bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrastructure of bone healing in defects grafted with a copolymer of polylactic/polyglycolic acids
Authors: Imbronito Ana Vitoria , Scarano Antonio , Orsini Giovanna , Piattelli Adriano , Arana‐Chavez Victor E. 
Published: June 2005

AbstractBone substitutes have been used for the treatment of bone defects. The objective of this study was to ultrastructurally evaluate the healing pattern of bone defects filled with a copolymer of polylactic/polyglycolic acid (Fisiograft®) at a time point in which it is expected to be only partially degraded, with the purpose to ultrastructurally analyze how the bone is forming around the grafting material. Three 5‐mm‐diameter bone defects were created in each tibia from 5 rabbits (average weight 2.5 kg) in which the material was randomly implanted. Animals were sacrificed 30 days after surgery and the 30 bone defects were fixed in 2% glutaraldehyde‐2.5% formaldehyde, under microwave irradiation, decalcified in EDTA, embedded in Spurr resin, and examined in a Jeol 1010 TEM. All the bone defects were filled with connective tissue, interspersed with different amounts of the filling material and newly formed bone trabeculae. In areas where the degrading copolymer was present in small amounts, newly formed bone matrix was detected; it was deposited by osteoblast‐like cells in close relation to the copolymer. In areas where the degrading copolymer formed accumulates, an amorphous multilayered material was identified between the connective tissue and the copolymer. In summary, the copolymer of PLA/PGA studied appears to be an osteoconductive material when it is used to fill bone defects. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
Growing up everyone's trusted confidante: Why I really became a psychotherapist
Authors: Kaslow Florence W. 
Published: June 2005

AbstractThis article traces the roots and evolution of my pathway to becoming a psychotherapist and my still evolving professional interests and horizons. It discusses the journey taken, influences felt, and experiences encountered that have contributed to my expanding perspective and modus operandi. It travels from past to present, articulates my current thinking, and describes some of my major involvements in the early 21st century. The words “que sera, sera” (what will be, will be) are also prophetic of the future. © 2005 Wiley Periodicals, Inc. J Clin Psychol/In Session 61: 965–972, 2005.
Becoming and being a psychotherapist: A psychodynamic memoir and meditation
Authors: Orlinsky David E. 
Published: June 2005

AbstractThe author reflects on the circumstances of his becoming a psychotherapist and meditates on their meaning. He notes the effect on his survival through childhood of his grandparents' emigration from Europe and the influence of his close‐knit family on his personal needs and values. He then reflects on his early vocational interests; the transformational power of his education, as a student and faculty, at the University of Chicago; and the constructive force of his professional collaboration and personal friendship with Kenneth Howard. Finally, he considers why it is important to him not only to have become but to continue to be a psychotherapist. © 2005 Wiley Periodicals, Inc. J Clin Psychol/In Session 61: 999–1007, 2005.
Choosing psychotherapy as a career: Why did we cross that road?
Authors: Farber Barry A. , Manevich Inessa , Metzger Jesse , Saypol Erica 
Published: June 2005

AbstractThis article addresses the question “Why do people become psychotherapists?” via two approaches. The first involves an examination of the empirical and clinical literature on motivations and influences common to most psychotherapists. The second approach explores multiple pathways to becoming a psychotherapist by considering distinct gender‐linked career trajectories. We identify 12 oft‐noted themes in the literature on therapists' career paths (e.g., cultural marginalization, a psychologically minded way of understanding self and others) and link these to the narratives of the eight authors in this issue. Finally, we discuss ways in which understanding career motivations may be useful for therapists in their practice. © 2005 Wiley Periodicals, Inc. J Clin Psychol/In Session 61: 1009–1031, 2005.
Choosing psychotherapy as a career: Beyond “I want to help people”
Authors: Norcross John C. , Farber Barry A. 
Published: June 2005

