bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic model of event‐free survival for patients with androgen‐independent prostate carcinoma
Authors: Shulman Michael J. , Benaim Elie A. 
Published: April 2005

AbstractBACKGROUNDThe current study was conducted to develop a prognostic model of event‐free survival (EFS) in men with androgen‐independent prostate carcinoma (AIPC).METHODSData from 160 patients diagnosed with AIPC between 1989–2002 were reviewed. No patient had received cytotoxic chemotherapy. A univariate Cox proportional hazards model identified significant predictors of EFS. Recursive partitioning analysis divided these significant variables into prognostic risk groups. The final prognostic model was tested with a Cox proportional hazards model.RESULTSThe final prognostic risk model included the presence of metastatic disease at the time of androgen‐independent disease progression (P = 0.040), time to prostate‐specific antigen (PSA) recurrence (P = 0.043), and PSA doubling time (P < 0.01). Three highly independent risk groups were identified. The observed median EFSs were 6.1 months (95% confidence interval [95= CI], 3.4–8.8 months), 33.6 months (95= CI, 25.3–41.9 months), and 96.1 months (95= CI, 57.9–134.3 months) for the low‐risk, intermediate‐risk, and high‐risk groups, respectively. Each risk group was found to be independently predictive of EFS (P < 0.01). Patients who died of prostate carcinoma experienced significantly more clinical events than those who died of other causes (P < 0.01).CONCLUSIONSThe prognostic model in the current study stratified patients into three highly significant and independent risk groups for EFS. A detailed PSA history and knowledge of metastatic disease are sufficient to risk‐stratify patients with AIPC. One very unique aspect of this model was that it was developed from a patient cohort that never received chemotherapy. Cancer 2005. © 2005 American Cancer Society.
Itraconazole added to a lipid formulation of amphotericin B does not improve outcome of primary treatment of invasive aspergillosis
Authors: Kontoyiannis Dimitrios P. , Boktour Maha , Hanna Hend , Torres Harrys A. , Hachem Ray , Raad Issam I. 
Published: April 2005

AbstractBACKGROUNDInvasive aspergillosis (IA) is associated with poor outcome in patients with hematologic malignancy treated with amphotericin B (AMB)‐based therapy. Itraconazole (ITC), a triazole with activity against Aspergillus, has been used in combination with AMB or lipid formulations of AMB (LipoAMB) in the treatment of IA, although the efficacy of this strategy is uncertain.METHODSTo determine whether the addition of ITC to LipoAMB improves outcome of IA, the authors retrospectively studied 179 consecutive patients with hematologic malignancies and definite or probable IA who received primary antifungal therapy with either LipoAMB (n = 146), or lipoAMB plus ITC (n = 33) between June 1993 and June 2003. In view of the erratic absorption of ITC tablets, only patients who received either intravenous or liquid ITC were analyzed. Patients who received < 1 week of treatment were excluded.RESULTSEvaluable patients in both groups (LipoAMB: n =101; ITC and LipoAMB: n = 11) had comparable distribution of risk factors of poor outcome such as neutropenia at onset of IA, persistent neutropenia, systemic steroids, previous antifungal prophylaxis, admission to the intensive care unit, disseminated IA, previous bone marrow transplant, and IA due to infection by a non‐fumigatus Aspergillus species. Response to primary antifungal therapy was equally poor in both groups (LipoAMB group: 10%; ITC and LipoAMB group: 0%; P = not significant).CONCLUSIONSIn the authors' 10‐year study of patients with hematologic malignancy and IA, the response rate to LipoAMB given as primary therapy was very poor. In a comparable group of patients, the addition of ITC did not result in a therapeutic benefit. Cancer 2005. © 2005 American Cancer Society.
Expression and distribution of TTX‐sensitive sodium channel alpha subunits in the enteric nervous system
Authors: Bartoo Aaron C. , Sprunger Leslie K. , Schneider David A. 
Published: April 2005

