bluuebunny/crossref_metadata_2025 huggingface dataset:
Immigrant Youth in the Labor Market
Authors: Perreira Krista M. , Harris Kathleen Mullan , Lee Dohoon
Published: January 2007

The past two decades witnessed unprecedented growth in the number of children of immigrants living in the United States. The successful socioeconomic adaptation of these youth to the United States will be determined, in part, by their early work experiences. The authors use data from the National Longitudinal Study of Adolescent Health (Add Health) to evaluate differences in the work participation of youth enrolled in high school by immigrant generation. They find that immigrant youth work significantly less during middle and high school than their native-born peers. However, these native-immigrant differences in youth labor-market participation decline as high school graduation approaches. Native-immigrant differences in youth labor-market participation partially reflect differences in the racial-ethnic compositions of first-, second-, and third+-generation cohorts. Beyond race and/or ethnicity, native-immigrant differences in youth labor-market participation also stem from systematic differences in their family socioeconomic characteristics, school orientations, social networks, and labor-market opportunities.
In the Company of Women
Authors: Baron James N. , Hannan Michael T. , Hsu Greta , Koçak Özgecan
Published: January 2007

Perspectives on inequality differ greatly regarding whether the logic of bureaucracy undermines sex-based ascription in work organizations by reducing subjectivity in personnel decisions, or instead merely serves to obscure or “scientize” inequality. Past research has tended to operationalize bureaucratization in terms of the adoption of formal procedures and structures; the authors argue instead that disagreements about whether bureaucracy promotes or ameliorates inequality and segregation have less to do with the contours of bureaucracy than with the underlying logic of bureaucratic organization. Accordingly, the authors assess the link between bureaucratic organization and labor-market ascription by characterizing the logics underlying organizational employment systems. Using data on young high-technology companies in California’s Silicon Valley, they find evidence that bureaucratization improves employment prospects for women in core scientific-technical roles within these enterprises. They further explore path dependence in organizational logics and find that such logics, when adopted, have powerful enduring effects on labor-force composition.
A Five-Year Experience With the Use of BiPAP in a Pediatric Intensive Care Unit Population
Authors: Joshi Gayatri , Tobias Joseph D.
Published: January 2007

The authors retrospectively reviewed their experience with bilevel positive airway pressure (BiPAP) to treat respiratory insufficiency in pediatric patients over a 5-year period. After excluding patients on chronic home BiPAP and those in whom BiPAP was used to facilitate tracheal extubation (because there were no pre-BiPAP values on which to judge its efficacy), the study cohort included 45 patients (1.5 to 22 years) in whom BiPAP was used for acute respiratory insufficiency. The primary indication for BiPAP was a primary pulmonary parenchymal process in 29 patients and postoperative atelectasis with respiratory insufficiency following cardiac or upper abdominal surgery in 16 patients. There were no differences in the pre-BiPAP values of oxygen requirement, PCO2, oxygen saturation, and respiratory rate between the 2 groups. With the application of BiPAP in patients with primary pulmonary parenchymal disease, there was a decreased oxygen requirement, PCO2, and respiratory rate. No change in oxygen saturation was noted. In patients with postoperative respiratory insufficiency, there was an improvement in all 4 parameters. There was no difference in post-BiPAP values of oxygen requirement, respiratory rate, or PCO2 between the 2 groups. The post-BiPAP oxygen saturation was greater in patients with postoperative respiratory insufficiency (96% ± 4%) than in patients with primary pulmonary parenchymal disease (92% ± 6%, P = .02). Endotracheal intubation was required in 11 of 29 patients with primary pulmonary parenchymal pathology versus 1 of 16 patients with postoperative atelectasis and/or respiratory insufficiency ( P = .03). The chances of requiring intubation were greater in patients ≤ 6 years of age (relative risk 1.9), if the oxygen requirement did not decrease to less than 60% within the first 24 hours of BiPAP use (relative risk 3.3) and if there were any PCO2 values ≥ 55 mmHg during the first 24 hours of BiPAP use (relative risk 9.8). No severe complications to BiPAP were noted. BiPAP safely and effectively improves the respiratory status of and might decrease the need for endotracheal intubation in pediatric patients with acute respiratory insufficiency of various etiologies.
Life-Threatening Arrhythmias in the Intensive Care Unit
Authors: Reising Scott , Kusumoto Fred , Goldschlager Nora
Published: January 2007

Symptomatic arrhythmias are frequently observed in the intensive care unit and often lead to significant hemodynamic compromise because of the presence of multisystem disease. In particular, prompt evaluation of patients with tachycardia is critical because treatment depends on the accurate diagnosis of the arrhythmia mechanism. The electrocardiogram remains the most important diagnostic tool for the evaluation of both wide complex and narrow complex tachycardia. For wide complex tachycardia, evaluation of the atrioventricular relationship and QRS morphology are critical, and for narrow QRS complex tachycardias, evaluation focuses on identification of the location and morphology of P waves. Bradycardia can arise from sinus node dysfunction or atrioventricular conduction block.
Indications for Aortic Valve Replacement in Aortic Stenosis
Authors: Stout Karen K. , Otto Catherine M.
Published: January 2007

