bluuebunny/crossref_metadata_2025 huggingface dataset:
Religious Involvement and 6-Year Course of Depressive Symptoms in Older Dutch Citizens:
Authors: Braam Arjan W. , Hein Erik , Deeg Dorly J. H. , Twisk Jos W. R. , Beekman Aartjan T. F. , van Tilburg Willem
Published: July 2004

Objectives: Expanding on cross-sectional studies, associations are examined between religious involvement and the 6-year course of depressive symptoms in older adults. Methods: Subjects are 1,840 community-dwelling older adults (aged 55 to 85) participating in three measurement cycles of the Longitudinal Aging Study, Amsterdam. Assessments include aspects of religious involvement, depressive symptoms, physical health, self-perceptions, social integration, urbanization, and alcohol use. Results: Church attendance is negatively associated with the course of depressive symptoms, also after adjustment for explanatory variables. Among respondents with functional limitations, lower depression scores are found for those who attend church on a regular basis. For respondents who are bereaved or nonmarried, however, slightly higher depression scores are found for those with high levels of orthodox beliefs. Discussion: There is a consistent negative association over time between church attendance and depressive symptoms in older Dutch citizens. Both stress-buffering as well as depression-evoking effects of religious involvement are found.
The Life Course of Activity Limitations:
Authors: Long J. Scott , Pavalko Eliza K.
Published: July 2004

Objective: To strengthen the foundations for the use of survey-based measures of functional limitations and to explore associations between limitations in a variety of activities across the adult life course. Method: Five panels of data from the young and mature women’s cohorts of the National Longitudinal Surveys are used to (a) examine patterns of limitations in activities as women age, (b) compare how limitations develop over the life course, (c) explore how limitations in one activity are associated with limitations in others, and (d) investigate whether limitations develop incrementally or occur in clusters. Results: We find that scales of functional limitations are not dependent on the age of the respondent, activity limitations emerge in clusters, and relationships between items do not consistently fall into upper and lower body groups. Discussion: Scales of functional limitations are equally applicable to younger and older women, but further research is needed to compare substantive results using different methods of scale construction.
Associations between Anticipated Support, Physical Functioning, and Education Level among a Nationally Representative Sample of Older Adults
Authors: Shaw Benjamin A. , Janevic Mary
Published: July 2004

Obective: The purpose of this study is to determine the extent to which levels of anticipated support reported by older adults are associated with functional disability. In addition, level of education is tested as a modifier of this relationship. Method: Survey data were collected from a nationwide sample of 1,103 adults aged 60 to 95. Ordinary least squares regression analysis was used to test a range of model specifications involving anticipated support and functional disability. Results: Levels of anticipated support are inversely associated with functional disability. Risk for functional disability is confined mostly to those reporting lower than average levels of anticipated support. This association is particularly strong with respect to instrumental support and among those older adults with low levels of education. Discussion: These findings expand our understanding of the benefits of social relationships by suggesting that the perception of access to social support may enhance physical functioning in older age.
Teasing and Bullying Experiences of Middle School Students
Authors: Horowitz June Andrews , Vessey Judith A. , Carlson Karen L. , Bradley Joan F. , Montoya Carolyn , McCullough Bill , David Joyce
Published: July 2004

BACKGROUND: In the United States, 9% to 15% of children experience chronic teasing and bullying that may be harmful. OBJECTIVE: The purpose was to explore teasing and bullying experiences of middle school students as part of the Child-Adolescent Teasing Scale (CATS) project. STUDY DESIGN: Seven focus groups were conducted with 11-to 14-year-old middle school students from Massachusetts, New Mexico, and Mississippi. Moderators used a semistructured interview guide to elicit views. Recorded sessions were transcribed; content analysis of verbatim accounts was used to identify sources of teasing and bullying. RESULTS: Sources of teasing and bullying were physical appearance, personal behavior, family and environment, and school relations. “Being different in any way” was the underlying theme. CONCLUSIONS: Teasing and bullying were universal and distressing, and were affected by context, frequency, and individually attributed meanings. Clinicians and school staff may use findings to identify children who might be at risk for psychological and physical harm.
State of the Science: Women and the Nonpharmacological Treatment of Substance Abuse
Authors: Gerolamo Angela M.
Published: July 2004

BACKGROUND: Substance abuse affects men and women differently, and as a result, treatment programs should be designed specific to their unique needs. The nonpharmacological treatment of substance abuse among women has been largely neglected in the literature. OBJECTIVE: The purpose of this review was to analyze critically the existing literature related to the nonpharmacological treatment of substance abuse among women. The methodological rigor of existing research was critiqued and gaps in knowledge identified. DESIGN : The databases Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, Sociological Abstracts, and MEDLINE were searched using the key words women and substance abuse treatment . Studies included in the review were those that were published between 1975 and 2003 and were related to the nonpharmacological treatment of substance abuse for women. RESULTS: Forty-three articles were reviewed. Evidence suggests that there are gender and cultural differences related to substance abuse. There is a dearth of research related to the effectiveness of treatment interventions designed specifically for women who abuse substances. The research that exists is limited in its theoretical foundation and methodological rigor. CONCLUSIONS : Few treatment programs reflect gender and cultural differences, leaving gaps in substance abuse treatment among women. Furthermore, existing research related to women and substance abuse treatment lacks a robust scientific foundation. Future research should be theoretically based and methodologically sound to advance the evidence base of substance abuse treatment for women.
Psychiatric Nurses: Transitioning from Student to Advance Beginner RN
Authors: Waite Roberta
Published: July 2004