AbstractThe expression and distribution of TTX‐sensitive voltage‐gated sodium channel (VGSC) alpha subunits in the enteric nervous system (ENS) has not been described. Using RT‐PCR, expression of Nav1.2, Nav1.3, Nav1.6, and Nav1.7 mRNA was detected in small and large intestinal preparations from guinea pigs. Expression of Nav1.1 mRNA as well as Nav1.1‐like immunoreactivity (‐li) were not observed in any intestinal region investigated. Nav1.2‐li was primarily observed within the soma of the majority of myenteric and submucosal neurons, although faint immunoreactivity was occasionally observed in ganglionic and internodal fibers. Nav1.3‐li was observed in dendrites, soma, and axons in a small group of myenteric neurons, as well as in numerous myenteric internodal fibers; immunoreactivity was rarely observed in the submucosal plexus. Nav1.6‐li was primarily observed in the initial axonal segment of colonic myenteric neurons. Nav1.7‐li was observed in dorsal root ganglia neurons but not in the myenteric plexus of the small and large intestine. In the ileum, 37% of Nav1.2‐li cell bodies colocalized with calbindin‐li while colocalization with calretinin‐li was rare. In contrast, 22% of Nav1.3‐li cell bodies colocalized with calretinin‐li but colocalization with calbindin‐li was not observed. In the colon, both Nav1.2‐li and Nav1.3‐li cell bodies frequently colocalized with either calretinin‐li or calbindin‐li. Nav1.2‐li cell bodies also colocalized with the majority of NeuN‐li cells in the small and large intestine. These data suggest that Nav1.1 may not be highly expressed in the ENS, but that Nav1.2, Nav1.3, and Nav1.6, and possibly Nav1.7, have broadly important and distinct functions in the ENS. J. Comp. Neurol. 486:117–131, 2005. © 2005 Wiley‐Liss, Inc.
β‐catenin–mediated cell‐adhesion is vital for embryonic forebrain development
Authors: Junghans Dirk , Hack Iris , Frotscher Michael , Taylor Verdon , Kemler Rolf 
Published: April 2005

AbstractForming a complex structure such as the mammalian brain requires a complex interplay between cells and different signalling cascades during embryonic development. β‐catenin plays pivotal roles in these processes by mediating cadherin‐based cell adhesion and Wnt signalling. We show for the first time that β‐catenin functions predominantly as a mediator of cell adhesion during early development of the mammalian telencephalon. Immunohistochemical analysis demonstrates that β‐catenin is localized, together with N‐cadherin, to adhesion junctions at the apical lining of the neuroepithelium. The ablation of β‐catenin specifically from the forebrain leads to a disruption of apical adherens junctions and a breakdown of neuroepithelial structures. We show that β‐catenin–deficient neuroepithelial cells delaminate and undergo apoptosis. Newborn β‐catenin mutants lack the entire forebrain and anterior facial structures. Our data also indicate a lack of TCF/LEF‐β‐catenin–dependent transcriptional activity in the telencephalon of Wnt reporter embryos. Together with the absence of nuclear β‐catenin, this finding suggests that canonical Wnt signalling is not active during early telencephalic development. In summary, we demonstrate that β‐catenin mediates cell–cell adhesion in the early telencephalon and is vital for maintaining the structural integrity of the neuroepithelium. Developmental Dynamics 233:528–539, 2005. © 2005 Wiley‐Liss, Inc.
Atoh1 null mice show directed afferent fiber growth to undifferentiated ear sensory epithelia followed by incomplete fiber retention
Authors: Fritzsch B. , Matei V.A. , Nichols D.H. , Bermingham N. , Jones K. , Beisel K.W. , Wang V.Y. 
Published: April 2005

AbstractInner ear hair cells have been suggested as attractors for growing afferent fibers, possibly through the release of the neurotrophin brain‐derived neurotrophic factor (BDNF). Atoh1 null mice never fully differentiate hair cells and supporting cells and, therefore, may show aberrations in the growth and/or retention of their innervation. We investigated the distribution of cells positive for Atoh1‐ or Bdnf‐mediated β‐galactosidase expression in Atoh1 null and Atoh1 heterozygotic mice and correlated the distribution of these cells with their innervation. Embryonic day (E) 18.5 Atoh1 null and heterozygotic littermates show Atoh1‐ and BDNF‐β‐galactosidase–positive cells in comparable distributions in the canal cristae and the cochlea apex. Atoh1‐β‐galactosidase–positive but only occasional Bdnf‐β‐galactosidase–positive cells are found in the utricle, saccule, and cochlea base of Atoh1 null mutant mice. Absence of Bdnf‐β‐galactosidase expression in the utricle and saccule of Atoh1 null mice is first noted at E12.5, a time when Atoh1‐β‐galactosidase expression is also first detected in these epithelia. These data suggest that expression of Bdnf is dependent on ATOH1 protein in some but does not require ATOH1 protein in other inner ear cells. Overall, the undifferentiated Atoh1‐ and Bdnf‐β‐galactosidase–positive cells show a distribution reminiscent of that in the six sensory epithelia in control mice, suggesting that ear patterning processes can form discrete patches of Atoh1 and Bdnf expression in the absence of ATOH1 protein. The almost normal growth of afferent and efferent fibers in younger embryos suggests that neither fully differentiated hair cells nor BDNF are necessary for the initial targeted growth of fibers. E18.5 Atoh1 null mice have many afferent fibers to the apex of the cochlea, the anterior and the posterior crista, all areas with numerous Bdnf‐β‐galactosidase–positive cells. Few fibers remain to the saccule, utricle, and the base of the cochlea, all areas with few or no Bdnf‐β‐galactosidase–positive cells. Thus, retention of fibers is possible with BDNF, even in the absence of differentiated hair cells. Developmental Dynamics 233:570–583, 2005. © 2005 Wiley‐Liss, Inc.
Muscle fiber differentiation in fish embryos as shown by in situ hybridization of a large repertoire of muscle‐specific transcripts
Authors: Chauvigné F. , Cauty C. , Rallière C. , Rescan P.Y. 
Published: April 2005