Aortic stenosis is a common condition, particularly in the elderly. The treatment is surgical, and any patient with symptomatic severe aortic stenosis should be considered for aortic valve replacement. Aortic stenosis causes an increase in afterload to the left ventricle, which when severe can lead to hemodynamic instability. Although the therapy of aortic stenosis is valve replacement, determining whether a patient has symptoms and accurately assessing the severity of stenosis can be difficult. The management of patients with severe aortic stenosis in the intensive care unit setting can be very challenging, particularly when comorbid medical conditions make aortic valve replacement difficult. This article reviews the diagnosis of aortic stenosis, methods of assessing symptoms and severity, and management of severe symptomatic stenosis, particularly in the intensive care unit setting. Components of the history that suggest symptomatic aortic stenosis are presented. The role of physical examination is discussed, as are the echocardiographic means of determining stenosis severity. Other means of assessing severity are addressed, as are circumstances in which there can be difficulty in interpretation, such as severe aortic stenosis and left ventricular dysfunction. Management of patients, focusing on the intensive care unit setting, is reviewed, with a focus on the timing of aortic valve replacement.
The Clinical Role of Central Venous Pressure Measurements
Authors: Magder Sheldon , Bafaqeeh Fahad
Published: January 2007

Central venous pressure (CVP) is commonly measured, but its clinical use is still not clear. We argue that the interpretation of the CVP needs to be considered in conjunction with an assessment of cardiac output. The objective of this study was to define an elevated CVP as one in which there is a low probability for cardiac output to increase with a volume infusion through a Starling mechanism by relating the initial CVP (measured relative to a reference point 5 cm below the sternal angle) to the response in cardiac output with volume infusion. The authors studied consecutive patients who had pulmonary artery catheters in place and who had a volume challenge as part of routine management as ordered by the treating physician. To ensure an adequate test of the Starling mechanism, data were included only if the volume infusion increased CVP by≥2 mm Hg. Responders were defined a priori as those with an increase in cardiac index ≥300 and nonresponders as <300 mL/min/m2. Patients failed to respond to volume infusion at all CVP values, and even 25% of those with CVP <5 mm Hg were nonresponders. However, when CVP was >10 mm Hg, physicians prescribed less fluid challenges, and when they did, a positive response was much less likely. Change in blood pressure or changes in urine output with volume infusion correlated poorly with change in cardiac index. A CVP of>10 mm Hg should be considered high, and the probability of an increase in cardiac output with volume infusion is low. This value is a reasonable upper limit for algorithms for empiric fluid challenges.
Understanding the NIMBY and LULU Phenomena: Reassessing Our Knowledge Base and Informing Future Research
Authors: Schively Carissa
Published: January 2007

A substantial amount of research relative to the not in my backyard (NIMBY) and locally unwanted land use (LULU) phenomena has been conducted during the past two decades. The article begins by illustrating the complex nature of these phenomena, noting variation in the types of facilities considered LULUs, the range of participants who exhibit NIMBY responses, and the varied manner in which these phenomena have been described. The focus of the article then moves to the influence of perceptions relative to NIMBY and methods available to respond to NIMBY concerns. The article summarizes research in these areas with the purpose of reminding us of what we know about NIMBY and LULU phenomena and what continues to challenge planning practitioners. The literature review points to research opportunities and the need to integrate the findings of previously distinct areas of inquiry to inform planning practice.
Market Reform and Social Protection: Lessons from the Czech Republic, Hungary, and Poland
Authors: Kaufman Robert R.
Published: January 2007

The countries of East Central Europe stand out as examples of the advantages of early and successful transitions to the market. Besides being early reformers, these countries also moved unusually quickly toward the establishment of broad social protection programs intended to cushion the shocks of the transition and to provide some longer-term protection against the uncertainties of the market economy. The success of these strategies has been uneven in terms of their impact on fiscal resources and their overall effect on the distribution of income. However, they must also be assessed in terms of the support they have generated for political and economic system among economically vulnerable but politically influential middle-class, blue-collar, and rural social sectors. In the countries of Central Europe, social transfers directed toward such groups have helped to win their acquiescence to painful adjustments and have facilitated longer-term support for democratic politics.
Between Historical Legacies and the Promise of Western Integration: Democratic Conditionality after Communism
Authors: Pop-Eleches Grigore
Published: January 2007

