators. However, there are few options available which provide a free and user-friendly solution to the BLAST result storage and data mining needs of biologists.

Results -

Here we describe NuclearBLAST, a batch BLAST analysis, storage and management system designed for the biologist. It is a wrapper for NCBI BLAST which provides a user-friendly web interface which includes a request wizard and the ability to view and mine the results. All BLAST results are stored in a MySQL database which allows for more advanced data-mining through supplied command-line utilities or direct database access. NuclearBLAST can be installed on a single machine or clustered amongst a number of machines to improve analysis throughput. NuclearBLAST provides a platform which eases data-mining of multiple BLAST results. With the supplied scripts, the program can export data into a spreadsheet-friendly format, automatically assign Gene Ontology terms to sequences and provide bi-directional best hits between two datasets. Users with SQL experience can use the database to ask even more complex questions and extract any subset of data they require.

Conclusion -

This tool provides a user-friendly interface for requesting, viewing and mining of BLAST results which makes the management and data-mining of large sets of BLAST analyses tractable to biologists.
Evaluation of amplified rDNA restriction analysis (ARDRA) for the identification of Mycoplasma species
Authors: Stakenborg Tim , Vicca Jo , Butaye Patrick , Maes Dominiek , De Baere Thierry , Verhelst Rita , Peeters Johan , de Kruif Aart , Haesebrouck Freddy , Vaneechoutte Mario
Published: June 2005

Background

Mycoplasmas are present worldwide in a large number of animal hosts. Due to their small genome and parasitic lifestyle, Mycoplasma spp. require complex isolation media. Nevertheless, already over 100 different species have been identified and characterized and their number increases as more hosts are sampled. We studied the applicability of amplified rDNA restriction analysis (ARDRA) for the identification of all 116 acknowledged Mycoplasma species and subspecies.

Methods

Based upon available 16S rDNA sequences, we calculated and compared theoretical ARDRA profiles. To check the validity of these theoretically calculated profiles, we performed ARDRA on 60 strains of 27 different species and subspecies of the genus Mycoplasma.

Results

In silico digestion with the restriction endonuclease AluI (AG^CT) was found to be most discriminative and generated from 3 to 13 fragments depending on the Mycoplasma species. Although 73 Mycoplasma species could be differentiated using AluI, other species gave undistinguishable patterns. For these, an additional restriction digestion, typically with BfaI (C^TAG) or HpyF10VI (GCNNNNN^NNGC), was needed for a final identification. All in vitro obtained restriction profiles were in accordance with the calculated fragments based on only one 16S rDNA sequence, except for two isolates of M. columbinum and two isolates of the M. mycoides cluster, for which correct ARDRA profiles were only obtained if the sequences of both rrn operons were taken into account.

Conclusion

Theoretically, restriction digestion of the amplified rDNA was found to enable differentiation of all described Mycoplasma species and this could be confirmed by application of ARDRA on a total of 27 species and subspecies.
Phase II trial of weekly 24-hour infusion of gemcitabine in patients with advanced gallbladder and biliary tract carcinoma
Authors: von Delius Stefan , Lersch Christian , Schulte-Frohlinde Ewert , Mayr Martina , Schmid Roland M , Eckel Florian
Published: June 2005

Background

Patients with advanced gallbladder and biliary tract carcinoma face a dismal prognosis, as no effective palliative chemotherapy exists. The antitumor effect of gemcitabine is schedule-dependent rather than dose-dependent. We evaluated the activity of a prolonged infusion of gemcitabine in advanced gallbladder and biliary tract carcinomas.

Methods

Nineteen consecutive eligible patients were enrolled. All patients were required to have histologically confirmed diagnosis and measurable disease. Gemcitabine was infused over 24 hours at a dose of 100 mg/m2 on days 1, 8, and 15. Treatment was repeated every 28 days until progression of disease or limiting toxicity. Tumor response was evaluated every second course by computed tomography (CT) scans.

Results

Eighteen patients were evaluable for response. A total of 89 cycles of therapy were administered. One partial response was observed (6%; 95% confidence interval (CI): 0–27%) and ten additional patients had stable disease for at least two months (disease control rate 61%; 95% CI: 36–83%). The therapy was well tolerated, with moderate myelosuppression as the main toxicity. The median time to tumor progression and median overall survival was 3.6 months (95% CI 2.6–4.6 months) and 7.5 months (95% CI 6.5–8.5 months), respectively.

