bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparison of Different Strategies to Collect Standard Gamble Utilities
Authors: Hammerschmidt Thomas , Zeitler Hans-Peter , Gulich Markus , Leidl Reiner
Published: September 2004

Objective. The authors performed a methodological comparison of the usual standard gamble with methods that could also be used in mailed questionnaires. Methods. Ninety-two diabetic patients valued diabetes-related health states twice. In face-to-face interviews, the authors used an iterative standard gamble (ISG) in which the probabilities were varied in a ping-pong manner and a self-completion method (SC) with top-down titration as search procedure (SC-TD) in 2 independent subsamples of 46 patients. Three months later, all patients received a mailed questionnaire in which the authors used the self-completion method with bottom-up (SCBU) and SC-TD as search procedures. Results. ISG and SCTD showed feasibility and consistency in the interviews. The ISG resulted in significantly higher utilities than the SC-TD. Two thirds of the mailed questionnaires provided useful results indicating some problems of feasibility. Utilities measured by SC-BU and SC-TD did not differ significantly showing procedural invariance. Further, patients indicated ambivalence when given the choice not to definitely state their preferences. Conclusions.The results show that different strategies to collect standard gamble utilities can yield different results. Compared with the usually applied ISG, the SC method is feasible in interviews and provides a consistent alternative that is less costly when used in mailed questionnaires, although its practicability has to be improved in this later setting.
Group Sequential Design for Comparative Diagnostic Accuracy Studies: Implications and Guidelines for Practitioners
Authors: Mazumdar Madhu
Published: September 2004

Purpose. Comparative diagnostic accuracy (CDA) studies are typically small retrospective studies supporting a higher accuracy for one modality over another for either staging a particular disease or assessing response to therapy, and they are used to generate hypotheses for larger prospective trials. The purpose of this article is to introduce the group sequential design (GSD) approach in planning these larger trials. Methods. Methodology needed for using GSD in the CDA studies is recently developed. In this article, GSD with the O’Brien and Fleming (OBF) stopping rule is described and guidelines for sample size calculation are provided. Simulated data is used to demonstrate the application of GSD in the design/analysis of a clinical trial in theCDAstudy setting. Results. The expected sample size needed for planning a trial with GSD (under the OBF stopping rule) is slightly inflated but may ultimately result in greater savings of patient resources. Conclusion. GSD is a specialized statistical method that is helpful in balancing the ethical and financial advantages of stopping a study early against the risk of an incorrect conclusion and should be adopted for planning CDAstudies.
Ethics Content in Nursing Education: Pondering with the Possible
Authors: Milton Constance L.
Published: September 2004

Accrediting bodies of nursing as well as other healthcare organizations require that nursing ethics content be incorporated in programs of study. How does nursing define the termnursing ethics? How is it distinguished or viewed in various levels of higher degree nursing education? What is the role of codes for nursing? These are but a few of the questions pondered in the following article that includes personal correspondence with two distinguished authors, educators, and consultants for biomedical ethics, Dr. Sara T. Fry and Dr. Nancy Berlinger of the Hastings Center.
The Theory of Human Becoming in Action: Continuation of the Dialogue
Authors: Fawcett Jacqueline
Published: September 2004

This column once again focuses on the use of Rosemarie Rizzo Parse’s theory of human becoming and the human becoming school of thought as a guide for nursing research and practice. Parse scholars William K. Cody, Gail J. Mitchell, Christine M. Jonas-Simpson, and Françoise V. Maillard Strüby share their work and explain the challenges they have overcome in learning and using the theory of human becoming. A previous column featured the work of Parse scholars Debra A. Bournes, Sandra Schmidt Bunkers, and Anthony J. Welch.
Life-Closing Spirituality and the Philosophic Assumptions of the Roy Adaptation Model
Authors: Dobratz Marjorie C.
Published: September 2004

Secondary analysis of data from a previous study that referenced spirituality was coded, categorized, and grouped into themes. Life-closing spirituality for 44 (45.4%) of 97 total participants was shaped by a core theme ofbelieving that was central to dying persons. Believing was linked to six other themes: comforting, releasing, connecting, giving, reframing, and requesting. These themes supported the philosophic assumptions and principles of humanism and veritivity as defined in the Roy adaptation model.
Similarities and Differences in Experiences of Hope
Authors: Baumann Steven L.
Published: September 2004

From a human becoming perspective, hope is considered to be a universal lived experience, which arises and fades in the human-universe process. This article is a comparison of sixParse research method studies on the lived experience of hope from five countries: Japan, Taiwan, Sweden, Finland, and the United States. The goal was to explore the similarities and differences in the findings of a nine-country study on hope. While the structure of the experience of hope was similar, some differences are discussed that enhance nursing practice and guide further study.
Theory of Dependent-Care in Research With Parents of Toddlers: The NEAT Project
Authors: Arndt Mary Jo , Horodynski Mildred A. Omar
Published: September 2004

This paper contains a description of the use of the theory of dependent-care in the Nutrition Aimed at Toddlers project, a nursing intervention study with parents of toddlers, and discusses the research and practice utility of the theory of dependent-care, a corollary theory to Orem’s self-care theory. In particular, the concepts of dependent-care, dependent-care agency, therapeutic self-care demand and an educative-supportive nursing system are discussed within the context of the Nutrition Aimed at Toddlers project.
A Dialogue about Two Nursing Science Traditions: The Roy Adaptation Model and the Human Becoming Theory
Authors: Dobratz Marjorie C. , Pilkington F. Beryl
Published: September 2004

