bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between REL amplification, REL function, and clinical and biologic features in diffuse large B-cell lymphomas
Authors: Houldsworth Jane , Olshen Adam B. , Cattoretti Giorgio , Donnelly Gerard B. , Teruya-Feldstein Julie , Qin Jing , Palanisamy Nallasivam , Shen Yingjing , Dyomina Katerina , Petlakh Marina , Pan Qiulu , Zelenetz Andrew D. , Dalla-Favera Riccardo , Chaganti R. S. K. 
Published: November 2003

AbstractAlthough it has been suggested that REL is the critical target gene of 2p12-16 amplification in diffuse large B-cell lymphoma (DLBCL), little experimental evidence supports this notion. In the present study, we sought to evaluate the relationship between REL amplification and REL function in a panel of 46 newly diagnosed DLBCLs and to correlate with DLBCL subgroups as identified by gene expression profiles and clinical features. The results indicate that amplification of the REL locus is not associated with accumulation of the active form of REL, as evaluated by immunofluorescence analysis. Upon subgrouping of the DLBCL cases based on gene expression signatures, REL amplification was detected in all subgroups, while high levels of nuclear-located REL were more frequently detected in activated B-cell–like DLBCL. Correlative analyses of REL copy number and REL nuclear accumulation with clinical parameters did not reveal any significant associations. Together these results indicate that 2p12-16 amplification does not lead to abnormal REL activation, suggesting that REL may not be the functional target of the amplification event. Nonetheless, these data indicate that DLBCLs are heterogeneous with respect to REL and thus nuclear factor–κB (NF-κB) activity.
Microglia, macrophages, perivascular macrophages, and pericytes: a review of function and identification
Authors: Guillemin Gilles J , Brew Bruce J 
Published: November 2003

AbstractThe phenotypic differentiation of systemic macrophages that have infiltrated the central nervous system, pericytes, perivascular macrophages, and the “real” resident microglial cells is a major immunocytochemical and immunohistochemical concern for all users of cultures of brain cells and brain sections. It is not only important in assessing the purity of cell cultures; it is also of fundamental importance in the assessment of the pathogenetic significance of perivascular inflammatory phenomena within the brain. The lack of a single membranous and/or biochemical marker allowing conclusive identification of these cells is still a major problem in neurobiology. This review briefly discusses the functions of these cells and catalogs a large number of membranous and biochemical markers, which can assist in the identification of these cells.
Endogenous GABA Release Inhibits the Firing of Adult Gonadotropin-Releasing Hormone Neurons
Authors: Han Seong-Kyu , Todman Martin G. , Herbison Allan E. 
Published: November 2003

Abstract
The effect of endogenous γ-aminobutyric acid (GABA)A receptor-mediated signaling on the excitability of adult male and female GnRH neurons was examined using gramicidin perforated-patch electrophysiology in GnRH-LacZ and GnRH-GFP (green fluorescent protein) transgenic mouse models. In both lines of mice, approximately 80% of GnRH neurons (n = 42) responded to the selective GABAA receptor antagonist bicuculline (20 μm) with a rapid and reversible membrane depolarization and/or increase in firing rate. Approximately 16% of GnRH neurons gave no response, and two neurons were inhibited by bicuculline. The same depolarizing responses (78%) were obtained from adult gonadectomized GnRH-GFP mice. The depolarizing response to bicuculline persisted in the presence of tetrodotoxin, demonstrating that even action potential-independent GABA release was acting to reduce GnRH neuron membrane potential. These observations show that endogenous GABA signaling through the GABAA receptor exerts a powerful net inhibitory effect upon the excitability of mature GnRH neurons.
Ablation of specific expression domains reveals discrete functions of ectoderm- and endoderm-derived FGF8 during cardiovascular and pharyngeal development
Authors: Macatee Timothy L. , Hammond Benjamin P. , Arenkiel Benjamin R. , Francis Lily , Frank Deborah U. , Moon Anne M. 
Published: November 2003