BACKGROUND: The transitional experience from student nurse to advance beginner registered nurse (RN) is met with significant stressors, challenges, rewards, and thrills. The process and experience undergone by the RN can be the deciding factor for his or her commitment to the profession. Identifying factors to enhance retention is critical given the nursing shortage and changes within the health care environment. OBJECTIVE: The purpose of this research was to describe and explore the transitional process and the lived experience of advance beginner nurses employed in mental health facilities. STUDY DESIGN: This was a qualitative study, which used a phenomenologic approach with audio-taped interviews of 15 nurses. RESULTS: There were significant variances regarding the nurses’ expectations, orientation process, responsibilities, and supportive interventions from colleagues. These participants identified several beneficial concepts that could mitigate negative affective states, which, in turn, may effectively reduce the premature exit of new nurses from the profession. CONCLUSIONS: The process of connecting educational experiences and practice was inadequate. However, participants identified strategies that might be useful in increasing retention and positively influencing the transitioning from student to RN.
The Old Ball Game
Authors: Baker Matthew , Miceli Thomas J. , Ryczek William J.
Published: July 2004

The first professional base ball clubs came in two varieties: stock clubs, which paid their players fixed wages, and player cooperatives, in which players shared the proceeds after expenses. The authors argue that stock clubs were formed with players of known ability, whereas co-ops were formed with players of unknown ability. Although residual claimancy served to screen out players of inferior ability in co-ops, the process was imperfect because of the team production problem. Based on this argument, the authors suggest that co-ops functioned as an early minor league system in which untried players could seek to prove themselves and eventually move up to wage teams. Empirical analysis of data on player performance and experience in early professional base ball provides support for the theory.
Pay and Performance
Authors: Debrock Lawrence , Hendricks Wallace , Koenker Roger
Published: July 2004

When we control for worker characteristics, we are able to directly test theories of efficiency wages and fairness. We find that high-quality workers continue to be associated with good outcomes. High-wage strategies are also associated with better won-lost performance and higher attendance figures. Conditioning on worker characteristics allows distinguishing wage dispersion that is “efficient” from wage dispersion around predicted wages. In baseball, it appears that the reason for observing the unconditional results of wage dispersion is that the best technology requires workers of similar quality. There is less support for wage “fairness” as an important consideration for firm outcomes.
Fit to be Tied
Authors: Abrevaya Jason
Published: July 2004

This article examines the incentive effects of different payoff structures in the National Hockey League. A rule change prior to the 1999-2000 season, which changed the way that teams were awarded points in overtime games, provides a natural experiment to test the reaction of teams to a change in the payoff structure. The rule change had the desired effect of increasing excitement during overtime play. This article shows, however, that the rule also had the effect of increasing the frequency of overtime games, an effect predictable from the change in incentives but one not intended by the league.
Olympic Success and ASEAN Countries
Authors: Hoffmann Robert , Ging Lee Chew , Ramasamy Bala
Published: July 2004

This study considers the factors behind the poor performance of ASEAN countries at the 2000 Sydney Olympics. We find that, inter alia, relative GNP, hosting activity, the political system, climate, and relative population size of a country are jointly able to predict its likely performance. In the ASEAN context, we show that although economic and demographic factors are significant, improvements in these variables through governmental policy are likely to have only a limited effect on the actual number of medals won. In contrast, an increasing cultural focus on sport offers some potential for increased Olympic performance but is likely to be outside direct policy influence. We also derive projections for future ASEAN Olympic medal performance based on economic forecasts.
Effects of MLN518, a dual FLT3 and KIT inhibitor, on normal and malignant hematopoiesis
Authors: Griswold Ian J. , Shen Lei J. , La Rosée Paul , Demehri Shadmehr , Heinrich Michael C. , Braziel Rita M. , McGreevey Laura , Haley Andrea D. , Giese Neill , Druker Brian J. , Deininger Michael W.N.
Published: July 2004

Internal tandem duplications (ITDs) of the FMS-like tyrosine kinase 3 (FLT3) receptor tyrosine kinase are found in approximately 30% of patients with acute myelogenous leukemia (AML) and are associated with a poor prognosis. FLT3 ITD mutations result in constitutive kinase activation and are thought to be pathogenetically relevant, implicating FLT3 as a plausible therapeutic target. MLN518 (formerly CT53518) is a small molecule inhibitor of the FLT3, KIT, and platelet-derived growth-factor receptor (PDGFR) tyrosine kinases with significant activity in murine models of FLT3 ITD-positive leukemia. Given the importance of FLT3 and KIT for normal hematopoietic progenitor cells, we analyzed the effect of MLN518 on murine hematopoiesis under steady-state conditions, after chemotherapy-induced myelosuppression, and during bone marrow transplantation. In these assays, we show that MLN518 has mild toxicity toward normal hematopoiesis at concentrations that are effective in treating FLT3 ITD-positive leukemia in mice. We also demonstrate that MLN518 preferentially inhibits the growth of blast colonies from FLT3 ITD-positive compared with ITD-negative patients with AML, at concentrations that do not significantly affect colony formation by normal human progenitor cells. In analogy to imatinib mesylate in BCR-ABL–positive acute leukemia, MLN518-induced remissions may not be durable. Our studies provide the basis for integrating this compound into chemotherapy and transplantation protocols.
Apoptotic bodies from endothelial cells enhance the number and initiate the differentiation of human endothelial progenitor cells in vitro
Authors: Hristov Mihail , Erl Wolfgang , Linder Stefan , Weber Peter C.
Published: July 2004

