bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal-Fetal Glucocorticoid Milieu Programs Hypothalamic-Pituitary-Thyroid Function of Adult Offspring
Authors: Slone-Wilcoxon Jennifer , Redei Eva E.
Published: June 2004

To assess the role of maternal glucocorticoid milieu on the hypothalamic-pituitary-thyroid function of the offspring, we adrenalectomized (ADX) pregnant dams on gestation d 8 and implanted a placebo pellet or a continuous release 50- or 75-mg corticosterone (CORT) pellet. Maternal ADX led to realignment of the balance between maternal and fetal plasma CORT levels, resulting in an increase in CORT of fetal origin in the maternal compartment. Maternal ADX and low levels of CORT replacement had no discernable effect on maternal pituitary-thyroid measures. In contrast, the increase in fetal CORT, as a consequence of the absence of maternal glucocorticoids, decreased birth weight in neonates, decreased adult hypothalamic TRH mRNA levels, and increased plasma TSH levels in both male and female adult offspring, all of which were reversed by administration of basal levels of CORT to the pregnant ADX dam. Decreased plasma T3 concentrations in female offspring were reversed by administration of the higher levels of CORT to the ADX dams. Our data indicate that maternal glucocorticoids modulate the developing hypothalamic-pituitary-thyroid axis.
Structural Determinants for High-Affinity Binding of Insulin-Like Growth Factor II to Insulin Receptor (IR)-A, the Exon 11 Minus Isoform of the IR
Authors: Denley Adam , Bonython Eric R. , Booker Grant W. , Cosgrove Leah J. , Forbes Briony E. , Ward Colin W. , Wallace John C.
Published: June 2004

The insulin receptor (IR) lacking the alternatively spliced exon 11 (IR-A) is preferentially expressed in fetal and cancer cells. The IR-A has been identified as a high-affinity receptor for insulin and IGF-II but not IGF-I, which it binds with substantially lower affinity. Several cancer cell types that express the IR-A also overexpress IGF-II, suggesting a possible autocrine proliferative loop. To determine the regions of IGF-I and IGF-II responsible for this differential affinity, chimeras were made where the C and D domains were exchanged between IGF-I and IGF-II either singly or together. The abilities of these chimeras to bind to, and activate, the IR-A were investigated. We also investigated the ability of these chimeras to bind and activate the IR exon 11+ isoform (IR-B) and as a positive control, the IGF-I receptor (IGF-1R). We show that the C domain and, to a lesser extent, the D domains represent the principal determinants of the binding differences between IGF-I and IGF-II to IR-A. The C and D domains of IGF-II promote higher affinity binding to the IR-A than the equivalent domains of IGF-I, resulting in an affinity close to that of insulin for the IR-A. The C and D domains also regulate the IR-B binding specificity of the IGFs in a similar manner, although the level of binding for all IGF ligands to IR-B is lower than to IR-A. In contrast, the C and D domains of IGF-I allow higher affinity binding to the IGF-1R than the analogous domains of IGF-II. Activation of IGF-1R by the chimeras reflected their binding affinities whereas the phosphorylation of the two IR isoforms was more complex.
Transduction of graded Hedgehog signaling by a combination of Gli2 and Gli3 activator functions in the developing spinal cord
Authors: Lei Qiubo , Zelman Alice K. , Kuang Ed , Li Shike , Matise Michael P.
Published: June 2004

The three vertebrate Gli proteins play a central role in mediating Hedgehog(Hh)-dependent cell fate specification in the developing spinal cord; however,their individual contributions to this process have not been fully characterized. In this paper, we have addressed this issue by examining patterning in the spinal cord of Gli2;Gli3 double mutant embryos, and in chick embryos transfected with dominant activator forms of Gli2 and Gli3. In double homozygotes, Gli1 is also not expressed; thus, all Gli protein activities are absent in these mice. We show that Gli3 contributes activator functions to ventral neuronal patterning, and plays a redundant role with Gli2 in the generation of V3 interneurons. We also show that motoneurons and three classes of ventral neurons are generated in the ventral spinal cord in double mutants, but develop as intermingled rather than discrete populations. Finally, we provide evidence that Gli2 and Gli3 activators control ventral neuronal patterning by regulating progenitor segregation. Thus, multiple ventral neuronal types can develop in the absence of Gli function, but require balanced Gli protein activities for their correct patterning and differentiation.
Computational comparative analyses of alternative splicing regulation using full-length cDNA of various eukaryotes
Authors: ITOH HITOMI , WASHIO TAKANORI , TOMITA MASARU
Published: June 2004

We previously reported a computational approach to infer alternative splicing patterns from Mus musculus full-length cDNA clones and microarray data. Although we predicted a large number of unreported splice variants, the general mechanisms regulating alternative splicing were yet unknown. In the present study, we compared alternative exons and constitutive exons in terms of splice-site strength and frequency of potential regulatory sequences. These regulatory features were further compared among five different species: Homo sapiens, M. musculus, Arabidopsis thaliana, Oryza sativa, and Drosophila melanogaster. Solid statistical validations of our comparative analyses indicated that alternative exons have (1) weaker splice sites and (2) more potential regulatory sequences than constitutive exons. Based on our observations, we propose a combinatorial model of alternative splicing mechanisms, which suggests that alternative exons contain weak splice sites regulated alternatively by potential regulatory sequences on the exons.
Quantitation of microRNAs using a modified Invader assay
Authors: ALLAWI HATIM T. , DAHLBERG JAMES E. , OLSON SARAH , LUND ELSEBET , OLSON MARILYN , MA WU-PO , TAKOVA TSETSKA , NERI BRUCE P. , LYAMICHEV VICTOR I.
Published: June 2004