Fibroblast growth factor 8 (Fgf8) is expressed in many domains of the developing embryo. Globally decreased FGF8 signaling during murine embryogenesis results in a hypomorphic phenotype with a constellation of heart, outflow tract, great vessel and pharyngeal gland defects that phenocopies human deletion 22q11 syndromes, such as DiGeorge. We postulate that these Fgf8 hypomorphic phenotypes result from disruption of local FGF8 signaling from pharyngeal arch epithelia to mesenchymal cells populating and migrating through the third and fourth pharyngeal arches.To test our hypothesis, and to determine whether the pharyngeal ectoderm and endoderm Fgf8 expression domains have discrete functional roles,we performed conditional mutagenesis of Fgf8 using novel Crerecombinase drivers to achieve domain-specific ablation of Fgf8gene function in the pharyngeal arch ectoderm and endoderm.Remarkably, ablating FGF8 protein in the pharyngeal arch ectoderm causes failure of formation of the fourth pharyngeal arch artery that results in aortic arch and subclavian artery anomalies in 95% of mutants; these defects recapitulate the spectrum and frequency of vascular defects reported in Fgf8 hypomorphs. Surprisingly, no cardiac, outflow tract or glandular defects were found in ectodermal-domain mutants, indicating that ectodermally derived FGF8 has essential roles during pharyngeal arch vascular development distinct from those in cardiac, outflow tract and pharyngeal gland morphogenesis. By contrast, ablation of FGF8 in the third and fourth pharyngeal endoderm and ectoderm caused glandular defects and bicuspid aortic valve, which indicates that the FGF8 endodermal domain has discrete roles in pharyngeal and valvar development. These results support our hypotheses that local FGF8 signaling from the pharyngeal epithelia is required for pharyngeal vascular and glandular development, and that the pharyngeal ectodermal and endodermal domains of FGF8 have separate functions.
MYH9 spectrum of autosomal‐dominant giant platelet syndromes: Unexpected association with fibulin‐1 variant‐D inactivation
Authors: Toren Amos , Rozenfeld‐Granot Galit , Heath Karen E. , Amariglio Ninette , Rocca Bianca , Crosson John , Epstein Charles J. , Laghi Ferdinando , Landolfi Raffaele , Carlsson Lena E. , Argraves Scott , Bizzaro Nicola , Moxey‐Mims Marva , Brok‐Simoni Frida , Martignetti John A. , Greinacher Andreas , Rechavi Gideon 
Published: November 2003

AbstractThe autosomal‐dominant giant platelet syndromes (Fechtner, Epstein, and Sebastian platelet syndromes and May‐Hegglin anomaly) represent a group of disorders characterized by variable degrees of macrothrombocytopenia with further combinations of neutrophil inclusion bodies and Alport‐like syndrome manifestations, namely, deafness, renal disease, and eye abnormalities. The disease‐causing gene of these giant platelet syndromes was previously mapped by us to chromosome 22. Following their successful mapping, these syndromes were shown to represent a broad phenotypic spectrum of disorders caused by different mutations in the nonmuscle myosin heavy chain 9 gene (MYH9). In this study, we examined the potential role of another gene, fibulin‐1, encoding an extracellular matrix protein as a disease modifier. Eight unrelated families with autosomal‐dominant giant platelet syndromes were studied for DNA sequence mutations and expression of the four fibulin‐1 splice variants (A–D). A mutation in the splice acceptor site of fibulin‐1 exon 19 was found in affected individuals of the Israeli Fechtner family, whereas no MYH9 mutations were identified. Unexpectedly, fibulin‐1 variant D expression was absent in affected individuals from all eight families and coupled with expression of a putative antisense RNA. Transfection of the putative antisense RNA into H1299 cells abolished variant D expression. Based on the observation that only affected individuals lack variant D expression and demonstrate antisense RNA overexpression, we suggest that these autosomal‐dominant giant platelet syndromes are associated, and may be modified, by aberrant antisense gene regulation of the fibulin‐1 gene. Am. J. Hematol. 74:254–262, 2003. © 2003 Wiley‐Liss, Inc.
CD52 expression in hairy cell leukemia
Authors: Quigley Michael M. , Bethel Kelly J. , Sharpe Robert W. , Saven Alan 
Published: November 2003