AbstractThis article briefly considers the career determinants of mental health professionals and then introduces the contents of the Journal of Clinical Psychology: In Session issue devoted to “why I became a psychotherapist.” Psychotherapists are assuredly a special sort because the average person prefers to minimize the psychic sufferings of fellow humans and to avoid extensive contact with troubled individuals. Although the most frequent and conscious reason for becoming a psychotherapist is a desire to “help others,” the decision is more complex and multidetermined than that. The multiple, intertwined motives are partly unconscious, impacted by chance encounters, and probably not well understood into late in one's career. © 2005 Wiley Periodicals, Inc. J Clin Psychol/In Session 61: 939–943, 2005.
A database of recombinant viruses and recombinant viral vectors available from the RIKEN DNA bank
Authors: Ugai Hideyo , Murata Takehide , Nagamura Yoshinori , Ugawa Yoshihiro , Suzuki Erika , Nakata Hatsumi , Kujime Yukari , Inamoto Sanae , Hirose Megumi , Inabe Kumiko , Terashima Miho , Yamasaki Takahito , Liu Bingbing , Nakade Koji , Pan Jianzhi , Kimura Makoto , Saito Izumu , Hamada Hirofumi , Obata Yuichi , Yokoyama Kazunari K. 
Published: June 2005

AbstractBackgroundViral vectors are required as gene‐delivery systems for gene therapy and basic research. Recombinant adenoviruses (rAds) expressing genes of interest are being developed as research tools and many studies in vitro and in vivo have already been performed with such rAds.MethodsShuttle vectors for rAds were constructed with full‐length cDNAs and rAds were generated in HEK293 cells by the COS‐TPC method. The rAds and shuttle vectors were developed by the Japanese research community and deposited in the RIKEN DNA Bank (RDB; http://www.brc.riken.jp/lab/dna/en/) for distribution to the scientific community. The Recombinant Virus Database (RVD; http://www.brc.riken.jp/lab/dna/rvd/) was established at the RIKEN BioResource Center (BRC) in Japan as the source of information about and distribution of the various resources.ResultsThe RIKEN BRC is releasing more than 300 recombinant viruses (RVs) and 500 shuttle vectors, as well as all related information, which is included in a newly established database, the RVD. The RVD consists of (i) information about the RVs, the inserted cDNAs and the shuttle vectors; (ii) data about sequence‐tagged sites (STSs) that are markers of viral DNAs; and (iii) experimental protocols for the use of RVs.ConclusionsThe new database and available resources should be very useful to scientists who are studying human gene therapy and performing related basic research. It is a web‐interfaced flat‐file database that can be accessed through the internet. Moreover, all of the resources deposited in the RDB, which is a public facility in Japan, are available to researchers around the world. Copyright © 2005 John Wiley & Sons, Ltd.
Disjoint directed quadrilaterals in a directed graph
Authors: Zhang Danhong , Wang Hong 
Published: June 2005

AbstractLet D be a directed graph of order 4k, where k is a positive integer. Suppose that the minimum degree of D is at least 6k − 2. We show that D contains k disjoint directed quadrilaterals with only one exception. © 2005 Wiley Periodicals, Inc. J Graph Theory
Microarrays and expression profiling in microglia research and in inflammatory brain disorders
Authors: Gebicke‐Haerter Peter J. 
Published: June 2005

AbstractExpression profiling by using microarrays is a powerful tool for investigating transcriptional changes in a variety of diseases. In this survey, microarray data selected from the literature from in vivo and in vitro studies are scrutinized to find differentially expressed genes in common within specific inflammatory conditions in brain or microglial cell cultures, if there are at least two independent investigations available. Viral encephalitis, multiple sclerosis, epileptic seizures, ischemic lesions, and traumatic brain injury are the disorders covered. Moreover, by taking into account expression data obtained from cultured microglia, two examples are presented of how one can deal (or should not deal) with lists of candidate genes showing up in these kinds of studies without sophisticated software programs. Finally, some general remarks are made about pivotal issues when beginning to use microarray technology. © 2005 Wiley‐Liss, Inc.
Visualization of microglia in living tissues using Iba1‐EGFP transgenic mice
Authors: Hirasawa T. , Ohsawa K. , Imai Y. , Ondo Y. , Akazawa C. , Uchino S. , Kohsaka S. 
Published: June 2005

