bluuebunny/crossref_metadata_2025 huggingface dataset:
G-Protein–Coupled Receptor Mas Is a Physiological Antagonist of the Angiotensin II Type 1 Receptor
Authors: Kostenis Evi , Milligan Graeme , Christopoulos Arthur , Sanchez-Ferrer Carlos F. , Heringer-Walther Silvia , Sexton Patrick M. , Gembardt Florian , Kellett Elaine , Martini Lene , Vanderheyden Patrick , Schultheiss Heinz-Peter , Walther Thomas
Published: April 2005

Background—

We previously identified the G-protein–coupled receptor Mas, encoded by the
Mas
proto-oncogene, as an endogenous receptor for the heptapeptide angiotensin-(1-7); however, the receptor is also suggested to be involved in actions of angiotensin II. We therefore tested whether this could be mediated indirectly through an interaction with the angiotensin II type 1 receptor, AT
1
.

Methods and Results—

In transfected mammalian cells, Mas was not activated by angiotensin II; however, AT
1
receptor–mediated, angiotensin II–induced production of inositol phosphates and mobilization of intracellular Ca
2+
was diminished by 50% after coexpression of
Mas
, despite a concomitant increase in angiotensin II binding capacity. Mas and the AT
1
receptor formed a constitutive hetero-oligomeric complex that was unaffected by the presence of agonists or antagonists of the 2 receptors. In vivo, Mas acts as an antagonist of the AT
1
receptor; mice lacking the
Mas
gene show enhanced angiotensin II–mediated vasoconstriction in mesenteric microvessels.

Conclusions—

These results demonstrate that Mas can hetero-oligomerize with the AT
1
receptor and by so doing inhibit the actions of angiotensin II. This is a novel demonstration that a G-protein–coupled receptor acts as a physiological antagonist of a previously characterized receptor. Consequently, the AT
1
-Mas complex could be of great importance as a target for pharmacological intervention in cardiovascular diseases.
Time Dependence of Platelet Inhibition After a 600-mg Loading Dose of Clopidogrel in a Large, Unselected Cohort of Candidates for Percutaneous Coronary Intervention
Authors: Hochholzer Willibald , Trenk Dietmar , Frundi Devine , Blanke Philipp , Fischer Benjamin , Andris Katharina , Bestehorn Hans-Peter , Büttner Heinz Joachim , Neumann Franz-Josef
Published: April 2005

Background—

Pretreatment with clopidogrel can reduce the risks associated with percutaneous coronary intervention (PCI). To shorten the time for clopidogrel to become effective, a 600-mg loading dose has been used. We sought to validate this regimen in a large cohort and investigated the time dependence of the antiplatelet effect of 600 mg of clopidogrel.

Methods and Results—

Our study included 1001 patients who were scheduled for cardiac catheterization as potential candidates for PCI. We obtained blood samples before administration of 600 mg of clopidogrel and at the time of catheterization, which varied according to logistic needs. We assessed platelet aggregation by optical aggregometry and surface expression of P-selectin and activated glycoprotein IIb/IIIa by flow cytometry. Platelet aggregation induced by 5 μmol/L ADP was 51±14% when catheterization was performed at <1 hour, 41±14% at 1 to <2 hours, 37±15% at 2 to <4 hours, 36±13% at 4 to <6 hours, and 35±14% at ≥6 hours after clopidogrel administration. After 2 hours (n=718), the level of platelet aggregation and the surface expression of P-selectin and activated glycoprotein IIb/IIIa did not change significantly with time after clopidogrel (
P
>0.24 by univariate or multivariate regression). Comedication with CYP3A4 metabolized statins did not significantly affect platelet aggregation after clopidogrel (
P
=0.62). Among the 428 patients undergoing PCI, the 30-day composite rate of major adverse cardiac events was 1.9%, with no significant difference between patients undergoing PCI within 2 hours after clopidogrel loading and those undergoing PCI at a later time point.

Conclusions—

After loading with 600 mg of clopidogrel, the full antiplatelet effect of the drug is achieved after 2 hours. Statins do not interfere with the level of platelet inhibition after this dose.
Essential Role of Endothelial Notch1 in Angiogenesis
Authors: Limbourg Florian P. , Takeshita Kyosuke , Radtke Freddy , Bronson Roderick T. , Chin Michael T. , Liao James K.
Published: April 2005

Background—

Notch signaling influences binary cell fate decisions in a variety of tissues. The Notch1 receptor is widely expressed during embryogenesis and is essential for embryonic development. Loss of global Notch1 function results in early embryonic lethality, but the cell type responsible for this defect is not known. Here, we identify the endothelium as the primary target tissue affected by Notch1 signaling.

Methods and Results—

We generated an endothelium-specific deletion of Notch1 using Tie2Cre and conditional Notch1
flox/flox
mice. Mutant embryos lacking endothelial Notch1 died at approximately embryonic day 10.5 with profound vascular defects in placenta, yolk sac, and embryo proper, whereas heterozygous deletion had no effect. In yolk sacs of mutant embryos, endothelial cells formed a primary vascular plexus indicative of intact vasculogenesis but failed to induce the secondary vascular remodeling required to form a mature network of well-organized large and small blood vessels, which demonstrates a defect in angiogenesis. These vascular defects were also evident in the placenta, where blood vessels failed to invade the placental labyrinth, and in the embryo proper, where defective blood vessel maturation led to pericardial and intersomitic hemorrhage. Enhanced activation of caspase-3 was detected in endothelial and neural cells of mutant mice, which resulted in enhanced apoptotic degeneration of somites and the neural tube.