AbstractSkeletal muscles are composed of different fiber types, largely defined by differential expression of protein isoforms involved in myofibrillogenesis or metabolism. To learn more about the gene activations that underlie the differentiation and the diversification of embryonic fish myotomal fibers, we investigated the developmental expression of 25 muscle genes in trout embryos by in situ hybridization of muscle‐specific transcripts. The earliest event of muscle differentiation, at approximately the 25‐somite stage, was the expression of a variety of muscle‐specific genes, including slow‐twitch and fast‐twitch muscle isoforms. The activation of these muscle genes started in the deep somitic domain, where the slow muscle precursors (the adaxial cells) were initially located, and progressively spread laterally throughout the width of the myotome. This mediolateral progression of gene expression was coordinated with the lateral migration of slow adaxial cells, which specifically expressed the slow myosin light chain 1 and the SLIM1/FHL1 genes. Subsequently, the fast and slow skeletal muscle isoforms precociously expressed in the course of the mediolateral wave of muscle gene activation became down‐regulated in the superficial slow fibers and the deep fast fibers, respectively. Finally, several muscle‐specific genes, including troponins, a slow myosin‐binding protein C, tropomodulins, and parvalbumin started their transcription only in late embryos. Taken together, these findings show in fish embryos that a common myogenic program is triggered in a mediolateral progression in all muscle cells. The acquisition of the slow phenotype involves the additional activation of several slow‐specific genes in migrating adaxial muscle cells. These events are followed by sequential gene activations and repressions in fast and slow muscle cells. Developmental Dynamics 233:659–666, 2005. © 2005 Wiley‐Liss, Inc.
Zac1 is expressed in progenitor/stem cells of the neuroectoderm and mesoderm during embryogenesis: Differential phenotype of the Zac1‐expressing cells during development
Authors: Valente Tony , Junyent Fèlix , Auladell Carme 
Published: April 2005

AbstractZac1, a new zinc‐finger protein that regulates both apoptosis and cell cycle arrest, is abundantly expressed in many neuroepithelia during early brain development. In the present work, we study the expression of Zac1 during early embryogenesis and we determine the cellular phenotype of the Zac1‐expressing cells throughout development. Our results show that Zac1 is expressed in the progenitor/stem cells of several tissues (nervous system, skeleton, and skeletal muscle), because they colocalize with several progenitor/stem markers (Nestin, glial fibrillary acidic protein, FORSE‐1, proliferating cell nuclear antigen, and bromodeoxyuridine). In postnatal development, Zac1 is expressed in all phases of the life cycle of the chondrocytes (from proliferation to apoptosis), in some limbic γ‐aminobutyric acid‐ergic neuronal subpopulations, and during developmental myofibers. Therefore, the intense expression of Zac1 in the progenitor/stem cells of different cellular lineages during the proliferative cycle, before differentiation into postmitotic cells, suggests that Zac1 plays an important role in the control of cell fate during neurogenesis, chondrogenesis, and myogenesis. Developmental Dynamics 233:667–679, 2005. © 2005 Wiley‐Liss, Inc.
dazed gene is necessary for late cell type development and retinal cell maintenance in the zebrafish retina
Authors: Perkins Brian D. , Nicholas Claire S. , Baye Lisa M. , Link Brian A. , Dowling John E. 
Published: April 2005

