bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retinoic acid activates human secretin gene expression by Sp proteins and Nuclear Factor I in neuronal SH‐SY5Y cells
Authors: Lee Leo Tsz‐On , Tan‐Un Kian‐Cheng , Lin Marie Chia‐Mi , Chow Billy Kwok‐Chong 
Published: March 2005

AbstractSecretin is a neuropeptide that is expressed in distinct central neurones. As there is no information on how the secretin gene is regulated in neuronal cells, a well established neuronal differentiation cell model, SH‐SY5Y, was used to study transcriptional regulation of the human secretin gene. High secretin transcript and peptide levels were found in this cell, and secretin gene expression and promoter activity were up‐regulated upon all‐trans retinoic acid (RA) treatment. Within the promoter, a functional GC‐box 1 (−131 from ATG, relative to the ATG initiation codon) was found to be regulated by a brain‐specific Sp protein, Sp4, and ubiquitous factors Sp1 and Sp3. The human secretin gene in SH‐SY5Y cells is controlled by the (Sp1 + Sp4)/Sp3 ratio and the RA‐induced activation is a partial result of a decrease in Sp3 levels. In addition to the GC‐box 1, an N1 motif in close proximity was also responsible for RA‐induced secretin gene activation. Competitive gel mobility shift and southwestern blot studies revealed binding of Nuclear Factor I (NFI) with the N1 motif. Overexpression of NFI‐C increased promoter activity upon RA treatment. Consistent with this observation, NFI‐C transcript levels were augmented after RA treatment. We conclude that RA induction of the secretin gene in neuronal cells is regulated by the combined actions of reducing Sp3 and increasing NFI‐C expression.
Integrative role of cPLA2 with COX‐2 and the effect of non‐steriodal anti‐inflammatory drugs in a transgenic mouse model of amyotrophic lateral sclerosis
Authors: Kiaei Mahmoud , Kipiani Khatuna , Petri Susanne , Choi Dong‐Kug , Chen Junyu , Calingasan Noel Y. , Beal M. Flint 
Published: March 2005

AbstractCyclooxygenase‐2 (COX‐2) is a key molecule in the inflammatory pathway in amyotrophic lateral sclerosis (ALS). Cytosolic phospholipase A (cPLA2) is an important enzyme providing substrate for cyclooxygenases. We therefore examined cPLA2 expression in human ALS and mutant Cu/Zn superoxide dismutase (SOD1) transgenic mice and its relation to COX‐2. Immunohistochemistry and real‐time RT‐PCR revealed elevated cPLA2 protein and its mRNA levels in the lumbar spinal cord of mutant SOD1 mice. COX‐2 immunoreactivity was increased in lumbar spinal cord sections from both familial ALS (FALS) and sporadic ALS (SALS) as compared to controls, and cPLA2 immunoreactivity was increased in a patient with FALS. Oral administration of the non‐selective cyclooxygenase (COX) inhibitor, sulindac, extended the survival (by 10%) of G93A SOD1 mice as compared to littermate controls. Sulindac, as well as the selective COX‐2 inhibitors, rofecoxib and celecoxib reduced cPLA2 immunoreactivity in the lumbar spinal cord of G93A transgenic mice. Sulindac treatment preserved motor neurons, and reduced microglial activation and astrocytosis, in the spinal cord of G93A SOD1 transgenic mice. These results suggest that cPLA2 plays an important role in supplying arachidonic acid to the COX‐2 driven inflammatory pathway in ALS associated with SOD1 mutations.
Expression of human FE65 in amyloid precursor protein transgenic mice is associated with a reduction in β‐amyloid load
Authors: Santiard‐Baron Dominique , Langui Dominique , Delehedde Maryse , Delatour Benoît , Schombert Brigitte , Touchet Nathalie , Tremp Günter , Paul Marie‐Françoise , Blanchard Véronique , Sergeant Nicolas , Delacourte André , Duyckaerts Charles , Pradier Laurent , Mercken Luc 
Published: March 2005

