bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell proliferation in the forebrain and midbrain of the sea lamprey
Authors: Villar‐Cheda Begoña , Pérez‐Costas Emma , Meléndez‐Ferro Miguel , Abalo Xesús Manoel , Rodríguez‐Muñoz Rolando , Anadón Ramón , Rodicio María Celina 
Published: December 2005

AbstractCell proliferation in the forebrain and midbrain of the sea lamprey (Petromyzon marinus L.) was investigated by proliferation cell nuclear antigen (PCNA) immunocytochemistry, with BrdU labeling as a complementary technique. Correspondence between proliferation regions and areas of early neuronal differentiation was also assessed using antibodies against HNK‐1 early differentiation marker. The brain of late embryos shows a homogeneously thick ventricular zone (VZ) containing PCNA‐immunoreactive (PCNA‐ir) nuclei. In early prolarvae, several discontinuities formed by PCNA‐negative cells, and differences among regions in VZ thickness, become apparent. In late prolarvae and early larvae, these differences in VZ thickness and appearance, as well as the presence of PCNA‐negative discontinuities, allowed us to correlate proliferation domains and neuroanatomical regions. In larvae, the number of PCNA‐ir cells in the VZs diminish gradually, although a few PCNA‐ir cells are present in the ependyma of most regions. In late larvae, proliferation becomes confined to a few ventricular areas (medial pallium, caudal habenula, ventral preoptic recess near the optic nerve, and tuberal portion of the posterior hypothalamic recess). During metamorphosis there appears to be no proliferation, but in upstream adults a few PCNA‐ir cells are observed in the most caudal habenula. The characteristics of the proliferative regions revealed in lamprey with PCNA immunocytochemistry show notable differences from those observed in other vertebrates, and these differences may be related to the peculiar life cycle of lampreys. J. Comp. Neurol. 494:986–1006, 2006. © 2005 Wiley‐Liss, Inc.
Cholinergic axons in the rat ventral tegmental area synapse preferentially onto mesoaccumbens dopamine neurons
Authors: Omelchenko Natalia , Sesack Susan R. 
Published: December 2005

AbstractCholinergic afferents to the ventral tegmental area (VTA) contribute substantially to the regulation of motivated behaviors and the rewarding properties of nicotine. These actions are believed to involve connections with dopamine (DA) neurons projecting to the nucleus accumbens (NAc). However, this direct synaptic link has never been investigated, nor is it known whether cholinergic inputs innervate other populations of DA and γ‐aminobutyric acid (GABA) neurons, including those projecting to the prefrontal cortex (PFC). We addressed these questions by using electron microscopic analysis of retrograde tract‐tracing and immunocytochemistry for the vesicular acetylcholine transporter (VAChT) and for tyrosine hydroxylase (TH) and GABA. In tissue labeled for TH, VAChT+terminals frequently synapsed onto DA mesoaccumbens neurons but only seldom contacted DA mesoprefrontal cells. In tissue labeled for GABA, one‐third of VAChT+terminals innervated GABA‐labeled dendrites, including both mesoaccumbens and mesoprefrontal populations. VAChT+synapses onto DA and mesoaccumbens neurons were more commonly of the asymmetric (presumed excitatory) morphological type, whereas VAChT+synapses onto GABA cells were more frequently symmetric (presumed inhibitory or modulatory). These findings suggest that cholinergic inputs to the VTA mediate complex synaptic actions, with a major portion of this effect likely to involve an excitatory influence on DA mesoaccumbens neurons. As such, the results suggest that natural and drug rewards operating through cholinergic afferents to the VTA have a direct synaptic link to the mesoaccumbens DA neurons that modulate approach behaviors. J. Comp. Neurol. 494:863–875, 2006. © 2005 Wiley‐Liss, Inc.
Connections of the lateral and medial divisions of the goldfish telencephalic pallium
Authors: Northcutt R. Glenn 
Published: December 2005