The short lengths of microRNAs (miRNAs) present a significant challenge for detection and quantitation using conventional methods for RNA analysis. To address this problem, we developed a quantitative, sensitive, and rapid miRNA assay based on our previously described messenger RNA Invader assay. This assay was used successfully in the analysis of several miRNAs, using as little as 50–100 ng of total cellular RNA or as few as 1,000 lysed cells. Its specificity allowed for discrimination between miRNAs differing by a single nucleotide, and between precursor and mature miRNAs. The Invader miRNA assay, which can be performed in unfractionated detergent lysates, uses fluorescence detection in microtiter plates and requires only 2–3 h incubation time, allowing for parallel analysis of multiple samples in high-throughput screening analyses.
Targeted mutagenesis of the murine IRP1 and IRP2 genes reveals context-dependent RNA processing differences in vivo
Authors: GALY BRUNO , FERRING DUNJA , BENESOVA MONIKA , BENES VLADIMIR , HENTZE MATTHIAS W.
Published: June 2004

We report the targeted mutagenesis of the murine iron regulatory protein (IRP)-1 and IRP2 genes, respectively, with a classical gene trap construct. Insertion of the targeting cassette into the second intron of either gene by homologous recombination interrupts their open reading frames near the N termini. Mice that are homozygous for the correctly modified IRP1 or IRP2 alleles, respectively, display a strong reduction (90%, IRP1−/−) or nondetectable levels (IRP2−/−) of the targeted proteins. Interestingly, the pre-mRNAs transcribed from the identical targeting cassettes are processed differently within the two different contexts. Detailed analysis of the respective products identifies the choice of alternative splice and 3′ end processing sites in the same tissues in vivo. We discuss the implications for the understanding of RNA processing and for targeting strategies for functional genomics in the mouse.
Pseudouridine-guide RNAs and other Cbf5p-associated RNAs in Euglena gracilis
Authors: RUSSELL ANTHONY G. , SCHNARE MURRAY N. , GRAY MICHAEL W.
Published: June 2004

In eukaryotes, box H/ACA small nucleolar RNAs (snoRNAs) guide sites of pseudouridine (Ψ) formation in rRNA. These snoRNAs reside in RNP complexes containing the putative Ψ synthase, Cbf5p. In this study we have identified Cbf5p-associated RNAs in Euglena gracilis, an early diverging eukaryote, by immunoprecipitating Cbf5p-containing complexes from cellular extracts. We characterized one box H/ACA-like RNA which, however, does not appear to guide Ψ formation in rRNA. We also identified four single Ψ-guide box AGA RNAs. We determined target sites for these putative Ψ-guide RNAs and confirmed that the predicted Ψ modifications do, in fact, occur at these positions in Euglena rRNA. The Cbf5p-associated snoRNAs appear to be encoded by multicopy genes, some of which are clustered in the genome together with methylation-guide snoRNA genes. These modification-guide snoRNAs and snoRNA genes are the first ones to be reported in euglenid protists, the evolutionary sister group to the kinetoplastid protozoa. Unexpectedly, we also found and have partially characterized a selenocysteine tRNA homolog in the anti-Cbf5p-immunoprecipitated sample.
A regulatory role for Sec tRNA[Ser]Sec in selenoprotein synthesis
Authors: JAMESON RUTH R. , DIAMOND ALAN M.
Published: June 2004

Selenium is biologically active through the functions of selenoproteins that contain the amino acid selenocysteine. This amino acid is translated in response to in-frame UGA codons in mRNAs that include a SECIS element in its 3′ untranslated region, and this process requires a unique tRNA, referred to as tRNA[Ser]Sec. The translation of UGA as selenocysteine, rather than its use as a termination signal, is a candidate restriction point for the regulation of selenoprotein synthesis by selenium. A specialized reporter construct was used that permits the evaluation of SECIS-directed UGA translation to examine mechanisms of the regulation of selenoprotein translation. Using SECIS elements from five different selenoprotein mRNAs, UGA translation was quantified in response to selenium supplementation and alterations in tRNA[Ser]Sec levels and isoform distributions. Although each of the evaluated SECIS elements exhibited differences in their baseline activities, each was stimulated to a similar extent by increased selenium or tRNA[Ser]Sec levels and was inhibited by diminished levels of the methylated isoform of tRNA[Ser]Sec achieved using a dominant-negative acting mutant tRNA[Ser]Sec. tRNA[Ser]Sec was found to be limiting for UGA translation under conditions of high selenoprotein mRNA in both a transient reporter assay and in cells with elevated GPx-1 mRNA. This and data indicating increased amounts of the methylated isoform of tRNA[Ser]Sec during selenoprotein translation indicate that it is this isoform that is translationally active and that selenium-induced tRNA methylation is a mechanism of regulation of the synthesis of selenoproteins.
Early Regeneration of Whole Skeletal Muscle Grafts Is Unaffected by Overexpression of IGF-1 in MLC/mIGF-1 Transgenic Mice
Authors: Shavlakadze Thea , Davies Marilyn , White Jason D. , Grounds Miranda D.
Published: June 2004