The authors engage in a dialogue about the ontology, epistemology, and methodologies in research within their respective theoretical perspectives, the Roy adaptation model and the human becoming theory, insofar as these represent different paradigms in nursing science. In the discussion of ontology as the lens through which humans view their world, they articulate the primacy of ontology over methodology in shaping knowledge development.
Mentoring: A Human Becoming Perspective
Authors: Carroll Karen
Published: September 2004

There have been reports of an absence or a lack of support for one another within the discipline of nursing. By establishing patterns of engagement, seasoned veterans connect with their novice colleagues to promote standards of excellence and scholarship. In order to provide the multidimensional benefits of a mentorship opportunity, a clear theoretical vision of mentoring is required. The theoretical perspective of human becoming provides a framework for mentors to establish gentle urgings with their mentees and thus provide for the growing of nurses as well as the discipline of nursing.
The Concept of Branding: Is It Relevant to Nursing?
Authors: Dominiak Mary C.
Published: September 2004

This concept exploration examines branding and its relevance to nursing. Branding is used to differentiate products through use of symbols. The symbols are the brands that are designed to communicate the value of products. Nursing has had many identifying symbols, such as the nurse’s cap and the white uniform, but these symbols have failed to clearly communicate the essence of nursing. Lack of a distinct nursing brand has led to confusion about the discipline. The Roy adaptation model provides a view of branding as a process for clearly defining the profession, improving its image, and differentiating its role within the healthcare milieu.
Current Challenges and Issues Facing Nursing in Australia
Authors: Jackson Debra , Daly John
Published: September 2004

This column is a discussion of nursing in Australia. The authors present current challenges and issues related to recruitment and retention, an aging workforce, violence and bullying, diversity, undergraduate and graduate education, professional development, information technology, clinical pathways, models of care delivery, and funding models. They also present what is happening in Australia in relation to nursing’s scope of practice, development of the nurse practitioner role, nursing leadership, and nursing research.
Neural Network Modeling in Cross-Cultural Research: A Comparison with Multiple Regression
Authors: Palocsay Susan W. , White Marion M.
Published: September 2004

This article describes the use of neural networks as an alternative method to investigate the links between various dimensions of culture and perceptions of justice and demonstrates their ability to model the data relationships with higher accuracy than multiple regression analysis. A complete discussion of the development and validation of the neural network models is included as a guide to researchers in management who are interested in exploring this methodology.
Being Both Too Liberal and Too Conservative: The Perils of Treating Grouped Data as though They Were Independent
Authors: Bliese Paul D. , Hanges Paul J.
Published: September 2004

Organizational data are inherently nested; consequently, lower level data are typically influenced by higher level grouping factors. Stated another way, almost all lower level organizational data have some degree of nonindependence due to work group, geographic membership, and so on. Unaccounted-for nonindependence can be problematic because it affects standard error estimates used to determine statistical significance. Currently, researchers interested in modeling higher level variables routinely use multilevel modeling techniques to avoid well-known problems with Type I error rates. In this article, however, the authors examine how nonindependence affects statistical inferences in cases in which researchers are interested only in relationships among lower level variables. They show that ignoring nonindependence when modeling only lower level variables reduces power (increases Type II errors), and through simulations, the authors show where this loss of power is most pronounced.
The adaptor protein 3BP2 associates with VAV guanine nucleotide exchange factors to regulate NFAT activation by the B-cell antigen receptor
Authors: Foucault Isabelle , Le Bras Séverine , Charvet Céline , Moon Chéol , Altman Amnon , Deckert Marcel
Published: September 2004

Engagement of the B-cell antigen receptor (BCR) activates kinases of the Src and Syk families and signaling complexes assembled by adaptor proteins, which dictate B-cell fate and function. The adaptor 3BP2/SH3BP2, an Abl Src homology domain 3 (SH3)–binding and Syk-kinases interacting protein, exhibits positive regulatory roles in T, natural killer (NK), and basophilic cells. However, its involvement in BCR signaling is completely unknown. Here we show that 3BP2 is tyrosine phosphorylated following BCR aggregation on B lymphoma cells, and that 3BP2 is a substrate for Syk and Fyn, but not Btk. To further explore the function of 3BP2 in B cells, we screened a yeast 2-hybrid B-lymphocyte library and found 3BP2 as a binding partner of Vav proteins. The interaction between 3BP2 and Vav proteins involved both constitutive and inducible mechanisms. 3BP2 also interacted with other components of the BCR signaling pathway, including Syk and phospholipase C γ (PLC-γ). Furthermore, overexpression and RNAi blocking experiments showed that 3BP2 regulated BCR-mediated activation of nuclear factor of activated T cells (NFATs). Finally, evidence was provided that 3BP2 functionally cooperates with Vav proteins and Rho GTPases to activate NFATs. Our results show that 3BP2 may regulate BCR-mediated gene activation through Vav proteins.
Interleukin-15 induces IL-12 receptor β1 gene expression through PU.1 and IRF 3 by targeting chromatin remodeling
Authors: Musikacharoen Tipayaratn , Oguma Asako , Yoshikai Yasunobu , Chiba Norika , Masuda Akio , Matsuguchi Tetsuya
Published: September 2004