AbstractMicroglia are thought to play important roles not only in repairing injured tissue but in regulating neuronal activity, and visualizing the cells is very useful as a means of further investigating the function of microglia in vivo. We previously cloned the ionized calcium‐binding adaptor molecule 1 (Iba1) gene, which is expressed selectively in microglia/microphages. To generate new transgenic mice to visualize microglia with enhanced green fluorescent protein (EGFP), we here constructed a plasmid carrying EGFP cDNA under control of the Iba1 promoter. This construct was injected into C57B/6 mouse zygotes, and the Iba1‐EGFP transgenic line was developed. Fluorescent in‐situ hybridization analysis revealed that the Iba1‐EGFP transgene was located on chromosome 11D. No obvious defects were observed during development or in adulthood, and the EGFP fluorescence remained invariant over the course of at least four generations. Judging from the immunoreactivity with anti‐Iba1 antibody, all EGFP‐positive cells in the adult brain were ramified microglia. In the developing transgenic embryos, EGFP signals were detected as early as embryonic Day 10.5. The most prominent EGFP signals were found in forebrain, spinal cord, eye, foreleg, yolk sac, liver, and vessel walls. At postnatal Day 6, clear EGFP signals were observed in the supraventricular corpus callosum, known as “fountain of microglia,” where ameboid microglia migrate into the brain parenchyma and mature into ramified microglia. Iba1‐EGFP transgenic mice thus permit observation of living microglia under a fluorescence microscope and provide a useful tool for studying the function of microglia in vivo. © 2005 Wiley‐Liss, Inc.
Norepinephrine protects cortical neurons against microglial‐induced cell death
Authors: Madrigal Jose L.M. , Feinstein Douglas L. , Russo Cinzia Dello 
Published: June 2005

AbstractInterleukin‐1 beta (IL‐1β) is one of the main cytokines involved in the inflammatory response; it has multiple effects that can contribute to cell damage, one of which is the upregulation of the inducible form of nitric oxide (NO) synthase (NOS2) in certain cell types. We demonstrated previously that in vivo, cortical microglial inflammatory responses were increased when noradrenaline (NE) levels were depleted, suggesting that NE can reduce microglial activation. In the present report, we examined the role of IL‐1β in neurotoxicity induced by microglial‐conditioned media, and possible neuroprotective effects of NE. Incubation of cortical neurons with conditioned media (CM) obtained from lipopolysaccharide (LPS)‐treated microglia induced neuronal NOS2 expression and increased neuronal cell death, and these responses were reduced if the neurons were coincubated with interleukin‐1 receptor antagonist. Cotreatment of microglial cells with LPS plus NE potently blocked IL‐1β production and reduced the ability of the CM to induce neuronal NOS2 and cell death. These results suggest that microglial release of IL‐1β is an important activator of neuronal inflammatory responses, and that protective effects of NE upon neurons involve a reduction of microglial‐derived IL‐1β. © 2005 Wiley‐Liss, Inc.
Microglia and multiple sclerosis
Authors: Jack Carolyn , Ruffini Francesca , Bar‐Or Amit , Antel Jack P. 
Published: June 2005

AbstractMicroglia participate in all phases of the multiple sclerosis (MS) disease process. As members of the innate immune system, these cells have evolved to respond to stranger/danger signals; such a response within the central nervous system (CNS) environment has the potential to induce an acute inflammatory response. Engagement of Toll‐like receptors (TLRs), a major family of pattern‐recognition receptors (PRRs), provides an important mechanism whereby microglia can interact with both exogenous and endogenous ligands within the CNS. Such interactions modulate the capacity of microglia to present antigens to cells of the adaptive immune system and thus contribute to the initiation and propagation of the more sophisticated antigen‐directed responses. This inflammatory response introduces the potential for bidirectional feedback between CNS resident and infiltrating systemic cells. Such interactions acquire particular relevance in the era of therapeutics for MS because the infiltrating cells can be subjected to systemic immunomodulatory therapies known to change their functional properties. Phagocytosis by microglia/macrophages is a hallmark of the MS lesion; however, the extent of tissue damage and the type of cell death will dictate subsequent innate responses. Microglia/macrophages are armed with a battery of effector molecules, such as reactive nitrogen species, that may contribute to CNS tissue injury, specifically to the injury of oligodendrocytes that is associated with MS. A therapeutic challenge is to modulate the dynamic properties of microglia/macrophages so as to limit potentially damaging innate responses, to protect the CNS from injury, and to promote local recovery. © 2005 Wiley‐Liss, Inc.
Neuroprotective role of microglia expressing interleukin‐4
Authors: Park K.W. , Lee D.Y. , Joe E.H. , Kim S.U. , Jin B.K. 
Published: June 2005