Conclusions—

These findings recapitulate the vascular phenotype of global Notch1
−/−
mutants and indicate an essential cell-autonomous role of Notch1 signaling in the endothelium during vascular development. These results may have important clinical implications with regard to Notch1 signaling in adult angiogenesis.
White Blood Cell Count Predicts Reduction in Coronary Heart Disease Mortality With Pravastatin
Authors: Stewart Ralph A.H. , White Harvey D. , Kirby Adrienne C. , Heritier Stephane R. , Simes R. John , Nestel Paul J. , West Malcolm J. , Colquhoun David M. , Tonkin Andrew M.
Published: April 2005

Background—

Elevated serum inflammatory marker levels are associated with a greater long-term risk of cardiovascular events. Because 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors (statins) may have an antiinflammatory action, it has been suggested that patients with elevated inflammatory marker levels may have a greater reduction in cardiovascular risk with statin treatment.

Methods and Results—

We evaluated the association between the white blood cell count (WBC) and coronary heart disease mortality during a mean follow-up of 6.0 years in the Long-Term Intervention With Pravastatin in Ischemic Disease (LIPID) Study, a clinical trial comparing pravastatin (40 mg/d) with a placebo in 9014 stable patients with previous myocardial infarction or unstable angina. An increase in baseline WBC was associated with greater coronary heart disease mortality in patients randomized to placebo (hazard ratio for 1×10
9
/L increase in WBC, 1.18; 95% CI, 1.12 to 1.25;
P
<0.001) but not pravastatin (hazard ratio, 1.02; 95% CI, 0.96 to 1.09;
P
=0.56;
P
for interaction=0.004). The numbers of coronary heart disease deaths prevented per 1000 patients treated with pravastatin were 0, 9, 30, and 38 for baseline WBC quartiles of <5.9, 6.0 to 6.9, 7.0 to 8.1, and >8.2×10
9
/L, respectively. WBC was a stronger predictor of this treatment benefit than the ratio of total to high-density lipoprotein cholesterol and a global measure of cardiac risk. There was also a greater reduction (
P
=0.052) in the combined incidence of cardiovascular mortality, nonfatal myocardial infarction, and stroke with pravastatin as baseline WBC increased (by quartile: 3, 41, 61, and 60 events prevented per 1000 patients treated, respectively).

Conclusions—

These data support the hypothesis that individuals with evidence of inflammation may obtain a greater benefit from statin therapy.
Antioxidative Effects of Exercise Training in Patients With Chronic Heart Failure
Authors: Linke Axel , Adams Volker , Schulze Paul Christian , Erbs Sandra , Gielen Stephan , Fiehn Eduard , Möbius-Winkler Sven , Schubert Andreas , Schuler Gerhard , Hambrecht Rainer
Published: April 2005

Background—

In chronic heart failure (CHF), cross-talk between inflammatory activation and oxidative stress has been anticipated in skeletal muscle (SM). The role of the radical scavenger enzymes superoxide dismutase (SOD), catalase (Cat), and glutathione peroxidase (GPX), which remove oxygen radicals, has never been assessed in the SM in this context. Moreover, it remains unknown whether exercise training augments the activity of these enzymes in CHF.

Methods and Results—

Twenty-three patients with CHF were randomized to either 6 months of exercise training (T) or a sedentary lifestyle (C); 12 age-matched healthy subjects (HS) were studied in parallel. Activity of Cat, SOD, and GPX was assessed in SM biopsies before and after 6 months (6 months). Oxidative stress was determined by measuring nitrotyrosine formation. SOD, Cat, and GPX activity was reduced by 31%, 57%, and 51%, respectively, whereas nitrotyrosine formation was increased by 107% in SM in CHF (
P
<0.05 versus HS). In CHF, exercise training augmented GPX and Cat activity in SM by 41% (
P
<0.05 versus before and group C) and 42% (
P
<0.05 versus before and group C), respectively, and decreased nitrotyrosine production by 35% (from 3.8±0.4% tissue area before to 2.5±0.3% after 6 months;
P
<0.05 versus before).

Conclusions—

The reduced activity of major antioxidative enzymes in the SM of CHF patients is associated with increased local oxidative stress. Exercise training exerts antioxidative effects in the SM in CHF, in particular, due to an augmentation in activity of radical scavenger enzymes.
Extrarenal ET
B
Plays a Significant Role in Controlling Cardiovascular Responses to High Dietary Sodium in Rats
Authors: Ohkita Mamoru , Wang Yuqin , Nguyen Ngoc Diep T. , Tsai Yu-Hwai , Williams S. Clay , Wiseman Richard C. , Killen Paul D. , Li Shujun , Yanagisawa Masashi , Gariepy Cheryl E.
Published: April 2005