Endothelial progenitor cells (EPCs) play a role in the repair of ischemic or injured tissue. Because endothelial injury can be associated with apoptosis, we have investigated whether apoptotic bodies from mature endothelial cells (ECs) may affect growth and differentiation of EPCs in vitro. A 24-hour incubation of isolated human EPCs with apoptotic bodies-rich medium (ABRM) from ECs led to a significant increase in the number of spindle-shaped attached cells. EPCs were characterized by DiI-Ac-LDL/lectin staining and measurement of CD34 and kinase insert domain receptor (KDR) expression. The treatment with ABRM resulted in a 2-fold increase of DiI-Ac-LDL/lectin-positive cells and up-regulation of CD34 (22% ± 2% versus 13% ± 3%, P < .05 and KDR (49% ± 12% versus 19% ± 7%, P < .05). Fluorescence and confocal laser microscopy demonstrated the uptake of apoptotic bodies by the EPCs. Apoptotic bodies-depleted medium had no effect, whereas the incubation with suspension of apoptotic bodies induced effects similar to those of ABRM. Our results suggest that apoptotic bodies from ECs are taken up by EPCs, increasing their number and differentiation state. Such a mechanism may facilitate the repair of injured endothelium and may represent a new signaling pathway between progenitor and damaged somatic cells. (Blood. 2004;104:2761-2766)
Enhancement of stress-induced apoptosis in B-lineage cells by caspase-9 inhibitor
Authors: Shah Nisha , Asch Rebecca J. , Lysholm Alana S. , LeBien Tucker W.
Published: July 2004

We have established human B-lineage (BLIN) acute lymphoblastic leukemia cell lines that retain a dependency on fibroblast monolayers for survival and proliferation. Eight hours following removal from adherent cell contact BLIN cells undergo a decrease in mitochondrial transmembrane potential and an increase in annexin V binding. Unexpectedly, the caspase-9 inhibitor (C9i) benzyloxycarbonyl-Leu-Glu-His-Asp-fluoromethylketone enhanced the appearance of apoptotic cells within 8 hours following removal of BLIN cells from fibroblast monolayers. C9i enhancement of apoptosis was dose dependent and did not occur with irreversible inhibitors of caspases-2, -3, -6, and -8. C9i also enhanced apoptosis in cord blood-derived CD19+ B-lineage cells (but not myeloid cells) removed from murine stromal cells. Longer exposure (> 18 hours) to C9i culminated in apoptosis in a panel of B-lineage acute lymphoblastic leukemia (ALL) cell lines in the presence or absence of fibroblast monolayers, as well as in 2 proliferating leukemic cell lines (RAMOS and CEM). BLIN-4L cells made deficient in caspase-9 by RNA interference exhibited no resistance to apoptotic signals and actually showed increased apoptotic sensitivity to staurosporine. These collective results suggest that a 4-amino acid caspase inhibitor of caspase-9 can promote apoptosis and that at least some types of apoptotic pathways in B-lineage ALL do not require caspase-9.
Enforced expression of an Flt3 internal tandem duplication in human CD34+ cells confers properties of self-renewal and enhanced erythropoiesis
Authors: Chung Ki Young , Morrone Giovanni , Schuringa Jan Jacob , Wong Bryan , Dorn David C. , Moore Malcolm A. S.
Published: July 2004

To investigate the role of constitutively active internal tandem duplication (ITD) mutants of the Fms-like tyrosine kinase 3 (Flt3) receptor in leukemogenesis, we introduced the Flt3-ITD, W51, into human cord blood CD34+ cells and evaluated their phenotype in diverse hematopoietic assays. W51 expression resulted in a strong proliferative advantage and enhanced erythropoiesis as determined by immunophenotyping, colony assays, and molecular analyses. In MS-5 stromal cocultures, numerous early cobblestone areas (CAs) were generated within 10 to 14 days. Such W51-associated early CAs disappeared by 4 weeks, yet retained self-renewal properties as demonstrated by generation of secondary and tertiary CAs upon replating. This phenotype appears related to the expression of W51 since it was abolished by exposure to the FLT3 inhibitor, AG1295, but not to the c-kit inhibitor PD16. Wild-type Flt3–overexpressing CD34+ cells exposed to high levels of its physiologic ligand did not produce early CAs, highlighting differences in intracellular signaling between wild-type Flt3 and W51. W51-associated signal transducer and activator of transcription 5 (Stat5) activation plays a major role in this phenotype, although additional downstream targets of W51 may be relevant. Flt3-ITD+ acute myeloid leukemia (AML) blasts from patients invariably generated early AG1295-sensitive CAs in MS-5 cocultures, further validating the phenotype observed in transduced CD34+ cells.
Leukocyte immunoglobulin-like receptors: novel innate receptors for human basophil activation and inhibition
Authors: Sloane David E. , Tedla Nicodemus , Awoniyi Muyiwa , MacGlashan Donald W. , Borges Luis , Austen K. Frank , Arm Jonathan P.
Published: July 2004