Interleukin-12 receptor β1 (IL12RB1) is expressed on a variety of immune cells, including T and natural killer (NK) cells and macrophages, and is involved in innate and adaptive immune responses. Levels of IL12RB1 mRNA are dynamically regulated by various cytokines, including interferon-γ (IFN-γ) and IL-15. To reveal the regulatory mechanisms governing IL12RB1 gene expression, we analyzed the transcriptional regulatory region of the mouse IL12RB1 gene. Promoter analyses in a mouse macrophage cell line, RAW264.7, revealed that the 2508-bp region upstream of the transcriptional start site is sufficient for the full transcriptional activation of the IL12RB1 gene by IFN-γ or IL-15. Analyses of the deletion mutants revealed critical roles of IRE/ISRE and ETS/PU.1 elements, to which IRF3 and PU.1, respectively, bound. Notably, chromatin immunoprecipitation (ChIP) assays revealed IL-15 rapidly induced histone H3 acetylation at the IL12RB1 promoter. Consistently, IL-15, as a histone deacetylase inhibitor, synergistically enhanced IL12RB1 gene expression and promoter activation by IFN-γ through increased protein binding to ETS/PU.1 and IRE/ISRE sites. Additionally, IL12RB1 promoter activation by IFN-γ was enhanced by the coexpression of a coactivator protein, CBP. Thus, IL-15 induces chromatin remodeling of the IL12RB1 gene promoter, increasing IL12RB1 mRNA expression in synergy with IFN-γ through the recruitment of PU.1 and IRF3.
Stromal cell–derived factor-1α/CXCL12–induced chemotaxis of T cells involves activation of the RasGAP-associated docking protein p62Dok-1
Authors: Okabe Seiichi , Fukuda Seiji , Kim Young-June , Niki Masaru , Pelus Louis M. , Ohyashiki Kazuma , Pandolfi Pier Paolo , Broxmeyer Hal E.
Published: September 2004

Events mediating stromal cell–derived factor-1 (SDF-1α/CXCL12) chemotaxis of lymphocytes are not completely known. We evaluated intracellular signaling through RasGAP-associated protein p62Dok-1 (downstream of tyrosine kinase [Dok-1]) and associated proteins. SDF-1α/CXCL12 stimulated Dok-1 tyrosine phosphorylation and association with RasGAP, adaptor protein p46Nck, and Crk-L in Jurkat T cells. The phosphorylation of Dok-1 was blocked by pretreatment of cells with the src kinase inhibitor PP2. Src kinase family member Lck was implicated. SDF-1α/CXCL12 did not phosphorylate Dok-1 in J.CaM1.6 cells, a Jurkat derivative not expressing Lck, but did phosphorylate Dok-1 in J.CaM1.6 cells expressing Lck. SDF-1α/CXCL12 induced the tyrosine phosphorylation of Pyk2 and the association of Pyk2 with zeta chain–associated protein-70 kilodaltons (Zap-70) and Vav. SDF-1α/CXCL12 enhanced the association of RasGAP with Pyk2. CXCR4–expressing NIH3T3 and Baf3 cells transfected with full-length Dok-1 cDNA were suppressed in their responses to SDF-1α/CXCL12–induced chemotaxis; mitogen-activated protein (MAP) kinase activity was also decreased. Chemotaxis to SDF-1/CXCL12 was significantly enhanced in Dok-1–/– CD4+ and CD8+ splenic T cells. These results implicate Dok-1, Nck, Crk-L, and Src kinases—especially Lck, Pyk2, Zap-70, Vav, and Ras-GAP—in intracellular signaling by SDF-1α/CXCL12, and they suggest that Dok-1 plays an important role in SDF-1α/CXCL12–induced chemotaxis in T cells.
Expression of hepcidin is down-regulated in TfR2 mutant mice manifesting a phenotype of hereditary hemochromatosis
Authors: Kawabata Hiroshi , Fleming Robert E. , Gui Dorina , Moon Seo Y. , Saitoh Takayuki , O'Kelly James , Umehara Yutaka , Wano Yuji , Said Jonathan W. , Koeffler H. Phillip
Published: September 2004

Transferrin receptor 2 (TfR2) is a membrane glycoprotein that mediates cellular iron uptake from holotransferrin. Homozygous mutations of this gene cause one form of hereditary hemochromatosis in humans. We recently reported that homozygous TfR2(Y245X) mutant mice, which correspond to the TfR2(Y250X) mutation in humans, showed a phenotype similar to hereditary hemochromatosis. In this study, we further analyzed the phenotype as well as iron-related gene expression in these mice by comparing the TfR2-mutant and wild-type siblings. Northern blot analyses showed that the levels of expression of hepcidin mRNA in the liver were generally lower, whereas those of duodenal DMT1, the main transporter for uptake of dietary iron, were higher in the TfR2-mutant mice as compared to the wild-type siblings. Expression of hepcidin mRNA in the TfR2 mutant mice remained low even after intraperitoneal iron loading. In isolated hepatocytes from both wild-type and TfR2 mutant mice, interleukin-6 and lipopolysaccharide each induced expression of hepcidin mRNA. These results suggest that up-regulation of hepcidin expression by inflammatory stimuli is independent of TfR2 and that TfR2 is upstream of hepcidin in the regulatory pathway of body iron homeostasis. (Blood. 2005;105:376-381)
Vascular endothelial growth factor regulation of Weibel-Palade–body exocytosis
Authors: Matsushita Kenji , Yamakuchi Munekazu , Morrell Craig N. , Ozaki Michitaka , O'Rourke Brian , Irani Kaikobad , Lowenstein Charles J.
Published: September 2004

