bluuebunny/crossref_metadata_2025 huggingface dataset:
Nucleosome stability mediated by histone variants H3.3 and H2A.Z
Authors: Jin Chunyuan , Felsenfeld Gary
Published: June 2007

Nucleosomes containing the histone variant H3.3 tend to be clustered in vivo in the neighborhood of transcriptionally active genes and over regulatory elements. It has not been clear, however, whether H3.3-containing nucleosomes possess unique properties that would affect transcription. We report here that H3.3 nucleosomes isolated from vertebrates, regardless of whether they are partnered with H2A or H2A.Z, are unusually sensitive to salt-dependent disruption, losing H2A/H2B or H2A.Z/H2B dimers. Immunoprecipitation studies of nucleosome core particles (NCPs) show that NCPs that contain both H3.3 and H2A.Z are even less stable than NCPs containing H3.3 and H2A. Intriguingly, NCPs containing H3 and H2A.Z are at least as stable as H3/H2A NCPs. These results establish an hierarchy of stabilities for native nucleosomes carrying different complements of variants, and suggest how H2A.Z could play different roles depending on its partners within the NCP. They also are consistent with the idea that H3.3 plays an active role in maintaining accessible chromatin structures in enhancer regions and transcribed regions. Consistent with this idea, promoters and enhancers at transcriptionally active genes and coding regions at highly expressed genes have nucleosomes that simultaneously carry both H3.3 and H2A.Z, and should therefore be extremely sensitive to disruption.
Mechanisms of obesity-associated insulin resistance: many choices on the menu
Authors: Qatanani Mohammed , Lazar Mitchell A.
Published: June 2007

Obesity-associated insulin resistance is a major risk factor for type 2 diabetes and cardiovascular disease. In the past decade, a large number of endocrine, inflammatory, neural, and cell-intrinsic pathways have been shown to be dysregulated in obesity. Although it is possible that one of these factors plays a dominant role, many of these factors are interdependent, and it is likely that their dynamic interplay underlies the pathophysiology of insulin resistance. Understanding the biology of these systems will inform the search for interventions that specifically prevent or treat insulin resistance and its associated pathologies.
Regulation of plant innate immunity by three proteins in a complex conserved across the plant and animal kingdoms
Authors: Palma Kristoffer , Zhao Qingguo , Cheng Yu Ti , Bi Dongling , Monaghan Jacqueline , Cheng Wei , Zhang Yuelin , Li Xin
Published: June 2007

Innate immunity against pathogen infection is an evolutionarily conserved process among multicellular organisms. ArabidopsisSNC1 encodes a Resistance protein that combines attributes of multiple mammalian pattern recognition receptors. Utilizing snc1 as an autoimmune model, we identified a discrete protein complex containing at least three members—MOS4 (Modifier Of snc1, 4), AtCDC5, and PRL1 (Pleiotropic Regulatory Locus 1)—that are all essential for plant innate immunity. AtCDC5 has DNA-binding activity, suggesting that this complex probably regulates defense responses through transcriptional control. Since the complex components along with their interactions are highly conserved from fission yeast to Arabidopsis and human, they may also have a yet-to-be-identified function in mammalian innate immunity.
Positive feedback between Dia1, LARG, and RhoA regulates cell morphology and invasion
Authors: Kitzing Thomas M. , Sahadevan Arul S. , Brandt Dominique T. , Knieling Helga , Hannemann Sebastian , Fackler Oliver T. , Großhans Jörg , Grosse Robert
Published: June 2007

The RhoA-effector Dia1 controls actin-dependent processes such as cytokinesis, SRF transcriptional activity, and cell motility. Dia1 polymerizes actin through its formin homology (FH) 2 domain. Here we show that Dia1 acts upstream of RhoA independently of its effects on actin assembly. Dia1 binds to the leukemia-associated Rho-GEF (LARG) through RhoA-dependent release of Dia1 autoinhibition. The FH2 domain stimulates the guanine nucleotide exchange activity of LARG in vitro. Our results reveal that Dia1 is necessary for LPA-stimulated Rho/ROCK signaling and bleb-associated cancer cell invasion. Thus, Dia1-dependent RhoA activation constitutes a positive feedback mechanism to modulate cell behavior.
Between-Species Analysis of Short-Repeat Modules in Cell Wall and Sex-Related Hydroxyproline-Rich Glycoproteins ofChlamydomonas
Authors: Lee Jae-Hyeok , Waffenschmidt Sabine , Small Linda , Goodenough Ursula
Published: June 2007

Protein diversification is commonly driven by single amino acid changes at random positions followed by selection, but, in some cases, the structure of the gene itself favors the occurrence of particular kinds of mutations. Genes encoding hydroxyproline-rich glycoproteins (HRGPs) in green organisms, key protein constituents of the cell wall, carry short-repeat modules that are posited to specify proline hydroxylation and/or glycosylation events. We show here, in a comparison of two closely related Chlamydomonas species—Chlamydomonas reinhardtii (CC-621) and Chlamydomonas incerta (CC-1870/3871)—that these modules are prone to misalignment and hence to both insertion/deletion and endoduplication events, and that the dynamics of the rearrangements are constrained by purifying selection on the repeat patterns themselves, considered either as helical or as longitudinal face modules. We suggest that such dynamics may contribute to evolutionary diversification in cell wall architecture and physiology. Two of the HRGP genes analyzed (SAG1 and SAD1) encode the mating-type plus and minus sexual agglutinins, displayed only by gametes, and we document that these have undergone far more extensive divergence than two HRGP genes (GP1 and VSP3) that encode cell wall components—an example of the rapid evolution that characterizes sex-related proteins in numerous lineages. Strikingly, the central regions of the agglutinins of both mating types have diverged completely, by selective endoduplication of repeated motifs, since the two species last shared a common ancestor, suggesting that these events may have participated in the speciation process.
A Novel Nucleus-Encoded Chloroplast Protein, PIFI, Is Involved in NAD(P)H Dehydrogenase Complex-Mediated Chlororespiratory Electron Transport in Arabidopsis
Authors: Wang Dafu , Portis Archie R.
Published: June 2007

