bluuebunny/crossref_metadata_2025 huggingface dataset:
Who Makes Weapons Procurement Decisions?
Authors: Holland Lauren
Published: April 2005

Despite the absence of scientific support for a tripartite alliance in defense policymaking, political scientists and the general public continue to subscribe to a sub government explanation. This article addresses the sub government dilemma as it applies to the area of weapons procurement. More precisely, it asks whether the sub government model accurately describes and adequately explains the decisions to develop and build major weapons systems. In answering this question, the critical assumptions or propositions that comprise the model are tested, relying upon published research and original data drawn from 19 cases of military hardware decisions. The findings do lend some qualified support for a military subgovernment.
How Much Privatization?
Authors: Greene Jeffrey D.
Published: April 2005

Although it is widely assumed that there has been a surge in the use of alternative service delivery methods, few empirical studies have examined the degree to which privatization actually has increased. This study examines the levels of privatization in cities over a 10–year period. The findings suggest that the use of privatization increased significantly between 1982 and 1992 for the 596 cities included in this inquiry.
School Choice in Milwaukee
Authors: Percy Stephen L. , Maier Peter
Published: April 2005

For decades educational reformers have identified school choice programs as a strategy for restructuring public school systems. Practically every state has considered or adopted a school assignment program that qualifies as a “choice” initiative, one in which students and parents have some choice in school selection. Increasingly, school districts are contemplating plans that include a choice of private, as well as public, schools. One of the most far‐reaching of these school choice plans is the Milwaukee (Wisconsin) Parental Choice Program, which, as legislated, allows parents to use vouchers to enroll their children in both sectarian and nonsectarian schools in the community. This paper explores the evolution of school choice in Milwaukee and examines the extent to which school choice is representative of other privatization efforts currently under way in the United States.
Reducing Toxic Chemical Releases and Transfers: Explaining Outcomes for a Voluntary Program
Authors: O'Toole Laurence J. , Yu Chilik , Cooley James , Cowie Gail , Crow Susan , DeMeo Terry , Herbert Stephanie
Published: April 2005

Relatively little is known about the possibilities and limitations of voluntary public programs. The so‐called 33/50 Program for reducing releases of certain toxic chemicals into the environment provides a useful instance for examination. In an investigation of toxics‐reduction outcomes, with states as units of analysis, economic and policy variables help to explain the results. In particular, channels and approaches used In communicating policy intentions are related to outcomes. Voluntary programs can make a difference, but the details of execution, including the extent and nature of field efforts, influence outcomes.
Determinants of Trade Orientation in Less Developed Countries
Authors: Nomi Tomoaki
Published: April 2005

The success of East Asian Newly Industrializing Countries often has been attributed to their outward‐oriented trade strategies. Cross‐national analysis of trade orientation reveals that the degree of export‐oriented industrialization (measured as manufacturing exports as a percentage of gross domestic product) is associated closely with relative factor endowments. While Singapore and Taiwan are more outward oriented than expected by the cross‐national norm, Hong Kong is less outward oriented than expected.
The White House and Congress on Child Care and Family Leave Policy: From Carter to Clinton
Authors: Wisensale Steven K.
Published: April 2005

Over the last two decades four presidents produced a variety of family policy initiatives with mixed results. Carter issued his nine‐point plan on the family and convened the first White House Conference on Families in American history. Reagan created the White House Working Group on the Family and issued Executive Order 12606, which established family impact statements. George Bush continued many of Reagan's policies and pushed family values to near the top of the political agenda by 1992, and Bill Clinton set forth his eight‐point plan on the family and moved quickly to reverse many of the policies of the Reagan‐Bush era. Discussed is the role of the White House and Congress in shaping two family policy initiatives in particular: The Child Care and Development Block Grant of 1990 and the Family and Medical Leave Act of 1993.
Policy Issues: License Renewal for Older Drivers‐Analysis of the Iowa Experience in Reexamination of High‐Risk Drivers
Authors: Mercier Cletus R. , Falb Scott R.
Published: April 2005

Loss of a driver license places an older person in the unhappy role of a transportation dependent. This dependence weighs heavily on that person' s family; if family members are nearby, they become either the sole or primary source of transportation for their transportation‐dependent parent(s). If there are no family members nearby, as occurs often in today's highly mobile society, then a major concern of that family may be their parent(s)' lack of mobility, with the parent becoming effectively restricted to home due to lack of access to adequate transportation facilities.

Most of those who are involved in the issue of driver license renewal favor keeping older drivers on the road as long as possible, rather than arbitrarily denying them the privilege to drive. But there is legitimate concern about the presence of impaired drivers on the road and accompanying safety risks. Many states address this concern by devising license renewal procedures that will cause at least some potentially unsafe drivers to be flagged and referred for reexamination.