Post-communist democracy promotion has been most important in “borderline” countries, which had less favorable structural conditions than the East-Central European frontrunners, but where a domestic democratic constituency nevertheless existed and could benefit from Western support. External democracy promotion efforts have ranged from “soft” diplomatic pressure to economic and military sanctions and have acted through a variety of channels: (1) promotion of democratic attitudes among citizens yearning for Western integration, (2) political incentives for elites (in government and in the opposition), (3) domestic power balance shifts in favor of democratic politicians, and (4) promotion of better democratic governance through incentives for public administration reform. The most effective approach to democracy promotion thus far, however, has been the combination of political conditionality with significant political/economic incentives, best exemplified by the European integration process. Furthermore, the success of any strategy hinges on its fit with the geopolitical and domestic environment of the country in question. In particular, external actors must be more sensitive to the national sovereignty implications of such interventions, which can be easily exploited by domestic antidemocratic actors to undermine democracy promotion efforts.
Encouraging Effective Democratic Competition
Authors: Grzymała-Busse Anna
Published: January 2007

Political party competition is critical to fostering good governance and preventing corruption. However, several aspects of competition—the number of parties, their vote share, or their specific ideology—have no demonstrable impact on corruption. In contrast, the robustness of competition is critical in constraining governments and monitoring policy. Parties have to clearly profile themselves, be credible coalition partners, and prioritize parliamentary monitoring above building organizations. Above all, political party competition must be inclusive: no party should be excluded a priori from governance or coalitions because of their ideology or the identity of the constituency they represent. This is especially the case in new democracies, where capable and stable competitors are in short supply. Consequently, former authoritarian parties need to be included: they have the greatest incentives to monitor the behavior of the new governing parties, and they often have the greatest capacity to do so.
The Uncertain Future of Russia's Weak State Authoritarianism
Authors: Hanson Stephen E.
Published: January 2007

The policies of President Vladimir Putin have undermined Russia's fledging democratic institutions but have also failed to generate any sort of coherent authoritarianism to take their place. Thus, fifteen years after the collapse of the USSR, the country still lacks any consensus about its basic principles of state legitimacy. To explain this, we must understand the ways in which the Soviet Union's institutional legacies have short-circuited all three historically effective types of legitimate rule—traditional, rational-legal, and charismatic— resulting in a highly corrupt state that still cannot fully control its borders, monopolize the legal means of violence, or clearly articulate its role in the contemporary world. If energy prices drop suddenly, leadership transition problems prove unmanageable, and/or economic inequalities provoke more widespread and sustained public protest, the growing mood of resentful nationalism could transform Russia from an unsteady and distrusted “strategic partner” of the West into something far more hostile.
European Regional Organizations, Political Conditionality, and Democratic Transformation in Eastern Europe
Authors: Schimmelfennig Frank
Published: January 2007

How and under which conditions have European regional organizations been effective promoters of democratic change in Central and Eastern Europe? In this article, the author argues that only the credible conditional promise of membership in the European Union and NATO has had the potential to produce compliance with liberal-democratic norms in norm-violating transformation countries. These incentives, however, were not sufficient when the power costs of compliance were high for the target governments. They did little to alter the policies of authoritarian governments, which forewent the benefits of accession rather than risk losing power as a result of democratic reforms. Thus, whereas political conditionality was largely redundant in the forerunner countries of democratization in Central and Eastern Europe (except for some specific reform issues) and generally ineffective with entrenched authoritarian regimes, it proved highly effective in supporting democratic forces and locking in democratic reforms in the unstable democratic countries of the region.
Linkage, Leverage, and the Post-Communist Divide
Authors: Way Lucan A. , Levitsky Steven
Published: January 2007

An important source of the post-Communist divide between a relatively democratic Central and Southeastern Europe on one side and a highly autocratic former Soviet Union on the other is the different character of the international environments in the two regions. Post-Communist countries differ along two key dimensions of the post–cold war international environment: Western leverage, or governments' vulnerability to external pressure; and linkage to the West, or the density of a country's economic, political, organizational, social, and communication ties to the European Union and the United States. High linkage and leverage in Central and Southeastern Europe generated intense international democratizing pressures, contributing to democratization even under unfavorable domestic conditions. By contrast, weaker linkage and leverage in the former Soviet Union has produced a much more permissive international environment. As a result, democratization has failed in the absence of a strong domestic push.
The Politics of Homeschooling
Authors: Cooper Bruce S. , Sureau John
Published: January 2007

Homeschooling has developed from a small, isolated, parent-led effort to a vibrant national movement to lobby for and legalize K-12 education at home in all 50 states. Although a majority of homeschool families are Evangelical Christians, the others come from a variety of religious and nonreligious backgrounds, giving homeschooling a broad national political and social base. Homeschool families have organized regional and national associations, gained children’s access to after-school and even during-school classes and activities in local public schools, and increasingly gained entry to college. About 1.35 million children in the country are being officially home-schooled, making it a vital and expanding form of private education and political force in U.S. society.
Moving Forward or Sliding Backward
Authors: Lacireno-Paquet Natalie , Holyoke Thomas T.
Published: January 2007