A transient rise in chlorophyll fluorescence after turning off actinic light reflects nonphotochemical reduction of the plastoquinone (PQ) pool. This process is dependent on the activity of the chloroplast NAD(P)H dehydrogenase (NDH) complex, which mediates electron flow from stromal reductants to the PQ pool. In this study, we characterized an Arabidopsis (Arabidopsis thaliana) T-DNA insertion mutant pifi (for postillumination chlorophyll fluorescence increase), which possesses an intact NDH complex, but lacks the NDH-dependent chlorophyll fluorescence increase after turning off actinic light. The nuclear gene PIFI (At3g15840) containing the T-DNA insertion encodes a chloroplast-targeted protein localized in the stroma and is annotated as a protein of unknown function. The pifi mutant exhibited a lower capacity for nonphotochemical quenching, but similar CO2 assimilation rates, photosystem II (PSII) quantum efficiencies (ΦPSII), and reduction levels of the primary electron acceptor of PSII (1 − qL) as compared with the wild type. The pifi mutant grows normally under optimal conditions, but exhibits greater sensitivity to photoinhibition and long-term mild heat stress than wild-type plants, which is consistent with lower capacity of nonphotochemical quenching. We conclude that PIFI is a novel component essential for NDH-mediated nonphotochemical reduction of the PQ pool in chlororespiratory electron transport.
ArabidopsisCytochrome P450 Monooxygenase 71A13 Catalyzes the Conversion of Indole-3-Acetaldoxime in Camalexin Synthesis
Authors: Nafisi Majse , Goregaoker Sameer , Botanga Christopher J. , Glawischnig Erich , Olsen Carl E. , Halkier Barbara A. , Glazebrook Jane
Published: June 2007

Camalexin (3-thiazol-2-yl-indole) is an indole alkaloid phytoalexin produced by Arabidopsis thaliana that is thought to be important for resistance to necrotrophic fungal pathogens, such as Alternaria brassicicola and Botrytis cinerea. It is produced from Trp, which is converted to indole acetaldoxime (IAOx) by the action of cytochrome P450 monooxygenases CYP79B2 and CYP79B3. The remaining biosynthetic steps are unknown except for the last step, which is conversion of dihydrocamalexic acid to camalexin by CYP71B15 (PAD3). This article reports characterization of CYP71A13. Plants carrying cyp71A13 mutations produce greatly reduced amounts of camalexin after infection by Pseudomonas syringae or A. brassicicola and are susceptible to A. brassicicola, as are pad3 and cyp79B2 cyp79B3 mutants. Expression levels of CYP71A13 and PAD3 are coregulated. CYP71A13 expressed in Escherichia coli converted IAOx to indole-3-acetonitrile (IAN). Expression of CYP79B2 and CYP71A13 in Nicotiana benthamiana resulted in conversion of Trp to IAN. Exogenously supplied IAN restored camalexin production in cyp71A13 mutant plants. Together, these results lead to the conclusion that CYP71A13 catalyzes the conversion of IAOx to IAN in camalexin synthesis and provide further support for the role of camalexin in resistance to A. brassicicola.
Prevention of Heart Disease in Women: Recommendations for Management of Risk Factors
Authors: King Kathleen B. , Mosca Lori
Published: June 2007

Coronary heart disease is the leading cause of death and disability in women in the U.S. Unfortunately, efforts for primary and secondary prevention of coronary heart disease are less than optimal. The need to emphasize prevention of coronary heart disease in women is important because first events are often fatal in women. Factors that are unique in terms of their influence on risk for coronary heart disease in women include age, reproductive and hormonal status, high density lipoprotein cholesterol and triglyceride levels, and the presence of diabetes. A consistent plan to address risk factor management of each woman is the key to long term risk reduction. Nurses and nurse practitioners, working in any setting, can use the recommendations presented in this paper to help women reduce their risk for coronary heart disease.
Intraaortic Balloon Pumping Through the Common Iliac Artery: Management of the Ambulatory Intraaortic Balloon Pump Patient
Authors: Garrett Kim , Grady Kathleen L.
Published: June 2007

Indications for use of the intraaortic balloon pump have expanded as advances in the treatment of heart disease have continued. The intraaortic balloon pump is the most widely used circulatory assist device inserted as short term or long term therapy. Because the percutaneous femoral artery approach requires bedrest, new techniques for intraaortic balloon pump insertion that allow greater mobility are being developed for patients who require long term ventricular support. The goal of ambulation in these patients is to prevent potential complications associated with prolonged immobility. This paper reviews the use of the common iliac artery as an alternate site for intraaortic balloon pump insertion that allows the patient to ambulate and exercise. Pre and post procedure management as well as potential complications of intraaortic balloon pump insertion are discussed.
Nursing Care of the Intraaortic Balloon Catheter's Inner Lumen
Authors: Quaal Susan J.
Published: June 2007