Endothelin-B receptor (ET
B
)-deficient rats have low-renin, salt-sensitive hypertension. We hypothesized this was caused by an absence of renal ET
B
signaling and performed a series of experiments to examine the effect of dietary sodium (Na) on endothelin-1 (ET1) expression and renal function in wild-type (WT) and ET
B
-deficient rats. We found that ET
B
deficiency, but not dietary Na, increases circulating and tissue (kidney and aorta) ET1 levels. Quantitative reverse-transcription polymerase chain reaction reveals that aortic and renal ET1 and endothelin-A receptor (ET
A
) mRNA, however, are similarly increased by dietary Na in ET
B
-WT and ET
B
-deficient rats. We then determined the effect of chronic ET
A
blockade on blood pressure (direct conscious measurements), urinary protein excretion, and creatinine clearance (Crcl). On a Na-deficient diet, ET
B
-deficient rats have mild proteinuria and impaired Crcl. On a high-Na diet, severe hypertension and renal dysfunction develop in ET
B
-deficient rats. Chronic ET
A
blockade prevents hypertension and renal injury. To determine the role of the renal versus the extrarenal endothelin system, we performed renal cross-transplantation. We found that ET
B
deficiency in the body is associated with renal injury and an impaired ability to excrete an Na load. We also found that ET
B
deficiency in the body affects blood pressure response to dietary Na. Expression of ET1 and ET
A
are regulated by dietary Na. ET
B
receptors outside of the kidney, likely by functioning as a clearance receptor for ET1, limit salt-sensitivity in rats.
Klk1
as One of the Genes Contributing to Hypertension in Dahl Salt-Sensitive Rat
Authors: Iwai Naoharu , Yasui Naomi , Naraba Hiroaki , Tago Naomi , Yamawaki Hideyuki , Sumiya Hiroshi
Published: April 2005

A genome-wide quantitative trait loci analysis for blood pressure was performed using 107 male F
2
rats derived from Dahl salt-sensitive and Lewis rats. Blood pressure was assessed by telemetry, and >400 microsatellite markers were used for genotyping. Two major quantitative trait loci for blood pressure were identified at chromosome 1 and chromosome 10. The expression levels of 366 transcripts around the chromosome 1 quantitative trait loci were assessed by RT-PCR, and we found that the
Klk1
(kallikrein 1) and
Ngfg
(nerve growth factor gamma) mRNA levels were significantly reduced in the kidneys of Dahl salt-sensitive rats compared with those in Lewis rats. The expression levels of kallikrein 1 protein were also suppressed in Dahl salt-sensitive rats compared with those in Lewis rats. Because the kallikrein–kinin system has been shown to be involved in renal function, including salt homeostasis, it is likely that the reduced expression of
Klk1
contributes to salt-sensitive hypertension in Dahl salt-sensitive rats.
Parent Management of School Choice in a Large Urban District
Authors: Neild Ruth Curran
Published: April 2005

With No Child Left Behind legislation permitting students to switch from so-called failing schools, key questions are whether parents will act to select another school and which schools they will choose. Long-standing school choice systems provide evidence about low-income parents’strategies to gather information and negotiate the application process. Interviews with parents of eighth graders in Philadelphia indicate that faced with little high-quality official information about schools, parents’ social networks played an important role in the decision. Most parents were hungry for information about schools but lacked specifics on academic performance or children’s chances of admission. The data suggest that more detailed school information and a district commitment to counseling parents are essential for making well-informed choices. Even so, in districts with few good school options for students, there are limits to parents’ability to find a school that represents a substantial improvement over the school their child already attends.
“For the Advancement of the Race”
Authors: Pruitt Bernadette
Published: April 2005

This article builds on the scholarship of Black urban history in general and the Great Migrations in particular. It examines the migration, community-building, class consciousness, and sociopolitical activist efforts of African American migrants who made their way to Houston, Texas, from farms, small towns, and medium sized cities in eastern Texas and Louisiana between 1914 and 1941. It defines migration to Houston as a form of accommodation-activism, one of many vehicles used by people of color to gradually achieve socioeconomic, sociopolitical, spiritual, personal, and racial autonomy. Relying on themselves and the chain migration networks of others, these individuals and families decisively abandoned their birthplaces for better wages, quality schools, decent homes, improved lifestyles, advanced social equality, and civil rights in industrializing Houston.
Leisure and Shopping in the Small Towns of Georgian England
Authors: Stobart Jon
Published: April 2005

This article brings a fresh perspective to the crowded field of early-modern consumption and material culture by offering an explicitly spatialized reading of the provision of and relationship between leisure and shopping. Exploring the entire urban network of northwest England, it demonstrates that leisure facilities, shops, and services became increasingly widespread during the course of the eighteenth century. This reflected both the broad dissemination of the spatial practices of polite society and the power of such activities to represent towns and their inhabitants as respectable. Yet the analysis also makes clear the importance of spatial-hierarchical interaction between towns and individual consumers’ imaginings of the regional retail and leisure space in shaping the spatial distribution of material culture in Georgian England.
Maximizing Intra-Agency Relationships through Advanced General Aviation Transport Experiments and Small Aircraft Transportation System
Authors: Metz Nanette Scarpellini , Bowen Brent D.
Published: April 2005

As the United States’s transportation system becomes more congested and time becomes more precious, the National Aeronautics and Space Administration (NASA) has explored ways to address these problems. In the early 1990s, NASA formed the Advanced General Aviation Transport Experiments (AGATE) program to develop technology that would operationalize a small aircraft transportation system (SATS) and take the country into the next century of transportation. This analysis employs the research methodology of the case study to investigate the success of AGATE and relates its description to the continued formation of SATS. AGATE’s success stemmed from facilitating industry cooperation and providing practical application of its outputs. Although AGATE and SATS had different goals and participants, SATS may benefit by recognizing problems the earlier program faced. By examining the lessons learned in AGATE, SATS will be better able to achieve its goals and help the American people take flight.
Planning to Include the Public
Authors: Stich Bethany , Eagle Kim
Published: April 2005