This study evaluates the bases for referral and reexamination currently used in the state of Iowa and assesses the validity of referrals. The results of our analysis indicate that the current referral process works quite well in identifying at‐risk drivers, resulting in a high percentage of suspensions or imposing additional restrictions on an existing license. Results also support policies instituted by some states using age as a criterion for more frequent license renewal–which would allow examiners to test and observe driver behavior more frequently. The choice of age 75 as a threshold is supported by these results.
Campaign Finance Reform and the 1994 Congressional Elections
Authors: Gross Donald A. , Shields Todd G. , Goidel Robert K.
Published: April 2005

Based on partisan arguments regarding the likely effect of campaign finance reform on electoral competition, one might suspect that, had spending limits been in place prior to the 1994 midterm elections, Republicans would not have been able to gain control of the House of Representatives. To examine this proposition, we first create a regression model designed to explain the Democratic percentage of the vote as a function of candidate spending, incumbency, nonincumbent candidate quality, and the underlying partisan leanings of the congressional districts. We then use this regression model to simulate the likely effects of campaign finance reform on the outcome of the 1994 midterm elections. Our results indicate that while spending limits would have limited the number of seats gained by the Republican party, Republicans likely would have gained control of the House of Representatives even if spending limits had been in place prior to the 1994 elections. In addition, our results indicate that campaign finance reform that includes some form of public subsidy in addition to spending limits actually may have enhanced rather than diminished the Republican “earthquake” in 1994.
Strategies for Regulatory Reform: Forward Compared to Backward Mapping
Authors: Fiorino Daniel J.
Published: April 2005

Most efforts to reform regulation have relied on a forward mapping strategy, which views policy design and implementation from the top down. The limited success of many such reform efforts suggests the need for an alternative approach, based on a backward mapping strategy. The advantages of such a strategy are that it brings affected stakeholders into the process of designing and implementing reforms; proceeds incrementally to build a consensus for change; and leads to proposals that allow greater discretion and flexibility at the ground level, which is the direction that nearly all critics of existing regulation argue should be taken. Recent initiatives in environmental policy illustrate the uses and potential strengths of a backward mapping strategy for regulatory reform.
Book Notes
Authors: Donoher William J.
Published: April 2005

Books reviewed in this article:

Erik Asard and W. Lance Bennett, Democracy and the Marketplace of Ideas: Communication and Government in Sweden and the United States.

Andre Blais, Donald E. Blake, and Stephane Dion, Governments, Parties, and Public Sector Employees.

William J. Breen, Labor Market Politics and the Great War: The Department of Labor, the States, and the First U.S. Employment Service, 1907–1933.

James W. Button, Barbara A. Rienzo, and Kenneth D. Wald, Private Lives, Public Conflicts: Battles Over Gay Rights in American Communities.

Lynton K. Caldwell and Robert V. Bartlett (Eds.), Environmental Policy: Transnational Issues and National Trends.

John Carver, Boards That Make a Difference: A New Design for Leadership in Nonprofit and Public Organizations (2nd ed.).

Larry N. Gerston, Public Policy Making: Process and Principles.

Michele M. Hoyman, Power Steering: Global Automakers and the Transformation of Rural Communities.

David L. Imbroscio, Reconstructing City Politics: Alternative Economic Development and Urban Regimes.

Sheldon Kamieniecki, George A. Gonzalez, and Robert O. Vos (Eds.), Flashpoints in Environmental Policymaking: Controversies in Achieving Sustainability.

Samuel Krislov, How Nations Choose Product Standards and Standards Change Nations.

Brian K. Landsberg, Enforcing Civil Rights: Race Discrimination and the Department of Justice.

Duncan MacRae, Jr. and Dale Whittington, Expert Advice for Policy Choice.

William R. Nester, American Industrial Policy: Free or Managed Markets?

William R. Nester, The War for America's Natural Resources.

Howard Risher, Charles H. Fay, and Associates, New Strategies for Public Pay: Rethinking Government Compensation Programs.
The Demand for and Supply of Technical Information and Analysis in State Legislatures
Authors: Guston David H. , Jones Megan , Branscomb Lewis M.
Published: April 2005

With states making more substantive decisions in technically complex policy areas, the capacity of state legislatures to gather and use technical information and analysis is crucial. Applying a “market” metaphor, the article examines the demand for and the supply of technical information and analysis in state legislatures. The demand among legislators and staff is widespread and increasing, and the supply is varied in origin, importance, and quality. Reliance on sources external to the legislature—usually perceived as biased—is related to a lack of professionalization in legislatures, although the level of satisfaction in the available technical information and analysis is not. Identifiable barriers on both the demand side and the supply side prevent better use of technical information and analysis. There are ways to strengthen the relationship between state legislatures and a broad array of sources, as well as to educate the legislative consumer of technical information and analysis.
Book Notes
Authors: Donoher William J.
Published: April 2005

Books reviewed in this article:

Judith Wagner DeCew, In Pursuit of Privacy: Law, Ethics, and the Rise of Technology.

Peter DeLeon, Democracy and the Policy Sciences.

Herbert Inhaber, Why Energy Conservation Fails.

Sheila Jasanoff, Science at the Bar: Law, Science, and Technology in America.

Marick F. Masters, Unions at the Crossroads: Strategic Membership, Financial, and Political Perspectives.

Susan E. Mayer, What Money Can't Buy: Family Income and Children's Life Chances.

Pietro S. Nivola (Ed.), Comparative Disadvantages? Social Regulations and the Global Economy.

Sudhir Chella Rajan, The Enigma of Automobility:Democratic Politics and Pollution Control.

Paul M. Sniderman and Edward G. Carmines, Reaching Beyond Race.

Elliott White (Ed.), Intelligence, Political Inequality, and Public Policy.