AbstractBiotinylated dextran amine and fluorescent carbocyanine dye (DiI) were used to examine connections of the lateral (Dl) and medial (Dm) divisions of the goldfish pallium. Besides numerous intrinsic telencephalic connections to Dl and Dm, major ascending projections to these pallial divisions arise in the preglomerular complex of the posterior tuberculum, rather than in the dorsal thalamus. The rostral subnucleus of the lateral preglomerular nucleus receives auditory input via the medial pretoral nucleus, lateral line input via the ventrolateral toral nucleus, and visual input via the optic tectum, and it projects to both Dl and Dm. The anterior preglomerular nucleus and caudal subnucleus of the lateral preglomerular nucleus receive auditory input via the central toral nucleus and project to Dm. This pallial division also receives chemosensory information via the medial preglomerular nucleus. The central posterior (CP) nucleus, which receives both auditory and visual inputs, also projects to Dm and is the only dorsal thalamic nucleus projecting to the pallium. Thus, both Dl and Dm clearly receive multisensory inputs. Major projections of CP and projections of all other dorsal thalamic nuclei are to the subpallium, however. Descending projections of Dl are primarily to the preoptic area and the caudal hypothalamus, whereas descending projections of Dm are more extensive and particularly heavy to the anterior tuber and nucleus diffusus of the hypothalamus. The topography and connections of Dl are remarkably similar to those of the hippocampus of tetrapods, whereas the topography and connections of Dm are similar to those of the amygdala. J. Comp. Neurol. 494:903–943, 2006. © 2005 Wiley‐Liss, Inc.
Developmental pattern of NADPH‐diaphorase positive neurons in chick optic tectum is sensitive to changes in visual stimulation
Authors: Scicolone Gabriel , Ortalli Ana Laura , Alvarez Gabriela , López‐Costa Juan José , Rapacioli Melina , Ferrán José Luis , Sanchez Viviana , Flores Vladimir 
Published: December 2005

AbstractThe chick retinotectal system is a suitable model to investigate the mechanisms involved in the establishment of synaptic connections in whose refinement nitric oxide was implicated. The purpose of this work was to describe the developmental pattern of the nitric oxide synthase (NOS)‐positive neurons as well as to determine if it is sensitive to changes in visual stimulation. The NADPH‐diaphorase histochemical method was used to describe and quantify NOS neurons in normally stimulated and subnormally stimulated chickens. Nine types of NOS neurons were identified; seven of them express NOS until adulthood, while two of them show only a transient expression. The developmental pattern of NOS neurons follows the process of laminar segregation. It can be divided into three phases. The first includes the onset of NOS expression in periventricular neurons and the formation of a deep network of NOS fibers during early development. These neurons do not show any significant change in subnormally stimulated animals. The second phase includes the appearance of two transient NOS populations of bipolar neurons that occupy the intermediate layers during the optic fibers ingrowth. One of them significantly changes in subnormally stimulated chicks. The third phase occurs when the transitory expression of bipolar neurons decreases. It includes NOS expression in six neuronal populations that innervate the superficial retinorecipient layers. Most of these cells suffer plastic changes in subnormally stimulated chicks. The diversity of neuronal types with regard to their morphology, location, and sensitivity to visual stimulation strongly suggests that they serve different functions. J. Comp. Neurol. 494:1007–1030, 2006. © 2005 Wiley‐Liss, Inc.
Radical Addition Reactions of Phosphorus Hydrides: Tuning the Reactivity of Phosphorus Hydrides, the Use of Microwaves and Horner–Wadsworth–Emmons‐Type Reactions
Authors: Jessop Christopher M. , Parsons Andrew F. , Routledge Anne , Irvine Derek J. 
Published: December 2005

AbstractThe reactivity of phosphorus hydrides in radical addition reactions are compared, and the substituents on phosphorus are shown to affect the efficiency of the reactions. The change in reactivity is attributed to the different bond dissociation energies of the P–H bonds, which have been calculated. Phosphorus hydrides with particularly weak P–H bonds are shown to undergo radical additions by microwave irradiation, in the absence of conventional initiators. These radical addition reactions produce phosphonothioates, phosphinothioates and phosphane sulfides, which react in HWE‐type reactions, to afford substituted alkenes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
A tree‐based model for allele‐sharing‐based linkage analysis in human complex diseases
Authors: Xu W. , Schulze T.G. , DePaulo J.R. , Bull S.B. , McMahon F.J. , Greenwood C.M.T. 
Published: December 2005