Early myogenic events in regenerating whole muscle grafts were compared between transgenic MLC/mIGF-1 mice with skeletal muscle-specific overexpression of the Exon-1 Ea isoform of insulin-like growth factor-1 (mIGF-1) and control FVB mice, from day 3 to day 21 after transplantation. Immunocytochemistry with antibodies against desmin showed that skeletal muscle-specific overexpression of IGF-1 did not affect the pattern of myoblast activation or proliferation or the onset and number of myotubes formed in regenerating whole muscle grafts. Hypertrophied myotubes were observed in MLC/mIGF grafts at day 7 after transplantation, although such hypertrophy was transient, and the transgenic and control grafts had a similar appearance at later time points (days 10, 14, and 21). Immunostaining with antibodies to platelet endothelial cell adhesion molecule-1, which identifies endothelial cells, demonstrated no difference in the formation of new vascular network in grafts of transgenic and control mice. Skeletal muscle-specific overexpression of mIGF-1 does not appear to stimulate the early events associated with myogenesis during regeneration of whole muscle grafts. (J Histochem Cytochem 52:873–883, 2004)
The Serine Protease HtrA1 Is Upregulated in the Human Placenta during Pregnancy
Authors: De Luca Antonio , De Falco Maria , Fedele Valentina , Cobellis Luigi , Mastrogiacomo Annunziata , Laforgia Vincenza , Tuduce Ioana L. , Campioni Mara , Giraldi Domenico , Paggi Marco G. , Baldi Alfonso
Published: June 2004

The placenta has a dynamic and continuous capacity for self-renewal. The molecular mechanisms responsible for controlling trophoblast proliferation are still unclear. It is generally accepted that the simultaneous activity of proteins involved in cell proliferation, apoptosis, and extracellular matrix degradation plays an important role in correct placental development. We investigated in depth the expression of the serine protease HtrA1 during pregnancy in human placenta by in situ hybridization and immunohistochemistry, we demonstrated that HtrA1 displayed a low level of expression in the first trimester of gestation and a strong increase of HtrA1 expression in the third trimester. Finally, by electron microscopy, we demonstrated that HtrA1 was localized either in the cytoplasm of placental cells, especially close to microvilli that characterized the plasma membrane of syncytiotrophoblast cells, or in the extracytoplasmic space of the stroma of placental villi, particularly in the spaces between collagen fibers and on collagen fibers themselves. The expression pattern of HtrA1 in human placentas strongly suggests a role for this protein in placental development and function. Moreover, on the basis of its subcellular distribution it can be postulated that HtrA1 acts on different targets, such as intracellular growth factors or extracellular matrix proteins, to favor the correct formation/function of the placenta. (J Histochem Cytochem 52:885–892, 2004)
Immunohistochemical Detection of EGFR in Paraffin-embedded Tumor Tissues
Authors: Atkins Derek , Reiffen Karl-August , Tegtmeier Conny Lund , Winther Henrik , Bonato Marcellus S. , Störkel Stephan
Published: June 2004

The epidermal growth factor receptor (EGFR) is highly expressed in a variety of solid malignant tumors and its expression has been correlated with disease progression and poor survival. With the advent of targeted therapies, especially IMC-C225 (Cetuximab), a monoclonal antibody (MAb) directed against the EGFR, there is an increasing interest in immunohistochemistry (IHC)-based EGFR screening methods using paraffin-embedded tumor specimens to select cancer patients eligible for treatment with Cetuximab. With the EGFRpharmDX kit, a complete assay for demonstration of EGFR is now available. Because no information about the preservation of the EGFR under various conditions of fixation is available, we performed a prospective study on a panel of commonly used fixatives to determine optimal tissue preservation protocols. The stability of the epitope on cut tissue sections stored for a period up to 24 month was also tested using material originating from patients with head and neck cancer, non-small-cell lung carcinomas, and colorectal adeno-carcinomas. Depending on the fixative used and the time of storage of cut tissue sections, a variation in the determined level of EGFR expression was demonstrated compared with the most optimal fixation procedure. (J Histochem Cytochem 52:893–901, 2004)
Localization of Alkaline Phosphatase and Proteins Related to Intercellular Junctions in Rat Hepatoma Cell Line McA-RH 7777
Authors: Chida Kohsuke , Taguchi Meiko
Published: June 2004

We investigated the localization of alkaline phosphatase (ALP) and three proteins related to intercellular junctions in the McA-RH 7777 rat hepatoma cell line to determine if the formation of junctions between adjacent McA-RH 7777 cells triggers translocation of ALP from cytoplasm to the plasma membrane. Contact between adjacent McA-RH 7777 cells promotes translocation of ALP from the Golgi area of the cytoplasm to the plasma membrane, and also promotes translocation of two proteins, E-cadherin and ZO-1, related to intercellular junctions, from cytoplasm to the plasma membrane. (J Histochem Cytochem 52:979–983, 2004)
Effect of Epsilon Toxin–GFP on MDCK Cells and Renal Tubules In Vivo
Authors: Soler-Jover Alex , Blasi Juan , de Aranda Inma Gómez , Navarro Piedad , Gibert Maryse , Popoff Michel R. , Martín-Satué Mireia
Published: June 2004