Vascular endothelial growth factor (VEGF) not only regulates angiogenesis, vascular permeability, and vasodilation but also promotes vascular inflammation. However, the molecular basis for the proinflammatory effects of VEGF is not understood. We now show that VEGF activates endothelial cell exocytosis of Weibel-Palade bodies, releasing vasoactive substances capable of causing vascular thrombosis and inflammation. VEGF triggers endothelial exocytosis in part through calcium and phospholipase C-γ (PLC-γ) signal transduction. However, VEGF also modulates endothelial cell exocytosis by activating endothelial nitric oxide synthase (eNOS) production of nitric oxide (NO), which nitrosylates N-ethylmaleimide sensitive factor (NSF) and inhibits exocytosis. Thus, VEGF plays a dual role in regulating endothelial exocytosis, triggering pathways that both promote and inhibit endothelial exocytosis. Regulation of endothelial exocytosis may explain part of the proinflammatory effects of VEGF.
CD1d-unrestricted human NKT cells release chemokines upon Fas engagement
Authors: Giroux Martin , Denis François
Published: September 2004

Attempts at inducing allograft immune privilege by enforced Fas ligand expression have shown accelerated rejection mediated by neutrophils. While it has been proposed that Fas ligand was directly chemotactic toward neutrophils, several lines of evidence argue for an indirect recruitment mechanism. This question was addressed by using in vitro migration assays that used highly purified human leukocyte subsets. Granulocytes did not migrate in response to Fas engagement and required the presence of T cells expressing several natural killer (NK) cell markers. These rare CD8 memory T cells expressed T and NK cell markers and were not restricted to CD1d, showing that they are distinct from conventional natural killer T (NKT) cells. These cells were able to kill both NK-sensitive and -insensitive targets and secreted several CC and CXC chemokines active toward granulocytes, monocytes, and NK cells upon Fas engagement. Chemotactic factor release depended on caspase activity, in the absence of NKT cell apoptosis. The ability of CD1d-unrestricted NKT cells to recruit innate immune system cells might play a role in cancer cell eradication and contribute to inflammatory diseases.
Transition of late-stage effector T cells to CD27+ CD28+ tumor-reactive effector memory T cells in humans after adoptive cell transfer therapy
Authors: Powell Daniel J. , Dudley Mark E. , Robbins Paul F. , Rosenberg Steven A.
Published: September 2004

In humans, the pathways of memory T-cell differentiation remain poorly defined. Recently, adoptive cell transfer (ACT) of tumor-reactive T lymphocytes to metastatic melanoma patients after nonmyeloablative chemotherapy has resulted in persistence of functional, tumor-reactive lymphocytes, regression of disease, and induction of melanocyte-directed autoimmunity in some responding patients. In the current study, longitudinal phenotypic analysis was performed on melanoma antigen-specific CD8+ T cells during their transition from in vitro cultured effector cells to long-term persistent memory cells following ACT to 6 responding patients. Tumor-reactive T cells used for therapy were generally late-stage effector cells with a CD27Lo CD28Lo CD45RA- CD62 ligand- (CD62L-) CC chemokine receptor 7- (CCR7-) interleukin-7 receptor αLo (IL-7RαLo) phenotype. After transfer, rapid up-regulation and continued expression of IL-7Rα in vivo suggested an important role for IL-7R in immediate and long-term T-cell survival. Although the tumor antigen-specific T-cell population contracted between 1 and 4 weeks after transfer, stable numbers of CD27+ CD28+ tumor-reactive T cells were maintained, demonstrating their contribution to the development of long-term, melanoma-reactive memory CD8+ T cells in vivo. At 2 months after transfer, melanoma-reactive T cells persisted at high levels and displayed an effector memory phenotype, including a CD27+ CD28+ CD62L- CCR7- profile, which may explain in part their ability to mediate tumor destruction. (Blood. 2005;105:241-250)
Stabilization of IFN-γ mRNA by MAPK p38 in IL-12– and IL-18–stimulated human NK cells
Authors: Mavropoulos Athanasios , Sully Gareth , Cope Andrew P. , Clark Andrew R.
Published: September 2004

The rapid induction of interferon-γ (IFN-γ) by innate cytokines such as interleukin 12 (IL-12) and IL-18 is critical for immunity against infectious pathogens. We investigated the molecular mechanisms underlying this response. IL-12 and IL-18 rapidly and synergistically induced the secretion of IFN-γ by freshly purified human peripheral blood lymphocytes. At early time points, IFN-γ was expressed almost exclusively by natural killer cells and in both CD56bright and CD56dim subpopulations. Mitogen-activated protein kinase p38 was activated strongly by IL-18 and weakly by IL-12 in natural killer cells but was not activated by either cytokine in T cells. The expression of IFN-γ mRNA and protein was dose-dependently blocked by SB203580, a specific inhibitor of mitogen-activated protein kinase p38, which also caused a dramatic destabilization of IFN-γ mRNA. The 3′ untranslated region (UTR) of IFN-γ mRNA conferred p38 responsiveness to a heterologous reporter mRNA. Therefore, the synergistic induction of IFN-γ by IL-12 and IL-18 in natural killer cells is mediated at least in part by p38-dependent and 3′ UTR-mediated stabilization of IFN-γ mRNA. (Blood. 2005;105:282-288)
Protein p16 as a marker of dysplastic and neoplastic alterations in cervical epithelial cells
Authors: Volgareva Galina , Zavalishina Larisa , Andreeva Yulia , Frank Georgy , Krutikova Ella , Golovina Darya , Bliev Alexander , Spitkovsky Dimitry , Ermilova Valeriya , Kisseljov Fjodor
Published: September 2004

Background

Cervical carcinomas are second most frequent type of women cancer. Success in diagnostics of this disease is due to the use of Pap-test (cytological smear analysis). However Pap-test gives significant portion of both false-positive and false-negative conclusions. Amendments of the diagnostic procedure are desirable. Aetiological role of papillomaviruses in cervical cancer is established while the role of cellular gene alterations in the course of tumor progression is less clear. Several research groups including us have recently named the protein p16INK4a as a possible diagnostic marker of cervical cancer. To evaluate whether the specificity of p16INK4a expression in dysplastic and neoplastic cervical epithelium is sufficient for such application we undertook a broader immunochistochemical registration of this protein with a highly p16INK4a-specific monoclonal antibody.