Basophils, recruited from the blood to tissues, have been implicated by their presence in diverse allergic disorders including bronchial asthma, allergic rhinitis, and cutaneous contact hypersensitivity. We hypothesized that like other leukocytes involved in inflammatory responses, basophils would express members of the leukocyte immunoglobulin-like receptor (LIR) family of immuno-regulatory molecules on their cell surface. We identified LIR7, an activating member coupled to the common Fc receptor gamma chain, and LIR3, an inhibitory member containing cytoplasmic immunoreceptor tyrosine-based inhibitory motifs, on these cells from human peripheral blood. Cross-linking of LIR7 resulted in the concentration-dependent net release of histamine (29.8 ± 10.8%) and cysteinyl leukotrienes (cysLTs) (31.4 ± 8.7 ng/106 basophils) that were maximal at 30 minutes, and of interleukin-4 (IL-4) (410.2 ± 61.6 pg/106 basophils) that was maximal at 4 hours and comparable with the response initiated by cross-linking of the high-affinity receptor for immunoglobulin E (FcϵRI). Coligation of LIR3 to LIR7 or to FcϵRI by means of a second monoclonal antibody significantly inhibited net histamine release, cysLT production, and IL-4 generation. That LIR3 is profoundly counter-regulatory for both adaptive and innate receptors suggests a broad role in containment of the inflammatory response.
E47, IRF-4, and PU.1 synergize to induce B-cell-specific activation of the class II transactivator promoter III (CIITA-PIII)
Authors: van der Stoep Nienke , Quinten Edwin , Rezende Marisa Marcondes , van den Elsen Peter J.
Published: July 2004

In B cells, expression of CIITA and resulting major histocompatibility complex II (MHCII) is mediated exclusively by promoter III (CIITA-PIII) activation. Recent studies have established that CIITA-PIII also participates in the expression of CIITA in activated human T cells, dendritic cells, and monocytes. In this study we characterized the various regulatory elements and interacting factors of CIITA-PIII that account for specific activation in B lymphocytes. We identified 2 E-box motifs and an Ets/ISRE-consensus element (EICE) in CIITA-PIII as playing a crucial role in the B-cell-specific transcriptional regulation of CIITA. Abolishment of factor binding to these elements resulted in a strong reduction of CIITA-PIII activation in B cells only, whereas it did scarcely affect or not affect the activity of CIITA-PIII in activated T cells and monocytes. We show that in B cells, E47 and PU.1/IRF-4 interact with the E-box motifs and the EICE, respectively, and act synergistically in the activation of CIITA-PIII. Moreover, functional inhibition of either E47 or IRF-4 resulted in strong reduction of CIITA-PIII activity in B lymphocytes only. The finding that PU.1, IRF-4, and E47 play an important role in the B-cell-mediated activation of CIITA-PIII provides a link between antigen presentation functions and activation and differentiation events in B lymphocytes.
The Cellular Basis for Volume Changes in the Rat Cortex during Puberty: White and Gray Matter
Authors: JURASKA JANICE M. , MARKHAM JULIE A.
Published: July 2004

Abstract: We have found that developmental changes through the adolescent period in the rat cerebral cortex provide parallels to those seen in the human cortex. Like humans, the rat cerebral white matter increases during this time due to increases in the number of axons that become myelinated even while the total number of axons decreases. We have preliminary evidence that estrogen decreases the rate of myelination, which results in a sex difference in adult rats. Another parallel to the human cortex is the nonlinear changes in the size of the cortex. We have found that in some cortical regions, female rats show decreases in cortical volume and number of neurons across the time of puberty, and removal of the ovaries stops these decreases. The rat cortex may serve as a model for the cellular changes underlying the volume changes seen in adolescent humans.
Lipids from Oxidized Low-Density Lipoprotein Modulate Human Trophoblast Invasion: Involvement of Nuclear Liver X Receptors
Authors: Pavan Laëtitia , Hermouet Axelle , Tsatsaris Vassilis , Thérond Patrice , Sawamura Tatsuya , Evain-Brion Danièle , Fournier Thierry
Published: July 2004

Human embryonic implantation involves major invasion of the uterine wall and remodeling of the uterine arteries by extravillous cytotrophoblast cells (EVCT). Abnormalities in these early steps of placental development lead to poor placentation and fetal growth defects and are frequently associated with preeclampsia, a major complication of human pregnancy. We recently showed that oxidized low-density lipoproteins (oxLDLs) are present in situ in EVCT and inhibit cell invasion in a concentration-dependent manner. The aim of the present study was to better understand the mechanisms by which oxLDL modulate trophoblast invasion. We therefore investigated the presence of oxLDL receptors in our cell culture model of human invasive primary EVCT. We found using immunocytochemistry and immunoblotting that the lectin-like oxLDL receptor-1 was the scavenger receptor mainly expressed in EVCT and was probably involved in oxLDL uptake. We next examined the effect of low-density lipoprotein oxidative state on trophoblast invasion in vitro using EVCT cultured on Matrigel-coated Transwell. We demonstrated that only oxLDL containing a high proportion of oxysterols and phosphatidylcholine hydroperoxide derivatives that provide ligands for liver X receptor (LXR) and peroxisomal proliferator-activated receptor γ (PPARγ), respectively, reduced trophoblast invasion. We next investigated the presence and the role of these nuclear receptors and found that in addition to PPARγ, human invasive trophoblasts express LXRβ, and activation of these nuclear receptors by specific synthetic or natural ligands inhibited trophoblast invasion. Finally, using a PPARγ antagonist, we suggest that LXRβ, rather than PPARγ, is involved in oxLDL-mediated inhibition of human trophoblast invasion in vitro.
Estrogen Induces Nitric Oxide Production via Activation of Constitutive Nitric Oxide Synthases in Human Neuroblastoma Cells
Authors: Xia Yun , Krukoff Teresa L.
Published: July 2004