Conclusion

Weekly 24-hour gemcitabine at a dose of 100 mg/m2 is well tolerated. There was a relatively high rate of disease control for a median duration of 5.3 months (range 2.8–18.8 months). However, the objective response rate of this regimen in gallbladder and biliary tract carcinomas was limited.
The effect of functional splinting on mild dysplastic hips after walking onset
Authors: Windhagen Henning , Thorey Fritz , Kronewid Heinrich , Pressel Thomas , Herold Dieter , Stukenborg-Colsman Christina
Published: June 2005

Background

For treatment of Graf class IIb dysplastic hips at walking onset a treatment concept with abduction splints allowing patterns as walking and crawling under constant abduction control was investigated. However, as the splint still incapacitates child movements the research question remains whether the physiologically progressing maturation of hips can be significantly altered using such abduction splints for walking children.

Methods

Of 106 children showing late hip dysplasia, 68 children treated with the Hoffman-Daimler (HD-splint) abduction splint were compared with 38 children with neglect of the abduction treatment in this retrospective study. Radiographic analyses were performed measuring the development of the age dependent acetabular angle.

Results

The regression analysis for splint treatment showed a significant linear regression for both splint treatment and no splint treatment group (r2 = 0,31 respectively r2 = 0,33). No statistical difference between both treatment groups was apparent.

Conclusion

Considering the characteristics of this study, there seems to be no strong rationale supporting the use of an abduction device in growing children. As no significant difference between treatment groups is apparent, a future controlled prospective study on splinting effects can be considered ethically allowed.
A prospective study of cumulative job stress in relation to mental health
Authors: Godin Isabelle , Kittel France , Coppieters Yves , Siegrist Johannes
Published: June 2005

Background

This study tests associations between psychosocial stress at work measured by the effort-reward imbalance model in a dynamic perspective, and multiple indicators of poor mental health, in a prospective design.

Methods

1986 male and female employees from four Belgian enterprises were followed-up over one year within the framework of the Somstress study. Based on two consecutive measurements, an index of cumulative job stress was constructed and its associations with five indicators of mental health were studied, excluding caseness at entry (for depression, anxiety, somatisation, chronic fatigue and psychotropic drug consumption respectively). Taking into account the longitudinal design, four categories of job stress are defined: 1) employees free from stress at both measures, 2) job stress present at first measure but not at the second one, 3) recent onset of job stress as evidenced by second measure 4) workers exposed to stress at both measures. Multivariate logistic regression with appropriate adjustments was applied.

Results

In bivariate analysis, a clear graded association of cumulative job stress with all five mental health indicators is observed, both in men and women. In multivariate logistic regression analysis, recent onset of stress is strongly associated with poor mental health among men (odds ratios ranging from 1.8 to 4.6), while cumulative stress shows strongest effects on mental health in women (odds ratios ranging from 1.4 to 7.1).

Conclusion

Cumulative experience and recent onset of job stress in terms of high effort spent and low reward received is associated with elevated risk of all five indicators of poor mental health at follow-up in a large cohort of employees.
Computational optical biopsy
Authors: Li Yi , Jiang Ming , Wang Ge
Published: June 2005

Optical molecular imaging is based on fluorescence or bioluminescence, and hindered by photon scattering in the tissue, especially in patient studies. Here we propose a computational optical biopsy (COB) approach to localize and quantify a light source deep inside a subject. In contrast to existing optical biopsy techniques, our scheme is to collect optical signals directly from a region of interest along one or multiple biopsy paths in a subject, and then compute features of an underlying light source distribution. In this paper, we formulate this inverse problem in the framework of diffusion approximation, demonstrate the solution uniqueness properties in two representative configurations, and obtain analytic solutions for reconstruction of both optical properties and source parameters.
A comparison of ultrasound measurements to assess carotid atherosclerosis development in subjects with and without type 2 diabetes
Authors: Pollex Rebecca L , Spence David J , House Andrew A , Fenster Aaron , Hanley Anthony JG , Zinman Bernard , Harris Stewart B , Hegele Robert A
Published: June 2005

Background

Subjects with type 2 diabetes are at an increased risk of vascular complications. The use of carotid ultrasound remains an attractive, non-invasive method to monitor atherosclerotic disease progression and/or response to treatment in patients with type 2 diabetes, with intima-media thickness routinely used as the gold standard to detect pathology. However, alternative measurements, such as plaque area or volume, may represent a potentially more powerful approach. Thus, the objective of this study was to compare the traditional intima-media thickness measurement against the novel total plaque volume measurement in analyzing carotid atherosclerosis development in individuals with type 2 diabetes.

Methods

The case-control study included 49 Oji-Cree adults with diabetes or impaired glucose tolerance, aged 21–69, and 49 sex- and age-matched normoglycemic subjects. At baseline, metabolic variables were measured, including body mass index, waist circumference, total cholesterol:high density lipoprotein ratio, plasma triglycerides, plasma glucose, and serum insulin. Carotid ultrasound measurements, 7 years later, assessed carotid arterial intima-media thickness and total plaque volume.