The following research is a Virginia case study evaluating planning processes as they implement the following legislation: NEPA (the National Environmental Policy Act), 1969, ISTEA (Intermodal Surface Transportation Efficiency Act), 1991, and TEA-21 (Transportation Equity Act for the 21st Century), 1998. Specifically, the implementation of the legislation requiring citizen participation will be reviewed in an effort to evaluate how the policy process and citizen participation relate to each other and to the legislation in order to determine how the process relates to the desired outcomes for involvement.
An Evaluation of the Relationship Between Hispanics and Major League Soccer
Authors: Jewell R. Todd , Molina David J.
Published: April 2005

This article examines the determinants of attendance in U.S. professional soccer. We concentrate on the relationship between the potential Hispanic fan base and yearly attendance in Major League Soccer. U.S. Hispanics have a long history of supporting professional soccer leagues in their home countries. In addition, the U.S. Hispanic community is the fastest-growing segment of the population. Although Major League Soccer has targeted the emerging U.S. Hispanic market, our results indicate that teams located in areas with relatively more Hispanics have lower attendance. This brings into question the efficacy as well as the direction of league marketing. Not surprisingly, we find that teams with better players and teams located in more populated regions have higher attendance. We also find, however, that local sports competition has a significant impact on attendance. These findings are important for the future viability of Major League Soccer.
Full Count
Authors: Long Judith Grant
Published: April 2005

Governments pay far more to participate in the development of major league sports facilities than is commonly understood due to the routine omission of public subsidies for land and infrastructure, and the ongoing costs of operations, capital improvements, municipal services, and foregone property taxes. Adjusting for these omissions increases the average public subsidy by $50 million per facility to a total of $177 million, representing a 40% increase over the industry-reported average of $126 million, based on all 99 facilities in use for the “big four” major leagues during 2001. For all 99 facilities, these uncounted public costs total $5 billion.
Casus Belli
Authors: Calabrese Andrew
Published: April 2005

In departing from the traditional principles of a “just war” theory, which demands that military action be taken only in self-defense, the U.S. government’s policy in its war against Iraq was preemptive, the logic being that the perceived risk of Iraqi aggression toward the United States ought to be avoided by attacking first. Perhaps this decision does not define imperialism, but it certainly has raised the specter in the eyes of much of the rest of the world. Of course, the obvious question became what evidence was there of imminent danger that should justify an attack? From the start, the principal challenge never was a matter of whether the U.S. military had the capacity to topple Saddam Hussein’s regime. Rather, the challenge has been all along a matter of how to sell the war and U.S. military occupation to the community of nations, the United Nations Security Council, the American people, and the Iraqi people.
“All about Nothing”:
Authors: Gunster Shane
Published: April 2005

Drawing on Lawrence Grossberg’s work on affect, difference, and postmodernity, this article discusses Seinfeldas emblematic of new cultural forms that produce temporary structures of difference out of a general indifference or sameness. The author begins by discussing how incessant commodification of difference in advertising and consumer culture compromises the ability and desire of many people to make stable and lasting investments of affect in many traditional forms of difference. In this context, it is argued that Seinfeld’s appeal lies not so much in the comic defamiliarization of everyday life but in the creation of privatized strategies of ironic agency that allow the show’s characters to create something out of nothing, difference out of sameness. The author concludes by assessing the broader political implications that attend these forms of agency.
Medroxyprogesterone improves nocturnal breathing in postmenopausal women with chronic obstructive pulmonary disease
Authors: Saaresranta Tarja , Aittokallio Tero , Utriainen Karri , Polo Olli
Published: April 2005

Background

Progestins as respiratory stimulants in chronic obstructive pulmonary disease (COPD) have been investigated in males and during wakefulness. However, sleep and gender may influence therapeutic responses. We investigated the effects of a 2-week medroxyprogesterone acetate (MPA) therapy on sleep and nocturnal breathing in postmenopausal women.

Methods

A single-blind placebo-controlled trial was performed in 15 postmenopausal women with moderate to severe COPD. A 12-week trial included 2-week treatment periods with placebo and MPA (60 mg/d/14 days). All patients underwent a polysomnography with monitoring of SaO2and transcutaneous PCO2(tcCO2) at baseline, with placebo, with medroxyprogesterone acetate (MPA 60 mg/d/14 days), and three and six weeks after cessation of MPA.

Results

Thirteen patients completed the trial. At baseline, the average ± SD of SaO2mean was 90.6 ± 3.2 % and the median of SaO2nadir 84.8 % (interquartile range, IQR 6.1). MPA improved them by 1.7 ± 1.6 %-units (95 % confidence interval (CI) 0.56, 2.8) and by 3.9 %-units (IQR 4.9; 95% CI 0.24, 10.2), respectively. The average of tcCO2median was 6.0 ± 0.9 kPa and decreased with MPA by 0.9 ± 0.5 kPa (95% CI -1.3, -0.54). MPA improved SaO2nadir and tcCO2median also during REM sleep. Three weeks after cessation of MPA, the SaO2mean remained 1.4 ± 1.8 %-units higher than at baseline, the difference being not significant (95% CI -0.03, 2.8). SaO2nadir was 2.7 %-units (IQR 4.9; 95% CI 0.06, 18.7) higher than at baseline. Increases in SaO2mean and SaO2nadir during sleep with MPA were inversely associated with baseline SaO2mean (r = -0.70, p = 0.032) and baseline SaO2nadir (r = -0.77, p = 0.008), respectively. Treatment response in SaO2mean, SaO2nadir and tcCO2levels did not associate with pack-years smoked, age, BMI, spirometric results or sleep variables.