AbstractLittle is known about the underlying mechanisms responsible for the death of activated microglia and the functional consequences of the death of these cells, especially in vivo. We show here that intracortical injection of lipopolysaccharide (LPS) led to upregulation of interleukin‐4 (IL‐4) immunoreactivity, followed by a substantial loss of microglia 3 days later, as visualized by complement receptor type 3 (OX‐42) immunostaining and tomato lectin staining. Cells positive for caspase‐3 and terminal deoxynucleotidyl transferase mediated fluorescein‐dUTP nick‐end labeling (TUNEL) were also localized within LPS‐activated microglia. IL‐4 immunoreactivity was detected as early as 12 hr post‐LPS, disappearing at 72 hr. Surprisingly, IL‐4 immunoreactivity was detected exclusively in microglia, but not in astrocytes or neurons. In addition, IL‐4‐neutralizing antibodies markedly increased the survival of activated microglia at 3 days post‐LPS. The expression of inducible nitric oxide synthase (iNOS) and tumor‐necrosis factor (TNF)‐α was sustained in parallel in activated microglia, consequently increasing neuronal cell death. To our knowledge, this study is the first to show the endogenous expression of IL‐4 in LPS‐activated microglia in vivo. Our findings suggest that IL‐4 may regulate brain inflammation by inducing the death of activated microglia in vivo and increasing neuronal survival. © 2005 Wiley‐Liss, Inc.
Perturbations in calcium‐mediated signal transduction in microglia from Alzheimer's disease patients
Authors: McLarnon James G. , Choi Hyun B. , Lue Lih‐Fen , Walker Douglas G. , Kim Seung U. 
Published: June 2005

AbstractCalcium‐sensitive fluorescence microscopy has been used to study Ca2+‐dependent signal transduction pathways in microglia obtained from Alzheimer's disease (AD) patients and non‐demented (ND) individuals. Data were obtained from nine AD cases and seven ND individuals and included basal levels of intracellular Ca2+ [Ca2+]i, peak amplitudes (Δ[Ca2+]i) and time courses of adenosine triphosphate (ATP) responses and amplitudes of an initial transient response and a subsequent second component of Ca2+ influx through store‐operated channels (SOC) induced by platelet‐activating factor (PAF). Overall, AD microglia were characterized by significantly higher (20%) basal Ca2+ [Ca2+]i relative to ND cells. The Δ[Ca2+]i of ATP and initial phase of PAF responses, which reflect rapid depletion of Ca2+ from endoplasmic reticulum stores, were reduced by respective values of 63% and 59% in AD cells relative to amplitudes recorded from ND microglia. Additionally, AD microglia showed diminished amplitudes (reduction of 61%) of SOC‐mediated Ca2+ entry induced by PAF and prolonged time courses (increase of 60%) of ATP responses with respect to ND microglia. We have generally replicated these results with exposure of human fetal microglia to beta amyloid (5 μM Aβ1–42 applied for 24 hr). Overall, these data indicate significant abnormalities are present in Ca2+‐mediated signal transduction in microglia isolated from AD patients. © 2005 Wiley‐Liss, Inc.
Modulation of glioma BK channels via erbB2
Authors: Olsen M.L. , Weaver A.K. , Ritch P.S. , Sontheimer H. 
Published: June 2005

AbstractGlioma cells show up‐regulation and constitutive activation of erbB2, and its expression correlates positively with increased malignancy. A similar correlation has been demonstrated for the expression of gBK, a calcium‐sensitive, large‐conductance K+ channel. We show here that glioma BK channels are a downstream target of erbB2/neuregulin signaling. Tyrphostin AG825 was able to disrupt the constituitive erbB2 activation in a dose‐dependent manner, causing a 30‐mV positive shift in gBK channel activation in cell‐attached patches. Conversely, maximal stimulation of erbB2 with a recombinant neuregulin (NRG‐1β) caused a 12‐mV shift in the opposite direction. RT‐PCR studies reveal no change in the BK splice variants expressed in treated glioma cells. Furthermore, isolation of surface proteins through biotinylation did not show a change in gBK channel expression, and probing with phospho‐specific antibodies showed no alteration in channel phosphorylation. However, fura‐II Ca2+ fluorescence imaging revealed a 35% decrease in the free intracellular Ca2+ concentration after erbB2 inhibition and an increase in NRG‐1β‐treated cells, suggesting that the observed changes most likely were due to alterations in [Ca2+]i. Consistent with this conclusion, neither tyrphostin AG825 nor NRG‐1β was able to modulate gBK channels under inside‐out or whole‐cell recording conditions when intracellular Ca2+ was fixed. Thus, gBK channels are a downstream target for the abundantly expressed neuregulin‐1 receptor erbB2 in glioma cells. However, unlike the case in other systems, this modulation appears to occur via changes in [Ca2+]i without changes in channel expression or phosphorylation. The enhanced sensitivity of gBK channels in glioma cells to small, physiological Ca2+ changes appears to be a prerequisite for this modulation. © 2005 Wiley‐Liss, Inc.
Human Gas7 isoforms homologous to mouse transcripts differentially induce neurite outgrowth
Authors: Chao Chuck C.‐K. , Chang P.‐Y. , Lu Henry H.‐P. 
Published: June 2005