Although it is becoming increasingly evident that nitric oxide (NO) mediates some of estrogen’s actions in the brain, the effects of estrogen on NO production through NO synthases (NOS) in neuronal cells have not yet been identified. Here we assessed changes in NO production induced by 17β-estradiol (E2) in cells of neuronal origin using human SK-N-SH neuroblastoma cells, which we show express all three isoforms of NOS. Involvement of NOS isoforms in E2-induced NO production was examined using isoform-specific NOS inhibitors. E2 (10−10–10−6m) induced rapid increases in NO release and changes in endothelial NOS (eNOS) expression, which were blocked by ICI 182,780, an antagonist of estrogen receptors. Increased levels of NO release and NOS activity induced by E2 were blocked by N5-(1-Imino-3-butenyl)-l-ornithine, a neuronal NOS inhibitor, and N5-(1-Iminoethyl)-l-ornithine, an eNOS inhibitor, but not by 1400W, an inducible NOS inhibitor. These results demonstrate that E2-stimulated NO production occurs via estrogen receptor-mediated activation of the constitutive NOSs, neuronal NOS and eNOS. The E2-induced NO increase was abolished when extracellular Ca2+ was removed from the medium or after the addition of nifedipine, an L-type channel blocker, and was partially inhibited using 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid acetoxymethyl ester, an intracellular Ca2+ chelator. However, 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid acetoxymethyl ester itself also caused an increase in NO release that was blocked by 1400W, suggesting that inducible NOS mediates this response. Together these data reveal that constitutive NOS activities are responsible for E2- induced NO production in neuroblastoma cells and that differential activation of NOS isoforms in these cells occurs in response to different treatments.
Developmental and Hormonally Regulated Messenger Ribonucleic Acid Expression of KiSS-1 and Its Putative Receptor, GPR54, in Rat Hypothalamus and Potent Luteinizing Hormone-Releasing Activity of KiSS-1 Peptide
Authors: Navarro V. M. , Castellano J. M. , Fernández-Fernández R. , Barreiro M. L. , Roa J. , Sanchez-Criado J. E. , Aguilar E. , Dieguez C. , Pinilla L. , Tena-Sempere M.
Published: July 2004

The gonadotropic axis is centrally controlled by a complex regulatory network of excitatory and inhibitory signals that is activated at puberty. Recently, loss of function mutations of the gene encoding G protein-coupled receptor 54 (GPR54), the putative receptor for the KiSS-1-derived peptide metastin, have been associated with lack of puberty onset and hypogonadotropic hypogonadism. Yet the pattern of expression and functional role of the KiSS-1/GPR54 system in the rat hypothalamus remain unexplored to date. In the present work, expression analyses of KiSS-1 and GPR54 genes were conducted in different physiological and experimental settings, and the effects of central administration of KiSS-1 peptide on LH release were assessed in vivo. Persistent expression of KiSS-1 and GPR54 mRNAs was detected in rat hypothalamus throughout postnatal development, with maximum expression levels at puberty in both male and female rats. Hypothalamic expression of KiSS-1 and GPR54 genes changed throughout the estrous cycle and was significantly increased after gonadectomy, a rise that was prevented by sex steroid replacement both in males and females. Moreover, hypothalamic expression of the KiSS-1 gene was sensitive to neonatal imprinting by estrogen. From a functional standpoint, intracerebroventricular administration of KiSS-1 peptide induced a dramatic increase in serum LH levels in prepubertal male and female rats as well as in adult animals. In conclusion, we provide novel evidence of the developmental and hormonally regulated expression of KiSS-1 and GPR54 mRNAs in rat hypothalamus and the ability of KiSS-1 peptide to potently stimulate LH secretion in vivo. Our current data support the contention that the hypothalamic KiSS-1/GPR54 system is a pivotal factor in central regulation of the gonadotropic axis at puberty and in adulthood.
Extracellular Signal-Regulated Kinases Are Involved in the Acute Activation of Steroidogenesis in Immature Rat Leydig Cells by Human Chorionic Gonadotropin
Authors: Martinelle N. , Holst M. , Söder O. , Svechnikov K.
Published: July 2004

We studied the involvement of the ERK cascade in human chorionic gonadotropin (hCG)-induced steroidogenesis by primary cultures of immature rat Leydig cells. Our findings indicate that protein kinase A and protein kinase C function as upstream kinases in connection with transduction of the signal from the gonadotropin receptor to the ERK cascade. These MAPKs enhance the stimulatory effects of hCG on the de novo synthesis of the steroidogenic acute regulatory protein and the activity of protein phosphatase 2A, which are associated with increased androgen production by the Leydig cell. Specific inhibition of ERK1/2 by Uo126 suppressed all of these cellular responses to hCG. In contrast, steroidogenesis from 22OHC (a cell-permeable form of cholesterol) is not inhibited by Uo126, suggesting that cholesterol delivery to mitochondria is being affected by this compound. We propose that the ERK cascade is an important part of the signal transduction pathway involved in the rapid hormonal responses of Leydig cells to trophic hormones. In hCG-activated Leydig cells, these MAPKs may play a role in controlling the biosynthesis of the steroidogenic acute regulatory protein as well as regulating protein phosphatase 2A activity, thereby governing cholesterol transport across the mitochondrial membrane.
Recent Developments in Studies of Electronic Excited States by Means of Electron Paramagnetic Resonance Spectroscopy
Authors: Yamauchi Seigo
Published: July 2004