Robet H. Wilson (Ed.), Public Policy and Community: Activism and Governance in Texas.
An Assessment of Health Policy Reform in Russia
Authors: Duffy Diane M.
Published: April 2005

Current fast‐track reforms in Russia's health sector involving decentralization and privatization are largely ineffective because they are mistargeted. They do not address the etiology of the major sources of health care problems (i.e., lifestyle, and living, working, and environmental conditions), and they even weaken coordinated efforts to address collective health needs. State government policy measures, democratization, self‐organization of society, and economic liberalization, as they are evolving currently, do not ensure sufficient citizen protection and interest articulation in the health sector.
Feminists in Power: Women Cabinet Ministers in the New Democratic Party (NDP) Government of Ontario, 1990–1995
Authors: Byrne Lesley Hyland
Published: April 2005

Faced with power all women, whether feminists or not, are confronted with three possible strategies: to become part of the existing structure of political power and find a position of equality within it; to challenge the existing power structure through parties whose goal it is to preempt such power in order to transform it; or to remain on the fringes of the established structures in order to engage in the pressure tactics of subversion.

Sylvie Paquerot, 1983

The difference between quantitative representation and qualitative (or “substantive”) representation has become of interest to scholars exploring the impact of the number of women elected to political institutions. Where once the focus was on the number alone, the most recent work emphasizes the significance of “interest representation.” Ultimately, the question is: Does it make a difference to have substantive representation of women, especially in positions of power? Does it make a difference in terms of policy outcomes? Does it make a difference in terms of institutional change? This research examines a case study of women cabinet ministers in the New Democratic Party government of Ontario, Canada, from 1990 to 1995. Based on lengthy interviews and an analysis of policy outcomes, this paper concludes that it did indeed make a difference, on both fronts, but that those transformations were not as dramatic as the feminist progressive components might project nor as extensive as the women's movement had hoped.
Significance of bacterial identification by molecular biology methods
Authors: Spratt David A.
Published: April 2005

Rapid advances in molecular biology over the last 20 years have provided a bewildering array of techniques aimed at helping us to tease apart all aspects of biology. The discipline of microbiology has gained greatly from these advances especially with respect to detection and identification of micro‐organisms. Indeed these molecular biology techniques have changed the way we classy all life on Earth. An important part of endodontic microbiology is detection and identification of the micro‐organisms associated with initiation and progression of this polymicrobial infection. A range of appropriate molecular techniques are reviewed in the present article and include aspects of comparative 16S rRNA gene sequencing, polymerase chain reaction detection, strategies for identification of unculturable bacteria, and whole community analysis. Some of these techniques are widely used in endodontic microbiology while others are used by only a few workers. The advantages and disadvantages of all the techniques are discussed and put into perspective.
Biofilms in endodontic infections
Authors: Svensäter Gunnel , Bergenholtz Gunnar
Published: April 2005

Biofilm biology has become an expanding field of research in human, industrial and environmental ecosystems. The knowledge accumulated suggests that organisms growing in biofilms develop properties different to those dwelling in the planktonic state. On surveying the endodontic literature it is obvious that this realization and the fact that biofilms afford the resident microorganisms protection/resistance against harmful exogeneous influences including anti‐microbial agents, is rather new to endodontology. Hence, the conditions under which biofilms occur in endodontic infections, and the measures that ought to be taken for their eradication, are not well understood. In this review the biofilm concept is presented and how it may apply to endodontic infections is discussed.
Effects of soil nutrient heterogeneity on the growth of plants under the various distributions and levels of nutrients in Zoysia japonica Steud.
Authors: Li Dezhi , Ito Mutsuyasu , Okajima Tsuyoshi
Published: April 2005

An experiment was carried out to analyze the effects of soil nitrogen heterogeneity in containers on the growth of a clonal plant of Zoysia japonica Steud. The overall soil nitrogen supply in the containers, their distribution and their interactions significantly affected the dry matter production of Zoysia japonica plants. Dry matter production in Zoysia japonica was benefited from heterogeneous nitrogen distributions when the overall soil nitrogen supply in the containers was relatively low. When the overall soil nitrogen was relatively high, stolon production was substantially higher in homogeneous soil nutrients. In heterogeneous distributions of nutrients, the positions of rich soil bands close to the initial Zoysia ramets positively affected the stolon production. The earlier Zoysia clones acquired abundant nitrogen from rich soil bands, the more they increased dry matter production in low nitrogen levels.
Inheritance of photoperiod‐sensitivity genes controlling flower initiation in sorghum, Sorghum bicolor Moench
Authors: Tarumoto Isao , Yanase Masanori , Kadowaki Hiroki , Yamada Tohru , Kasuga Shigemitu
Published: April 2005