Conclusion

MPA-induced respiratory improvement in postmenopausal women seems to be consistent and prolonged. The improvement was greater in patients with lower baseline SaO2values. Long-term studies in females are warranted.
Expression of the α7 nicotinic acetylcholine receptor in human lung cells
Authors: Plummer Howard K , Dhar Madhu , Schuller Hildegard M
Published: April 2005

Background

We and others have shown that one of the mechanisms of growth regulation of small cell lung cancer cell lines and cultured pulmonary neuroendocrine cells is by the binding of agonists to the α7 neuronal nicotinic acetylcholine receptor. In addition, we have shown that the nicotine-derived carcinogenic nitrosamine, 4(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is a high affinity agonist for the α7 nicotinic acetylcholine receptor. In the present study, our goal was to determine the extent of α7 mRNA and protein expression in the human lung.

Methods

Experiments were done using reverse transcription polymerase chain reaction (RT-PCR), a nuclease protection assay and western blotting using membrane proteins.

Results

We detected mRNA for the neuronal nicotinic acetylcholine receptor α7 receptor in seven small cell lung cancer (SCLC) cell lines, in two pulmonary adenocarcinoma cell lines, in cultured normal human small airway epithelial cells (SAEC), one carcinoid cell line, three squamous cell lines and tissue samples from nine patients with various types of lung cancer. A nuclease protection assay showed prominent levels of α7 in the NCI-H82 SCLC cell line while α7 was not detected in SAEC, suggesting that α7 mRNA levels may be higher in SCLC compared to normal cells. Using a specific antibody to the α7 nicotinic receptor, protein expression of α7 was determined. All SCLC cell lines except NCI-H187 expressed protein for the α7 receptor. In the non-SCLC cells and normal cells that express the α7 nAChR mRNA, only in SAEC, A549 and NCI-H226 was expression of the α7 nicotinic receptor protein shown. When NCI-H69 SCLC cell line was exposed to 100 pm NNK, protein expression of the α7 receptor was increased at 60 and 150 min.

Conclusion

Expression of mRNA for the neuronal nicotinic acetylcholine receptor α7 seems to be ubiquitously expressed in all human lung cancer cell lines tested (except for NCI-H441) as well as normal lung cells. The α7 nicotinic receptor protein is expressed in fewer cell lines, and the tobacco carcinogen NNK increases α7 nicotinic receptor protein levels.
Analysis of the CCR3 promoter reveals a regulatory region in exon 1 that binds GATA-1
Authors: Zimmermann Nives , Colyer Jessica L , Koch Laura E , Rothenberg Marc E
Published: April 2005

Background

CC Chemokine Receptor 3 (CCR3), the major chemokine receptor expressed on eosinophils, binds promiscuously to several ligands including eotaxins 1, 2, and 3. Even though the only cells that consistently accumulate following eotaxin administration in vivo are myeloid cells (primarily eosinophils), other cell types have recently been shown to express CCR3. It is therefore important to elucidate the molecular mechanisms regulating receptor expression.

Results

In order to define regions responsible for CCR3 transcription, a DNAse hypersensitive site was identified in the vicinity of exon 1. Coupled with our previous data implicating exon 1 in CCR3 transcription, we hypothesized that transcription factors bind to exon-1. Electrophoretic mobility shift analysis revealed that nuclear proteins in eosinophilic cells bound to exon 1. Furthermore, antibody interference and mutation studies demonstrated GATA-1 binding to exon 1. In order to test the 1.6-kb CCR3 promoter element (that includes exon 1) for in vivo function, this region was used to generate transgenic mice that expressed a reporter protein. Strong transgene expression was achieved, with the pattern of expression suggesting a broad acting promoter.

Conclusion

The transcription factor GATA-1 binds to CCR3 exon 1. The 1.6-kb CCR3 promoter element, that includes exon 1, is a strong promoter in vivo.
Bartonella seropositivity in children with Henoch-Schonlein purpura
Authors: Robinson Joan L , Spady Donald W , Prasad Errol , McColl Dorothy , Artsob Harvey
Published: April 2005

Background

An association between Henoch-Schonlein purpura (HSP) and seropositivity for Bartonella henselae (BH) has been described. The objective of this study was to see if such an association exists in northern Alberta.

Methods

Immunofluorescent antibody testing utilizing an antigen prepared from B. henselae was undertaken on sera from six children with current HSP, 22 children with remote HSP, and 28 controls that were matched for age. Blood from the six children with current HSP was analysed by polymerase chain reaction (PCR) assay with primers derived from the citrate synthase (gltA) gene for the detection of Bartonella DNA.

Results

The seropositivity rate for BH was 61% in cases versus 21% in controls (p < 0.03). The PCR assay was negative in all six current cases.

Conclusion

There is an increased seropositivity rate for BH in children with HSP. However, it is not clear if infection with B. henselae or a related Bartonella species can result in HSP, or if the increased seropositivity is from non-specific or cross-reacting antibodies.
Clinical practice guideline on the optimal radiotherapeutic management of brain metastases
Authors: Tsao May N , Lloyd Nancy S , Wong Rebecca KS ,   the Supportive Care Guidelines Group of Cancer Care Ontario's Program in Evidence-based Care
Published: April 2005

Background

An evidence-based clinical practice guideline on the optimal radiotherapeutic management of single and multiple brain metastases was developed.

Methods

A systematic review and meta-analysis was performed. The Supportive Care Guidelines Group formulated clinical recommendations based on their interpretation of the evidence. External review of the report by Ontario practitioners was obtained through a mailed survey, and final approval was obtained from Cancer Care Ontario's Practice Guidelines Coordinating Committee (PGCC).