What is the fate of charter school policy in the American states? The authors argue that dramatic new policies brought about by a radical reconfiguration of interests and politics are frequently short lived, though new policies are rarely erased; instead, they reach a compromise between competing sets of interests. The authors test this notion in a study of the evolution of charter school policy in Michigan and the District of Columbia. They find in Michigan that the original law, dramatic in the breadth of its change to public education, has slowly reverted to reflect a balance of power between the ideal positions preferred by pro- and anti-charter school interests. But in the District of Columbia, the innovativeness of the new law has largely been sustained, mainly because organized opposing interests largely failed to emerge.
Education Tax Credits in a Post-Zelman Era
Authors: Huerta Luis A. , d’Entremont Chad
Published: January 2007

This article examines an emerging preference for education tax credit programs in a post- Zelman era. First, the authors detail the origin of tax credits and the types of existing plans. Second, they review the assumptions underlying the supposed advantages that may favor tax credits as a feasible alternative to vouchers. Third, they analyze legal, political, and policy implications of this form of school choice. They review evidence from recent research on tax credit programs and analyze new evidence collected for this article on the Minnesota Tax Credits and Deduction Program. They posit that although education tax credit plans may be more widely accepted than education vouchers, substantial obstacles may still restrict their implementation.
Restricted Choices, Limited Options
Authors: Fusarelli Lance D.
Published: January 2007

This article reviews implementation of the school choice and supplementary educational services provisions contained in the No Child Left Behind Act. School district progress, resistance, and obstacles to implementation are discussed and a number of practical remedies to improve implementation of school choice and supplemental educational services are offered. Much more research is needed in these areas to determine whether choice and supplementary educational services improve educational opportunities for disadvantaged children trapped in failing schools. Recommendations for future studies are made.
The Politics of Privatization in American Education
Authors: Boyd William L.
Published: January 2007

The long-sustained effort of conservatives and their think tanks and media outlets to win support for school choice, market forces, and privatization schemes in education is paying off. But it is encountering steady resistance from the public education establishment and its supporting teachers’ unions. Actions, reactions, strategies, and the unfolding political struggle between these adversaries are the subjects of this brief overview of this topic.
A Self-Schema Approach to Healthy Eating
Authors: Kendzierski Deborah
Published: January 2007

Obesity is a major health problem in the United States. This makes weight management an issue for all patient populations and especially for the psychiatric patient population because of the possibility of medication-induced weight gain. Mood stabilizers, antipsychotics, and antidepressants can induce weight gain, potentially resulting in both health risks and nonadherence to psychotropic therapy. Screening and intervention to promote healthier eating habits are recommended. This article reviews the research on healthy eating and other self-schemas (i.e., personally important domain-specific self-definitions) to provide a framework for understanding how the way people define themselves in terms of their eating habits affects their thoughts and behavior. Finally, implications of a self-schema approach for effective screening and dietary intervention are outlined.
Clinical quantitation of diagnostic and predictive gene expression levels in follicular and diffuse large B-cell lymphoma by RT-PCR gene expression profiling
Authors: Sakhinia Ebrahim , Glennie Caroline , Hoyland Judith A. , Menasce Lia P. , Brady Gerard , Miller Crispin , Radford John A. , Byers Richard J.
Published: January 2007

Recent microarray gene expression profiling studies have identified gene signatures predictive of outcome, so-called “indicator” genes, for diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). However, measurement of these genes in routine practice remains difficult. We applied real-time polymerase chain reaction (PCR) to polyA cDNAs prepared from 106 archived human frozen lymph nodes (63 of FL, 25 of DLBCL, 10 reactive lymph nodes, and cases with paired samples of FL [4] and subsequent DLBCL [4]). Reverse transcription and polyA reverse transcriptase (RT)–PCR was performed, and resultant cDNA was probed by real-time PCR for 36 candidate indicator genes, selected from microarray studies. Nine genes showed statistically significant different expression between FL and DLBCL, including cyclin B, COL3A1, NPM3, H731, PRKCB1, OVGL, ZFPC150, HLA-DQ-a, and XPB. Of these, cyclin B, NPM3, and COL3A1 were higher in DLBCL. Six genes showed statistically significant higher expression in the neoplastic nodes compared with reactive nodes, namely PRKCB1, BCL-6, EAR2, ZFX, cyclin B, YY1. High levels of YY.1 were associated with a shorter survival interval in both FL and DLBCL. The method is simple, sensitive, and robust, facilitating routine use and may be used as a platform for clinical measurement of prognostic gene signatures.
NK cytotoxicity mediated by CD16 but not by NKp30 is functional in Griscelli syndrome
Authors: Gazit Roi , Aker Memet , Elboim Moran , Achdout Hagit , Katz Gil , Wolf Dana G. , Katzav Shulamit , Mandelboim Ofer
Published: January 2007