The existence of a sorghum (Sorghum bicolor Moench) photoperiod sensitivity gene has been proposed to account for postponing flower initiation until Tentaka and Kazetachi meet with short daylengths below 12.5 h. To investigate the inheritance of this gene, three parental varieties, F1, F2, BC1F1 and BC1F2 populations of Tentaka and Kazetachi were evaluated for days‐to‐emergence of flag leaf (DEFL) under the field condition of long daylength (>13 h) and minimum temperatures over 20°C for at least 51 days after sowing in 1999, 2000 and 2001. The F1 hybrids, Tentaka (MS79 × Chohin232) and Kazetachi (MS138 × Chohin232), showed strong photoperiod sensitivity and very late DEFL, in spite of the photoperiod insensitivity of their parental varieties. In two different F2 populations, the segregation of early, middle and late plants for DEFL fitted in with the expected ratio of 7 : 30 : 27 under the three genes hypothesis, TtD1d1D2d2 for Tentaka and Kazetachi. Additionally, the expected ratio of early : middle : late (1 : 2 : 1) was observed in the segregation of BC1F1 of Tentaka × Chohin232 and Kazetachi × Chohin232 in 2000. These results suggest that two photoperiod sensitivity genes, D1 and D2 which show complementary dominant effects, are existent and the flowering phenotype of Tentaka and Kazetachi are expressed by the interactive operation both of a dominant thermo‐sensitivity gene (T) and complementary dominant photoperiod sensitivity genes (D1, D2), that is, the genotype TtD1d1D2d2.
Is prostate-specific membrane antigen a multifunctional protein?
Authors: Rajasekaran Ayyappan K. , Anilkumar Gopalakrishnapillai , Christiansen Jason J.
Published: April 2005

Prostate-specific membrane antigen (PSMA) is a metallopeptidase expressed predominantly in prostate cancer (PCa) cells. PSMA is considered a biomarker for PCa and is under intense investigation for use as an imaging and therapeutic target. Although the clinical utility of PSMA in the detection and treatment of PCa is evident and is being pursued, very little is known about its basic biological function in PCa cells. The purpose of this review is to highlight the possibility that PSMA might be a multifunctional protein. We suggest that PSMA may function as a receptor internalizing a putative ligand, an enzyme playing a role in nutrient uptake, and a peptidase involved in signal transduction in prostate epithelial cells. Insights into the possible functions of PSMA should improve the diagnostic and therapeutic values of this clinically important molecule.
Metabolic communication from cardiac myocytes to vascular endothelial cells
Authors: Brzezinska Anna K. , Merkus Daphne , Chilian William M.
Published: April 2005

The endothelium releases substances that affect both vascular and cardiac myocytes. However, under conditions of augmented metabolic demands and cardiac work, signals from the cardiac myocytes may be critical for the endothelium to fulfill its secretory and regulatory function in the vascular bed. Therefore, we hypothesized that cardiac myocytes produce substances that alter the resting membrane potential of endothelial cells and thus vascular tone. Isolated rat cardiac myocytes were electrically stimulated at the rate of 0 and 400 beats/min (Po2 = 150 mmHg), and supernatants were collected from each group (Sup-0; control) and (Sup-400) and used within 6 mo. These supernatants were applied to human coronary endothelial cells that were subsequently analyzed by using the whole cell and cell-attached patch-clamp modes. Sup-0 had no effect on the whole cell current and the zero-current potential. The Sup-0 from myocytes treated with aprotinin, an inhibitor of kallikrein and serine protease, reduced whole cell current between −120 and −60 mV. Sup-400 depolarized endothelial cells from the resting membrane potential of −45 to −5 mV ( P < 0.05), increased the magnitude of an inward current, and activated an outward current. Moreover, Sup-400 cells assayed in cell-attached patches increased single channel amplitude and the probability of a channel being in the open state. These effects were reversed by the Sup-400 from aprotinin-treated cells. We conclude that under certain metabolic conditions, isolated cardiac myocytes produce and release vasoactive substances that alter the function of K+ channels in vascular endothelial cells. Thus cardiac myocytes seem to communicate metabolic information to the endothelium, which could potentially influence vascular tone.
Coronary microcirculatory vasoconstriction is heterogeneously distributed in acutely ischemic myocardium
Authors: Sambuceti Gianmario , Marzilli Mario , Mari Andrea , Marini Cecilia , Schluter Mathis , Testa Roberto , Papini Michaela , Marraccini Paolo , Ciriello Giuseppe , Marzullo Paolo , L'Abbate Antonio
Published: April 2005

The classical model of coronary physiology implies the presence of maximal microcirculatory vasodilation during myocardial ischemia. However, Doppler monitoring of coronary blood flow (CBF) documented severe microcirculatory vasoconstriction during pacing-induced ischemia in patients with coronary artery disease. This study investigates the mechanisms that underlie this paradoxical behavior in nine patients with stable angina and single-vessel coronary disease who were candidates for stenting. While transstenotic pressures were continuously monitored, input CBF (in ml/min) to the poststenotic myocardium was measured by Doppler catheter and angiographic cross-sectional area. Simultaneously, specific myocardial blood flow (MBF, in ml·min−1·g−1) was measured by 133Xe washout. Perfused tissue mass was calculated as CBF/MBF. Measurements were obtained at baseline, during pacing-induced ischemia, and after stenting. CBF and distal coronary pressure values were also measured during pacing with intracoronary adenosine administration. During pacing, CBF decreased to 64 ± 24% of baseline and increased to 265 ± 100% of ischemic flow after adenosine administration. In contrast, pacing increased MBF to 184 ± 66% of baseline, measured as a function of the increased rate-pressure product ( r = 0.69; P < 0.05). Thus, during pacing, perfused myocardial mass drastically decreased from 30 ± 23 to 12 ± 11 g ( P < 0.01). Distal coronary pressure remained stable during pacing but decreased after adenosine administration. Stenting increased perfused myocardial mass to 39 ± 23 g ( P < 0.05 vs. baseline) as a function of the increase in distal coronary pressure ( r = 0.71; P < 0.02). In conclusion, the vasoconstrictor response to pacing-induced ischemia is heterogeneously distributed and excludes a tissue fraction from perfusion. Within perfused tissue, the metabolic demand still controls the vasomotor tone.
Insulin resistance in critically ill patients with acute renal failure
Authors: Basi Seema , Pupim Lara B. , Simmons Edith M. , Sezer M. Tugrul , Shyr Yu , Freedman Stephanie , Chertow Glenn M. , Mehta Ravindra L. , Paganini Emil , Himmelfarb Jonathan , Ikizler T. Alp ,   Program to Improve Care in Acute Renal Disease Study Group
Published: April 2005