AbstractHairy cell leukemia (HCL) is a rare chronic B‐cell lymphoproliferative disorder characterized by splenomegaly, pancytopenia, and circulating atypical lymphocytes with circumferential cytoplasmic projections. Although uncommon, HCL cases refractory to standard therapy occur, and effective alternatives are limited. There is evolving literature supporting monoclonal antibody therapy in the treatment of B‐cell lymphoid malignancies, including anti‐CD52 (Campath‐1H, alemtuzumab). We have examined nine cases of HCL and one case of HCL variant by flow cytometry for CD52 expression. All cases expressed CD52 antigen in 92–100% of the malignant cells. The demonstration of CD52 antigen expression on HCL cells provides the rationale for the use of alemtuzumab in refractory HCL. Am. J. Hematol. 74:227–230, 2003. © 2003 Wiley‐Liss, Inc.
Creation of the Chinese visible human data set
Authors: Zhang Shao‐Xiang , Heng Pheng‐Ann , Liu Zheng‐Jin , Tan Li‐Wen , Qiu Ming‐Guo , Li Qi‐Yu , Liao Rong‐Xia , Li Kai , Cui Gao‐Yu , Guo Yan‐Li , Yang Xiao‐Ping , Liu Guang‐Jiu , Shan Jing‐Lu , Liu Ji‐Jun , Zhang Wei‐Guo , Chen Xian‐Hong , Chen Jin‐Hua , Wang Jian , Chen Wei , Lu Ming , You Jian , Pang Xue‐Li , Xiao Hong , Xie Yong‐Ming 
Published: November 2003

AbstractThe United States Visible Human Project (VHP) created a digital image data set of complete human male (data acquisition finished in November 1994) and female (data acquisition finished in December 1995) cadavers in magnetic resonance imaging (MRI), computed tomography (CT), and anatomical (anatomic serial section) modes. VHP aroused worldwide enthusiasm for Visible Human Research (VHR), and the data set is being used in a variety of research and educational domains. The Visible Korean Human (VKH) male was produced in March 2001. To accelerate worldwide VHR and to promote virtual anatomy as a revolutionary break with conventional anatomy, more visible human data sets representative of different populations of the world are in demand. The Chinese Visible Human (CVH) male (created in October 2002) and female (created in February 2003) project achieved greater integrity of images, easier blood vessel identification, and were free of organic lesion (unlike the other visible human projects). We performed data acquisition, three‐dimensional (3D) reconstruction, and visualization with improved technology to create CVH male and female. CVH is the first volumetric data representing a complete normal adult human male and female of an Asian population. This article presents the history of Chinese Visible Human cadavers and the methods and technology used to produce the data set. Anat Rec (Part B: New Anat) 275B:190–195, 2003. © 2003 Wiley‐Liss, Inc.
Biology, ethics, and public policy: Deliberations at an unstable intersection
Authors: Zwanziger Lee L. 
Published: November 2003

AbstractBiology, ethics, and politics intersect in many public policy issues. The unique features of the meeting point in each case are affected by changes in scientific and technological knowledge, moral analysis in a pluralistic society, and political relations. No one of the three can be ignored without repercussions. This essay, however, concentrates on ethics. The ethical dimension must allow for genuine differences in fundamental moral stance, which always persist alongside scientific developments. Two scientific/medical issues with considerable ethical and political implications are discussed: (1) application of human embryonic stem cell research in regenerative medicine and (2) neuroscientific reductionism in the context of behavioral research and moral responsibility. Public advisory committees and other governmental structures for pursuing public policy should not rely merely on cost‐benefit analysis to form policy, as if it were uniquely objective, but should also recognize the necessity of considering science and ethics together as two separate yet complementary foundations of policy. Minimizing the distinctness of the biological and ethical dimensions will make any conclusions unstable and their later implementation more difficult. Anat Rec (Part B: New Anat) 275B:185–189, 2003. © 2003 Wiley‐Liss, Inc.
Stereoselective metabolism of methadone N‐demethylation by cytochrome P4502B6 and 2C19
Authors: Gerber John G. , Rhodes Robert J. , Gal Joseph 
Published: November 2003