Epsilon toxin (∊-toxin), produced by Clostridium perfringens types B and D, causes fatal enterotoxemia, also known as pulpy kidney disease, in livestock. Recombinant ∊-toxin–green fluorescence protein (∊-toxin–GFP) and ∊-prototoxin–GFP were successfully expressed in Escherichia coli. MTT assays on MDCK cells confirmed that recombinant ∊-toxin–GFP retained the cytotoxicity of the native toxin. Direct fluorescence analysis of MDCK cells revealed a homogeneous peripheral pattern that was temperature sensitive and susceptible to detergent. ∊-Toxin–GFP and ∊-prototoxin-GFP bound to endothelia in various organs of injected mice, especially the brain. However, fluorescence mainly accumulated in kidneys. Mice injected with ∊-toxin–GFP showed severe kidney alterations, including hemorrhagic medullae and selective degeneration of distal tubules. Moreover, experiments on kidney cryoslices demonstrated specific binding to distal tubule cells of a range of species. We demonstrate with new recombinant fluorescence tools that ∊-toxin binds in vivo to endothelial cells and renal tubules, where it has a strong cytotoxic effect. Our binding experiments indicate that an ∊-toxin receptor is expressed on renal distal tubules of mammalian species, including human. (J Histochem Cytochem 52:931–942, 2004)
Gene Expression Patterns of Pro-opiomelanocortin-processing Enzymes PC1 and PC2 During Postnatal Development of Rat Corticotrophs
Authors: Kato Hidetaka , Kuwako Ken-ichirou , Suzuki Masakazu , Tanaka Shigeyasu
Published: June 2004

We examined the expression and localization of the prohormone convertases, PC1 and PC2, in the anterior pituitary cells of developing rats by a double staining procedure using in situ RT-PCR and an immunofluorescence technique. In the adult, both PC1 mRNA and PC2 mRNA were expressed in corticotrophs, gonadotrophs, thyrotrophs, and mammotrophs. These cells, except for corticotrophs, had previously been considered to be ones in which proprotein processing does not take place, but both PC1 and PC2 may be necessary to process other proteins, such as granin family proteins, having proteolytic cleavage sites and located in secretory granules of the above trophs. In addition, no PC1 or PC2 mRNA was expressed in somatotrophs, which is consistent with the fact that somatotrophs do not contain these granins. In addition, 7B2 mRNA was expressed in these PC2-positive trophs, suggesting that there is a functional relationship between PC2 and 7B2 proteins. We found that α-MSH was expressed in the corticotrophs of the postnatal rat and that the number of α-MSH-immunopositive corticotrophs decreased as development proceeded. Because the changes in the pattern of POMC processing are considered to depend on the relative expression levels of PC1 and PC2, PC1 and PC2 mRNAs were examined in corticotrophs during postnatal development. We found a decrease in the number of PC2 mRNA-positive cells, which coincided with one in the number of α-MSH-immunopositive corticotrophs, as postnatal development proceeded. Our present data demonstrate that the α-MSH production varies directly in accordance with the expression of PC2. We also discuss the possible significance of α-MSH production during the postnatal period. (J Histochem Cytochem 52:943–957, 2004)
Corticotropin-releasing Factor 2 Receptor Localization in Skeletal Muscle
Authors: Samuelsson Steven , Lange Jana S. , Hinkle Richard T. , Tarnopolsky Mark , Isfort Robert J.
Published: June 2004

Our objective in this study was to localize the corticotropin-releasing factor 2 receptor (CRF2R) in rodent and human skeletal muscle. We found CRF2R protein to be abundant in neural tissues in skeletal muscle, including large nerve fibers and bundles, neural tissue associated with mechanoreceptors, muscle spindles, and the Golgi tendon organ. CRF2R protein was also abundant in blood vessels in skeletal muscle. CRF2R protein was also observed, although with less abundance, in the endo/perimysial regions in skeletal muscle. The localization of the CRF2R to blood vessels is consistent with the CRF2R-mediated vascular phenomena observed previously, but the observation of CRF2R in neural tissue in skeletal muscle is a novel finding with an unknown function. (J Histochem Cytochem 52:967–977, 2004)
25-Hydroxyvitamin D3-1α-hydroxylase Expression in Normal and Malignant Human Colon
Authors: Bises Giovanna , Kállay Enikö , Weiland Tina , Wrba Friedrich , Wenzl Etienne , Bonner Elisabeth , Kriwanek Stefan , Obrist Peter , Cross Heide S.
Published: June 2004

1,25-dihydroxyvitamin D3 has anti-mitotic, pro-differentiating, and pro-apoptotic activity in tumor cells. We demonstrated that the secosteroid can be synthesized and degraded not only in the kidney but also extrarenally in intestinal cells. Evaluation of 1,25-dihydroxyvitamin D3-synthesizing CYP27B1 hydroxylase mRNA (real-time PCR) and protein (immunoblotting, immunofluorescence) showed enhanced expression in high- to medium-differentiated human colon tumors compared with tumor-adjacent normal mucosa or with colon mucosa from non-cancer patients. In high-grade undifferentiated tumor areas expression was lost. Many cells co-expressed CYP27B1 and the vitamin D receptor. We suggest that autocrine/paracrine antimitotic activity of 1,25-dihydroxyvitamin D3 could prevent intestinal tumor formation and progression. (J Histochem Cytochem 52:985–989, 2004)
Allele-Specific Change of Concentration and Functional Gene Dose for the Prediction of Steady-State Serum Concentrations of Amitriptyline and Nortriptyline in CYP2C19 and CYP2D6 Extensive and Intermediate Metabolizers
Authors: Steimer Werner , Zöpf Konstanze , von Amelunxen Silvia , Pfeiffer Herbert , Bachofer Julia , Popp Johannes , Messner Barbara , Kissling Werner , Leucht Stefan
Published: June 2004

Background: Recently, new polymorphisms were described in connection with intermediate and ultrarapid CYP2D6 metabolism. These may allow a much desired prediction of metabolic activity within the extensive metabolizer group. The functional consequences are still being discussed with few data available for clinical patients.