New trends of electron paramagnetic resonance (EPR) are reviewed in studies of the electronic excited states conducted during this decade. The studies include EPR of excited triplet states in fluid solution and excited multiplet states in a triplet–radical pair system. Together with these new areas, advanced methods and techniques such as two dimensional pulsed EPR and high frequency high field EPR have been developed to analyze the new findings. In addition, time-resolved EPR with cw microwave has now become a general and very useful technique in time-domain experiments. Our recent works on porphyrins, phthalocyanines, and fullerenes are described in more detail.
Transport Properties and Effective Intermolecular Potentials for O2–O2, N2–N2, and O2–N2
Authors: Maghari Ali , Jalili Amir Hossein
Published: July 2004

Effective intermolecular potential-energy functions for O2–O2, N2–N2, and O2–N2 are obtained directly from the extended law of corresponding states for viscosity and experimental second virial coefficient data. The results are then used to obtain a best Morse–Spline–van der Waals (MSV) potential model. The present potential functions provide the best overall agreement for the available low-density gas-phase thermophysical data, i.e., second virial coefficient and transport properties. The effective intermolecular potential energies from the inversion of thermophysical data reproduce the viscosity, diffusion coefficient, and other transport coefficients within the experimental accuracy.
A Vibrational Analysis on Possible Peroxo Forms of Soluble Methane Monooxygenase
Authors: Yumura Takashi , Yoshizawa Kazunari
Published: July 2004

The vibrational structures for two possible peroxo intermediates of soluble methane monooxygenase (sMMO), in which O2 binds into the diiron(II) active site with end-on and side-on bridging modes, are analyzed from quantum chemical calculations at the B3LYP DFT level of theory. Dioxygen bridging modes should be controlled by carboxylate coordinations around the diiron active site. Two bridging carboxylato ligands are contained in the end-on peroxo complex, whereas one bridging carboxylato ligand is contained in the side-on peroxo complex. DFT calculations demonstrate that the end-on bridging mode into the diiron active site is energetically more stable than the side-on bridging mode. The end-on peroxo complex has a vibrational mode of O–O stretching at 909 cm−1, the isomer shift of which upon 18O2 substitution is 57 cm−1. The side-on peroxo complex exhibits a lower O–O stretching mode at 841 cm−1, and the isotope shift is 45 cm−1. The frequency of the O–O stretching mode and the 18O2 isotope shift are dependent on the dioxygen bridging modes in the active site of sMMO. The O–O stretching frequency in the end-on complex falls within the range measured in peroxo intermediates of other non-heme diiron enzymes and cis-μ-1,2 peroxo-bridged diiron(III) synthetic complexes. From the viewpoint of energetics and the vibrational frequencies, it is predicted that O2 should coordinate into the diiron active site of sMMO in an end-on cis-μ-1,2 fashion rather than a side-on fashion.
Photoinduced Electron-Transfer Processes of Fullerene (C60) with Amine Donors: Excited Triplet Route vs Excited Singlet Route
Authors: Sandanayaka Atula S D , Araki Yasuyuki , Luo Chuping , Fujitsuka Mamoru , Ito Osamu
Published: July 2004

Dynamic quenching processes of the excited states of C60 with amine donors have been studied by changing donor strength, donor concentration, and solvent polarity using steady-state and transient absorption and fluorescence spectroscopic techniques. Fluorescence quenching of C60 by amines was observed, which suggests a dynamic quenching process via the excited singlet state of C60 (1C60*) in polar and nonpolar solvents. In polar solvents, electron transfer via the excited triplet state of C60 (3C60*) producing radical ions (C60•− and amine•+) was observed by the nanosecond laser flash photolysis (ca. 6 ns laser pulse). When the donor concentrations are below 10–20 mmol dm−3, the concentrations of the radical ions increased with the donor concentrations. With further increase of the concentrations of the donors up to 100 mmol dm−3, on the other hand, the yields of the radical ions generated via 3C60* decreased. These findings indicate that dynamic quenching of 1C60* by amines increases with donor concentrations, resulting in a decrease of the intersystem crossing path to 3C60*; thus, the yields of the radical ions generated via 3C60* decreased even in the highly polar solvent. This implies that the radical ions generated by the dynamic quenching of 1C60* may be quite short-lived, even in polar solvents, compared with the radical ions via 3C60*.
Partitioning, Rotational Correlation, and Spin–Lattice Relaxation of Small Spin Probes in Dispersions of a Triglyceride Membrane
Authors: Nakagawa Kouichi
Published: July 2004

The partitioning, rotational correlation times (τR), and electron spin–lattice relaxation times (T1e) of various small spin probes in dispersions of a triglyceride membrane were investigated using CW-ESR (continuous wave-electron spin resonance) and SR (saturation recovery) spectroscopies. The partitioning of small spin probes, DTBN and TEMPO, in the aqueous and vesicle phases was determined by an ESR linewidth simulation. The results suggest that DTBN and TEMPO have a similar partitioning in the vesicle phase throughout the temperatures studied. The simulation results were quite different from those of conventional intensity analysis. In addition, the rotational correlation times of the vesicle phase for both probes varied from 1.2 × 10−10 to 4.9 × 10−10 s. The activation energy (Ea) calculated from the τR values in the phase was ∼29 [kJ/mol] for the probes. The thermal behavior based on the Ea value is that in between the 12-doxylstearic acid (12-DSA) and 16-DSA moieties of the membrane. The longer τR and shorter T1e (∼0.33 μs) values of DTBN in the vesicle phase were obtained, and could be attributed to the probe environment in the membrane. Thus, the present experimental evidence has provided a qualitative understanding of the probe dynamics as well as the membrane properties.
One-Step Electrochemical Cyanation Reaction of Pyrene in Polymer Microchannel-Electrode Chips
Authors: Ueno Kosei , Kitagawa Fumihiko , Kitamura Noboru
Published: July 2004