An inner lumen exists within the intra‐aortic balloon for the purpose of introducing a guidewire to facilitate balloon insertion. This inner cannula also can be used for continuous arterial pressure monitoring. However, special precautions are necessary when utilizing this port for arterial monitoring as compared to a conventional radial arterial line. The proximal tip of this arterial pressure monitoring source rests within the proximal aorta in close proximity to the trifurcated vessels coming off the aorta. The possibility of a clot dislodging and entering the trifurcated vessels. Because of the inner lumen's small size and location, special guidelines need to be followed for its care and maintenance. This paper reviews physiological specific to the intraaortic balloon's inner cannula and recommends practice guidelines regarding heparinized or nonheparinized flush solutions, flushing of the inner lumen, and troubleshooting a damped inner cannula arterial waveform.
Determination of the Burden of Care in Families of Cardiac Surgery Patients
Authors: Stolarik Anne , Lindsay Patrice , Sherrard Heather , Woodend A. Kirsten
Published: June 2007

“Burden of care” is a term that describes the effects of the multifaceted stressors associated with providing care to an ill family member. Descriptions of burden of care in acute care populations, such as families of patients who have had coronary artery bypass grafting, are very limited. The three purposes of this study were to describe the burden of care in families of coronary artery bypass grafting surgery patients, to compare the burden of care in families grouped by length of stay, and to provide evidence for the validity of the Caregiving Burden Scale in acute care populations. A survey was done using a longitudinal design over the first six weeks following coronary artery bypass grafting surgery. The 124 spouses of coronary artery bypass grafting surgery patients who participated reported a moderate degree of burden in caring for post cardiac surgery family members. Providing emotional support, taking over household tasks, and monitoring patients' conditions created the greatest burden for the participants. Length of stay in hospital did not have an impact on burden of care. The analysis of the data supports the validity of the Caregiving Burden Scale when used in the cardiac surgery population.
Barriers to Participation in and Adherence to Cardiac Rehabilitation Programs: A Critical Literature Review
Authors: Daly John , Sindone Andrew P. , Thompson David R. , Hancock Karen , Chang Esther , Davidson Patricia
Published: June 2007

Despite the documented evidence of the benefits of cardiac rehabilitation (CR) in enhancing recovery and reducing mortality following a myocardial infarction, only about one third of patients participate in such programs. Adherence to these programs is an even bigger problem, with only about one third maintaining attendance in these programs after 6 months. This review summarizes research that has investigated barriers to participation and adherence to CR programs. Some consistent factors found to be associated with participation in CR programs include lack of referral by physicians, associated illness, specific cardiac diagnoses, reimbursement, self‐efficacy, perceived benefits of CR, distance and transportation, self‐concept, self‐motivation, family composition, social support, self‐esteem, and occupation. Factors associated with non‐adherence include being older, female gender, having fewer years of formal education, perceiving the benefits of CR, having angina, and being less physically active during leisure time. However, many of the studies have methodologic flaws, with very few controlled, randomized studies, making the findings tentative. Problems in objectively measuring adherence to unstructured, non‐hospital‐based programs, which are an increasingly popular alternative to traditional programs, are discussed. Suggestions for reducing barriers to participation and adherence to CR programs, as well as for future research aimed at clearly identifying these barriers, are discussed.
Emergent Cardiovascular Risk Factor: Homocysteine
Authors: Warren Cindy J.
Published: June 2007

Homocysteine is an independent, modifiable risk factor for cardiovascular disease. It is an intermediate amino acid formed during the metabolism of methionine. Plasma homocysteine is normally ≤12 μmol/L, but when elevated has many deleterious cardiovascular effects. This review explains homocysteine metabolism, the effects of elevated homocysteine, factors contributing to high homocysteine, and its measurement. Risk factors for elevated homocysteine and intervention with B vitamins are discussed. Cardiovascular nurses are encouraged to facilitate homocysteine awareness through a variety of educational means.
Healing the Heart: Integrating Complementary Therapies and Healing Practices Into the Care of Cardiovascular Patients
Authors: Kreitzer Mary Jo , Snyder Mariah
Published: June 2007

Complementary therapies and healing practices have been found to reduce stress, anxiety, and lifestyle patterns known to contribute to cardiovascular disease. Promising therapies include imagery and hypnosis, meditation, yoga, tai chi, prayer, music, exercise, diet, and use of dietary supplements. Many of these complementary approaches to healing have been within the domain of nursing for centuries and can readily be integrated into the care of patients with cardiovascular disease. While individual complimentary modalities hold considerable merit, it is critical that the philosophy underlying these therapies—caring, holism, and harmony—also be understood and honored.
African Americans' Knowledge of and Attitudes Toward Coronary Artery Bypass Surgery as a Treatment Option
Authors: Celia Barbara
Published: June 2007

The objective of this study was to determine if African Americans possess knowledge of cardiac bypass surgery as a treatment option, and their willingness to undergo the procedure if it were recommended by a cardiologist. Primary data were collected over a 2‐week period. The study setting was a primary care clinic located in an urban area. The clinic is associated with a university medical center that provides high‐technology cardiac services. An exploratory, prospective survey and interview technique was utilized to elicit responses from a convenience sample of 50 African American participants. The majority (80%) were knowledgeable about coronary artery bypass surgery and stated a positive preference for the procedure, if it were recommended. The author concluded that although African Americans are knowledgeable about coronary bypass, awareness of these procedures as a treatment option needs to be supported by nurses and physicians.
Syncope: A Fall From Grace
Authors: Colgan Jane
Published: June 2007