Methods: We conducted a prospective, blinded two-center study seeking correlations between CYP2C19 (*2,*3, and *4; conventional PCR) and CYP2D6 genotypes (*1 to *10, *35, and *41; real-time and multiplex PCR) and drug concentrations (Emit® and HPLC) in 50 Caucasians receiving amitriptyline (AT; 75 mg twice a day).

Results: Eighteen CYP2C19 heterozygotes (*1/*2) had higher AT (P = 0.033) and lower nortriptyline (NT; P = 0.059) concentrations than 30 homozygotes (*1/*1). For CYP2D6, we calculated two new indices, i.e., the allele-specific change of concentration on identical background (ASCOC) and a quantitative functional gene dose. The ASCOC describes the change in NT concentration attributable to a mutant allele compared with the wild type. We found significantly higher concentrations for alleles *4 (95.6%; P <0.0001), *10 (63.3%; P <0.001), and *41 (39.8%; P <0.0001) but not for *2 and *35. Assigning of semiquantitative gene doses of 0, 0.5, or 1 to each allele instead of applying the current classification system (predicted phenotypes: 3 intermediate metabolizers, 46 extensive metabolizers, and 1 ultrarapid metabolizer) produced significant NT concentration differences: gene doses of 0.5 (n =3), 1 (n = 14), 1.5 (n = 11), 2 (n = 21) and 3 (n = 1; P <0.00001).

Conclusions: AT and NT concentrations can be predicted within the group of CYP2D6 extensive metabolizers. The ASCOC provides substantial advantages compared with current methods of analysis. CYP2D6 but not CYP2C19 correlates with the sum of both concentrations used to guide AT therapy.
“There's a Spirit That Transcends the Border”: Faith, Ritual, and Postnational Protest at the U.S.-Mexico Border
Authors: Hondagneu-Sotelo Pierrette , Gaudinez Genelle , Lara Hector , Ortiz Billie C.
Published: June 2004

Religion is increasingly moving beyond private confines to public venues, where it challenges and informs public morality and civil society. This article focuses on the Posada Sin Fronteras, an annual political and religious-informed event that calls attention to the rising death toll at the U.S.-Mexico border caused by changes in U.S. border enforcement policies. Based on ethnographic data and on-the-spot interviews with participants at the event, this article analyzes the Posada as a collective ritual and examines the meanings it holds for its varied participants. The crisis in U.S. immigration and border enforcement policies, and the cultural influences brought about by Mexican and, to lesser extent, Central American immigration provide the conditions for the Posada. Interfaith religious morality allows for the adoption of Mexican and Catholic cultural forms by diverse groups, including people who are of neither Mexican nor Catholic heritage. We refer to this process as “religio-ethnic cultural expansion,” and we suggest that religious discourse of Christian kinship, unity, and shared humanity constitute one of the key forces animating the post-national challenge to nation-state border and citizenship policies.
Race, Family Structure, and Wealth: The Effect of Childhood Family on Adult Asset Ownership
Authors: Keister Lisa A.
Published: June 2004

Racial differences in wealth ownership are among the most extreme and persistent forms of stratification in the United States, but the factors that contribute to this inequality are unclear. One potentially important contributing factor is family background. It is a critical determinant of attainment, and both childhood family resources and family structure vary racially. This article reports that family size during childhood contributes significantly to racial differences in adult wealth. I find that siblings strain material and nonmaterial resources during childhood and decrease adult home ownership, stock ownership, and total assets. Having extended family in the home also decreases wealth for those from intact families, but an extended family minimizes the negative effect of divorce and separation and increases wealth in disrupted families. I also find that childhood family size and family structure are related to racial differences in adult wealth accumulation trajectories, allowing whites to begin accumulating high-yield assets earlier in life. The results provide insight into the role of family background in creating and maintaining inequality, particularly racial stratification in wealth ownership.
The Social Psychology of Tokenism: Status and Homophily Processes on Wall Street
Authors: Roth Louise Marie
Published: June 2004

While conscious action may produce some inequality, most discrimination occurs through cognitive processes that are automatic and unconscious. I examine the role of two cognitive mechanisms that affect gender inequality in the securities industry: homophily preferences and status expectations. I argue that homophily preferences and status expectations are the general cognitive processes that produce the effects of “tokenism,” which were originally identified by Kanter for female tokens. These processes also lead to differences in the experiences of male and female tokens. I use qualitative data on 76 Wall Street professionals to illustrate how homophily and status processes maintain and reproduce stratification in securities firms. Moreover, the compensation system in this industry, which rewards employees based on performance evaluations, aggravates the effects of these cognitive processes. Strong mentors, the possession of specialized skills, and objective performance indicators seem to mitigate these effects for a minority of women.
Routes to the Informal Economy in New York's East Village: Crisis, Economics, and Identity
Authors: Snyder Karrie Ann
Published: June 2004

This article looks at how individuals become involved in the informal economy. Among a group of self-employed workers in New York City's East Village neighborhood, I find three routes to the informal sector: constricted opportunities in the formal sector, individual economic motivations, or individual identity motivations. Most current literature focuses on the external pressures (e.g., unemployment) that force workers into the informal economy. However, I find that most workers are drawn to this economic niche as a way to explore a new work identity. Even among those workers who entered the informal economy because of reduced opportunities in the formal sector, most developed a commitment to the informal sector as a long-term career plan. I also discuss the opportunity structure of the East Village's informal sector. I consider barriers to informal sector employment and obstacles to using the informal sector as a conduit of identity change and transformation.
Tissue Plasminogen Activator Inhibits Reactive Oxygen Species Production by Macrophages
Authors: Stringer Kathleen A.
Published: June 2004

Study Objective. To determine whether tissue plasminogen activator (tPA) alters macrophage reactive oxygen species (ROS) production.