AbstractFE65 is an adaptor protein that interacts with the cytoplasmic tail of the amyloid precursor protein (APP). In cultured non‐neuronal cells, the formation of the FE65‐APP complex is a key element for the modulation of APP processing, signalling and β‐amyloid (Aβ) production. The functions of FE65 in vivo, including its role in the metabolism of neuronal APP, remain to be investigated. In this study, transgenic mice expressing human FE65 were generated and crossbred with APP transgenic mice, known to develop Aβ deposits at 6 months of age. Compared with APP mice, APP/FE65 double transgenic mice exhibited a lower Aβ accumulation in the cerebral cortex as demonstrated by immunohistochemistry and immunoassay, and a lower level of APP‐CTFs. The reduced accumulation of Aβ in APP/FE65 double transgenics, compared with APP mice, could be linked to the low Aβ42 level observed at 4 months of age and to the lower APP‐CTFs levels. The present work provides evidence that FE65 plays a role in the regulation of APP processing in an in vivo model.
Erythropoietin protects primary hippocampal neurons increasing the expression of brain‐derived neurotrophic factor
Authors: Viviani Barbara , Bartesaghi Stefano , Corsini Emanuela , Villa Pia , Ghezzi Pietro , Garau Angela , Galli Corrado L. , Marinovich Marina 
Published: March 2005

AbstractErythropoietin, the principal regulator of erythroids progenitor cells, also promotes neuronal survival. Using primary cultures of rat hippocampal neurons, we investigated whether erythropoietin could mediate neuroprotection favouring the transcription of brain‐derived neurotrophic factor (BDNF). Erythropoietin 2.7 nm reduced by ∼ 50% the neuronal death triggered by the prototypic neurotoxicant trimethyltin (TMT) and time‐dependently induced BDNF mRNA. This effect resulted in an increased production of biologically active BDNF, which led to a sustained activation of the specific BDNF receptor tyrosine kinase B (TrkB). Reduction of TMT‐induced neuronal death by erythropoietin was specifically prevented by a neutralizing anti‐BDNF antibody (15 µg/mL), indicating the involvement of this neurotrophin in erythropoietin neuroprotective effect. Intracerebroventricular administration of erythropoietin in mice significantly increases BDNF mRNA expression in brain, supporting the idea of the involvement of this neurotrophin in erythropoietin action within the CNS. BDNF expression in neuronal cells is induced by activation of voltage Ca2+‐channels and recruitment of Ca2+‐sensitive transcription factors. Consistently, 2.7 nm erythropoietin increased intracellular Ca2+ in 5 min and cAMP response element binding protein (CREB) phosphorylation at Ser 133 in 30 min. Both effects were abolished by 1 µm nitrendipine, a selective blocker of L‐type voltage Ca2+‐channels. These data demonstrate that erythropoietin activates the CREB transcription pathway and increases BDNF expression and production, which contributes to erythropoietin mediated neuroprotection.
A family of octapamine receptors that specifically induce cyclic AMP production or Ca2+ release in Drosophila melanogaster
Authors: Balfanz Sabine , Strünker Timo , Frings Stephan , Baumann Arnd 
Published: March 2005

AbstractIn invertebrates, the biogenic‐amine octopamine is an important physiological regulator. It controls and modulates neuronal development, circadian rhythm, locomotion, ‘fight or flight’ responses, as well as learning and memory. Octopamine mediates its effects by activation of different GTP‐binding protein (G protein)‐coupled receptor types, which induce either cAMP production or Ca2+ release. Here we describe the functional characterization of two genes from Drosophila melanogaster that encode three octopamine receptors. The first gene (Dmoa1) codes for two polypeptides that are generated by alternative splicing. When heterologously expressed, both receptors cause oscillatory increases of the intracellular Ca2+ concentration in response to applying nanomolar concentrations of octopamine. The second gene (Dmoa2) codes for a receptor that specifically activates adenylate cyclase and causes a rise of intracellular cAMP with an EC50 of ∼3 × 10−8 m octopamine. Tyramine, the precursor of octopamine biosynthesis, activates all three receptors at ≥ 100‐fold higher concentrations, whereas dopamine and serotonin are non‐effective. Developmental expression of Dmoa genes was assessed by RT–PCR. Overlapping but not identical expression patterns were observed for the individual transcripts. The genes characterized in this report encode unique receptors that display signature properties of native octopamine receptors.
Overexpression of human copper/zinc‐superoxide dismutase in transgenic animals attenuates the reduction of apurinic/apyrimidinic endonuclease expression in neurons after in vitro ischemia and after transient global cerebral ischemia
Authors: Narasimhan Purnima , Sugawara Taku , Liu Jing , Hayashi Takeshi , Noshita Nobuo , Chan Pak H. 
Published: March 2005