Falls by the elderly are not always what they appear to be on the surface. In the following paper, a woman must experience a long process of trial and error, as well as injury and suffering, before the underlying condition is finally uncovered by an astute nurse practitioner. The path to the diagnosis of syncope is a complex one, with economic, physical, and even social and psychological repercussions. Grace's “fall” not only contributes to burns and fractures, but damages her self‐esteem and threatens her very independence. Armed with a thorough assessment, complete history, and the use of cardiac event recorders, a cardiovascular nurse has the unique opportunity to make a difference in the life of a patient suffering from suspicious falls and help her maintain a high quality of life.
Staying on Course: The Effects of an Adherence Facilitation Intervention on Home Exercise Participation
Authors: Duncan Kathleen A. , Pozehl Bunny
Published: June 2007

The purpose of this investigation was to test the effectiveness of an adherence facilitation intervention consisting of goal setting, graphic feedback, and provider guidance to support adherence to home exercise in a sample of patients with heart failure who had completed a supervised exercise program. The sample consisted of 13 patients with an ejection fraction of 40% or less who were randomly assigned to either the exercise only group (n=6) or the exercise with adherence facilitation group (n=7). The format of the intervention was graphic depiction of each patient's exercise goals in comparison to each patient's exercise participation. Graphs were mailed at 3‐week intervals for 12 weeks. Results indicate that patients who received the intervention demonstrated higher exercise adherence and greater confidence in continuing to exercise in the future. The adherence facilitation intervention may be helpful to heart failure patients in adapting to a program of home exercise.
Atrial Fibrillation: The Newest Frontier in Arrhythmia Management
Authors: McCabe Pamela J. , Geoffroy Susan
Published: June 2007

At least 2.3 million people in the United States have atrial fibrillation. Since the risk for developing atrial fibrillation increases with age, the number of people with atrial fibrillation is expected to rise sharply. Atrial fibrillation is a complex condition that adversely influences mortality, morbidity, quality of life, and use of health care resources. Knowledge generated from extensive research has led to innovative management strategies. As the number of individuals with atrial fibrillation increases and treatment options expand, nurses in a variety of settings will be challenged to respond to the multifaceted needs of this population. This review discusses the significance of atrial fibrillation and summarizes research findings influencing current management strategies. Pharmacologic therapies are reviewed and new technologies for atrial fibrillation treatment are introduced. Nursing assessment and treatment of patients' response to atrial fibrillation are discussed. Recommendations for patient education are offered. A plan describing specific nursing diagnoses, outcomes, interventions, and activities for care of patients with atrial fibrillation is presented.
Small LDL and Its Clinical Importance as a New CAD Risk Factor: A Female Case Study
Authors: Superko H. Robert , Nejedly Mary , Garrett Brenda
Published: June 2007

The underlying metabolic cause of coronary heart disease in many patients is not high blood cholesterol. In fact, the Framingham study has reported that 80% of individuals who go on to have coronary artery disease have the same total blood cholesterol values as those who do not go on to have a cardiovascular event. The most common metabolic contributor to coronary artery disease is the atherogenic lipoprotein profile, characterized by an abundance of highly atherogenic small, dense low‐density lipoprotein particles and a deficiency of the high‐density lipoprotein (HDL) subtype most associated with coronary artery disease protection (HDL2b). This trait is present in 50% of men with coronary artery disease and is not reflected by total or low‐density lipoprotein cholesterol values. While fasting triglycerides tend to he higher, and HDL cholesterol lower in patients with the atherogenic lipoprotein profile, the majority have triglyceride and HDL cholesterol values generally accepted to be in the “normal” range. An abundance of basic science and clinical trial evidence convincingly indicates that the presence of an atherogenic lipoprotein profile signifies a three‐fold increased risk for a cardiovascular event and rapid arteriographic progression, but it also identifies a group of patients who respond particularly well to specific therapeutic interventions. Often the most effective interventions are the least expensive.
Adherence to Angiotensin‐Converting Enzyme Inhibitor Therapy for Heart Failure
Authors: Bohachick Patricia , Burke Lora E. , Sereika Susan , Murali Srinivas , Dunbar‐Jacob Jacqueline
Published: June 2007

This study examined adherence to angiotensin‐converting enzyme inhibitor therapy among 171 heart failure clinic patients. Adherence was monitored over a 3‐month period with an electronic event monitor housed in a medication bottle cap, which recorded the date and time the cap was opened and closed. The average percentage of days that the prescribed number of doses (regimen adherence) was taken over the observation period was 84%. Seventy‐one percent of patients showed 85%–100% adherence with their daily regimen; 19% exhibited less than 70% adherence. The overall high rates of adherence to angiotensin‐converting enzyme inhibitor therapy observed among heart failure clinic patients is consistent with research that shows improved outcomes for patients managed in heart failure clinics. Electronic medication monitoring can be useful in identifying a substantial fraction of patients who are poorly adherent so that interventions to improve adherence can be targeted toward them. Additional research is needed to develop and test adherenceenhancing interventions.
Role of Inflammation in Cardiovascular Disease: How to Use C‐Reactive Protein in Clinical Practice
Authors: Zebrack James S. , Anderson Jeffrey L.
Published: June 2007