Methods

Paraffin-embedded samples of diagnostic biopsies and surgical materials were used. Control group included vaginal smears of healthy women and biopsy samples from patients with cervical ectopia. We examined 197 samples in total. Monoclonal antibody E6H4 (MTM Laboratories, Germany) was used.

Results

In control samples we did not find any p16INK4a-positive cells. Overexpression of p16INK4a was detected in samples of cervical dysplasia (CINs) and carcinomas. The portion of p16INK4a-positive samples increased in the row: CIN I – CIN II – CIN III – invasive carcinoma. For all stages the samples were found to be heterogeneous with respect to p16INK4a-expression. Every third of CINs III and one invasive squamous cell carcinoma (out of 21 analyzed) were negative.

Conclusions

Overexpression of the protein p16INK4a is typical for dysplastic and neoplastic epithelium of cervix uteri. However p16INK4a-negative CINs and carcinomas do exist. All stages of CINs and carcinomas analyzed are heterogeneous with respect to p16INK4a expression. So p16INK4a-negativity is not a sufficient reason to exclude a patient from the high risk group. As far as normal cervical epithelium is p16INK4a-negative and the ratio p16INK4a-positive/ p16INK4a-negative samples increases at the advanced stages application of immunohisto-/cytochemical test for p16INK4a may be regarded as a supplementary test for early diagnostics of cervical cancer.
In vivo evidences that insulin regulates human polymorphonuclear neutrophil functions
Authors: Walrand S , Guillet C , Boirie Y , Vasson M-P
Published: September 2004

Polymorphonuclear neutrophils (PMN) are able to destroy invasive mircoorganisms by a wide variety of functions. Whereas insulin does not stimulate hexose transport in PMN, previous reports have clearly shown that this hormone regulates glucose metabolism inside this cell, raising the question of insulin action on PMN functions in humans. It is interesting that in vitro studies established a strong relationship between specific binding of insulin to its PMN membrane receptor and the activation of the main PMN functions. Therefore, investigation in healthy subjects under strict euglycemia and physiological insulinemia was performed to understand the in vivo-specific action of insulin on PMN functions without hyperglycemia interferences. We determined numerous PMN functions before and after hyperinsulinemia (0.5 mU/kg/min) and euglycemia (0.9 g/l) clamp for 4 h in eight adult healthy volunteers (24±6 years). The total number of PMN and the number of PMN expressing CD11b, CD15, CD62L, and CD89 were significantly increased over baseline (P<0.001), whereas the density of these receptors was down-regulated (P<0.01) by insulin. PMN chemotaxis (+117%, P<0.05), phagocytosis (+29%, P<0.001), and bactericidal (+17–25%, P<0.001) capacities were increased during the insulin clamp (P<0.05). Therefore, insulin treatment may modulate PMN functions not only by attainment of a better metabolic control, as suggested by in vivo studies in diabetic patients, but also through a direct effect of insulin.
Expression of Human Hormone-Sensitive Lipase (HSL) in Postmeiotic Germ Cells Confers Normal Fertility to HSL-Deficient Mice
Authors: Wang Shu Pei , Chung Shari , Soni Krishnakant , Bourdages Hugo , Hermo Louis , Trasler Jacquetta , Mitchell Grant A.
Published: September 2004

Hormone-sensitive lipase (HSL, Lipe, E.C.3.1.1.3) is a multifunctional fatty acyl esterase that is essential for male fertility and spermatogenesis and that also plays important roles in the function of adipocytes, pancreatic β-cells, and adrenal cortical cells. Gene-targeted HSL-deficient (HSL−/−) male mice are infertile, have a 2-fold reduction in testicular mass, a 2-fold elevation of the ratio of esterified to free cholesterol in testis, and unique morphological abnormalities in round and elongating spermatids. Postmeiotic germ cells in the testis express a specific HSL isoform. We created transgenic mice expressing a normal human testicular HSL cDNA from the mouse protamine-1 promoter, which mediates expression specifically in postmeiotic germ cells. Testicular cholesteryl esterase activity was undetectable in HSL−/− mice, but in HSL−/− males expressing the testicular transgene, activity was 2-fold greater than normal. HSL transgene mRNA became detectable in testes between 19 and 25 days of age, coinciding with the first wave of postmeiotic transcription in round spermatids. In contrast to nontransgenic HSL−/− mice, HSL−/− males expressing the testicular transgene were normal with respect to fertility, testicular mass, testicular esterified/free cholesterol ratio, and testicular histology. Their cauda epididymides contained abundant, normal-appearing spermatozoa. We conclude that human testicular HSL is functional in mouse testis and that the mechanism of infertility in HSL-deficient males is cell autonomous and resides in postmeiotic germ cells, because HSL expression in these cells is in itself sufficient to restore normal fertility.
Interaction of Stress-Activated Protein Kinase-Interacting Protein-1 with the Interferon Receptor Subunit IFNAR2 in Uterine Endometrium
Authors: Wang Shu-Zong , Roberts R. Michael
Published: September 2004