Mortality in critically ill patients with acute renal failure (ARF) remains high. Hyperglycemia associated with insulin resistance has been associated with adverse outcomes in critically ill intensive care unit (ICU) patients but has not been examined specifically in patients with ARF. We used data from a subcohort ( n = 90) of the Program to Improve Care in Acute Renal Disease (PICARD), an observational study of 618 adult ICU patients with ARF in whom nephrology service consultation was obtained. We obtained simultaneous measurements of serum glucose, insulin, insulin-like growth factor (IGF)-I, and IGF-1 binding proteins (IGFBP) in 90 patients. Daily glucose determinations were obtained from a larger fraction of the PICARD cohort ( n = 509). Among the 90 patients with intensive metabolic monitoring, glucose concentrations in survivors were significantly lower than in nonsurvivors throughout the 5-wk period ( P = 0.008, adjusted P = 0.013). In the larger PICARD cohort ( n = 509), hyperglycemia was also significantly associated with in-hospital mortality. Mean insulin concentrations were significantly higher (431 ± 508 vs. 234 ± 189 pmol/l, P = 0.03), mean homeostasis model of insulin resistance levels were significantly higher (24.1 ± 30.0 vs. 11.7 ± 12.5, P = 0.04), and IGFBP-3 concentrations were significantly lower (1,190 ± 498 vs. 1,470 ± 581 μg/l, P = 0.02) among nonsurvivors compared with survivors. Insulin resistance as defined by hyperglycemia in the setting of higher insulin concentrations may be associated with mortality in critically ill patients with ARF. The IGF-IGFBP axis may play an important role in this process.
Distinct Upregulation of Extracellular Matrix Genes in Transition From Hypertrophy to Hypertensive Heart Failure
Authors: Rysä Jaana , Leskinen Hanna , Ilves Mika , Ruskoaho Heikki
Published: April 2005

Cardiac hypertrophy in response to pressure overload is initially beneficial but eventually leads to heart failure, a major cause of morbidity and mortality in the Western countries. Although abnormalities in left ventricular (LV) diastolic filling are early features associated with pressure overload-induced LV hypertrophy, the molecular mechanisms regulating transition to diastolic heart failure are poorly understood. We analyzed global changes in gene expression in 12-, 16-, and 20-month-old spontaneously hypertensive rats (SHR) and their age-matched controls, Wistar Kyoto rats, using DNA microarrays. In SHR, a progressive LV hypertrophy was associated with increased expression of hypertrophy-associated genes including contractile protein and natriuretic peptide genes. Echocardiography indicated that 16-month-old SHR had features of diastolic dysfunction leading to diastolic failure at age 20 months without significant changes in LV systolic function. Comparison analysis revealed that the extracellular matrix genes strikingly dominated the list of altered genes after transition to the heart failure, whereas there was no major shift in gene expression patterns involved in calcium homeostasis and neurohumoral activation, as well as myofilament contractile and cytoskeletal proteins. The microarray analysis also revealed differential gene expression of several novel factors, such as thrombospondin-4 and matrix Gla protein, as well as unknown expressed sequence tags. Our data show that transition from LV hypertrophy to diastolic hypertensive heart failure is almost exclusively associated with progressive remodeling of the extracellular matrix and provide new insights into the pathogenesis of hypertrophy by suggesting existence of novel regulators of LV remodeling.
Carvedilol Reduces Plasma 8-Hydroxy-2′-Deoxyguanosine in Mild to Moderate Hypertension
Authors: Lee Juyong , Lee Mejeong , Kim Jeong-Uk , Song Kyung Il , Choi Yun Seok , Cheong Sang-Sig
Published: April 2005

The purpose of this pilot study was to test whether carvedilol has a protective effect against oxidative deoxyribonucleic acid (DNA) damage in human hypertension in vivo. Carvedilol’s antioxidant effect has mostly focused on lipid or amino acid so far. However, there has been no data that carvedilol reduces DNA damage in human hypertension. Never-treated mild to moderate hypertension patients and age- and sex-matched control subjects volunteered for the study. The hypertension subjects were given 12.5 or 25 mg of carvedilol or hydrochlorothiazide orally for 2 months and controls were not given any. Fasting blood samples were collected before and after carvedilol. Plasma highly sensitive 8-hydroxy-2′-deoxyguanosine (hs8-OHdG) and high-sensitivity C-reactive protein (hsCRP) were checked with the samples. There were no statistical differences in clinical characteristics in 3 groups. The hs8-OHdG declined from 9.07±4.23 ng/mL to 5.74±3.89 ng/mL (
P
=0.002) after carvedilol. However, it did not show significant reduction after hydrochlorothiazide (9.01±3.89 versus 8.23±4.12 ng/mL;
P
=NS). In the control group, the hs8-OHdG concentration was 3.41±2.03 ng/mL and 3.01±2.65 ng/mL at baseline and 2 months later, respectively (
P
=NS). The baseline hs8-OHdG levels were higher in hypertension groups compared with control (
P
=0.000). The hsCRP had no significant difference before and after the tested drugs in 2 hypertension groups (group A: 0.21±0.51 versus 0.19±0.37 mg/dL; group B: 0.20±0.45 versus 0.18±0.42 mg/dL). In conclusion, DNA damage caused by reactive oxygen species occurs more in the hypertension patients than normals. Carvedilol significantly reduces DNA damage in the hypertension patients.
Angiotensin Type 2 Receptor–Mediated Phosphorylation of eNOS in the Aortas of Mice With 2-Kidney, 1-Clip Hypertension
Authors: Hiyoshi Hiromi , Yayama Katsutoshi , Takano Masaoki , Okamoto Hiroshi
Published: April 2005