Intervention. Cultured macrophages were exposed to either phorbol myristate acetate (PMA) or zymosan (ZMA) after a 1‐hour incubation with either tPA 100 μg/ml or l‐arginine 3.5 mg/ml, an excipient used in the formulation of tPA.

Measurements and Main Results. Production of ROS was measured using chemiluminescence (CL). Tissue plasminogen activator reduced the mean peak CL of macrophages exposed to PMA or ZMA by 20% and 36%, respectively (p=0.0008 and p=0.028, analysis of variance). l‐arginine had no effect on either PMA‐ or ZMA‐induced macrophage CL.

Conclusion. Our results suggest that tPA has broad inhibitory effects on inflammatory cell ROS production. In diseases such as atherosclerosis and acute respiratory distress syndrome, these data suggest the possible utility of exogenous tPA as an antiinflammatory agent and a physiologic role for endogenous tPA that goes beyond maintenance of homeostasis.
Pharmacokinetics of Intravenous Trovafloxacin in Critically Ill Adults
Authors: Olsen Keith M. , Rebuck Jill A. , Weidenbach Tavis , Fish Douglas N.
Published: June 2004

The pharmacokinetic disposition of numerous antimicrobial agents is altered in critically ill patients. Pharmacokinetics of trovafloxacin, a fluoroquinolone indicated specifically for severe, life‐threatening infections in the intensive care unit, have not been well studied in this population. We characterized the pharmacokinetic disposition of trovafloxacin after administration of alatrofloxacin, the intravenous prodrug, in critically ill adults. Seven patients (3 men, 4 women; mean ± SD age 59.4 ± 20.6 yrs; baseline aspartate aminotransferase [AST]/alanine aminotransferase [ALT] 66.0 ± 40.6/51.5 ± 37.5 IU/L; median Acute Physiology and Chronic Health Evaluation [APACHE II] score 27, range 15–32) were studied at estimated steady state. Calculated (mean ± SD) half‐life, clearance at steady state, and volume of distribution in all patients were 10.9 ± 1.8 hours, 161.3 ± 41.1 ml/minute, and 1.4 ± 0.4 L/kg. In patients receiving 300 mg, maximum concentration, minimum concentration, and area under the curve from 0–24 hours were 3.6 ± 0.5 mg/L, 0.6 ± 0.3 mg/L, and 34.2 ± 10.6 mg•hr/L, respectively. These results are consistent with published values in other patient populations, indicating that trovafloxacin pharmacokinetics are not substantially altered in critically ill patients with normal or mildly impaired hepatic function.
Prevalence of Osteoporosis Risk Factors and Treatment Among Women Aged 50 Years and Older
Authors: Kirk Julienne K. , Spangler John G. , Celestino Frank S.
Published: June 2004

We conducted a cross‐sectional, retrospective review to evaluate screening, diagnosis, and treatment of 389 women aged 50 years or older at risk for osteoporosis in a large primary care practice. Records randomly selected from a computerized database were reviewed for drug history, age, height, weight, and osteoporosis‐related diagnoses, symptoms, and risk factors. Among the 389 women, 255 (65.5%) were receiving bone‐preserving treatment (247 estrogen replacement exclusively). Most (70.4%) were white, with an average age of 61 years, and an average of 3.3 risk factors for osteoporosis. Risk factors were postmenopausal status 94%, age 65 years or older 53%, hysterectomy 39%, cigarette smoking 33%, and physical inactivity 30%. By logistic regression, the only positive predictor of antiresorptive therapy was hysterectomy (adjusted odds ratio [AOR] 2.52, 95% confidence interval [CI] 1.54–4.14). Negative predictors were physical inactivity (AOR 0.44, 95% CI 0.25–0.71), rheumatoid arthritis (AOR 0.31, 95% CI 0.12–0.79), and age 65 years and older (AOR 0.54, 95% CI 0.34–0.86). Controlling for age, women with four or more risk factors were 62% less likely to be receiving antiresorptive treatment (AOR 0.38, 95% CI 0.23–0.64) than those with fewer risk factors.
Comparison of the Fluoroquinolones Based on Pharmacokinetic and Pharmacodynamic Parameters
Authors: Pickerill Katherine E. , Paladino Joseph A. , Schentag Jerome J.
Published: June 2004

Assessment of pharmacodynamic activity from standard in vitro minimum inhibitory concentrations (MICs) alone is insufficient to predict in vivo potency. Achievable serum and tissue concentrations as well as pharmacokinetic characteristics must be considered. When pharmacokinetic and pharmacodynamic values are combined, the area under the inhibitory curve (AUIC) and peak concentration: MIC ratio predict clinical cure for fluoroquinolones. Clinical data and animal models indicate that a peak:MIC of 10:1 and above and an AUIC of 125 and above are predictive of a clinical cure for this class of antimicrobials against gram‐negative organisms. The values may be used to compare and contrast fluoroquinolones to determine which would be best for treating a specific microorganism. Pharmacodynamic data also can be used to design regimens that minimize the risk of suboptimal drug levels. Ensuring the optimal fluoroquinolone dosage based on pharmacodynamic principles would diminish the emergence of resistant organisms and prevent treatment failures.
Types of Interventions Made by Clinical Pharmacists in the IMPROVE Study
Authors: Ellis Samuel L. , Billups Sarah J. , Malone Daniel C. , Carter Barry L. , Covey Douglas , Mason Barbara , Jue Sandra , Carmichael Jannet , Guthrie Kelly , Sintek Charles D. , Dombrowski Robert , Geraets Douglas R. , Amato Mary
Published: June 2004