Results

One hundred and nine Ontario practitioners responded to the survey (return rate 44%). Ninety-six percent of respondents agreed with the interpretation of the evidence, and 92% agreed that the report should be approved. Minor revisions were made based on feedback from external reviewers and the PGCC. The PGCC approved the final practice guideline report.

Conclusions

For adult patients with a clinical and radiographic diagnosis of brain metastases (single or multiple) we conclude that,

• Surgical excision should be considered for patients with good performance status, minimal or no evidence of extracranial disease, and a surgically accessible single brain metastasis.

• Postoperative whole brain radiotherapy (WBRT) should be considered to reduce the risk of tumour recurrence for patients who have undergone resection of a single brain metastasis.

• Radiosurgery boost with WBRT may improve survival in select patients with unresectable single brain metastases.

• The whole brain should be irradiated for multiple brain metastases. Standard dose-fractionation schedules are 3000 cGy in 10 fractions or 2000 cGy in 5 fractions.

• Radiosensitizers are not recommended outside research studies.

• In select patients, radiosurgery may be considered as boost therapy with WBRT to improve local tumour control. Radiosurgery boost may improve survival in select patients.

• Chemotherapy as primary therapy or chemotherapy with WBRT remains experimental.

• Supportive care is an option but there is a lack of Level 1 evidence as to which subsets of patients should be managed with supportive care alone.

Qualifying statements addressing factors to consider when applying these recommendations are provided in the full report. The rigorous development, external review and approval process has resulted in a practice guideline that is strongly endorsed by Ontario practitioners.
A polymorphism at codon 31 of gene p21 is not associated with primary open angle glaucoma in Caucasians
Authors: Ressiniotis Thomas , Griffiths Philip G , Keers Sharon M , Chinnery Patrick F , Birch Michael
Published: April 2005

Background

Primary open angle glaucoma (POAG) is considered to be a neurodegenerative optic neuropathy, in which cell death occurs by apoptosis. p21, is an important protective component of the apoptotic pathway, regulating cellular arrest in the presence of DNA damage. An unstable or altered p21 protein could modify the cellular response to genomic injury and abolish the effect of p21. A previous study on a Chinese cohort suggested that the p21 codon 31 polymorphism may alter the state of apoptosis in glaucomatous optic neuropathy, failing to protect the ganglion cells. The aim of this study was to test the hypothesis that a p21 codon 31 polymorphism is associated with POAG on a Caucasian cohort.

Methods

140 POAG patients and a control group of 73 healthy individuals were included in the study. All the subjects were of Caucasian origin. Genomic DNA was amplified by polymerase chain reaction, followed by enzymatic restriction fragment length polymorphism technique (PCR-RFLP). Patients and controls were genotyped for a single nucleotide polymorphism (C/A transversion) in the third base of codon 31 of p21, which leads to a serine (Ser)/arginine (Arg) substitution.

Results

The distribution of the genotypes in the POAG patients showed 128 (91.4%) Ser homozygotes, 10 (7.1%) Ser/Arg heterozygotes and 2 (1.5%) Arg homozygotes. In the control cohort, there were 61 (83.6%) Ser homozygotes and 12 (16.4%) Ser/Arg heterozygotes. No Arg homozygotes were present amongst the control group. Both the allelic and genotypic frequencies of the Ser or Arg residues at codon 31 were not significantly different between POAG patients and controls (Fisher's exact test, P = 0.20 for alleles and P = 0.0561 for genotypes).

Conclusion

This study suggests that the p21 codon 31 polymorphism does not contribute to the risk of POAG in the Caucasian population.
The relationship between video display terminals (VDTs) usage and dermatologic manifestations : a cross sectional study
Authors: Aminian Omid , Mansoori Parvin , Sharifian Akbar , Rafeemanesh Ehsan , Mazaheri Maria , Iraniha Mohammadreza
Published: April 2005

Background

Recently, it has been observed that Video Display Terminals (VDTs) usage for long periods can cause some dermatological manifestations on the face. An analytical cross-sectional study was designed in order to determine this relationship.

Methods

In this study, 600 office workers were chosen randomly from an organization in Tehran (Iran).

The subjects were then divided into two groups based on their exposure to VDTs.

306 workers were considered exposure negative (non VDT user) who worked less than 7 hours a week with VDTs. The remainders 294 were exposure-positive, who worked 7 hours or more with VDTs. The frequency of dermatologic manifestations was compared in these two groups.

Results

In the exposure-positive and exposure-negative groups, the frequency of these dermatologic manifestations were 27 and 5 respectively.

After statistical analysis, a P.value of < 0.05 was obtained indicating a statistically significant difference between these two groups for dermatological manifestations.

Conclusion

According to our study, there is a relationship between dermatologic manifestations on the face and exposure to VDTs.
Mathematical model describing erythrocyte sedimentation rate. Implications for blood viscosity changes in traumatic shock and crush syndrome
Authors: Ismailov Rovshan M , Shevchuk Nikolai A , Khusanov Higmat
Published: April 2005

Background

The erythrocyte sedimentation rate (ESR) is a simple and inexpensive laboratory test, which is widespread in clinical practice, for assessing the inflammatory or acute response. This work addresses the theoretical and experimental investigation of sedimentation a single and multiple particles in homogeneous and heterogeneous (multiphase) medium, as it relates to their internal structure (aggregation of solid or deformed particles).

Methods

The equation system has been solved numerically. To choose finite analogs of derivatives we used the schemes of directional differences.