AbstractBy adapting a well‐known affected‐relative‐pair linkage model that can incorporate covariate or sub‐phenotype information [Olson, 1999: Am J Hum Genet 65:1760–1769], we have developed a recursive‐partitioning (RP) algorithm (tree‐based model) for identifying phenotype and covariate groupings that interact with the evidence for linkage. This strategy is designed to identify subgroups of affected relative pairs demonstrating increased evidence for linkage, where subgroups are defined by pair‐level or family‐level covariates. After growing a full tree, we identified optimal tree size through a form of tree pruning and chose the best covariate at each split by using bootstrap algorithms. Simulation studies showed that power to detect linkage can increase in the presence of gene‐environment interactions, depending on the magnitude of the interaction. As expected, however, power can decrease by examining more covariates, despite the pruning to optimize tree size. The RP model correctly identifies tree structure in a large proportion of simulations. We applied the RP model to a dataset of families with bipolar affective disorder (BPAD) where linkage regions on chromosome 18 have been previously identified. Using the all‐pairs score in Genehunter, the NPL tests showed no regions with strong linkage evidence on chromosome 18. However, using the RP model, several suggestive regions were found on chromosome 18. Two covariates appeared to influence the degree of linkage: the type II BPAD subtype and a pattern of displaying mania before or after a depressive episode. The RP model has the potential to identify previously unknown gene‐environmental interactions; here we have demonstrated the practical utility and potential this new methodology holds. Genet. Epidemiol. 2006. © 2005 Wiley‐Liss, Inc.
Efficient activation of aflatoxin B1 by cytochrome P450 2A13, an enzyme predominantly expressed in human respiratory tract
Authors: He Xiao‐Yang , Tang Lili , Wang Shou‐Lin , Cai Qing‐Song , Wang Jia‐Sheng , Hong Jun‐Yan 
Published: December 2005

AbstractThe worldwide human exposure to aflatoxin B1 (AFB1), particularly in developing countries, remains to be a serious public health concern. Although AFB1 is best known as a hepatocarcinogen, epidemiological studies have shown a positive association between human lung cancer occurrence and inhalation exposure to AFB1. Cytochrome P450 (CYP)‐catalyzed metabolic activation is required for AFB1 to exert its carcinogenicity. Previous studies have identified CYP1A2 and CYP3A4 as the major enzymes for AFB1 activation in human liver. However, the key CYP enzymes in human lung that can efficiently activate AFB1in situ are unknown. In the present study, we demonstrate that CYP2A13, an enzyme predominantly expressed in human respiratory tract, has a significant activity in metabolizing AFB1 to its carcinogenic/toxic AFB1‐8,9‐epoxide and AFM1‐8,9‐epoxide at both low (15 μM) and high (150 μM) substrate concentrations. Under the same conditions, there was no detectable AFB1 epoxide formation by CYP2A6, which was also reported to be involved in the metabolic activation of AFB1. Consistent with the activity data, there was an ∼800‐fold difference in LC50 values of AFB1 (48‐hr treatment) between Chinese hamster ovary (CHO) cells expressing CYP2A13 and CYP2A6 (50 nM versus 39 μM). We further demonstrate that amino acid residues Ala117 and His372 in CYP2A13 protein are important for AFB1 epoxidation and its related cytotoxicity. Our results suggest that CYP2A13‐catalyzed metabolic activation in situ may play a critical role in human lung carcinogenesis related to inhalation exposure to AFB1. © 2005 Wiley‐Liss, Inc.
In vivo imaging of tumor response to therapy using a dual‐modality imaging strategy
Authors: Medarova Zdravka , Pham Wellington , Kim Young , Dai Guangping , Moore Anna 
Published: December 2005

AbstractIn vivo assessment of the outcome of cancer therapy is hampered by the paucity of imaging probes that target tumors specifically and noninvasively. The importance of such probes increases with the continuous development of chemotherapeutics and the necessity to evaluate their effectiveness in a clinical setting. We have recently reported on a dual‐modality imaging probe specifically targeting the underglycosylated mucin‐1 tumor‐specific antigen (uMUC‐1), which is one of the early hallmarks of tumorigenesis in a wide variety of tumors. This probe consists of crosslinked superparamagnetic iron oxide nanoparticles (CLIO) for MR imaging, modified with Cy5.5 dye (for near infrared optical fluorescence imaging (NIRF)), and has peptides (EPPT), specifically recognizing uMUC‐1, attached to the nanoparticle's dextran coat. In the present study, we demonstrated that this probe could not only detect orthotopically implanted preclinical models of adenocarcinomas but could also track tumor response to chemotherapy in vivo in real time. Considering the high cost associated with the development and testing of new cancer therapeutics and the need for accurate, noninvasive assessment of their effectiveness, we believe that the developed probe represents a valuable research tool relevant to clinical discovery. © 2005 Wiley‐Liss, Inc.
Molecular biology of Hodgkin's and Reed/Sternberg cells in Hodgkin's lymphoma
Authors: Bräuninger Andreas , Schmitz Roland , Bechtel Dörte , Renné Christoph , Hansmann Martin‐Leo , Küppers Ralf 
Published: December 2005