To evaluate the role of vascular angiotensin II (Ang II) type 2 (AT
2
) receptor in renovascular hypertension, we investigated expressions of AT
2
receptor and endothelial nitric oxide synthase (eNOS) in thoracic aortas of mice with 2-kidney, 1-clip (2K1C) hypertension. The mRNA levels of AT
2
receptor in aortas, but not those of AT
1
and bradykinin B
2
receptors, increased 14 days but not 42 days after clipping. The contractile response to Ang II (>0.1 μmol/L) was attenuated in aortic rings excised 14 days after clipping and was restored to that of rings from sham mice by antagonists of AT
2
receptor (PD123319) and B
2
receptor (icatibant). The aortic levels of total eNOS, phosphorylated eNOS at Ser
1177
(p-eNOS), total Akt, and phosphorylated Akt at Ser
473
(p-Akt) were increased in 2K1C mice on day 14, whereas only eNOS levels were increased on day 42. The aortic cGMP levels were ≈20-fold greater in 2K1C mice on day 14 compared with sham mice. Administration of nicardipine for 4 days before the excision of aortas 14 days after clipping not only reduced blood pressure but also decreased the aortic levels of eNOS, p-eNOS, Akt, p-Akt, and cGMP to sham levels, whereas the administration of PD123319 or icatibant to 2K1C mice decreased p-eNOS and cGMP to sham levels without affecting blood pressure and the levels of eNOS, Akt and p-Akt. These results suggest that vascular NO production is enhanced by increased eNOS phosphorylation via the activation of AT
2
receptors in the course of 2K1C hypertension.
Red Wine and Beer Elevate Blood Pressure in Normotensive Men
Authors: Zilkens Renate R. , Burke Valerie , Hodgson Jonathan M. , Barden Anne , Beilin Lawrence J. , Puddey Ian B.
Published: April 2005

A positive relationship between alcohol consumption and blood pressure (BP) is well-established but the relative effect of specific alcoholic beverages is controversial. This study aimed to determine whether red wine may improve vascular function and have less of an impact on blood pressure because of its high content of antioxidant vasodilator polyphenolic compounds. Healthy normotensive men entered a 4-period crossover study comparing in random order 4 weeks of control–abstinence with similar periods of daily consumption of red wine (375 mL; 39 grams alcohol), de-alcoholized red wine (375 mL), or beer (1125 mL; 41 grams alcohol). Ambulatory systolic BP and diastolic BP and heart rate (HR) were measured together with vascular function as assessed by flow-mediated dilatation (FMD) and glyceryl trinitrate-mediated (GTNMD) dilatation of the brachial artery. The systolic and diastolic BP and HR were not different between control–abstinence and de-alcoholized red wine. However, compared with control–abstinence, both red wine and beer increased awake systolic BP (2.9 and 1.9 mm Hg, respectively;
P
<0.05) and asleep HR (5.0 and 4.4 bpm;
P
<0.05). There were no specific effects of red wine, de-alcoholized red wine, or beer on FMD or GTNMD. Daily consumption of ≈40 grams alcohol as either red wine or beer for 4 weeks results in similar increases in systolic BP and HR. De-alcoholized red wine did not lower BP, and neither red wine nor de-alcoholized red wine influenced vascular function, suggesting that red wine polyphenolics do not have a significant role in mitigating the blood pressure-elevating effects of alcohol in men.
Elevated C-Reactive Protein Augments Increased Arterial Stiffness in Subjects With the Metabolic Syndrome
Authors: Tomiyama Hirofumi , Koji Yutaka , Yambe Minoru , Motobe Kohki , Shiina Kazuki , Gulnisa Zaydun , Yamamoto Yoshio , Yamashina Akira
Published: April 2005