Griscelli syndrome (GS) type 2 is an autosomal recessive disorder represented by pigment dilution and impaired cytotoxic T lymphocyte (CTL) activity. NK activity has been scarcely investigated in GS patients. Here, we describe a new patient, possessing a hemophagocytic syndrome with a homozygous Q118X nonsense RAB27A mutation. Single specific primer–polymerase chain reaction (SSP-PCR) was developed based on this mutation and is currently used in prenatal genetic analysis. As expected, CTLs in the patient are not functional and NK cytotoxicity against K562 or 721.221 cells is diminished. Surprisingly, however, we demonstrate that CD16-mediated killing is intact in this patient and is therefore RAB27A independent, whereas NKp30-mediated killing is impaired and is therefore RAB27A dependent. We further analyzed the signaling pathways of these 2 receptors and demonstrated phosphorylation of Vav1 after CD16 activation but not after NKp30 engagement. Thus, we identify a novel homozygous mutation in the RAB27A gene of a new GS patient, observe for the first time that some activating NK receptors function in GS patients, and demonstrate a functional dichotomy in the killing mediated by these human NK-activating receptors.
The role of PKC and PDK1 in monocyte lineage specification by Ras
Authors: Pearn Lorna , Fisher Janet , Burnett Alan K. , Darley Richard L.
Published: January 2007

Although hyperactivation of Ras is a common feature of myeloid malignancy, its role in subverting hematopoiesis is unclear. We have examined the influence of Ras on normal human uncommitted myeloid subsets and show that expression of this oncogene strongly favors monocyte lineage selection in bipotential granulocyte/macrophage progenitors while inhibiting colony formation in other uncommitted subsets. Ras also promoted monocytic differentiation but not the proliferation of these cells. The mechanism through which Ras drives monocyte lineage selection was dependent on PKC activity and Ras was found to promote the expression, membrane translocation, and phosphorylation of conventional and novel PKC isoforms. We further show that Ras promoted the expression of the AGC kinase master regulator, PDK1, which maintains the stability and activity of PKC isoforms. Consistent with this, overexpression of PDK1 itself promoted monocyte colony formation and translocation of PKC. Overexpression of PDK1 was found to be a common feature of acute myeloid leukemia (45% of patients) and was closely associated with hyperphosphorylation of PKC. These data demonstrate that Ras is able to promote monocyte lineage selection via PKC and show for the first time the involvement of the kinase master regulator, PDK1, in both lineage specification and in human leukemia.
Reversible anergy of sIgM-mediated signaling in the two subsets of CLL defined by VH-gene mutational status
Authors: Ian Mockridge C. , Potter Kathleen N. , Wheatley Isla , Neville Louise A. , Packham Graham , Stevenson Freda K.
Published: January 2007

The 2 subsets of chronic lymphocytic leukemia (CLL), of worse or better prognosis, likely derive from pre-GC unmutated B cells, or post-GC mutated B cells, respectively. Different clinical behavior could relate to the ability of tumor cells to respond to surface (sIg)–mediated signals. Unmutated cases (U-CLL) have an increased ability to phosphorylate p72Syk in response to sIgM ligation compared to mutated cases (M-CLL). We now confirm and further investigate this differential signaling in a large cohort by [Ca2+]i mobilization. Cases responding to sIgM ligation express higher levels of CD38, ZAP-70, and sIgM. However, CD38 does not influence signaling in vitro or associate with response in bimodal CD38-expressing cases. Similarly, ZAP-70 expression is not required for response in either U-CLL or M-CLL. Strikingly, partially or completely anergized sIgM responses from each subset can recover both sIgM expression and signal capacity spontaneously in vitro or following capping/endocytosis. This provides direct evidence for engagement of putative antigen in vivo. Signaling via sIgD differs markedly being almost universally positive in both U-CLL and M-CLL, with no association with CD38 or ZAP-70 expression. Downstream signaling pathways, therefore, appear intact in CLL, locating anergy to sIgM, mainly in M-CLL. Integration of differential isotype-specific effects mediated by (auto)antigen may determine tumor behavior.
Novel expressed sequences identified in a model of androgen independent prostate cancer
Authors: Quayle Steven N , Hare Heidi , Delaney Allen D , Hirst Martin , Hwang Dorothy , Schein Jacqueline E , Jones Steven JM , Marra Marco A , Sadar Marianne D
Published: January 2007

Background

Prostate cancer is the most frequently diagnosed cancer in American men, and few effective treatment options are available to patients who develop hormone-refractory prostate cancer. The molecular changes that occur to allow prostate cells to proliferate in the absence of androgens are not fully understood.

Results

Subtractive hybridization experiments performed with samples from anin vivomodel of hormonal progression identified 25 expressed sequences representing novel human transcripts. Intriguingly, these 25 sequences have small open-reading frames and are not highly conserved through evolution, suggesting many of these novel expressed sequences may be derived from untranslated regions of novel transcripts or from non-coding transcripts. Examination of a large metalibrary of human Serial Analysis of Gene Expression (SAGE) tags demonstrated that only three of these novel sequences had been previously detected. RT-PCR experiments confirmed that the 6 sequences tested were expressed in specific human tissues, as well as in clinical samples of prostate cancer. Further RT-PCR experiments for five of these fragments indicated they originated from large untranslated regions of unannotated transcripts.