AbstractMethadone is a clinically used opioid agonist that is oxidatively metabolized by cytochrome P450 (CYP) isoforms to a stable metabolite, EDDP. Methadone is a chiral drug administered as the racemic mixture of (R)‐(–)‐ and (S)‐(+)‐methadone, but (R)‐methadone is the active isomer. The cytochrome P450 (CYP) isoform involved in methadone's metabolism is thought to be CYP3A4, but human drug–drug interaction studies are not consistent with this. The ability of the common human drug‐metabolizing CYPs (obtained from baculovirus‐infected insect cell supersomes) to generate 2‐ethylidene‐1,5‐dimethyl‐3,3‐diphenylpyrrilidine (EDDP) from racemic methadone was examined and then determined if the CYP isoforms metabolized methadone stereoselectively. Only CYP2B6, 2C19, and 3A4 generated measurable EDDP from 1 μg/ml of racemic methadone. The hierarchy of EDDP generation was CYP2B6 > CYP2C19 ≥ CYP3A4. At 10 μg/ml of methadone, CYP2C9 and CYP2D6 also generated EDDP, but in at least 10‐fold lower quantities than CYP2B6. Michaelis‐Menten kinetic data demonstrated that CYP2B6 had the highest Vmax (44 ng/min/10pmol) and the lowest Km (12.6 μg/ml) for EDDP formation of all the CYP isoforms. In human liver microsomes with high and low CYP2B6 expression but equivalent CYP3A4 expression, high CYP2B6 expression microsomes generated twice the amount of EDDP from 10 μg/ml of methadone than low CYP2B6 expression microsomes. When stereoselective metabolism of racemic methadone by CYP2B6, 2C19, and 3A4 was examined using an enantiospecific methadone assay, CYP2B6 preferentially metabolized (S)‐methadone, CYP2C19 preferentially metabolized (R)‐methadone, and CYP3A4 showed no preference. These data suggest that multiple CYPs metabolized methadone but CYP2B6 had the highest Vmax/Km. In addition, only CYP2B6 and 2C19 showed stereoselective metabolism. Our data could explain why the plasma concentration ratio of R/S methadone is variable and why drugs that induce CYP2B6 such as nevirapine and efavirenz also induce methadone metabolism, while the CYP3A4 inducer rifabutin has no effect on methadone pharmacokinetics. Chirality 16:36–44, 2004. © 2003 Wiley‐Liss, Inc.
The role of environmental stochasticity in a toxic phytoplankton–non‐toxic phytoplankton–zooplankton system
Authors: Sarkar R. R. , Chattopadhayay J. 
Published: November 2003

AbstractThe effects of toxin producing plankton and environmental stochasticity are intriguing problems in marine plankton ecology. To observe the effect of stochastic fluctuation, a non‐toxic phytoplankton, toxic phytoplankton and zooplankton (NTP‐TPP‐Z) system with an assumption that the grazing pressure of zooplankton decreases due to toxic phytoplankton is proposed and analysed. The nature of the dynamics of the system is observed for both the deterministic model and the model with stochastic perturbation around the positive equilibrium. Exchange of stability is also observed for both the cases. To validate the analytical results, numerical experiments and field collected sample observations are also presented. We conclude that the deterministic extinction may be controlled by monitoring the intensity of white noise or artificial eutrophication. Copyright © 2003 John Wiley & Sons, Ltd.
Nucleophosmin/B23 is a proliferate shuttle protein associated with nuclear matrix
Authors: Yun Jing‐Ping , Chew Eng Ching , Liew Choong‐Tsek , Chan John Y.H. , Jin Mei‐Lin , Ding Ming‐Xiao , Fai Yam Hin , Li H.K. Richard , Liang Xiao‐Man , Wu Qiu‐Liang 
Published: November 2003

AbstractIt has become obvious that a better understanding and potential elucidation of the nucleolar phosphoprotein B23 involving in functional interrelationship between nuclear organization and gene expression. In present study, protein B23 expression were investigated in the regenerative hepatocytes at different periods (at days 0, 1, 2, 3, 4, 7) during liver regeneration after partial hepatectomy on the rats with immunohistochemistry and Western blot analysis. Another experiment was done with immunolabeling methods and two‐dimensional (2‐D) gel electrophoresis for identification of B23 in the regenerating hepatocytes and HepG2 cells (hepatoblastoma cell line) after sequential extraction with detergents, nuclease, and salt. The results showed that its expression in the hepatocytes had a locative move and quantitative change during the process of liver regeneration post‐operation. Its immunochemical localization in the hepatocytes during the process showed that it moved from nucleoli of the hepatocytes in the stationary stage to nucleoplasm, cytoplasm, mitotic spindles, and mitotic chromosomes of the hepatocytes in the regenerating livers. It was quantitatively increased progressively to peak level at day 3 post‐operation and declined gradually to normal level at day 7. It was detected in nuclear matrix protein (NMP) composition extracted from the regenerating hepatocytes and HepG2 cells and identified with isoelectric point (pI) value of 5.1 and molecular weight of 40 kDa. These results indicated that B23 was a proliferate shuttle protein involving in cell cycle and cell proliferation associated with nuclear matrix. © 2003 Wiley‐Liss, Inc.
Involvement of growth factors in thymic involution
Authors: García‐Suárez Olivia , Pérez‐Pérez Marta , Germanà Antonino , Esteban Isabel , Germanà Giovanni 
Published: November 2003