AbstractGas7, a growth‐arrest‐specific protein, is expressed preferentially in the brain and is required for neurite outgrowth in cultured cerebellar and peripheral murine neurons. Gas7 interacts with F‐actin and colocalizes with the terminal part of actin microfilament in cells in which membrane outgrowth is present. Gas7 isoforms were discovered in murine brain by alternative splicing. This work reports the identification of two human Gas7 cDNA: hGas7‐a with 2,427 nucleotides, which encodes 330 amino acids, and hGas7‐b with 2,610 nucleotides, which encodes 412 amino acids according to predicted open‐reading‐frames. The predicted hGas7‐b protein is 97% homologous to murine homologues, whereas the hGas7‐a is homologous to the mouse Gas7‐cb form that is expressed preferentially in cerebellum. Alignment analysis of the Gas7 protein sequences revealed a high homology to that in humans: 99% for the monkey, 97% in murine, and around 75% for the puffer fish and chicken. The hGas7‐b protein comprises a WW domain, which often associates with other domains that are typically present in proteins in signal transduction processes, and an FCH domain, which participates in rearranging the cytoskeleton. The hGas7‐a comprises only the FCH domain. Analysis of the human Gas7 sequences using the DNA database revealed that the two forms resulted from the canonical alternative splicing of a Gas7 genomic sequence. The abundance of both hGas7 mRNA levels, determined by quantitative PCR in tissues including brain, breast cancer, placenta, and head‐neck cancer, revealed that the level of hGas7‐a was 14 times that of hGas7‐b in these tissues. Transfection of cells with hGas7‐a or hGas7‐b cDNA yielded the predicted 38‐kDa or 50‐kDa protein, respectively. The ectopic expression of hGas7 caused neurite‐like cell processes in both mouse Neuro‐2a and human SH‐SY5Y neuroblastoma cells. Interestingly, the hGas7‐a preferentially elicited the small lamellipodia, whereas the hGas7‐b elicited the small filopodia phenotype. These findings reveal the evolutionary conservation of the structure and function of Gas7. They also suggest that the FCH domain in Gas7 may participate in the development of lamellipodia, and the WW domain may participate in the fine‐tuning of the filopodia. © 2005 Wiley‐Liss, Inc.
Manganese transport by rat brain endothelial (RBE4) cell‐based transwell model in the presence of astrocyte conditioned media
Authors: Fitsanakis Vanessa A. , Piccola Greg , Aschner Judy L. , Aschner Michael 
Published: June 2005

AbstractManganese (Mn), an essential nutrient, is neurotoxic at high levels and has been associated with the development of a parkinsonian syndrome termedmanganism. Currently, the mechanisms responsible for transporting Mn across the blood–brain barrier (BBB) are unknown. By using rat brain endothelial 4 (RBE4) cell monolayers cultured in astrocyte‐conditioned media (ACM), we examine the effects of temperature, energy, proton (pH), iron (Fe), and sodium (Na+) dependence on Mn transport. Our results suggest that Mn transport is temperature, energy, and pH dependent, but not Fe or Na+dependent. These data suggest that Mn transport across the BBB is an active process, but they also demonstrate that the presence of ACM in endothelial cell cultures decreases the permeability of these cells to Mn, reinforcing the use of ACM or astrocyte cocultures in studies examining metal transport across the BBB. © 2005 Wiley‐Liss, Inc.