Results

(1) Our model takes into account the influence of the vessel wall on group aggregation of particles in tubes as well as the effects of rotation of particles, the constraint coefficient, and viscosity of a mixture as a function of the volume fraction. (2) This model can describe ESR as a function of the velocity of adhesion of erythrocytes; (3) Determination of the ESR is best conducted at certain time intervals, i.e. in a series of periods not exceeding 5 minutes each; (4) Differential diagnosis of various diseases by means of ESR should be performed using the aforementioned timed measurement of ESR; (5) An increase in blood viscosity during trauma results from an increase in rouleaux formation and the time-course method of ESR will be useful in patients with trauma, in particular, with traumatic shock and crush syndrome.

Conclusion

The mathematical model created in this study used the most fundamental differential equations that have ever been derived to estimate ESR. It may further our understanding of its complex mechanism.
Complementary and alternative medicine utilisation in NHS and private clinic settings: a United Kingdom survey of 400 infertility patients
Authors: Coulson Catherine , Jenkins Julian
Published: April 2005

Some evidence suggests that complementary and alternative medicine (CAM) has found increased utilisation among patients seeking infertility treatment, although there is little information available to quantify this phenomenon. This is important information as there is marketing for CAM directed to this group and professionals need to be aware of the treatments their patients are receiving. Patients attending for infertility diagnosis and treatment often ask the physician about CAM; this paper seeks to compare the prevalence of CAM use among infertility patients in National Health Service (NHS) and private clinics. This paper provides results of a survey of couples (n = 400) divided equally between NHS and private settings. Our data suggest a high use of CAM particularly among female private patients, although patients appear sceptical of the efficacy of such treatment which is consistent with the literature.
Local and systemic activity of the polysaccharide chitosan at lymphoid tissues after oral administration
Authors: Porporatto Carina , Bianco Ismael D , Correa Silvia G
Published: April 2005

Chitosan is a cationic polysaccharide derived from the partial deacetylation of chitin, which exhibits particular properties: interacts with negatively charged sites on the cell surface; changes the permeability of intestinal epithelium, enhancing the uptake of peptides and proteins; and activates leukocytes. Antigens coadministered or encapsulated with the polysaccharide show improved mucosal and systemic humoral immune responses, although the mechanism is poorly understood. Herein, we characterized in Peyer's patches mesenteric lymph nodes and spleen molecular events triggered after oral administration of chitosan in the absence of protein antigen. Sixteen hours after feeding, we studied the uptake and distribution of the polysaccharide, the phenotype of recruited antigen-presenting cells (APC), the induction of cytokines such as tumor necrosis factor α, interleukin (IL)-12, IL-4, IL-10, and transforming growth factor-β (TGF-β), and the activation of T lymphocytes. We show here that the uptake of chitosan at inductive mucosal sites involves CD11b/c+ APC and that chitosan feeding increases the percentage of OX62+ dendritic cells, which up-regulate the major histocompatibility complex class II antigens without changing the expression of costimulatory CD80 or CD86 molecules. The polysaccharide elicits the release of IL-10 as well as the expression of IL-4 and TGF-β in mucosa, and in spleen, the activation of CD3+ T cells occurs. Our results demonstrate that chitosan acts by enhancing the T helper cell type 2 (Th2)/Th3 microenvironment in the mucosa. A single dose of this polysaccharide exhibits local and systemic effects, and its activity could be relevant in the maintenance of the intestinal homeostasis.
Maturation requirements for dendritic cells in T cell stimulation leading to tolerance versus immunity
Authors: Tan Jonathan K H , O'Neill Helen C
Published: April 2005

The model that dendritic cell (DC) “maturation” describes the change from an immature, antigen-capturing cell to a mature, antigen-presenting cell is well-established. Classification of DCs in terms of function has been problematic previously. It is therefore proposed that mature and not immature DCs are responsible for antigen presentation and stimulation of T cells. Furthermore, DC antigen presentation to T cells can have two outcomes: tolerance or immunity. The particular outcomes appear to be determined by the activation state of the mature DC. DCs can be activated by a range of environmental stimuli or “danger signals”. Here, the hypothesis is advanced that activated, mature DCs induce T cell immunity, and resting, nonactivated but fully differentiated mature antigen-presenting DCs can induce tolerance. This proposal extends to conventional DCs and plasmacytoid DCs. The paper also concentrates on the spleen as a site for DC maturation, in light of evidence from this laboratory for differentiation of DCs from splenic precursors in long-term, stroma-dependent cultures. The hypothesis advanced here serves to simplify many current issues regarding DC maturation and function.
An evaluation of the acute impact of pursed lips breathing on walking distance in nonspontaneous pursed lips breathing chronic obstructive pulmonary disease patients
Authors: Garrodl R , Dallimore K , Cook J , Davies V , Quade K
Published: April 2005