Acute coronary syndromes, stroke, and sudden death are common complications of a disrupted atherosclerotic plaque. Unstable plaque is a result of multiple factors but is commonly characterized by an infiltrate of inflammatory cells. Medical research strongly supports a role for inflammation in the pathogenesis, progression, and disruption of atherosclerotic plaque. Medical science also has improved our understanding of the complex interactions between our environment and our immune, coagulation, and cardiovascular systems. Clinical studies have demonstrated systemic markers of inflammation to be strong predictors of clinical events, and specific treatments of atherosclerosis and its risk factors have been associated with reductions in inflammatory markers. The authors review the current understanding of the role of inflammation in the pathogenesis of atherosclerosis, the common inflammatory markers, and potential anti‐inflammatory therapy. Among several potential circulating markers of vascular inflammation, high sensitivity C‐reactive protein is best validated and standardized as a marker for cardiovascular risk assessment. Nevertheless, there remain many uncertainties in utilizing C‐reactive protein in clinical practice. Here, the authors describe the central role of C‐reactive protein in atherosclerosis, review the studies demonstrating predictive value of C‐reactive protein, describe the factors requiring consideration when utilizing C‐reactive protein, discuss clinical scenarios in which measurement of C‐reactive protein may be helpful, and suggest ways to interpret and treat elevated C‐reactive protein levels. Finally, the authors summarize future expectations for assessing and modulating the vascular inflammation to inhibit initiation and progression of the atherosclerotic process.
p53 Gene mutations in esophageal squamous cell carcinoma and their relevance to etiology and pathogenesis: Results in Japan and comparisons with other countries
Authors: Egashira Akinori , Morita Masaru , Kakeji Yoshihiro , Sadanaga Noriaki , Oki Eiji , Honbo Takuya , Ohta Mitsuhiko , Maehara Yoshihiko
Published: June 2007

Esophageal squamous cell carcinoma is a form of cancer that has varying incidence rates among different countries, distinct geographic areas and different ethnic groups. According to previous reports, p53 gene mutations have been identified in 20–80% of these tumors, and these mutations have occurred at an early stage. These findings suggest that such mutations play an important role in esophageal carcinogenesis, and highlight the importance of mutagens, which cause sequence alterations in the p53 gene. In order to clarify the environmental factors and the molecular mechanisms that may be responsible for the occurrence and prevention of a specific mutation in the process of esophageal carcinogenesis, we analyzed p53 gene mutations in 95 samples of esophageal squamous cell carcinoma. We further reviewed published reports investigating the frequency of p53 gene mutations in esophageal cancer from high‐risk areas to normal‐risk areas and compared these findings to our results in Japan. The frequency of p53 gene mutations in Japanese esophageal cancer is 47.4% and there are three prominent features: (1) a predominance of transversions, in particular the G:C to T:A transversion; (2) a relatively low frequency of transitions; and (3) a relatively high percentage of frameshift mutations. These results indicate the possible importance of the benzo[a]pyrene metabolite and oxidative DNA damage in esophageal carcinogenesis and scarcely correlate with DNA replication errors or alkylation in comparison to other gastrointestinal cancers. In addition, we observed a peculiar sequence of frameshift mutations. Taken together, these data suggest that this tumor suppressor gene plays a critical role in the multistep carcinogenesis process for esophageal squamous cell cancer. (Cancer Sci 2007; 98: 1152–1156)
Defective Jak–Stat activation in renal cell carcinoma is associated with interferon‐α resistance
Authors: Shang Donghao , Liu Yuting , Ito Noriyuki , Kamoto Toshiyuki , Ogawa Osamu
Published: June 2007

Chemotherapy is ineffective against metastatic renal cell carcinoma (RCC). Interferon (IFN)‐α has become the most common agent used in clinical therapy to overcome this malignant tumor, although a satisfactory response has not been achieved and the mechanism of resistance of RCC to IFN‐α remains unclear. The purpose of the present study was to evaluate the susceptibility of RCC cells to IFN‐α and clarify the mechanism of IFN‐α resistance in RCC. Six RCC cell lines and three types of IFN‐α were used, and the expression, activation and effects of transfection of possible proteins or factors reported to be involved in IFN‐α signaling were examined to clarify the mechanism of resistance. The results suggest that the resistance of RCC to IFN‐α is associated with the lack of Jak1, Tyk2 and Stat1 expression and defective Jak–Stat activation, but not with a lack of IFN‐α receptor, suppressors of cytokine signaling induction or other factors examined. Moreover, phosphorylation of Jak–Stat pathway components and reversion of IFN‐α resistance in RCC were observed upon transfection with Jak1, Tyk2 or Stat1 vector. These results suggest that restoring the expression of Jak or Stat1 might strikingly increase the susceptibility of RCC to IFN‐α and may be a new strategy for improving the response of RCC to IFN‐α treatment. The Jak–Stat pathway should therefore be an appropriate target for the treatment of RCC. (Cancer Sci 2007; 98: 1259–1264)
Thrombin generation: the functional role of alpha‐2‐macroglobulin and influence of developmental haemostasis
Authors: Ignjatovic V. , Greenway A. , Summerhayes R. , Monagle P.
Published: June 2007

Currently available chromogenic and fluorogenic substrates for endogenous thrombin potential (ETP) measurement are cleaved by both free (active) and alpha‐2‐macroglobulin‐bound (inactive) thrombin, leading to an overestimation of ETP. Commercial methods for ETP measurement determine this using a mathematical algorithm, which assumes the contribution of alpha‐2‐macroglobulin to the ETP. This limits application of such methods to populations where variation in alpha‐2‐macroglobulin concentrations is observed, primarily children. This study examined the contribution of alpha‐2‐macroglobulin‐bound thrombin to the ETP measurement in neonates, children and adults, to determine whether automated methods are appropriate for use in neonates and children.
Meanings of eating disorders discerned from family treatment and its implications for family education: the case of Shenzhen
Authors: Ma Joyce L. C.
Published: June 2007