Polymer microchannel chips (100 μm width × 20 μm depth) integrated with electrodes were fabricated and applied to a one-step electrochemical cyanation reaction of pyrene (PyH). An acetonitrile solution of PyH containing tetrabutylammonium perchlorate and an aqueous NaCN solution were brought into the chip by pressure-driven flow, PyH was then oxidized at the working band electrode in the channel (1.5 V vs Ag). Under the optimum conditions, 1-cyanopyrene (PyCN) was produced very efficiently in the microchannel: 61% yield. It was also confirmed that, although 1,3-dicyanopyrene (Py(CN)2) was produced by bulk electrolysis (14% yield), its yield decreased to 4% in the microchip, with the PyCN/Py(CN)2 yield ratio being 2.9 or 15.3 for the bulk or chip experiments, respectively. In the case of an oil/water interfacial reaction system, a propylene carbonate solution of PyH and an aqueous NaCN solution were introduced to the channel, where an electrochemical cyanation reaction of PyH analogous to that mentioned above was conducted. The interfacial reaction in the microchip was successful and the yield of PyCN as the sole product was shown to be controlled by both the flow rate and the electrode position in the chip. In-situ space-resolved absorption spectroscopy of the electrochemical intermediate in the channel chip was also conducted to allow discussion of the reaction mechanisms.
Stability of FSM-16 in a Highly Moist and Aquatic Condition
Authors: Hashizume Hideo
Published: July 2004

The stability of a mesoporous material, FSM-16, against water vapor and water was investigated using an X-ray diffractometer with a relative humidity and temperature controlling unit. Under high relative humidity, the peaks for FSM-16 became smaller than the initial one from 60% of the relative humidity (RH) during an increase of the relative humidity from 10 to 95%, and the peak height was a minimum from 80 to 95% RH. However, the peaks for FSM-16 increased and returned back to the initial ones at 20% RH, while the relative humidity decreased. In soaked FSM-16 in water at 95% RH, the peaks for FSM-16 diminished owing to water. However, the peaks for FSM-16 appeared again, while water evaporated, and the peak heights were almost the same as the initial ones at 20% RH. However, the peak heights were about 25% lower than the initial ones after soaking FSM-16 in water for a long term. It might be supposed that the particles of FSM-16 on a sample holder were rearranged due to the pouring water, or that some of the mesopores for FSM-16 collapsed due to water.
μ-Acetato-di-μ-phenolato-metal(II)cobalt(II) (Metal = Fe, Co, Ni, Cu, Zn) Complexes with Low-Spin Co(II): Synthesis, Structures, and Magnetism
Authors: Matsumoto Kohta , Sekine Noboru , Arimura Keisuke , Ohba Masaaki , Sakiyama Hiroshi , Okawa Hisashi
Published: July 2004

The dinucleating macrocyclic ligand (L2;2)2−, prepared by the [1:1] cyclic condensation of N,N′-dimethyl-N,N′-ethylenedi(5-bromo-3-formyl-2-hydroxybenzylamine) and ethylenediamine, has dissimilar N(amine)2O2 and N(imine)2O2 metal-binding sites sharing two phenolic oxygen atoms. It has afforded μ-acetato-di-μ-phenolato-metal(II)cobalt(II) complexes (metal(II) = FeII, CoII, NiII, CuII, ZnII). X-ray crystallographic studies indicate that the MII is bound to the N(amine)2O2 site and has a square-pyramidal geometry with an acetate oxygen at the axial site. The CoII bound to the N(imine)2O2 site has a square-pyramidal geometry with an acetate oxygen at the apex or a distorted octahedral geometry with further coordination of a methanol molecule. The CoII in the N(imine)2O2 site is of low-spin and has one unpaired electron in its dz2 orbital. Magnetic studies indicate an antiferromagnetic interaction in the FeCo and CoCo complexes whereas a ferromagnetic interaction in the NiCo and CuCo complexes. The magnetic properties of the complexes are discussed in terms of the electronic structure of the MII ion and the dinuclear MCo core structure.
Preparation, Methylation, and Coupling Reaction of 1,2-Dithienyl-3,4-bis[(2,4,6-tri-t-butylphenyl)phosphinidene]cyclobutenes
Authors: Toyota Kozo , Abe Keita , Horikawa Keiko , Yoshifuji Masaaki
Published: July 2004