Conclusion

This study underlines the value of using complementary techniques in the annotation of the human genome. The tissue-specific expression of 4 of the 6 clones tested indicates the expression of these novel transcripts is tightly regulated, and future work will determine the possible role(s) these novel transcripts may play in the progression of prostate cancer.
Post-marketing assessment of content and efficacy of preservatives in artemisinin-derived antimalarial dry suspensions for paediatric use
Authors: Atemnkeng Magnus A , De Cock Katelijne , Plaizier-Vercammen Jacqueline
Published: January 2007

Background

Artemisinin-derivative formulations are now widely used to treat falciparum malaria. However, the dry powder suspensions developed for children are few and/or are of poor quality. In addition to the active compound, the presence of a suitable preservative in these medicines is essential. In this study, an evaluation of the preservative content and efficacy in some dry suspensions available on the Kenyan market was performed.

Method

UV spectrophotometry was used to identify the preservatives in each sample while HPLC-UV was used for quantification. After reconstitution of the powders in water, the dissolution of the preservatives was followed for 7 days. Antimicrobial efficacy of the preservatives was assessed by conducting a preservative efficacy test (PET) following the European pharmacopoeia standards.

Results

Four different preservatives were identified namely methylparahydroxybenzoate (MP), propylparahydroxybenzoate (PP), benzoic acid and sorbic acid. MP and PP were identified in Artesiane®(artemether 300 mg/100 ml), Alaxin®(dihydroartemisinin 160 mg/80 ml) andGvither®(artemether 300 mg/100 ml) respectively. Sorbic acid was presentin Artenam®(artemether 180 mg/60 ml) while benzoic acid was identified in Santecxin®(dihydroartemisinin 160 mg/80 ml) andArtexin®(dihydroartemisinin 160 mg/80 ml) respectively. Cotecxin®(dihydroartemisinin 160 mg/80 ml) did not contain any of the above preservatives. After reconstitution in water, preservativesin 50%(3/6) of the products did not completely dissolve and the PET results revealed that only Artenam®and Gvither®met the requirements for antimicrobial efficacy. The other products did not conform.

Conclusion

These results show that paediatric antimalarial dry powder formulations on the market may contain ineffective or incorrect amounts of preservatives. This is a potential risk to the patient. Studies conducted on the dry powder suspensions should include the analysis of both the active ingredient and the preservative, including the efficacy of the latter.
Morphological instability and cancer invasion: a 'splashing water drop' analogy
Authors: Guiot Caterina , Delsanto Pier P , Deisboeck Thomas S
Published: January 2007

Background

Tissue invasion, one of the hallmarks of cancer, is a major clinical problem. Recent studies suggest that the process of invasion is driven at least in part by a set of physical forces that may be susceptible to mathematical modelling which could have practical clinical value.

Model and conclusion

We present an analogy between two unrelated instabilities. One is caused by the impact of a drop of water on a solid surface while the other concerns a tumor that develops invasive cellular branches into the surrounding host tissue. In spite of the apparent abstractness of the idea, it yields a very practical result, i.e. an index that predicts tumor invasion based on a few measurable parameters. We discuss its application in the context of experimental data and suggest potential clinical implications.
Use of medicinal plants for human health in Udzungwa Mountains Forests: a case study of New Dabaga Ulongambi Forest Reserve, Tanzania
Authors: Kitula Rukia A
Published: January 2007

The dependence of local people on plant medicine from natural forests has a long tradition in Tanzania and is becoming increasingly popular among rural and urban communities due to among others increase in living costs. The study on utilization of medicinal plants for meeting heath care needs was carried out between March 2001 and March 2002 in New Dabaga Ulongambi Forest Reserve, Tanzania. The study aimed at generating necessary data for the Udzungwa Mountains Forest Management project to draft sound Joint Forest Management plans. Specific objectives of the study among others were to assess knowledge associated with utilization of medicinal plants for health care needs as well as factors associated in using plant medicines in the study area. A questionnaire survey, market survey and literature review were used to collect information. Tools used for data analysis were Statistical Packages for Social Science and content analysis. A total of 45 plant species were documented curing about 22 human diseases. Medicinal plants were readily available throughout the year and plentiful in the forest reserve. Roots and leaves were the plant parts harvested for medicinal purposes. Processing of plant medicines involved boiling, pounding, soaking in water and chewing. Distance to health facility, income level of the household and beliefs contributed to the use of plant medicines. The study concluded that medicinal plants play an important role in providing primary health care to the rural communities. It is recommended that in achieving joint forest management (JFM), villagers adjacent to the forest reserve should be sensitised on the importance of JFM through seminars, workshops, drama, school songs or video show. During the development of a joint draft management plan, villagers as an informal institution must define their priority needs of use of parts of the forest in collaboration with the Udzungwa Mountains Forest Management project.
Telomeric DNA induces apoptosis and senescence of human breast carcinoma cells
Authors: Yaar Mina , Eller Mark S , Panova Izabela , Kubera John , Wee Lee Hng , Cowan Kenneth H , Gilchrest Barbara A
Published: January 2007

Introduction

Cancer is a leading cause of death in Americans. We have identified an inducible cancer avoidance mechanism in cells that reduces mutation rate, reduces and delays carcinogenesis after carcinogen exposure, and induces apoptosis and/or senescence of already transformed cells by simultaneously activating multiple overlapping and redundant DNA damage response pathways.