Contrary to the simplistic myth that eating disorders are the result of a tendency to adopt the Western beauty standard of being slim and thin, the symptoms have been found to symbolize the struggles of adolescents and their development in a rapidly changing society, and in particular, to illuminate the continual conflicts inherent in the afflicted adolescents, their families and the accepted societal values and norms. This paper reports the results of a qualitative study conducted in Shenzhen, the first Special Economic Zone in China that has experienced rapid economic growth and a significant population increase from 314 100 to 6 million in the past two decades. With an aim to identify the meanings of eating disorders at the individual and family levels, this study has employed a multiple‐case study research design. Data have been collected through peer reviews on the family treatment sessions for 10 families, each with an adolescent daughter suffering from eating disorders, and with the sessions being videotaped with written consent from the families. Two themes evolved from the family narratives, namely the adolescents' attempt to master the uncontrollable life in facing the rapid transition of society, and their struggle between remaining young and growing up. Implications for family education in Shenzhen are discussed at the end of the paper.
Novel IgE peptide‐based vaccine prevents the increase of IgE and down‐regulates elevated IgE in rodents
Authors: Peng Z. , Liu Q. , Wang Q. , Rector E. , Ma Y. , Warrington R.
Published: June 2007

BackgroundImmunotherapy with anti‐IgE antibodies for treatment of allergy is promising but a short half‐life and extremely high cost limit its application.

ObjectiveWe sought to develop IgE vaccines that induce longer‐lasting auto‐antibodies to neutralize self‐IgE as an alternative therapy.

MethodsThe vaccine was made by conjugating three synthetic peptides corresponding to human IgE receptor‐binding sites to a carrier, hepatitis B surface antigen. To test the immunogenicity of the vaccine, rats were immunized with the vaccine or hepatitis B surface antigen as control. Serum IgG titres to human IgE and the IgE of other species were measured. The inhibition by rat antisera of the binding of human IgE to its receptor was assessed by ELISA, flow cytometry analysis, and passive cutaneous anaphylaxis (PCA), and its ability to recognize receptor‐bound IgE was examined. Thein vivoeffect of the vaccine was evaluated in trichosanthin‐sensitized mice and rats. In the preventative study, vaccination started before sensitization commenced, while in the treatment study, vaccination started after sensitization. Sensitized mice and rats receiving injections of the carrier served as controls. Trichosanthin‐specific IgE was measured using PCA.

ResultsSera from vaccine‐immunized rats contained high titre antibodies that reacted with soluble and plate‐bound but not with receptor‐bound human IgE; they also reacted with mouse, rat, and dog IgE. Furthermore, the sera inhibited the binding of human IgE to its receptor in a dose‐dependent manner. In preventative and treatment studies, serum trichosanthin‐specific IgE levels were significantly reduced in vaccinated groups compared with controls.

ConclusionAntibodies against self‐IgE can be induced by IgE peptide‐based vaccines, which are effective in preventing the increase of IgE and in down‐regulating IgE in sensitized animals.
Effect of obesity on airway inflammation: a cross‐sectional analysis of body mass index and sputum cell counts
Authors: Todd D. C. , Armstrong S. , D'Silva L. , Allen C. J. , Hargreave F. E. , Parameswaran K.
Published: June 2007

Background
Several observational studies have demonstrated an association between obesity and asthma. Studies evaluating exhaled nitric oxide levels and obesity have revealed that a higher body mass index (BMI) is associated with elevated exhaled nitric oxide levels. Airway inflammation using sputum cell counts has not been assessed in obese patients with airway diseases.

Objective
The primary aim of this study was to determine whether obesity (based on BMI) is associated with eosinophilic or neutrophilic bronchitis.

Methods
The results from a database of induced sputum cell counts were compared with BMI and analysed using correlation statistics, regression and parametric and non‐parametric analysis.

Results
Seven‐hundred and twenty‐seven adult participants with an equal number of sputum samples were included in the analysis. BMI varied from 14.5 to 55 kg/m2. Sputum total cell count (mean±SD: 12.9 × 106 cell/g±21.5), eosinophil percent (median; min to max: 0.3%; 0–89.0), and neutrophil percent (mean±SD: 63.5±26.6%) were within normal limits. Participants with asthma had a higher percentage of sputum eosinophils than those without asthma (P=0.01). However, there was no difference in the total or differential cell counts among the obese and non‐obese participants, when the data were analysed according to BMI category, gender, dose of inhaled corticosteroid, and presence or absence of asthma.

Conclusion
In this large sample of adult asthmatic and non‐asthmatic participants, there was no association between BMI and airway inflammation measured by sputum cell counts. Other mechanisms to explain the relationship between obesity and asthma will need to be explored if this association is to be better understood.
The changing face of food hypersensitivity in an Asian community
Authors: Chiang W. C. , Kidon M. I. , Liew W. K. , Goh A. , Tang J. P. L. , Chay O. M.
Published: June 2007

Background
Food allergy seems to be increasing in Asia as well as world‐wide. Our aim was to characterize food protein sensitization patterns in a population of Asian children with possible food allergy.

Methods
Children presenting to our allergy clinic over 3 years with symptomatic allergic disease and at least one specific food allergen sensitization documented on skin prick testing were included in the analysis.