Sterically protected 1,2-di(2-thienyl)- and 1,2-di(3-thienyl)-3,4-bis[(2,4,6-tri-t-butylphenyl)phosphinidene]cyclobutenes were prepared and their properties were studied. When the dithienyldiphosphinidenecyclobutenes were allowed to react with butyllithium and then with iodomethane, the corresponding methylthienyl derivatives were obtained. The structure of (E,E)-1,2-bis(5-methyl-3-thienyl)-3,4-bis[(2,4,6-tri-t-butylphenyl)phosphinidene]cyclobutene was analyzed by X-ray crystallography. Lithiation of the dithienyldiphosphinidenecyclobutenes, followed by treatment with CuCl2, afforded the corresponding coupling products on the thiophene rings.
Synthesis, Isolation, and Characterization of Diels–Alder Adducts between 1,4-Dialkoxyanthracenes and Maleic Anhydride
Authors: Kitamura Chitoshi , Hasegawa Munehiro , Ishikawa Hiroshi , Fujimoto Jun , Ouchi Mikio , Yoneda Akio
Published: July 2004

In the Diels–Alder reaction of 1,4-dialkoxyanthracenes and maleic anhydride, which can afford syn- and anti-cycloadducts, the bridgehead methine proton of the cycloadducts has proved to be a useful probe for determining syn/anti selectivity, as supported by isolation of diastereomers, 1H NMR spectroscopy, and X-ray analysis. In the case of methoxy and propoxy substituents, a slight anti-preference was observed, on the other hand, the reaction of 1,4-bis(benzyloxy)anthracene gave a small syn-preference. Theoretical calculations of transition states of 1,4-dimethoxyanthracene and maleic anhydride showed no stereochemical preference. From UV–vis spectra, the formation of charge transfer complexes of anthracenes and maleic anhydride is possible.
Kinetics of Copper(I)-Catalyzed Dimerization and Hydration of Acetylene in Water
Authors: Tokita Yuichi , Okamoto Akio , Nishiwaki Kenichiro , Kobayashi Mineto , Nakamura Eiichi
Published: July 2004

The kinetics of the dimerization and hydration of acetylene in water with a copper(I) catalyst, a so-called Nieuwland catalyst, were investigated. The stationary state kinetics for both reactions could be described assuming that the rate-controlling step is a second-order reaction of an activated catalyst, [H···Cl–Cu–C2H], formed in the reaction mixture, with acetylene or water. The activation energies and activation entropies were 12.4 kcal·mol−1 and −33.3 cal·mol−1·K−1 for the acetylene dimerization, and 17.5 kcal·mol−1 and −34.2 cal·mol−1·K−1 for the acetylene hydration, respectively. The large negative values of activation entropy for these reactions may be accounted for by the role of water as a kind of cocatalyst.
The Correlation between Electrically Induced Stress and Mechanical Tensile Strength of Polypyrrole Actuators
Authors: Zama Tetsuji , Hara Susumu , Takashima Wataru , Kaneto Keiichi
Published: July 2004

Highly stretchable and powerful PPy film actuators, prepared electrochemically from a methyl benzoate solution of tetra-n-butylammonium tetrafluoroborate (TBABF4), showed a positive correlation between the electrochemical stress and the mechanical tensile strength. The more flexible CF3SO3−-doped PPy suits multi-wound or multi-folded actuators that can be used as artificial muscles.
Postoperative Radiotherapy and Survival in Oral Cavity Squamous Cell Carcinoma With Mandibulectomy
Authors: Harley Randall J. , Iheagwara Uzoma K. , Faraji Farhoud , Sridharan Shaum , Kubik Mark W.
Published: February 2024

Importance

Oral cavity squamous cell carcinoma (SCC) tumors with mandibular invasion are upstaged to pT4a regardless of their size. Even small tumors with boney invasion, which would otherwise be classified as pT1-2, are recommended for the locally advanced treatment pathway to receive administration of postoperative radiotherapy (PORT).

Objective

To evaluate the association of PORT with overall survival according to tumor size among patients who received mandibulectomy for pT4aN0 oral cavity SCC.

Design, Setting, and Participants

This was a retrospective analysis using data from the US National Cancer Database from January 1, 2004, through December 31, 2019. All patients who received mandibulectomy for treatment-naive pT4aN0 oral cavity SCC with negative surgical margins were included. Data analyses were performed in January 2023 and finalized in July 2023.

Exposure

PORT vs no PORT.

Main Outcomes and Measures

Entropy balancing was used to balance covariate moments between treatment groups. Weighted multivariable Cox proportional hazards regression was used to measure the association of PORT with overall survival associated with tumor size.

Results

Among 3268 patients with pT4aN0 oral cavity SCC (mean [SD] age, 65.9 [12.1] years; 2024 [61.9%] male and 1244 [38.1%] female), 1851 (56.6%) received PORT and 1417 (43.4%) did not receive PORT. On multivariable analysis was adjusted for age, insurance status, Charlson Comorbidity Index score, tumor site, tumor grade, tumor size, and PORT. Findings indicated that PORT was associated with improved overall survival and that this relative survival advantage trended upwards with increasing tumor size. That is, the larger the tumor, the greater the survival advantage associated with the use of PORT. For the 1068 patients with tumors greater than 4 cm, the adjusted hazard ratio (aHR) in favor of PORT was 0.63 (95% CI, 0.48-0.82); for the 1774 patients with tumors greater than 2 cm but less than or equal to 4 cm, the aHR was 0.76 (95% CI, 0.62-0.93); and for 426 patients with tumors less than 2 cm, the aHR was 0.81 (95% CI, 0.57-1.15).

Conclusions and Relevance

In this retrospective analysis of patients who received mandibulectomy for pT4aN0 oral cavity SCC, PORT was associated with improved overall survival, the benefit of which improved relatively with increasing tumor size. These findings suggest that tumor size should be considered in guidelines for PORT administration in this patient population.