The purpose of this study was to describe and evaluate the activities and interventions provided by ambulatory care clinical pharmacists during the IMPROVE (Impact of Managed Pharmaceutical Care on Resource Utilization and Outcomes in Veterans Affairs Medical Centers) study. A total of 523 patients were randomized into the intervention arm at nine Veterans Affairs medical centers if they were considered to be at high risk for drug‐related problems. Patients randomized to the control group had no interventions and they are not reported. Using a standard form, pharmacists were asked to document the length of visit, method of contact, medical conditions addressed, and drug‐related problems addressed and resolved during each contact. Seventy‐eight ambulatory care clinical pharmacists documented 1855 contacts over 12 months, an average of 3.54 ± 2.31/patient. The length of visits was 15 minutes or more for 73% of contacts. In‐person contacts accounted for 1421 visits (76.6%), with the remainder being telephone contacts. During each contact the average number of drug‐related problems addressed and resolved were 1.64 ± 1.16 and 1.14 ± 0.98, respectively. More drug‐related problems were addressed and resolved when visits were 15 minutes or longer (p= 0.001) and when the contact was in person (p= 0.001). These data may provide information to clinical pharmacists developing pharmacy‐managed clinics for patients at high risk for drug‐related problems. The information may be a benchmark for types of interventions that can be made, as well as the time commitments required to make them.
Cost‐Effectiveness of Sparfloxacin Compared with Other Oral Antimicrobials in Outpatient Treatment of Community‐Acquired Pneumonia
Authors: Najib Mohammad M. , Stein Gary E. , Goss Thomas F.
Published: June 2004

We examined the cost‐effectiveness of sparfloxacin compared with other selected oral antimicrobials in outpatient treatment of community‐acquired pneumonia (CAP) using clinical pathway‐based decision analysis. Cost estimates were obtained from medical claims databases and Medicare reimbursement schedules. Probability estimates were derived from published clinical trials, the medical literature, and clinical expert opinion. Overall adjusted efficacy rates were 89% for sparfloxacin, 79.4% for azithromycin, 77.8% for clarithromycin, 73% for cefaclor, 70.8% for amoxicillin‐clavulanic acid, and 69% for erythromycin. The expected total cost/CAP episode of treatment with sparfloxacin was $216.07 compared with $258.97, $297.08, $345.75, $389.80, and $395.93 for azithromycin, clarithromycin, erythromycin, amoxicillin‐clavulanic acid, and cefaclor, respectively. Therapy with sparfloxacin for managing CAP is cost effective‐relative to other commonly prescribed antibiotics, resulting in net cost savings.
Immediate‐Release Oxybutynin versus Tolterodine in Detrusor Overactivity: A Population Analysis
Authors: Lawrence Margareta , Guay David R. P. , Benson Steven R. , Anderson Michael J.
Published: June 2004

We evaluated adherence to treatment with immediate‐release (IR) oxybutynin (515 patients) and tolterodine (505 patients) for detrusor overactivity through retrospective analysis of a pharmacy claims database. Outcomes included percentage of patients continuing therapy for 6 months, medication possession ratios, and time to discontinuation of therapy. The proportion of patients continuing therapy for 6 months was statistically superior for tolterodine (32%) compared with IR oxybutynin (22%, p<0.001). Medication possession ratios were also superior for patients in the tolterodine group (medians 0.83 and 0.64, ranges 0.11–1.15 and 0.07–1.13, respectively, p<0.001). Oxybutynin was discontinued significantly earlier (mean 45 days) than tolterodine (mean 59 days, p<0.001) and was switched to another therapy more commonly than tolterodine (19% and 14%, respectively). Tolterodine was favored over oxybutynin for several measurements of patient adherence. However, less than one‐third of patients continued therapy with either agent for 6 months. The clinical relevance of these differences is unknown.
Hypertensive Urgency Induced by an Interaction of Mirtazapine and Clonidine
Authors: Abo‐Zena Reem A. , Bobek Mary Beth , Dweik Raed A.
Published: June 2004

Mirtazapine is a new antidepressant with a tetracyclic chemical structure that is not related to selective serotonin reuptake inhibitors, tricyclic antidepressants, or monoamine oxidase inhibitors. The antidepressant effect results from stimulation of the noradrenergic system through antagonism at central a2‐inhibitory receptors. Clonidine exerts its antihypertensive effect by stimulating these receptors to cause a reduction in endogenous release of norepinephrine. Therefore, the two agents have mechanisms of action that potentially oppose one another. We report a case of hypertensive urgency that ensued after a patient stabilized on clonidine began taking mirtazapine.
Psychotic Symptoms and Confusion Associated with Intravenous Ganciclovir in a Heart Transplant Recipient
Authors: Southworth Mary Ross , Dunlap Stephanie H.
Published: June 2004

A 65‐year‐old man underwent orthotopic cardiac transplantation and was prophylactically treated for cytomegalovirus infection with intravenous ganciclovir. He received standard dosages and had normal renal function. After 6 days of therapy he experienced psychotic symptoms with hallucinations, confusion, and disorientation. His altered mental status resolved after the drug had been discontinued for 5 days. Ganciclovir was suspected as a cause of the symptoms. Alternative etiologies of were explored and excluded.
On writing qualitative research
Authors: Alvermann Donna E. , O'Brien David G. , Dillon Deborah R.
Published: June 2004