Results

At baseline, the two groups were well matched for smoking habits, hypertension, body mass index, and waist circumference. Differences were noted in baseline measurements of total cholesterol:high density lipoprotein (P = 0.0006), plasma triglycerides (P < 0.0001) and fasting glucose (P < 0.0001). After seven years, carotid ultrasound scans revealed that total plaque volume measurements (P = 0.037), but not intima-media thickness measurements, were higher in subjects with diabetes/impaired glucose tolerance compared to the normoglycemic controls. Correlation between intima-media thickness and total plaque volume was moderate. Based on our study findings, to achieve power levels >0.70 when comparing intima-media thickness measurements for diabetics versus non-diabetics, thousands of study subjects are required. For comparing total plaque volume measurements, only hundreds of study subjects are required.

Conclusion

The development of atherosclerotic plaque is greater in subjects with diabetes/impaired glucose tolerance. Total plaque volume appears to capture the atherosclerotic disease burden more effectively in subjects with type 2 diabetes, and would be an appropriate outcome measure for studies aimed at changing the diabetic milieu.
Test-retest reliability of a questionnaire to assess physical environmental factors pertaining to physical activity
Authors: Evenson Kelly R , McGinn Aileen P
Published: June 2005

Background

Despite the documented benefits of physical activity, many adults do not obtain the recommended amounts. Barriers to physical activity occur at multiple levels, including at the individual, interpersonal, and environmental levels. Only until more recently has there been a concerted focus on how the physical environment might affect physical activity behavior. With this new area of study, self-report measures should be psychometrically tested before use in research studies. Therefore the objective of this study was to document the test-retest reliability of a questionnaire designed to assess physical environmental factors that might be associated with physical activity in a diverse adult population.

Methods

Test and retest surveys were conducted over the telephone with 106 African American and White women and men living in either Forsyth County, North Carolina or Jackson, Mississippi. Reliability of self-reported environmental factors across four domains (e.g., access to facilities and destinations, functionality and safety, aesthetics, natural environment) was determined using intraclass correlation coefficients (ICC) overall and separately by gender and race.

Results

Generally items displayed moderate and sometimes substantial reliability (ICC between 0.4 to 0.8), with a few differences by gender or race, across each of the domains.

Conclusion

This study provides some psychometric evidence for the use of many of these questions in studies examining the effect of self-reported physical environmental measures on physical activity behaviors, among African American and White women and men.
Accelerated development of arthritis in mice lacking endothelial selectins
Authors: Ruth Jeffrey H , Amin M Asif , Woods James M , He Xiaodong , Samuel Sharon , Yi Nengjun , Haas Christian S , Koch Alisa E , Bullard Daniel C
Published: June 2005

The selectins, along with very late antigen-4 and CD44, have been implicated in mediating leukocyte rolling interactions that lead to joint recruitment and inflammation during the pathogenesis of rheumatoid arthritis. Previously, we showed that P-selectin deficiency in mice resulted in accelerated onset of joint inflammation in the murine collagen-immunized arthritis model. Here, we report that mice deficient either in E-selectin or in E-selectin and P-selectin (E/P-selectin mutant) also exhibit accelerated development of arthritis compared with wild type mice in the CIA model, suggesting that these adhesion molecules perform overlapping functions in regulating joint disease. Analyses of cytokine and chemokine expression in joint tissue from E/P-selectin mutant mice before the onset of joint swelling revealed significantly higher joint levels of macrophage inflammatory protein-1α and IL-1β compared to wild-type mice. IL-1β remained significantly increased in E/P-selectin mutant joint tissue during the early and chronic phases of arthritis. Overall, these data illustrate the novel finding that E-selectin and P-selectin expression can significantly influence cytokine and chemokine production in joint tissue, and suggest that these adhesion molecules play important regulatory roles in the development of arthritis in E/P-selectin mutant mice.
Study protocol: The DOse REsponse Multicentre International collaborative initiative (DO-RE-MI)
Authors: Kindgen-Milles Detlef , Journois Didier , Fumagalli Roberto , Vesconi Sergio , Maynar Javier , Marinho Anibal , Bolgan Irene , Brendolan Alessandra , Formica Marco , Livigni Sergio , Maio Mariella , Marchesi Mariano , Mariano Filippo , Monti Gianpaola , Moretti Elena , Silengo Daniela , Ronco Claudio
Published: June 2005

Introduction

Current practices for renal replacement therapy in intensive care units (ICUs) remain poorly defined. The DOse REsponse Multicentre International collaborative initiative (DO-RE-MI) will address the issue of how the different modes of renal replacement therapy are currently chosen and performed. Here, we describe the study protocol, which was approved by the Scientific and Steering Committees.