AbstractSeveral molecules, such as growth factors and neurotrophic factors, are required both for the differentiation of specific retinal cell types and the long‐term cell survival of all retinal neurons. As diffusible factors, these molecules act non–cell‐autonomously. Here, we describe the loss of function phenotype for dazed (dzd), a gene that acts cell‐autonomously for retinal cell survival and affects the differentiation of rod photoreceptors and the Müller glia. By 3 days after fertilization, dazed mutant embryos have small eyes and slight heart edema. Acridine orange staining indicated a significant degree of retinal cell death occurring by 48 hr after fertilization, and histological analysis revealed that dying cells were found in the inner and outer nuclear layers and near the marginal zones. Although molecular and morphological differentiation of the inner retina and cone photoreceptors occurred, rod photoreceptors failed to differentiate beyond a small patch in the ventral retina and rod precursors failed to respond to exogenously added retinoic acid, which normally potentiated rod differentiation. Mosaic analysis indicated that the dazed gene acts cell‐autonomously for rod production and cell survival, as dazed clones failed to produce rods outside the ventral patch and dazed cells were not maintained in wild‐type hosts. Raising mutants under constant light resulted in severe retinal degeneration, whereas raising embryos under constant darkness did not provide any additional protection from cell death. Behavioral analysis showed that a subpopulation of adult fish that were heterozygous for the dazed mutation had elevated visual thresholds and were night blind, suggesting that dazed may also be required for long‐term dim‐light vision. Taken together, our studies suggest a role for the dazed gene in rod and Müller cell development and overall retinal cell survival and maintenance. Developmental Dynamics 233:680–694, 2005. © 2005 Wiley‐Liss, Inc.
Retroactive, a membrane‐anchored extracellular protein related to vertebrate snake neurotoxin‐like proteins, is required for cuticle organization in the larva of Drosophila melanogaster
Authors: Moussian Bernard , Söding Johannes , Schwarz Heinz , Nüsslein‐Volhard Christiane 
Published: April 2005

AbstractMutations in the rtv gene cause disarrangement of chitin fibers in the cuticle of the Drosophila larva, and occasionally the cuticle detaches from the epidermis. We have identified the rtv gene, and using the new HHpred homology detection method, we show that the Rtv protein defines a new family of disulfide‐rich proteins in insects that are related to vertebrate snake neurotoxin‐like proteins, including CD59 and transforming growth factor‐β type II receptors. Rtv is an extracellular membrane‐anchored protein exposing six aromatic residues that may mediate binding to chitin. We propose that this binding function of Rtv may assist the organization of chitin fibers at the epidermal cell surface during cuticle assembly. Developmental Dynamics 233:1056–1063, 2005. © 2005 Wiley‐Liss, Inc.
Function of the mammalian postorbital bar
Authors: Heesy Christopher P. 
Published: April 2005

AbstractComplete postorbital bars, bony arches that encompass the lateral aspect of the eye and form part of a circular orbit, have evolved homoplastically multiple times during mammalian evolution. Numerous functional hypotheses have been advanced for postorbital bars, the most promising being that postorbital bars function to stiffen the lateral orbit in taxa that have significant angular deviation between the temporal fossa and the bony orbit. Without a stiff lateral orbit the anterior temporalis muscle and fascia potentially would pull on the postorbital ligament, deform the orbit, and cause disruption of oculomotor precision. Morphometric data were collected on 1,329 specimens of 324 taxa from 16 orders of extant eutherian and metatherian mammals in order to test whether the orientation of the orbit relative to the temporal fossa is correlated with the replacement of the postorbital ligament with bone. The allometric and ecological influences on orbit orientation across mammals are also explored. The morphometric results corroborate the hypothesis: Shifts in orbit orientation relative to the temporal fossa are correlated with the size of the postorbital processes, which replace the ligament. The allometric and ecological factors that influence orbit orientation vary across taxa. Postorbital bars stiffen the lateral orbital wall. Muscle pulleys, ligaments, and other connective tissue attach to the lateral orbital wall, including the postorbital bar. Without a stiff lateral orbit, deformation due to temporalis contraction would displace soft tissues contributing to normal oculomotor function. J. Morphol., 2005. © 2005 Wiley‐Liss, Inc.
Quantification of angiogenesis induced in rabbit cornea by breast carcinoma of women treated with tamoxifen
Authors: da Silva Benedito Borges , da Silva Raimundo Gerônimo , Borges Umbelina Soares , da Silveira Filho Marcos Antônio Guedes , Pimentel Igor Clausius Carvalho , Gebrim Luiz Henrique , Simões Manuel de Jesus , Baracat Edmund Chada 
Published: April 2005