Results
Two hundred and twenty‐seven patients fulfilled inclusion criteria. Ninety (40%) of the positive skin tests were positive to egg, 87 (39%) to shellfish, 62 (27.3%) to peanut, 30 (13.2%) to fish, 27 (11.8%) to cow's milk, 21 (9.3%) to sesame, 13 (3.7%) to wheat and eight (3.2%) to soy. Peanut sensitization was the third most common sensitizing allergen, and seen mostly in young atopic children with multiple food hypersensitivities and a family history of atopic dermatitis. The median reported age of first exposure to fish and shellfish was 6 and 12 months, respectively. The mean age at presentation of children with shellfish hypersensitivity was at 6.7 years of age. The likelihood of shellfish sensitization was increased in children with concomitant sensitization to cockroaches.

Conclusions
In contrast to previously reported low peanut allergy rates in Asia, in our review, peanut sensitization is present in 27% (62/227) of food‐allergic children, mostly in patients with multiple food protein sensitizations. Temporal patterns of first exposure of infants to fish and shellfish are unique to the Asian diet. Shellfish are a major sensitizing food source in Asian children, especially in allergic rhinitis patients sensitized to cockroaches.
Temporal trends of aeroallergen sensitization over twenty‐five years
Authors: Linneberg A. , Gislum M. , Johansen N. , Husemoen L. L. N. , Jørgensen T.
Published: June 2007

Background
Little is known about time trends of allergic respiratory disease in adults, in particular in older adults. Furthermore, few trend studies have used objective measurements of IgE sensitization against inhalant allergens.

Objectives
To investigate time trends of aeroallergen sensitization in adults over a 25‐year period.

Methods
The study includes a total of 7820 persons, aged 30, 40, 50, and 60 years, who participated in three repeated cross‐sectional studies of the general population of Copenhagen, Denmark, in 1976–1977, 1982–1984, and 1999–2001, respectively. Respiratory allergy was assessed by determination of specific IgE aeroallergen sensitization in stored serum samples.

Results
Over this 25‐year period, a marked and statistically significant increase in the prevalence of aeroallergen sensitization had occurred. This increase was seen in all age‐groups challenging the notion that the allergy epidemic only affects generations born 1960 onwards. For example, in 40‐year‐olds the prevalence (with 95% confidence intervals) of aeroallergen sensitization was 14.9% (12.7–17.1), 19.7% (17.1–22.3), and 27.6% (25.1–30.1) in 1976–1977, 1982–1984, and 1999–2001, respectively.

Conclusions
Our results support that the allergy epidemic has spread to older adults resulting in a continuing increase in the overall prevalence of aeroallergen sensitization and an increase in the mean age of allergic patients.
Children with peanut allergy recognize predominantly Ara h2 and Ara h6, which remains stable over time
Authors: Flinterman A. E. , Van Hoffen E. , Den Hartog Jager C. F. , Koppelman S. , Pasmans S. G. , Hoekstra M. O. , Bruijnzeel‐Koomen C. A. , Knulst A. C. , Knol E. F.
Published: June 2007

Background
In peanut‐allergic adults, IgE is mainly directed to Ara h1 and Ara h2. More recently, a role for Ara h6 has been suggested. In contrast to adults, IgE in children can fluctuate over time. Therefore, children may have a more dynamic reactivity to peanut.

Objective
To examine the IgE reactivity to major peanut allergens in peanut‐allergic children at two subsequent time‐points.

Methods
Twenty children (3–15 years old) with peanut allergy, confirmed by a double‐blind placebo‐controlled food challenge (DBPCFC), were included. Just before and 20 months after DBPCFC, IgE reactivity to purified Ara h1, Ara h2, Ara h3 and Ara h6 was studied by immunoblots and skin prick tests (SPTs).

Results
Before DBPCFC, all peanut‐allergic children showed IgE reactivity to Ara h2; Ara h6 was recognized by 16 children, and Ara h1 and Ara h3 by 10 children. After 20 months, peanut‐specific IgE levels (median 23 kU/L) and the individual recognition of major allergens were comparable with the levels and recognition before challenge (median 28.2 kU/L). SPT with Ara h2 and Ara h6 was positive in most children, whereas SPT with Ara h1 and Ara h3 was positive in approximately half of the children. Ara h6 induced the largest weals. None of the parameters were related to the severity of peanut allergy.

Conclusion
Ara h2 and Ara h6 are the most frequently recognized major peanut allergens in children. The individual reactivity to the major peanut allergens remained stable over time, despite DBPCFC.
Relationships of methacholine and AMP responsiveness with peak expiratory flow variability in children with asthma
Authors: Yoo Y. , Kim D. K. , Yu J. , Choi S. H. , Kim C. K. , Koh Y. Y.
Published: June 2007

Background
Both bronchial responsiveness (BR) and peak expiratory flow (PEF) variability are increased in asthma. PEF variability is presumed to reflect the degree of BR in asthma. BR is commonly assessed by bronchial challenges using direct or indirect stimuli.

Objective
The aim of this study was to compare methacholine and adenosine 5′‐monophosphate (AMP) responsiveness with regard to their relationships with PEF variability in children with asthma.

Methods
Methacholine and AMP challenge tests were performed in 79 children with mild to moderate asthma, and a provocative concentration causing a 20% decline in forced expiratory volume in 1 s (PC20) was calculated for each challenge. Subjects recorded PEF each morning and each evening for 14 consecutive days. PEF variability was expressed as amplitude percentage mean (amp%mean; high PEF minus low PEF on each day, expressed as a percentage of their mean, averaged over 14 days), and as the lowest percentage highest (low%high; the lowest PEF expressed as a percentage of the highest PEF recorded over the period).