AbstractHodgkin's and Reed/Sternberg (HRS) cells, the tumour cells in classical Hodgkin's lymphoma (HL), represent transformed B cells in nearly all cases. The detection of destructive somatic mutations in the rearranged immunoglobulin (Ig) genes of HRS cells in classical HL indicated that they originate from preapoptotic germinal centre (GC) B cells that lost the capacity to express a high‐affinity B‐cell receptor (BCR). Several aberrantly activated signalling pathways and transcription factors have been identified that contribute to the rescue of HRS cells from apoptosis. Among the deregulated signalling pathways, activation of multiple receptor tyrosine kinases in HRS cells appears to be a specific feature of HL. In about 40% of cases of classical HL the HRS cells are infected by Epstein‐Barr virus (EBV), indicating an important role of EBV in HL pathogenesis. Interestingly, nearly all cases of HL with destructive Ig gene mutations eliminating BCR expression (e.g. nonsense mutations) are EBV‐positive, suggesting that EBV‐encoded genes have a particular function to prevent apoptosis of HRS‐cell precursors that acquired such crippling mutations. This idea is further supported by the recent demonstration that isolated human GC B cells harbouring crippled Ig genes can be rescued by EBV from cell death, giving rise to lymphoblastoid cell lines. The molecular analysis of composite Hodgkin's and non‐Hodgkin's lymphomas indicated that many cases develop from a common GC B‐cell precursor in a multistep transformation process with both shared and distinct oncogenic events. © 2005 Wiley‐Liss, Inc.
The topoisomerase II–Hsp90 complex: A new chemotherapeutic target?
Authors: Barker Catherine R. , Hamlett Jane , Pennington Stephen R. , Burrows Francis , Lundgren Karen , Lough Rachel , Watson Alastair J.M. , Jenkins John R. 
Published: December 2005

AbstractThe modulation of DNA topology by topoisomerase II plays a crucial role during chromosome condensation and segregation in mitosis and has thus become a highly attractive target for chemotherapeutic drugs. However, these drugs are highly toxic, and so new approaches are required. One such strategy is to target topoisomerase II‐interacting proteins. Here we report the identification of potential topoisomerase II‐associated proteins using immunoprecipitation, followed by 1‐D and 2‐D gel electrophoresis and MALDI‐TOF mass spectrometry. A total of 23 proteins were identified and, of these, 17 were further validated as topoisomerase IIα‐associated proteins by coimmunoprecipitation and Western blot. Six of the interacting proteins were cellular chaperones, including 3 members of the heat shock protein‐90 (Hsp90) family, and so the effect of Hsp90 modulation on the antitumor activity of topoisomerase II drugs was tested using the sulforhodamine B assay, clonogenic assays and a xenograft model. The Hsp90 inhibitors geldanamycin, 17‐AAG (17‐allylamino‐17‐demethoxygeldanamycin) and radicicol significantly enhanced the activity of the topoisomerase II poisons etoposide and mitoxantrone in vitro and in vivo. Thus, our method of identifying topoisomerase II‐interacting proteins appears to be effective, and at least 1 novel topoisomerase IIα‐associated protein, Hsp90, may represent a valid drug target in the context of topoisomerase II‐directed chemotherapy. © 2005 Wiley‐Liss, Inc.
In vivo enhancement of herpes simplex virus thymidine kinase/ganciclovir cancer gene therapy with polyamine biosynthesis inhibition
Authors: Wahlfors Tiina , Hakkarainen Tanja , Jänne Juhani , Alhonen Leena , Wahlfors Jarmo 
Published: December 2005

AbstractWe have earlier demonstrated that inhibition of polyamine biosynthesis with difluoromethylornithine (DFMO) can be used to enhance the cytotoxicity of herpes simplex virus thymidine kinase/ganciclovir (HSV‐TK/GCV) gene therapy in different tumor cell lines. Here, the utility of this treatment combination was tested in vivo in a nude mouse tumor model. First, the effect of DFMO was verified by treating mice bearing subcutaneous 9L rat glioma tumors with 2% DFMO in drinking water. The drug treatment induced almost complete suppression of ornithine decarboxylase activity, and as a result, a strong decrease in intratumoral putrescine and spermidine concentrations, which were normalized 4 days after drug removal. Consequently, the tumors displayed a significant reduction in the proliferation activity that was increased to 20% higher than the normal level at day 4 and returned to normal level 7 days after DFMO removal. Next, 9L tumors with 30% of TK‐GFP fusion gene positive cells were induced and the animals were given DFMO and GCV in 2 treatment schemes, with the drug administration periods overlapping either 5 or 2 days. The analysis of tumor size at the end of the treatment revealed that DFMO can enhance HSV‐TK/GCV cytotoxicity when the overlap between DFMO and GCV was 5 days, but the result was not significant. However, the 2‐day overlap scheme yielded a significantly (p < 0.05, ANOVA) enhanced antitumor effect. In conclusion, the data here confirms that a novel combination of 2 clinically relevant treatment modalities, polyamine deprivation and HSV‐TK/GCV suicide gene therapy, can be used synergistically in vivo. © 2005 Wiley‐Liss, Inc.
Loss of expression of Epstein‐Barr virus nuclear antigen‐2 correlates with a poor prognosis in cases of pyothorax‐associated lymphoma
Authors: Takakuwa Tetsuya , Ham Maria Francisca , Luo Wen‐Juan , Nakatsuka Shin‐ichi , Daibata Masanori , Aozasa Katsuyuki 
Published: December 2005