AbstractBackgroundThe aim of this study was to evaluate the effect of tamoxifen on angiogenesis induced in rabbit cornea by breast carcinoma from post‐menopausal women.MethodsThirteen post‐menopausal women with operable, estrogen receptor‐positive breast carcinomas, treated with 20 mg of tamoxifen daily for 30 days prior to undergoing definitive surgery, participated in this study. Twenty‐six virgin female New Zealand white rabbits, 3–4 months old, weighing approximately 2.5 kg each, were divided into two groups of 13 animals and received corneal implants of tumor either pre‐ or post‐tamoxifen treatment. After 10 days, the animals were sacrificed, the region of the cornea between the tumor implant and the limbus was removed and quantification of angiogenesis was carried out by evaluating the entire hematoxylin‐eosin stained slide, using a 10× objective lens (100× magnification). Student t‐test was used in the statistical analysis of the data and statistical significance was established at P < 0.05.ResultsMean microvessel count was 106.8 ± 5.9 pre‐tamoxifen treatment and 54 ± 5.6 post‐treatment. According to Student t‐test, there was a significant reduction in mean microvessel density following treatment with tamoxifen (P < 0.001).ConclusionsRabbit cornea proved to be an interesting experimental model for the quantification of angiogenesis. Tamoxifen, when administered for 30 days to post‐menopausal women with breast cancer, significantly inhibited angiogenesis induced by tumor fragments in rabbit cornea. J. Surg. Oncol. 2005;90:77–80. © 2005 Wiley‐Liss, Inc.
Activation of MMP‐2 and MMP‐9 in patients with oral squamous cell carcinoma
Authors: Patel Beena P. , Shah Pankaj M. , Rawal Upendra M. , Desai Amisha A. , Shah Shakuntala V. , Rawal Rakesh M. , Patel Prabhudas S. 
Published: April 2005

AbstractBackground and ObjectivesOral cancer accounts for one third of all malignancies in India where habit of tobacco consumption is the major etiologic factor, which causes field cancerization in oral mucosa. Multiple molecular events in oral mucosa due to field cancerization may be the cause of local and regional lymph node involvement in oral cancer resulting into low overall survival, high recurrence rate, and poor prognosis. Several matrix metalloproteinases (MMPs) have been shown to play an important role in the invasion and metastasis of oral squamous cell carcinoma (SCC). MMP‐2 and MMP‐9 are capable of degrading type‐IV collagen, which is a major component of basement membrane. Therefore, we studied MMP‐2 and MMP‐9 activation by gelatin zymography, which is cost effective alternate to ELISA method, in patients with oral SCCs to predict their role in metastatic potentials.Materials and MethodsThirty‐nine patients of oral SCCs were classified as non‐metastatic (n = 28), and metastatic (n = 11) according to regional lymph node involvement. Malignant and adjacent normal tissues of the patients were collected at the time of surgery. Gelatin zymography was carried out using 7.5% polyacrylamide gel under non‐denaturing and non‐reducing conditions. Zymograms were analyzed densitometrically. Latent and active forms of MMP‐2 and MMP‐9 were expressed as ng/50 μg of protein.ResultsLatent and active forms of MMP‐2 and MMP‐9 were significantly elevated in malignant tissues as compared to their adjacent normal tissues (P < 0.05). Total MMP‐2 and MMP‐9 activities were also significantly elevated in malignant tissues as compared to adjacent normal tissues (P = 0.005 and P = 0.028, respectively). Activation ratio of MMP‐2 and MMP‐9 were significantly elevated in malignant tissues as compared to adjacent normal tissues. Activation of MMP‐2 was prominent (11%) than MMP‐9 (5%) in malignant tissues. Activation ratio of MMP‐2 was significantly elevated in patients with lymph node metastasis than patients without lymph node metastasis (P = 0.005). Receiver's operating characteristic (ROC) curve analysis revealed that activation ratio of MMP‐2 discriminate better than and activation ratio of MMP‐9 between patients with and without lymph node metastasis. Activation ratio of MMP‐2 could predict risk of lymph node metastasis development in patients without lymph node involvement.ConclusionThe study concluded that activation of MMP‐2 and MMP‐9 was significantly higher in malignant tissues as compared to adjacent normal tissues. Further, activation ratio of MMP‐2 was significantly elevated in patients with lymph node metastasis as compared to patients without lymph node metastasis, which could predict risk of lymph node metastasis development in node negative patients. J. Surg. Oncol. 2005;90:81–88. © 2005 Wiley‐Liss, Inc.