This study was designed to test the effects of pursed lips breathing (PLB) during exercise in patients with chronic obstructive pulmonary disease (COPD) who did not spontaneously perform PLB. Sixtynine COPD patients, mean FEV, (SD) 1.09 (0.5), age 68 (51-83) were recruited to the study. They performed three incremental shuttle walk tests (ISWT). The first walk was designed to identify natural PLBs and the next two walks were performed in a random order; ISWT + PLB or ISWT whilst breathing normally. Measures of respiratory rate (RR), breathlessness and oxygen saturation were taken before and after walks. Data was analysed using the t-test. Fifteen patients demonstrated PLB on baseline ISWT and were therefore excluded from further walking tests although baseline data was included in the analysis. There was no significant difference between walks, mean (SD), 298.5 (173.7)PLB and non-PLB; 292.5 (161.9) nor any difference in dyspnoea. There was a significant reduction in end exercise RR and recovery time with PLB, mean difference (95% CI); 6.2 (4.5-7.9) and 24.9 (2.8-47.0) seconds, respectively. Patients who showed a good response with the PLB walk (41%) had significantly higher baseline breathlessness, Borg score, mean (SD), 1.5 (1.0) versus 0.74 (0.96) (P = 0.02). Natural PLB patients demonstrated lower exercise tolerance on the baseline walk (P = 0.01) and a trend towards greater resting breathlessness than those who did not. This study shows PLB during exercise and recovery results in lower post exercise RR and speeds return to pre exercise breathlessness, compared with exercise and non-PLB. Reductions in RR appear to be greatest in those patients with resting breathlessness.
Supported and unsupported arm exercise capacity following lung volume reduction surgery: a pilot study
Authors: McKeoughl Z J , Alison J A , Bayfield M S , Bye P T.P
Published: April 2005

Study Objectives: Lung volume reduction surgery (LVRS) has been shown to improve lung function, leg exercise capacity and quality of life in subjects with severe COPD. This is the first study to examine the effect of LVRS on supported and unsupported arm exercise capacity. Design: Eight subjects with COPD (% pred FEV1 ±SD = 31.1 ± 9.8%) completed testing. At baseline (TI), after eight weeks pulmonary rehabilitation (T2) and four months after LVRS (T3), each subject had tests of lung function, and performed three symptom-limited exercise tests to peak work capacity:supported arm exercise (SAE), unsupported arm exercise (UAE) and leg exercise (LE).Measurements: The FEV1 (% pred) increased from 27.8 ± 7.4 (mean ± SD) at T2 to 36.3 ± 7.1 at T3 (P <0.05). Peak oxygen consumption (VO2) remained similar from TI to T2 for SAE, UAE and LE (all P=1.0) but increased from T2 to T3 (P <0.05) (SAE: T2 = 0.59 ± 0.2 L/min,T3 = 0.72 ± 0.1 L/min; UAE: T2 = 0.45 ± 0.1 L/min, T3 = 0.54 ± 0.1 L/min; LE:T2-0.68 ± 0.2 L/min, T3 = 0.81 ± 0.2 L/min). The ratio of end-expiratory lung volume to total lung capacity was reduced at peak SAE and LE from T2 to T3 (P < 0.01) (SAE:T2 = 81 ± 4.0%, T3 = 76 ± 2.7%; LE: T2-81 ± 5.1%, T3 = 75 ± 3.6%). Conclusion: There was a significant increase in SAE and UAE capacity following LVRS. Dynamic hyperinflation wras reduced during SAE following LVRS.
Weaning from long-term mechanical ventilation
Authors: Scalise P J , Vottol J J
Published: April 2005

As many as 5% of patients who need mechanical ventilation will require prolonged mechanical ventilation (PMV). The cost of their care and its associated morbidity is alarming; however, good outcomes can be achieved when their care is specialized and delivered in a programmatic manner. In this article, we review some of the common and potentially reversible reasons why patients fail successfully liberation from mechanical ventilation. We examine the outcomes of patients requiring PMV and present evidence that supports the development of specialized units where patients can be cohorted and may produce better outcomes than would be likely if these patients remained in the ICU.
Multicenter, Phase II Study of Cetuximab in Combination With Carboplatin in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma
Authors: Chan Anthony T.C. , Hsu Mow-Ming , Goh Boon C. , Hui Edwin P. , Liu Tsang-Wu , Millward Michael J. , Hong Ruey-Long , Whang-Peng Jacqueline , Ma Brigette B.Y. , To Ka F. , Mueser Matthias , Amellal Nadia , Lin Xiao , Chang Alex Y.
Published: April 2005

Purpose

To evaluate efficacy and toxicity of cetuximab plus carboplatin in recurrent or metastatic nasopharyngeal carcinoma (NPC) resistant to platinum treatment.

Patients and Methods

A multicenter, open-label, single-arm, phase II study in patients with epidermal growth factor receptor–expressing NPC who progressed on or within 12 months after termination of platinum-based chemotherapy for recurrent or metastatic disease. Cetuximab was administered at an initial dose of 400 mg/m2 followed by weekly doses of 250 mg/m2. Carboplatin area under the curve 5 was administered every 3 weeks up to a maximum of eight cycles.

Results

Sixty patients were enrolled (46 males, 14 females; median age, 44.5 years; range, 23 to 64 years), and all patients were included in the intent-to-treat and safety analyses. Of the 59 patients assessable for efficacy, there were seven partial responses (11.7%), 29 patients (48.3%) with stable disease, and 23 patients (38.3%) with progressive disease, giving an overall response rate of 11.7% (95% CI, 4.8% to 22.6%). The median time to progression was 81 days in all patients and was longest in the group of patients with a confirmed response (173 days). The median overall survival time was 233 days in all patients. Six patients (10%) experienced serious treatment-related adverse events. Grade 3 or 4 toxicities occurred in 31 patients (51.7%); of these patients, only 19 (31.7%) were considered to have toxicity related to cetuximab.

Conclusion

Cetuximab in combination with carboplatin demonstrates clinical activity and an acceptable safety profile in heavily pretreated patients with recurrent or metastatic NPC who had previously experienced treatment failure with platinum-based therapy.