During early pregnancy in ruminants, a type I interferon (IFN-τ) signals from the conceptus to the mother to ensure the functional survival of the corpus luteum. IFN-τ operates through binding to the type I IFN receptor (IFNR). Here we have explored the possibility that IFNAR2, one of the two subunits of the receptor, might interact with hitherto unknown signal transduction factors in the uterus that link IFN action to pathways other than the well established Janus kinase-signal transducer and activator of transcription pathways. A yeast two-hybrid screen of an ovine (ov) endometrial cDNA library with the carboxyl-terminal 185 amino acids of ovIFNAR2 as bait identified stress-activated protein kinase-interacting protein 1 (ovSin1) as a protein that bound constitutively through its own carboxyl terminus to the receptor. ovSin1 is a little studied, 522-amino acid-long polypeptide (molecular weight, 59,200) that is highly conserved across vertebrates, but has identifiable orthologs in Drosophila and yeast. It appears to be expressed ubiquitously in mammals, although in low abundance, in a wide range of mammalian tissues in addition to endometrium. Sin1 mRNA occurs in at least two alternatively spliced forms, the smaller of which lacks a 108-bp internal exon. ovSin1, although not exhibiting features of a membrane-spanning protein, such as IFNAR2, is concentrated predominantly in luminal and glandular epithelial cells of the uterine endometrium. When ovSin1 and ovIFNAR2 are coexpressed, the two proteins can be coimmunoprecipitated and colocalized to the plasma membrane and to perinuclear structures. Sin1 provides a possible link among type I IFN action, stress-activated signaling pathways, and control of prostaglandin production.
Teenage Pregnancy and Associated Risk Behaviors Among Sexually Abused Adolescents
Authors: Saewyc Elizabeth M. , Magee Lara Leanne , Pettingell Sandra E.
Published: September 2004

CONTEXT

Previous research suggests a link between adolescent pregnancy and sexual abuse history, but most studies have used clinical samples of females only and single measures of abuse.

METHODS

Associations between pregnancy involvement, risk behaviors and sexual abuse were examined in sexually experienced teenagers from the Minnesota Student Surveys of 1992 (N = 29,187) and 1998 (N = 25,002). Chi‐square tests assessed differences in pregnancy involvement and related risk behaviors among four groups of adolescents, categorized by type of abuse experienced: none, incest only, nonfamilial only or both. Odds ratios for pregnancy involvement and risk behaviors, adjusted for grade level and race, were calculated for each gender by using logistic regression analysis.

RESULTS

Sexual abuse was reported by 6% of males and 27% of females in 1992, and by 9% and 22% in 1998. Reports of pregnancy involvement were significantly more common among abused adolescents (13–26% of females and 22–61% of males, depending on type of abuse) than among nonabused adolescents (8–10%). Abused adolescents were more likely than others to report risk behaviors, and teenagers reporting both abuse types had the highest odds of pregnancy involvement and risk behaviors. The differential in the odds of pregnancy involvement and most behaviors was larger between nonabused and abused males than between nonabused and abused females.

CONCLUSIONS

Teenage pregnancy risk is strongly linked to sexual abuse, especially for males and those who have experienced both incest and nonfamilial abuse. To further reduce the U.S. teenage pregnancy rate, the pregnancy prevention needs of these groups must be adequately addressed.
“Throwing the Dice”: Pregnancy Decision‐Making Among HIV‐Positive Women in Four U.S. Cities
Authors: Kirshenbaum Sheri B. , Hirky A. Elizabeth , Correale Jacqueline , Goldstein Rise B. , Johnson Mallory O. , Rotheram‐Borus Mary Jane , Ehrhardt Anke A.
Published: September 2004

CONTEXT

Although AIDS‐related deaths among U.S. women have decreased, the number of HIV‐positive women, especially of reproductive age, has increased. A better understanding of the interaction between HIV and family planning is needed, especially as antiretroviral medications allow HIV‐positive women to live longer, healthier lives.

METHODS

Qualitative methods were used to examine pregnancy decision‐making among 56 HIV‐positive women in four U.S. cities. Biomedical, individual and socio cultural themes were analyzed in groups of women, categorized by their pregnancy experiences and intentions.

RESULTS

Regardless of women's pregnancy experiences or intentions, reproductive decision‐making themes included the perceived risk of vertical transmission, which was often overestimated; beliefs about vertical transmission risk reduction strategies; desire for motherhood; stigma; religious values; attitudes of partners and health care providers; and the impact of the mother's health and longevity on the child. Most women who did not want children after their diagnosis cited vertical transmission risk as the reason, and most of these women already had children. Those who became pregnant or desired children after their diagnosis seemed more confident in the efficacy of risk reduction strategies and often did not already have children.

CONCLUSIONS

Future studies may help clarify the relationship between factors that influence pregnancy decision‐making among HIV‐positive women. HIV‐positive and at‐risk women of childbearing age may benefit from counseling interventions sensitive to factors that influence infected women's pregnancy decisions.
The Acceptability of the Female and Male Condom: A Randomized Crossover Trial
Authors: Kulczycki Andrzej , Kim Dhong‐Jin , Duerr Ann , Jamieson Denise J. , Macaluso Maurizio
Published: September 2004

CONTEXT

Although studies have assessed the acceptability of male and female condoms, comparative trial data are lacking.