AbstractPyothorax‐associated lymphoma (PAL) is a non‐Hodgkin's lymphoma, which develops in the pleural cavity of patients who have had pyothorax for over 20 years, and is strongly associated with Epstein‐Barr virus (EBV) infection. The expression of latent genes, especially EBV nuclear antigen‐2 (EBNA‐2), influences the growth characteristics and malignant features of EBV‐infected cells. Here, the effect of EBNA‐2 expression on clinical features was examined in 13 cases of PAL. The EBNA‐2 transcript was detected in 8 cases but was absent in 5. There was a significant difference in survival between patients with the transcripts and those without: the 1‐year survival rate was 87.5 and 0%, respectively (p < 0.01). There was a discrepancy between EBNA‐2 expression and EBNA promoter usage in 6 cases. The Cp/Wp promoter was used in 3 EBNA‐2‐negative cases, whereas the Qp promoter or multiple promoters were used in 3 EBNA‐2‐positive cases. Analysis of PAL cell lines provided a clue as to the mechanism underlying the discrepancy between EBNA‐2 expression and EBNA promoter usage. Loss of EBNA‐2 expression, irrespective of the latency pattern, is correlated with a poor prognosis, suggesting that down‐regulation of the EBNA‐2 expression could be selection pressure for the progression of PAL. © 2005 Wiley‐Liss, Inc.
Fucosylated haptoglobin is a novel marker for pancreatic cancer: A detailed analysis of the oligosaccharide structure and a possible mechanism for fucosylation
Authors: Okuyama Noriko , Ide Yoshihito , Nakano Miyako , Nakagawa Tsutomu , Yamanaka Kanako , Moriwaki Kenta , Murata Kohei , Ohigashi Hiroaki , Yokoyama Shigekazu , Eguchi Hidetoshi , Ishikawa Osamu , Ito Toshifumi , Kato Michio , Kasahara Akinori , Kawano Sunao , Gu Jianguo , Taniguchi Naoyuki , Miyoshi Eiji 
Published: December 2005

AbstractChanges in oligosaccharide structures have been reported in certain types of malignant transformations and, thus, could be used for tumor markers in certain types of cancer. In the case of pancreatic cancer cell lines, a variety of fucosylated proteins are secreted into their conditioned media. To identify fucosylated proteins in the serum of patients with pancreatic cancer, we performed western blot analyses using Aleuria Aurantica Lectin (AAL), which is specific for fucosylated structures. An ∼40 kD protein was found to be highly fucosylated in pancreatic cancer and an N‐terminal analysis revealed that it was the β chain of haptoglobin. While the appearance of fucosylated haptoglobin has been reported in other diseases such as hepatocellular carcinoma, liver cirrhosis, gastric cancer and colon cancer, the incidence was significantly higher in the case of pancreatic cancer. Fucosylated haptoglobin was observed more frequently at the advanced stage of pancreatic cancer and disappeared after an operation. A mass spectrometry analysis of haptoglobin purified from the serum of patients with pancreatic cancer and the medium from a pancreatic cancer cell line, PSN‐1, showed that the α 1‐3/α 1‐4/α 1‐6 fucosylation of haptoglobin was increased in pancreatic cancer. When a hepatoma cell line, Hep3B, was cultured with the conditioned media from pancreatic cancer cells, haptoglobin secretion was dramatically increased. These findings suggest that fucosylated haptoglobin could serve as a novel marker for pancreatic cancer. Two possibilities were considered in terms of the fucosylation of haptoglobin. One is that pancreatic cancer cells, themselves, produce fucosylated haptoglobin; the other is that pancreatic cancer produces a factor, which induces the production of fucosylated haptoglobin in the liver. © 2005 Wiley‐Liss, Inc.