Results
Methacholine PC20 correlated significantly but weakly with both indices of PEF variability (amp%mean: r=−0.285, P=0.011; low%high: r=0.238, P=0.034). However, there was a significant and strong correlation between AMP PC20 and both amp%mean (r=−0.583, P=0.000) and low%high (r=0.496, P=0.000). For AMP PC20, the correlations were stronger than for methacholine PC20 (comparison of correlation coefficients with amp%mean: P=0.021; with low%high: P=0.063).

Conclusion
Both methacholine PC20 and AMP PC20 correlated significantly with PEF variability. However, the stronger correlations for AMP PC20 than for methacholine PC20 suggest that PEF variability may be better reflected by BR assessed by AMP than by methacholine.
An evaluation of the relationship between adult height and health‐related quality of life in the general UK population
Authors: Christensen T. L. , Djurhuus C. B. , Clayton P. , Christiansen J. S.
Published: June 2007

Objective  Short stature has previously been shown to influence several social factors during childhood and adult life. However, limited data exist to determine the influence of short stature on health‐related quality of life (HRQoL) because of underpowered studies and the fact that children find questionnaires very difficult to complete. The objective of this study was to examine the influence of height on HRQoL for the general adult population in the UK.

Design  The 2003 Health Survey for England (HSE03), commissioned by the Department of Health, provides a random general population sample for the population living in private households in England. Observations for 14 416 adults (aged > 18 years) were included in the analysis.

Measurements  The survey involved a questionnaire‐based interview and a nurse visit, where measurements and blood samples were taken. HRQoL was measured using the EQ‐5D questionnaire. Social class (I–V) was derived according to definitions from UK National Statistics. Height was converted from centimetres to height standard deviation scores (HSDS).

Results  Mean EQ‐5D scores were lower in subjects with greater height deficit than in taller subjects. Three significantly different subgroups were identified using an analysis of variance (anova). The first subgroup ‘HSDS ≤ –2·0’ had significantly lower EQ‐5D scores compared with the second group ‘–2·0 > HSDS ≤ 0’ and the third group ‘HSDS > 0’. Multivariate linear regression analysis showed significant correlations between height and HRQoL, such that an increase in height of 1 HSDS predicts an improvement in EQ‐5D score of 6·1% for subjects shorter than –2·0 HSDS. Social class was a significant predictor of HRQoL in taller, but not in shorter, subjects.

Conclusion  The results of this study demonstrate that height in adult life is correlated with HRQoL and that short stature in adult life may be associated with a significant reduction in HRQoL.
Predictors of remission of hyperprolactinaemia after long‐term withdrawal of cabergoline therapy
Authors: Colao Annamaria , Di Sarno Antonella , Guerra Ermelinda , Pivonello Rosario , Cappabianca Paolo , Caranci Ferdinando , Elefante Andrea , Cavallo Luigi M. , Briganti Francesco , Cirillo Sossio , Lombardi Gaetano
Published: June 2007

Background  Remission rates of 76, 69·5 and 64·3% have been reported in patients with nontumoural hyperprolactinaemia (NTH), microprolactinoma and macroprolactinoma, respectively, 2–5 years after cabergoline (CAB) withdrawal.

Objective  To report the estimated recurrence rate at 24–96 months after CAB withdrawal and indicate predictors of disease remission.

Design  Observational, analytical, prospective.

Patients  Of 381 previously untreated de novo patients with hyperprolactinaemia, 221 (58%) (173 women, 48 men; 27 with NTH, 115 with micro‐, and 79 with macroprolactinoma) were studied.

Measurements  Using multiple regression analysis the diagnostic accuracy of nadir PRL levels (t = 7·6, P < 0·0001) and nadir maximal tumour diameter at CAB withdrawal (t = 3·9, P < 0·001) was analysed using receiver operating characteristic (ROC) curves.

Results  The recurrence of hyperprolactinaemia was 25·9, 33·9 and 53·1% in patients with NTH, micro‐ or macroprolactinoma, respectively. To predict the last PRL level after withdrawal, the optimum cut‐off of nadir PRL levels at withdrawal was 162 mU/l (5·4 µg/l) [sensitivity (95% CI) 76% (67–84%), specificity 65% (51–77%)] and that of nadir maximal tumour diameter was 3·1 mm [sensitivity 52% (41–63%), specificity 86% (79–91%)]. The patients achieving both nadir PRL levels ≤ 162 mU/l and maximal tumour diameter ≤ 3·1 mm (n = 111) at CAB withdrawal had a significantly lower Kaplan–Meier estimate of recurrence of hyperprolactinaemia (20%) at 24–96 months than those who did not fulfil any of these criteria [(n = 38) 90%; P < 0·0001]. Patients achieving nadir PRL levels ≤ 162 mU/l (n = 26) or maximal tumour diameter ≤ 3·1 mm during CAB treatment (n = 46) had an estimated recurrence rate of hyperprolactinaemia of 50 and 56%, respectively.

Conclusion  Persistent remission of hyperprolactinaemia without any evidence of tumour re‐growth after 24–96 months of CAB withdrawal occurred in the majority of patients with NTH and microprolactinoma and in about half of those with macroprolactinoma. Nadir PRL levels and maximal tumour diameter at CAB withdrawal of ≤ 162 mU/l and ≤ 3·1 mm predicted remission of hyperprolactinaemia in 80% of patients.