METHODS

A sample of 108 women in stable relationships recruited from an urban, reproductive health clinic were randomly assigned to use 10 male or female condoms, followed by use of 10 of the other type. A nurse provided instruction in correct method use. Demographic information was collected in a baseline questionnaire; acceptability data were collected in follow‐up and exit questionnaires and coital logs. Nonparametric and chi‐square statistics were used to analyze measures of the methods’relative acceptability. Bowker's test of symmetry was adapted to test the null hypothesis of no difference in acceptability between condom types.

RESULTS

Participants used 678 female and 700 male condoms. Although neither method scored high on user satisfaction measures, the 63 women completing the study protocol preferred the male condom to the female condom for ease of application or insertion, ease of removal, general fit, feel of the condom during intercourse and ease of penetration. Participants reported that their partner also favored the male condom, although women generally appeared to like this method more than their partner did. In a direct comparison between the methods at the end of the study, women generally judged male condoms superior on specified preference criteria.

CONCLUSIONS

Across a range of criteria, the female condom was less acceptable than the male condom to most women and their partners. Although both types had low acceptability, they are needed and valid methods of pregnancy and disease prevention. That neither rated high on user satisfaction measures underscores the need for more barrier methods that women and men can use.
Practitioners' Perspectives on Effective Practices For Hispanic Teenage Pregnancy Prevention
Authors: Russell Stephen T. , Lee Faye C. H. ,   the Latina/o Teen Pregnancy Prevention Workgroup
Published: September 2004

CONTEXT: In the United States, the pregnancy rate and birthrate of Hispanic teenagers are higher than those of other races and ethnicities. Although recommendations for culturally appropriate pregnancy prevention programs are commonplace, little is known about how practitioners address such recommendations.

METHODS: In individual interviews, 58 teenage pregnancy prevention practitioners who work primarily with Mexican American female teenagers from two regions in California were asked about their understanding of recommendations for best practices and discussed the strategies they have used and challenges they have faced in implementing the recommendations. Qualitative methods were used to categorize responses and identify themes.

RESULTS: Practitioners indicated that knowledge and awareness of Hispanic culture are essential, as is commitment to teenagers and their needs. They regard activities that encourage educational and career achievement as critical program components, and view both male partners' and family members' involvement in programs as important but challenging. Furthermore, practitioners feel that the implicit program goals of continued education and female self‐sufficiency are often at odds with traditional Hispanic cultural values.

CONCLUSIONS: Practitioners have valuable insight into the reality of implementing culturally sensitive programs. Programs need to balance the often competing values and goals of prevention programs with those of Hispanic youth culture and experiences.
Specific Immunoassays for Detection of Intact and Cleaved Forms of the Urokinase Receptor
Authors: Piironen Timo , Laursen Birgitte , Pass Jesper , List Karin , Gårdsvoll Henrik , Ploug Michael , Danø Keld , Høyer-Hansen Gunilla
Published: September 2004

Background: The cell surface receptor (uPAR) for urokinase plasminogen activator (uPA) is a strong prognostic marker in several types of cancer. uPA cleaves the three-domain protein uPAR(I-III) into two fragments: uPAR(I), which contains domain I; and uPAR(II-III), which contains domains II and III. Established immunoassays measure a combination of uPAR forms. Our aim was to design immunoassays for specific quantification of the individual forms of uPAR.

Methods: Using appropriate combinations of epitope-mapped monoclonal antibodies (Mabs) for capture and europium-labeled detection Mabs, we designed two-site sandwich time-resolved fluorescence immunoassays (TR-FIAs): TR-FIA 1 to measure uPAR(I-III) alone; TR-FIA 2 to measure both uPAR(I-III) and uPAR(II-III); and TR-FIA 3 to measure uPAR(I). To avoid detection of uPAR(I-III) in TR-FIA 3, we used a combination of the peptide uPAR antagonist AE120 and a domain I antibody, R3. AE120 blocks the binding of R3 to uPAR(I-III). In contrast, AE120 does not interact with liberated domain I and therefore does not interfere with the binding of R3 to uPAR(I).

Results: The limits of quantification (CV <20%) determined by adding the proteins to uPAR-depleted plasma were <3 pmol/L in all three assays. The interassay CVs in plasma with added analytes were <11%, and recoveries were between 93% and 105%. Cross-reactivities of purified proteins in the three TR-FIAs were no more than 4%. Studies on chymotrypsin cleavage of uPAR and size-exclusion chromatography of plasma with and without added protein further supported the specificity of the assays.

Conclusions: The three novel TR-FIAs accurately quantify uPAR(I-III) alone, uPAR(I-III) together with uPAR(II-III), and uPAR(I), respectively, in biological samples, including plasma, and thus are well suited for studies of the diagnostic and prognostic value of individual uPAR forms in cancer patients.
High Intraindividual Variation of B-Type Natriuretic Peptide (BNP) and Amino-Terminal proBNP in Patients with Stable Chronic Heart Failure
Authors: Bruins Sanne , Fokkema M Rebecca , Römer Jeroen W P , DeJongste Mike J L , van der Dijs Fey P L , van den Ouweland Jody M W , Muskiet Frits A J
Published: September 2004

Background: Plasma B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are promising markers for heart failure diagnosis, prognosis, and treatment. Insufficient data on the intraindividual biological variation (CVi) of BNP and NT-proBNP hamper interpretation of changes in concentration on disease progression or treatment optimization. We therefore investigated CVi values in stable heart failure patients.