Methods

DO-RE-MI is an observational, multicentre study conducted in ICUs. The primary end-point will be the delivered dose of dialysis, which will be compared with ICU mortality, 28-day mortality, hospital mortality, ICU length of stay and number of days of mechanical ventilation. The secondary end-point will be the haemodynamic response to renal replacement therapy, expressed as percentage reduction in noradrenaline (norepinephrine) requirement. Based on the the sample analysis calculation, at least 162 patients must be recruited. Anonymized patient data will be entered online in electronic case report forms and uploaded to an internet website. Each participating centre will have 2 months to become acquainted with the electronic case report forms. After this period official recruitment will begin. Patient data belong to the respective centre, which may use the database for its own needs. However, all centres have agreed to participate in a joint effort to achieve the sample size needed for statistical analysis.

Conclusion

The study will hopefully help to collect useful information on the current practice of renal replacement therapy in ICUs. It will also provide a centre-based collection of data that will be useful for monitoring all aspects of extracorporeal support, such as incidence, frequency, and duration.
Responding to the HIV/AIDS epidemic: lessons from the case of Eritrea
Authors: Müller Tanja R.
Published: June 2005

This paper discusses the political response to HIV/AIDS in Eritrea, a country where the epidemic appears to have stabilized at an average prevalence rate of around 3%. It shows that Eritrea has mobilized an effective multisectoral response to cope with the epidemic and its impact under conditions of full-scale war followed by a still-fragile postconflict situation, compounded by recurring drought and economic decline. As one key factor for successful policy action, the commitment of a centralized government with the capacity to implement its decisions and mobilize other stakeholders is identified. Another important factor might be the high level of social cohesion prevalent within Eritrean society.
Characterization of the Rat INSL3 Receptor
Authors: SCOTT D J , FU P , SHEN P‐J , GUNDLACH A , LAYFIELD S , RIESEWIJK A , TOMIYAMA H , HUTSON J M , TREGEAR G W , BATHGATE R A D
Published: June 2005

Abstract: Human LGR8, initially discovered as a low‐affinity relaxin receptor, has now been characterized as the INSL3 receptor. To investigate LGR8 function in the rat, an LGR8 ortholog was identified in the rat genome, and the full‐length sequence was cloned and expressed. Rat LGR8 bound INSL3 with high affinity, clearly demonstrating that it is the rat INSL3 receptor. Interestingly, native rat relaxin did not activate rat LGR8, indicating that relaxin is not an endogenous ligand for rat LGR8. LGR8 mRNA expression was demonstrated in the gubernaculum at the time of testis descent and in the testis associated with germ cells.
Genetic Targeting of Relaxin and Insl3 Signaling in Mice
Authors: FENG SHU , BOGATCHEVA NATALIA V. , KAMAT APARNA A. , AGOULNIK ALEXANDER I.
Published: June 2005

Abstract: We studied ligand‐receptor interactions between relaxin (RLN), insulin‐like 3 peptide (INSL3), and LGR7 and LGR8 receptors. The phenotypic effects of deficiency for Lgr7 and Lgr8 receptors, transgenic overexpression of Rln1 and Insl3, and different combinations of these mutations in mice were analyzed. It was reported that Rln1‐deficient mice exhibit abnormal nipple development, prolonged parturition, age‐related pulmonary fibrosis, and abnormalities in the testis and prostate. Mutation of Lgr8 or its cognate ligand Insl3 causes cryptorchidism. Mutant females deficient for the Lgr7 receptor have grossly undeveloped nipples and are unable to feed their progeny. Parturition is prolonged in these females, resulting in a significantly higher number of stillborn pups. Histologic analysis of Lgr7 mutant lung tissues demonstrates increased collagen accumulation and perivenular smooth muscle hypertrophy. However, Lgr7‐deficient males do not exhibit abnormalities of male reproductive organs as seen in Rln1 knockout mice. Double‐mutant males deficient for Lgr7 and Lgr8 have a normal prostate, suggesting that Lgr8 does not account for differences in Rln1−/− and Lgr7−/− phenotypes. We also produced mice with transgenic overexpression of Rln1 under rat insulin 2 promoter. Rln1 transgenic females exhibited increased nipple size, whereas Rln1 transgenic females deficient in Lgr7 had undeveloped nipples, indicating that Lgr7 is the only receptor for relaxin that mediates this effect. Transgenic overexpression of Rln1 does not affect gonadal descent in females, and transgenic overexpression of Insl3 does not rescue the mutant phenotype of Lgr7‐deficient mice, suggesting the non‐overlapping functions of two signaling pathways. In summary, our data indicate that the Insl3/Lgr8 and Rln1/Lgr7 pathways are distinct and separate in vivo. Therefore, we propose to rename Lgr8 as Insl3r (Insl3 receptor) and Lgr7 as Rlnr (relaxin receptor).