The authors explore the challenges of conducting and writing up qualitative research studies, and discuss four key issues: problems in distinguishing between levels of theory; holistic and microlevel issues in methodology; crises in representation and legitimation; and differences in the writing and write‐up process.
Asking Different Questions: Critical Analyses and Reading Research
Authors: Edmondson Jacqueline
Published: June 2004

The author describes two research frames—functionalist research and critical analyses—focusing on the different questions they raise. Her purpose is to suggest that reading researchers must extend the tendency to conduct policy‐driven research toward critical and pragmatic questions about reading education, research, and policy. [Note: This article is reprinted in Reading Education Policy. www.reading.orgpublicationsbbvbooksbk568]
Freedom and form: The language and literacy practices of two Mexican schools
Authors: JIMÉNEZ ROBERT T. , SMITH PATRICK H. , MARTÍNEZ‐LEÓN NATALIA
Published: June 2004

ABSTRACTS

This study examined the language and literacy practices in two Mexican schools over a period of approximately six months. Our project was guided by the theoretical notion that these practices reflect both societal influences and some of the ways that a given society itself is shaped. We applied this idea to the linguistic interactions that we recorded in four classrooms, two beginning primary classrooms and two grade 4 classrooms. Classroom observations, teacher and administrator interviews, school‐produced documents, and publicly displayed texts constituted the data corpus. Findings indicated that students were provided with considerable freedom in terms of their spoken language which contrasted greatly with the emphasis on form in the production of written language. Reading constituted a middle ground depending on whether students were directed to read silently or aloud. We concluded that these practices shaped a particular type of literate habitus, one that positioned both teachers and students to accept as natural the idea that, at best, schooling could provide only partial access to the kinds of linguistic capital valued by dominant interests. On the basis of our findings, we recommend a retheorization of these language and literacy practices in terms of how they might be reformulated to challenge the dominance of particular literacies. Retheorizing these practices requires deeper understanding of the types of literate capital available to students in specific locations, and also that asymmetries between these types are not merely questions of knowledge or technical mastery, but also questions of power and access to power.
Closing the gap: Addressing the vocabulary needs of English‐language learners in bilingual and mainstream classrooms
Authors: CARLO MARÍA S. , AUGUST DIANE , MCLAUGHLIN BARRY , SNOW CATHERINE E. , DRESSLER CHERYL , LIPPMAN DAVID N. , LIVELY TERESA J. , WHITE CLAIRE E.
Published: June 2004

ABSTRACTS

Gaps in reading performance between Anglo and Latino children are associated with gaps in vocabulary knowledge. An intervention was designed to enhance fifth graders' academic vocabulary. The meanings of academically useful words were taught together with strategies for using information from context, from morphology, from knowledge about multiple meanings, and from cognates to infer word meaning. Among the principles underlying the intervention were that new words should be encountered in meaningful text, that native Spanish speakers should have access to the text's meaning through Spanish, that words should be encountered in varying contexts, and that word knowledge involves spelling, pronunciation, morphology, and syntax as well as depth of meaning. Fifth graders in the intervention group showed greater growth than the comparison group on knowledge of the words taught, on depth of vocabulary knowledge, on understanding multiple meanings, and on reading comprehension. The intervention effects were as large for the English‐language learners (ELLs) as for the English‐only speakers (EOs), though the ELLs scored lower on all pre‐ and posttest measures. The results show the feasibility of improving comprehension outcomes for students in mixed ELL‐EO classes, by teaching word analysis and vocabulary learning strategies.
Characterization of leukocyte subtypes in chicken inner ear sensory epithelia
Authors: O'Halloran Elizabeth K. , Oesterle Eliazabeth C.
Published: June 2004

Human hearing and balance require intact inner ear sensory hair cells, which transduce mechanical stimuli into electrical signals that are transmitted to the brain. Loss of hair cells after birth in mammals is irreversible, whereas birds are able to regenerate hair cells after insult and demonstrate ongoing hair cell production in the vestibular epithelia. Leukocytes reside in undamaged sensory epithelia of the avian inner ear and increase in number after trauma, prior to the proliferation of hair cell progenitors. It has been hypothesized that leukocyte‐produced growth factors or cytokines may be involved in triggering hair cell regeneration. Little is known about the specific leukocyte subtypes present in avian ear. Immunohistochemistry with a panel of monoclonal antibodies to chicken leukocytes was used to identify leukocyte subtypes in normal posthatch chicken ear sensory epithelia. The responsiveness of the leukocytes to aminoglycoside‐induced damage was also observed. Based on immunocytochemical and morphological criteria, we quantified leukocyte subtypes in normal and drug‐damaged auditory and vestibular sensory epithelia. Data indicate that lymphocytes (B and T cells) do not reside in normal or drug‐damaged ear sensory epithelia at 1–3 days post insult but are present in adjacent nonsensory tissues. The most common leukocytes in inner ear sensory epithelia are ramified cells of the myeloid lineage. Many of these are MHC class II positive, and a small percentage are mature tissue macrophages. An absence of leukocytes in lesioned areas of the auditory sensory epithelium suggests they may not play a critical role in triggering hair cell regeneration. J. Comp. Neurol. 475:340–360, 2004. © 2004 Wiley‐Liss, Inc.