Methods: We recruited 43 patients with stable chronic heart failure living in Curaçao (22 males, 21 females; median age, 63 years; range, 20–86 years; New York Heart Association classes I–III). Samples were collected for within-day CVi (n = 6; every 2 h starting at 0800), day-to-day CVi (n = 5; samples collected between 0800 and 1000 on 5 consecutive days), and week-to-week CVi (n = 6; samples collected between 0800 and 1000 on the same day of the week for 6 consecutive weeks). NT-proBNP (Roche) and BNP (Abbott) were measured by immunoassay.

Results: Median (range) concentrations were 134 (0–1630) ng/L (BNP) and 570 (17–5048) ng/L (NT-proBNP). Analytical variation, week-to-week CVi, and reference change values were 8.4%, 40%, and 113% (BNP), and 3.0%, 35%, and 98% (NT-proBNP). Week-to week CVis were inversely related to median BNP concentrations. Week-to week CVis for BNP were 44% (BNP ≤350 ng/L) and 30% (BNP >350 ng/L). Both BNP and NT-proBNP increased between 0800 and 1000. Median NT-proBNP/BNP ratios were inversely related to median BNP concentrations.

Conclusions: The high CVis hamper interpretation of changes in BNP and NT-proBNP concentrations and may partly explain their poor diagnostic values in chronic heart failure. Easily modifiable determinants to lower CVi have not been identified. The value of BNP and NT-proBNP for chronic heart failure diagnosis, and especially for follow-up and treatment optimization of individuals, remains largely to be established.
Are there genetically controlled habitat‐specific differences in spatial aggregation of drosophilids?
Authors: Rohlfs Marko , Hoffmeister Thomas S.
Published: September 2004

Variation in spatial patterns of competing organisms is of fundamental importance for community and population processes. Yet the mechanisms controlling subjects like the degree of spatial aggregation in competing insect larvae across fragmented resources have rarely been addressed. In the present study, we tested for systematic differences in the spatial distribution patterns ofDrosophila subobscurain natural fly communities, and found significant differences in two habitats that differ in the availability of breeding substrate types (decaying fruits). Assuming that the spatial egg‐laying behaviour of drosophilids is under genetic control, and that different breeding substrates mediate different density‐dependent larval fitness consequences, we tested whether adaptive genotypic variability is involved in the local variation of egg distribution patterns. We extracted isofemale lines from both habitats and analysed the spatial distribution of eggs achieved by single female flies under controlled laboratory conditions. This is a reasonable first test, because spatial patterns at the fly population level can be attributed to individual egg‐laying behaviour. The degree of individual egg aggregation significantly depended on fly line identity, which indicates the existence of behavioural variants in natural populations. Based on habitat‐dependent differences in the degree of spatial aggregation, we discuss to what extent our findings may reflect a behavioural adaptation to local breeding conditions.
Revisiting Hispanic Adolescents' Resilience to the Effects of Parental Problem Drinking and Life Stress
Authors: Barrera Manuel , Hageman Devon N. , Gonzales Nancy A.
Published: September 2004

Two previous studies found that life stress and parental alcoholism were not as highly related to distress for Hispanic adolescents as they were for European American adolescents (M. Barrera Jr., S. A. Li, and L. Chassin, 1993, 1995). Those findings could be interpreted as evidence of Hispanic youths' resilience, but limitations of the stress measure and the homogeneity of the Hispanic sample threatened this interpretation. The present study improved on those previous studies by using a new measure of uncontrollable stressors and a more heterogeneous Mexican American sample. Participants in this study were 175 Mexican American and 59 European American adolescents and their parents. Unlike the previous studies, results did not show that Mexican American adolescents were more resilient to parental problem drinking or life stress than were European American adolescents. Overall, life stress was related to adolescents', mothers', and fathers' reports of adolescents' psychological distress above and beyond the effects of ethnicity and socioeconomic factors.
The Social Networks of Women Experiencing Domestic Violence
Authors: Levendosky Alytia A. , Bogat G. Anne , Theran Sally A. , Trotter Jennifer S. , Eye Alexander von , Davidson William S.
Published: September 2004

The research literature has demonstrated that battered women living in shelters experience impaired social support. This study examines this phenomenon among battered women living in the community. This study compared a group of pregnant battered women (n=145) and a group of pregnant nonbattered women (n=58) in terms of their structural [e.g., total number of supporters, network members in violent relationships with their partners (an index of homophily or nonhomophily) and functional (e.g., emotional)] social support. Four reasons for impaired support in battered women were proposed and examined, including social isolation, failure to disclose abuse, homophily, and low SES. Only homophily was related to impaired support among battered women. In addition, the relationship between structural and functional support and mental health outcomes (e.g., depression, self‐esteem) was examined. Criticism, practical support, homophily, and disclosure were all significant predictors of mental health for battered women. Implications for community‐based interventions are discussed in the context of current intervention strategies with battered women.
Facilitators and Inhibitors of Positive School Feelings: An Exploratory Study
Authors: Langhout Regina Day
Published: September 2004

This paper brings together the educational psychology and place experience literatures to explore 8 children's experiences of school behavior settings. Within this framework, the goal is to think of school as a place comprised of multiple behavior settings, disentangle behavior and engagement, and problematize the construct of engagement. Results indicate that children liked places where the physical space was open, and they had some autonomy, independence, choice, opportunities for leadership, and social support. Conversely, they disliked places that were physically chaotic, where they perceived an abuse of power, and that inhibited choice, independence, and autonomy. Finally, children engaged their disliked places by attempting to personalize these spaces to bring in other parts of their identities. Implications include creating behavior settings that lead to positive experiences, attending to social justice, and the use of project‐based pedagogies.