AbstractThe thymus undergoes an age‐dependent degenerative process which is mainly characterized by a progressive loss of lymphoid tissue. Thymic involution is particularly important in relation to immunosenescence and its various associated diseases; this fact has prompted many studies aimed at understanding the causes and mechanisms of thymic degeneration which may, ultimately, lead to the possibility of manipulating it. In this sense, one of the aspects which has deserved most attention is the thymic microenvironment, and more precisely, the many growth factors to which the cells present in the organ are exposed. Thus, the levels of several of such factors have been reported to undergo age‐dependent changes in the thymus, which may point at an influence on the regression of the organ. In this article we consider which growth factors and growth factor receptors occur in the vertebrate thymus. Then, focusing on those whose influences are better documented, i.e., neurotrophins, cytokines and IGFs, we discuss their potential role in the organ and the possibility of their being involved in thymic involution. Microsc. Res. Tech. 62:514–523, 2003. © 2003 Wiley‐Liss, Inc.
Aggregate content influences the Th1/Th2 immune response to influenza vaccine: Evidence from a mouse model
Authors: Babiuk Shawn , Skowronski Danuta M. , De Serres Gaston , HayGlass Kent , Brunham Robert C. , Babiuk Lorne 
Published: November 2003

AbstractDuring the 2000–2001 season, a newly identified oculo‐respiratory syndrome (ORS) was detected across Canada as an adverse effect to one influenza vaccine. The implicated vaccine contained a higher than expected proportion of unsplit and aggregated influenza virions. Clinical and epidemiologic features of ORS were suggestive of type 2‐like influences on the immune response. We hypothesized that the implicated vaccine from the 2000–2001 season would induce greater Th2‐like polarization relative to the non‐implicated vaccine from the same season. Three groups consisting of eight mice each were either immunized with implicated vaccine, immunized with non‐implicated vaccine or not immunized. Antigen‐specific cellular responses were characterized based on the balance of Th2 (IL‐4, IL‐5) and Th1 (IFN‐γ) cytokines in vitro. We confirm that vaccine aggregates deviate the immune response to a greater Th2 cytokine pattern with potential implications for vaccine screening, safety, and efficacy. J. Med. Virol. 72:138–142, 2004. © 2004 Wiley‐Liss, Inc.
An application of fractional integration to a long temperature series
Authors: Gil‐Alana L. A. 
Published: November 2003

AbstractSome recently proposed techniques of fractional integration are applied to a long UK temperature series. The tests are valid under general forms of serial correlation and do not require estimation of the fractional differencing parameter. The results show that central England temperatures have increased about 0.23 °C per 100 years in recent history. Attempting to summarize the conclusions for each of the months, we are left with the impression that the highest increase has occurred during the months from October to March. Copyright © 2003 Royal Meteorological Society
The derived demand for faculty research
Authors: Becker Elizabeth , Lindsay Cotton M. , Grizzle Gary 
Published: November 2003

AbstractEstimation of the demands for many services supplied by government and charitable organizations are hampered by two practices common to the supply of these services. The suppliers often employ non‐price rationing of these services, and they price discriminate. The supply of college training, for example, is rationed on the basis of academic ability as well as willingness to pay, and more able students are typically quoted lower net prices (associated with scholarships) than less able students. This paper suggests a method for dealing with both practices in the analysis of cross‐sectional data. This methodology is used to investigate the question of why university faculty members are expected to do research as well as teach. One answer supported by our empirical work is that the customers (e.g., the students) demand it. Thus, controlling for price and non‐academic features, better students will choose to attend a university where more scholarly research is performed. Moreover, our empirical findings also support a strong negative link between faculty time devoted to teaching and the supply of research. Copyright © 2003 John Wiley & Sons, Ltd.