bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractThe 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

Abstract
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

Abstract
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&lt;0.001), whereas the density of these receptors was down-regulated (P&lt;0.01) by insulin. PMN chemotaxis (+117%, P&lt;0.05), phagocytosis (+29%, P&lt;0.001), and bactericidal (+17–25%, P&lt;0.001) capacities were increased during the insulin clamp (P&lt;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

Abstract
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

AbstractDuring 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

CONTEXTPrevious 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.METHODSAssociations 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.RESULTSSexual 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.CONCLUSIONSTeenage 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

CONTEXTAlthough 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.METHODSQualitative 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.RESULTSRegardless 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.CONCLUSIONSFuture 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

CONTEXTAlthough studies have assessed the acceptability of male and female condoms, comparative trial data are lacking.METHODSA 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.RESULTSParticipants 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.CONCLUSIONSAcross 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

AbstractBackground: 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 &lt;20%) determined by adding the proteins to uPAR-depleted plasma were &lt;3 pmol/L in all three assays. The interassay CVs in plasma with added analytes were &lt;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

Abstract
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 &gt;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

AbstractVariation 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.