Methods

The human breast carcinoma cell line MCF-7, the adriamycin-resistant MCF-7 (Adr/MCF-7) cell line, as well as normal human mammary epithelial (NME) cells were treated with DNA oligonucleotides homologous to the telomere 3' overhang (T-oligos). SCID mice received intravenous injections of MCF-7 cells followed by intravenous administration of T-oligos.

Results

Acting through ataxia telangiectasia mutated (ATM) and its downstream effectors, T-oligos induced apoptosis and senescence of MCF-7 cells but not NME cells, in which these signaling pathways were induced to a far lesser extent. In MCF-7 cells, experimental telomere loop disruption caused identical responses, consistent with the hypothesis that T-oligos act by mimicking telomere overhang exposure. In vivo, T-oligos greatly prolonged survival of SCID mice following intravenous injection of human breast carcinoma cells.

Conclusion

By inducing DNA damage-like responses in MCF-7 cells, T-oligos provide insight into innate cancer avoidance mechanisms and may offer a novel approach to treatment of breast cancer and other malignancies.
Delayed Mammary Gland Involution in Mice with Mutation of the Insulin-Like Growth Factor Binding Protein 5 Gene
Authors: Ning Yun , Hoang Bao , Schuller Alwin G. P. , Cominski Tara P. , Hsu Ming-Sing , Wood Teresa L. , Pintar John E.
Published: January 2007

IGFs (IGF-I and IGF-II) are essential for development, and their bioactivities are tightly regulated by six related IGF-binding proteins (IGFBPs). IGFBP-5 is the most highly conserved binding protein and is expressed in several key developmental lineages as well as in multiple adult tissues including the mammary gland. To explore IGFBP-5 actions in vivo, we produced IGFBP-5 knockout (KO) mice. Whole-body growth, selected organ weights, and body composition were essentially normal in IGFBP-5 KO mice, presumably because of substantial compensation by remaining IGFBP family members. The IGFBP-5 KO mice also exhibited normal mammary gland development and were capable of nursing their pups. We then directly evaluated the proposed role of IGFBP-5 in apoptosis and remodeling of mammary gland during involution. We found that the process of involution after forced weaning was delayed in IGFBP-5 KO mice, with both the appearance of apoptotic cells and the reappearance of adipocytes retarded in mutant mice, compared with controls. We also determined the effects of IGFBP-5 deletion on mammary gland development in pubertal females after ovariectomy and stimulation with estradiol/progesterone. In this paradigm, IGFBP-5 KO mammary glands exhibited enhanced alveolar bud formation consistent with enhanced IGF-I action. These results demonstrate that IGFBP-5, although not essential for normal growth, is required for normal mammary gland involution and can regulate mammary gland morphogenesis in response to hormone stimulation.
Centrally and Peripherally Administered Ghrelin Potently Inhibits Water Intake in Rats
Authors: Hashimoto Hirofumi , Fujihara Hiroaki , Kawasaki Makoto , Saito Takeshi , Shibata Minori , Otsubo Hiroki , Takei Yoshio , Ueta Yoichi
Published: January 2007

Ghrelin is known as a potent orexigenic hormone through its action on the brain. In this study, we examined the effects of intracerebroventricular (icv) and iv injection of ghrelin on water intake, food intake, and urine volume in rats deprived of water for 24 h. Water intake that occurred after water deprivation was significantly inhibited by icv injection of ghrelin (0.1, 1, and 10 nmol/rat) in a dose-related manner, although food intake was stimulated by the hormone. The antidipsogenic effect was as potent as the orexigenic effect. Similarly, water intake was inhibited, whereas food intake was stimulated dose dependently after iv injection of ghrelin (0.1, 1, and 10 nmol/kg). The inhibition of drinking was comparable with, or even more potent than, atrial natriuretic peptide (ANP), an established antidipsogenic hormone, when administered icv, although the antidipsogenic effect lasted longer. ANP had no effect on food intake. Urine volume decreased dose relatedly after icv injection of ghrelin but not by ANP. Intravenous injection of ghrelin had no effect on urine volume. Because drinking usually occurs with feeding, food was withdrawn to remove the prandial drinking. Then the antidipsogenic effect of ghrelin became more potent than that of ANP and continued longer than when food was available. Expression of Fos was increased in the area postrema and the nucleus of the tractus solitarius by using immunohistochemistry after icv and iv injection of ghrelin. The present study convincingly showed that ghrelin is a potent antidisogenic peptide in rats.
Neonatal Exposure to Estrogens Suppresses Activin Expression and Signaling in the Mouse Ovary
Authors: Kipp Jingjing L. , Kilen Signe M. , Bristol-Gould Sarah , Woodruff Teresa K. , Mayo Kelly E.
Published: January 2007