We examined whether the presence of an increasing number of metabolic syndrome “disorders” was associated with an increasing pulse wave velocity, which is recognized as a marker of cardiovascular risk, and evaluated whether an elevated plasma C-reactive protein level augments this increasing pulse wave velocity. Using a cross-sectional study design, C-reactive protein, metabolic syndrome–related anthropometric parameters, and pulse wave velocity were measured in 5752 middle-aged Japanese men (44±10 years old). In linear regression analyses, all of the metabolic “disorders” and the logarithm of the C-reactive protein significantly correlated with pulse wave velocity. Multiple linear regression analysis demonstrated that triglycerides, HDL cholesterol, mean blood pressure, fasting glucose, and the logarithm of the C-reactive protein were significant independent positive predictors of pulse wave velocity (R-square=0.38). The presence of an increasing number of metabolic “disorders” in the subjects was associated with an increasing pulse wave velocity (no disorders 1228±139 cm/s ≥3 disorders 1437±250 cm/s;
P
<0.01). Among subjects with the metabolic syndrome, pulse wave velocity was higher in cases with (1508±278 cm/s) than in those without an elevated C-reactive protein (1427±243 cm/s;
P
<0.01). In conclusion, an increase in arterial stiffness may constitute a pathophysiological basis for the increased risk of cardiovascular disease in patients with the metabolic syndrome and that an elevated C-reactive protein level may aggravate this cardiovascular risk.
Torture: Flesh, Truth, and the Fourth Gospel
Authors: Glancy Jennifer
Published: April 2005

In the Roman world, torture, conceived as a mechanism to extract truth from flesh, was used in judicial interrogation, most commonly in interrogation of slaves and other low-status persons. The flogging of Jesus in John 19:1-3, a flogging that occurs in the midst of the trial before Pilate, is best read as an instance of such judicial torture. If understood as an act of judicial torture, the flogging is also an act of witnessing to the truth: the flesh of the Johannine Jesus is flush with truth (John 1:14). And because Jesus' flesh is flush with truth, the Johannine passion narrative is an account of torture, torture as defined in Roman law: "By torture we mean the infliction of anguish and agony on the body to elicit the truth" (Dig. 48.10.15.41). As I trace the lineaments of truth in Jesus' corpus, I ask how the Fourth Gospel implicates the project of torture. Confronted by the horror of a U.S. policy of distilling truth from foreign bodies, I ask this question urgently. Is it possible to embrace flesh as a locus of truth and still to condemn the practice of torture? Through my carnal reading of the Johannine passion narrative, I attempt to do so.
Lectura psicopolitica del discurso de un militar argentino supuestamente arrepentido
Authors: Rodriguez-Kauth Angel
Published: April 2005

Se reproduce textualmente—con comentarios intercalados por el autor—el documento enviado por un militar del Ejército Argentino, el primero que reconoce su participación y responsabilidad en los crímenes de lesa humanidad cometidos durante el Proceso de Reconstrucción Nacional (entre 1976 y 1983). La reproducción textual tiene por objeto poner en conocimiento público una documentación única, no sólo por su valor histórico, sino también por lo desgarrador de su discurso. Con las comentarios se intenta avanzar hacia una lectura psicosocial y psicopolítica que permita interpretar desde una perspectiva más amplia lo ocurrido en aquel período de la historia argentina.
Altered expression of membrane-bound and soluble CD95/Fas contributes to the resistance of fibrotic lung fibroblasts to FasL induced apoptosis
Authors: Bühling Frank , Wille Aline , Röcken Christoph , Wiesner Olaf , Baier Anja , Meinecke Ingmar , Welte Tobias , Pap Thomas
Published: April 2005

Background

An altered susceptibility of lung fibroblasts to Fas-induced apoptosis has been implicated in the pathogenesis of pulmonary fibrosis; however, the underlying mechanism is not completely understood. Here, we studied the susceptibility of lung fibroblasts, obtained from patients with (f-fibs) and without pulmonary fibrosis (n-fibs), to FasL- (CD95L/APO-1) induced apoptosis in relation to the expression and the amounts of membrane-bound and soluble Fas. We also analysed the effects of tumor necrosis factor-β on FasL-induced cell death.

Methods

Apoptosis was induced with recombinant human FasL, with and without prior stimulation of the fibroblasts with tumor necrosis factor-α and measured by a histone fragmentation assay and flow cytometry. The expression of Fas mRNA was determined by quantitative PCR. The expression of cell surface Fas was determined by flow cytometry, and that of soluble Fas (sFas) was determined by enzyme-linked immunosorbent assay.

Results

When compared to n-fibs, f-fibs were resistant to FasL-induced apoptosis, despite significantly higher levels of Fas mRNA. F-fibs showed lower expression of surface-bound Fas but higher levels of sFas. While TNF-α increased the susceptibility to FasL-induced apoptosis in n-fibs, it had no pro-apoptotic effect in f-fibs.

Conclusions

The data suggest that lower expression of surface Fas, but higher levels of apoptosis-inhibiting sFas, contribute to the resistance of fibroblasts in lung fibrosis against apoptosis, to increased cellularity and also to increased formation and deposition of extracellular matrix.
Evolutionary distance estimation and fidelity of pair wise sequence alignment
Authors: Rosenberg Michael S
Published: April 2005

Background

Evolutionary distances are a critical measure in comparative genomics and molecular evolutionary biology. A simulation study was used to examine the effect of alignment accuracy of DNA sequences on evolutionary distance estimation.

Results

Under the studied conditions, distance estimation was relatively unaffected by alignment error (50% or more of the sites incorrectly aligned) as long as 50% or more of the sites were identical among the sequences (observed P-distance < 0.5). Beyond this threshold, the alignment procedure artificially inflates the apparent sequence identity, skewing distance estimates, and creating alignments that are essentially indistinguishable from random data. This general result was independent of substitution model, sequence length, and insertion and deletion size and rate.