In the ovary, the steroid hormone estrogen and the TGF-β superfamily member activin are both produced by granulosa cells and they both have intraovarian functions. Emerging evidence has indicated an interaction of these two signaling pathways. Based on the fact that estrogen and activin can impact early follicle formation and development, we hypothesize that estrogen treatment may alter activin signaling in the neonatal ovary. Therefore, this study was designed to examine the effect of neonatal diethylstilbestrol (DES) and estradiol (E2) exposure on the mRNA and protein levels of the key factors involved in activin signaling in the mouse ovary. CD-1 mouse pups were given daily injections of DES, E2, or oil on postnatal d 1–5, and ovaries and sera were collected on d 19. Neonatal DES or E2 exposure decreased the number of small antral follicles, induced multioocytic follicle formation, and decreased activin β-subunit mRNA and protein levels. Consistent with local loss of β-subunit expression, the phosphorylation of Smad 2, a marker of activin-dependent signaling, was decreased in the estrogen-treated ovaries. The decreased β-subunit expression resulted in a decrease in serum inhibin levels, with a corresponding increase in FSH. Estrogen also suppressed activin subunit gene promoter activities, suggesting a direct transcriptional effect. Overall, this study demonstrates that activin subunits are targets of estrogen action in the early mouse ovary.
Increased Oocyte Degeneration and Follicular Atresia during the Estrous Cycle in Anti-Müllerian Hormone Null Mice
Authors: Visser Jenny A. , Durlinger Alexandra L. L. , Peters Isolde J. J. , van den Heuvel Edwin R. , Rose Ursula M. , Kramer Piet , de Jong Frank H. , Themmen Axel P. N.
Published: January 2007

Anti-Müllerian hormone (AMH) plays an important role in folliculogenesis. AMH null mice display an increased recruitment of primordial follicles. Nevertheless, these mice do not have proportionally more preovulatory follicles. Therefore, AMH null mice provide an interesting genetic model to study the regulation of species-specific number of preovulatory follicles. We studied the follicle pool throughout the estrous cycle at 4 months of age. Analysis of the follicle pool revealed that AMH null mice have an increased and earlier cyclic recruitment of growing follicles despite a blunted FSH surge at estrus. However, FSH levels at estrus were apparently too low to support growth to the preovulatory stage because an increased level of atresia was observed, which neutralized the increased cyclic recruitment. When AMH null mice were subjected to a superovulation scheme, the rise in FSH levels resulted in the rescue of the recruited cohort of growing follicles. Analysis of the follicle pool also revealed that the increased recruitment of primordial follicles in AMH null mice was neutralized by an increased loss of follicles during the transition from small preantral to large preantral follicle. This major loss of follicles was not completely reflected by a corresponding augmentation of atresia but did correspond with an increased number of oocyte remnants observed in AMH null mice. We conclude that a combination of increased oocyte degeneration and increased follicular atresia neutralizes the increased initial and cyclic recruitment in AMH null mice to a normal number of preovulatory follicles.
Hyperglycemia Alters the Responsiveness of Smooth Muscle Cells to Insulin-Like Growth Factor-I
Authors: Maile Laura A. , Capps Byron E. , Ling Yan , Xi Gang , Clemmons David R.
Published: January 2007

IGF-I stimulation of smooth muscle cell (SMC) migration and proliferation requires αVβ3 ligand occupancy. We hypothesized that changes in the levels of extracellular matrix proteins induced by alterations in glucose concentrations may regulate the ability of SMCs to respond to IGF-I. IGF-I stimulated migration and proliferation of SMCs that had been maintained in 25 mm glucose containing media, but it had no stimulatory effect when tested using SMCs that had been grown in 5 mm glucose. IGF-I stimulated an increase in Shc phosphorylation and enhanced activation of the MAPK pathway in SMCs grown in 25 mm glucose, whereas in cells maintained in 5 mm glucose, IGF-I had no effect on Shc phosphorylation, and the MAPK response to IGF-I was markedly reduced. In cells grown in 25 mm glucose, the levels of αVβ3 ligands, e.g. osteopontin, vitronectin, and thrombospondin, were all significantly increased, compared with cells grown in 5 mm glucose. The addition of these αVβ3 ligands to SMCs grown in 5 mm glucose was sufficient to permit IGF-I-stimulated Shc phosphorylation and downstream signaling. Because we have shown previously that αVβ3 ligand occupancy is required for IGF-I-stimulated Shc phosphorylation and stimulation of SMC growth, our data are consistent with a model in which 25 mm glucose stimulates increases in the concentrations of these extracellular matrix proteins, thus enhancing αVβ3 ligand occupancy, which leads to increased Shc phosphorylation and enhanced cell migration and proliferation in response to IGF-I.