Conclusion

Examination of the estimated sequence identity may yield some guidance as to the accuracy of the alignment. Inaccurate alignments are expected to have large effects on analyses dependent on site specificity, but analyses that depend on evolutionary distance may be somewhat robust to alignment error as long as fewer than half of the sites have diverged.
Comparative mapping of expressed sequence tags containing microsatellites in rainbow trout (Oncorhynchus mykiss)
Authors: Rexroad Caird E , Rodriguez Maria F , Coulibaly Issa , Gharbi Karim , Danzmann Roy G , DeKoning Jenefer , Phillips Ruth , Palti Yniv
Published: April 2005

Background

Comparative genomics, through the integration of genetic maps from species of interest with whole genome sequences of other species, will facilitate the identification of genes affecting phenotypes of interest. The development of microsatellite markers from expressed sequence tags will serve to increase marker densities on current salmonid genetic maps and initiate in silico comparative maps with species whose genomes have been fully sequenced.

Results

Eighty-nine polymorphic microsatellite markers were generated for rainbow trout of which at least 74 amplify in other salmonids. Fifty-five have been associated with functional annotation and 30 were mapped on existing genetic maps. Homologous sequences were identified for 20 of the EST containing microsatellites to identify comparative assignments within the tetraodon, mouse, and/or human genomes.

Conclusion

The addition of microsatellite markers constructed from expressed sequence tag data will facilitate the development of high-density genetic maps for rainbow trout and comparative maps with other salmonids and better studied species.
Expression analysis of secreted and cell surface genes of five transformed human cell lines and derivative xenograft tumors
Authors: Stull Robert A , Tavassoli Roya , Kennedy Scot , Osborn Steve , Harte Rachel , Lu Yan , Napier Cheryl , Abo Arie , Chin Daniel J
Published: April 2005

Background

Since the early stages of tumorigenesis involve adhesion, escape from immune surveillance, vascularization and angiogenesis, we devised a strategy to study the expression profiles of all publicly known and putative secreted and cell surface genes. We designed a custom oligonucleotide microarray containing probes for 3531 secreted and cell surface genes to study 5 diverse human transformed cell lines and their derivative xenograft tumors. The origins of these human cell lines were lung (A549), breast (MDA MB-231), colon (HCT-116), ovarian (SK-OV-3) and prostate (PC3) carcinomas.

Results

Three different analyses were performed: (1) A PCA-based linear discriminant analysis identified a 54 gene profile characteristic of all tumors, (2) Application of MANOVA (Pcorr < .05) to tumor data revealed a larger set of 149 differentially expressed genes. (3) After MANOVA was performed on data from individual tumors, a comparison of differential genes amongst all tumor types revealed 12 common differential genes. Seven of the 12 genes were identified by all three analytical methods. These included late angiogenic, morphogenic and extracellular matrix genes such as ANGPTL4, COL1A1, GP2, GPR57, LAMB3, PCDHB9 and PTGER3. The differential expression of ANGPTL4 and COL1A1 and other genes was confirmed by quantitative PCR.

Conclusion

Overall, a comparison of the three analyses revealed an expression pattern indicative of late angiogenic processes. These results show that a xenograft model using multiple cell lines of diverse tissue origin can identify common tumorigenic cell surface or secreted molecules that may be important biomarker and therapeutic discoveries.
Accumulation of marginal zone B cells and accelerated loss of follicular dendritic cells in NF-κB p50-deficient mice
Authors: Ferguson Andrew R , Corley Ronald B
Published: April 2005

Background

Marginal zone (MZ) B cells play important roles in the early phases of humoral immune responses. In addition to possessing an inherent capacity to rapidly differentiate into antibody secreting cells, MZ B cells also help to regulate the fate of both T-independent and T-dependent blood-borne antigens in the spleen. For T-dependent antigens, MZ B cells bind IgM-antigen complexes in a complement-dependent manner. Once MZ B cells bind IgM-containing immune complexes (IgM-IC), they transport them into B cell follicles for deposition onto follicular dendritic cells (FDCs), an important component of secreted IgM's ability to enhance adaptive immune responses. To further define the requirement for MZ B cells in IgM-IC deposition, mice deficient in the NF-κB protein p50, which have been reported to lack MZ B cells, were analyzed for their ability to trap IgM-IC onto FDCs.

Results

Mice (2 months of age) deficient in p50 (p50-/-) had small numbers of MZ B cells, as determined by cell surface phenotype and localization in the splenic MZ. These cells bound high levels of IgM-IC both in vivo and in vitro. Subsequent to the binding of IgM-IC by the MZ B cells in p50-/- mice, small amounts of IgM-IC were found localized on FDCs, suggesting that the MZ B cells retained their ability to transport these complexes into splenic follicles. Strikingly, MZ B cells accumulated with age in p50-/- mice. By 6 months of age, p50-/- mice contained normal numbers of these cells as defined by CD21/CD23 profile and high level expression of CD1d, CD9, and IgM, and by their positioning around the marginal sinus. However, FDCs from these older p50-/- mice exhibited a reduced capacity to trap IgM-IC and retain complement components.

Conclusion

These results demonstrate that while the p50 component of the NF-κB transcription complex plays an important role in the early development of MZ B cells, MZ B cells can develop and accumulate in mice lacking this protein. These results highlight the interface between genetic deficiencies and age, and suggest that different transcription factors may play distinct roles in the development and maintenance of cell populations at different ages.