AbstractOxidative stress after ischemia/reperfusion has been shown to induce DNA damage and subsequent DNA repair activity. Apurinic/apyrimidinic endonuclease (APE) is a multifunctional protein in the DNA base excision repair pathway which repairs apurinic/apyrimidinic sites in DNA. We investigated the involvement of oxidative stress and expression of APE in neurons after oxygen–glucose deprivation and after global cerebral ischemia. Our results suggest that overexpression of human copper/zinc‐superoxide dismutase reduced oxidative stress with a subsequent decrease in APE expression. Production of oxygen free radicals and inhibition of the base excision repair pathway may play pivotal roles in the cell death pathway after ischemia.
Functional SDF1α/CXCR4 signaling in the developing spinal cord
Authors: Luo Yongquan , Cai Jingli , Xue Haipeng , Miura Takumi , Rao Mahendra S. 
Published: March 2005

AbstractStromal cell‐derived factor (SDF1) and its cognate receptor CXCR4 have been shown to play a central role in the development of the cerebellum, hippocampus, and neocortex. However, little is known about the functions of SDF1/CXCR4 in early spinal cord progenitor cell differentiation. Here, we show that a functional SDF1α/CXCR4 signaling pathway is present in developing spinal cord cells (a spliced variant of SDF1). RT–PCR analysis of SDF1α and CXCR4 showed that they were present in E10.5 neural tube and their expression increased as neuroepithelial cells differentiated into more committed spinal cord progenitors. Stimulation of the more differentiated progenitors (E14.5) with SDF1α resulted in rapid activation of the extracellular signal‐regulated kinase (ERK)1/2. This SDF1α‐induced ERK activity was dose dependent and could be inhibited by pre‐treatment of the cells with either pertussis toxin, an inactivator of G‐protein‐coupled receptors, or PD98059, a MEK1 inhibitor. Concomitant with ERK activation, SDF1α also activated the downstream transcription factor Ets, a substrate for ERK phosphorylation. Further, downstream activation of genes associated with cell survival, differentiation and migration was assessed using a G‐protein‐coupled receptor pathway‐focused microarray. We found that 23 genes, including PDK1, Egr‐1, Grm5, and E‐selectin, were up‐regulated by SDF1α. Furthermore, SDF1α induced chemotaxis in both neural and glial progenitors in in vitro migration assays. Pre‐treatment of the cells with either pertussis toxin or PD98059 completely inhibited SDF1α‐induced chemotaxis. Thus, our data suggest that SDF1α may function through a CXCR4/ERK/Ets‐linked signalling pathway in spinal cord neural development to modulate migration of progenitor cells.
Activated mitogen‐activated protein kinase kinase 7 redistributes to the cytosol and binds to Jun N‐terminal kinase‐interacting protein 1 involving oxidative stress during early reperfusion in rat hippocampal CA1 region
Authors: Li Chun‐Hong , Wang Rui‐Min , Zhang Quan‐Guang , Zhang Guang‐Yi 
Published: March 2005

AbstractMitogen‐activated protein kinase kinase (MKK) 7, a specific upstream activator of Jun N‐terminal kinases (JNKs) in the stress‐activated protein kinase (SAPK)/JNK signaling pathway, plays an important role in response to global cerebral ischemia. We investigated the subcellular localization of activated (phosphorylated) MKK (p‐MKK) 7 using western blotting, immunoprecipitation and immunohistochemistry analysis in rat hippocampus. Transient forebrain ischemia was induced by the four‐vessel occlusion method on Sprague‐Dawley rats. Our results showed that both protein expression and activation of MKK7 were increased rapidly with peaks at 10 min of reperfusion in the nucleus of the hippocampal CA1 region. Simultaneously, in the cytosol activated MKK7 enhanced gradually and peaked at 30 min of reperfusion. In addition, we also detected JNK‐interacting protein (JIP) 1, which accumulated in the perinuclear region of neurons at 30 min of reperfusion. Interestingly, at the same time‐point the binding of JIP‐1 to p‐MKK7 reached a maximum. Consequently, we concluded that MKK7 was rapidly activated and then translocated from the nucleus to the cytosol depending on its activation in the hippocampal CA1 region. To further elucidate the possible mechanism of MKK7 activation and translocation, the antioxidant N‐acetylcysteine was injected into the rats 20 min before ischemia. The result showed that the levels of MKK7 activation, translocation and binding of p‐MKK7 to JIP‐1 were obviously limited by N‐acetylcysteine in the cytosol at 30 min after reperfusion. The findings suggested that MKK7 activation, translocation and binding to JIP‐1 were closely associated with reactive oxygen species and might play a pivotal role in the activation of the JNK signaling pathway in brain ischemic injury.
Children's Rating of Itch: An Experimental Study
Authors: Wahlgren Carl‐Fredrik 
Published: March 2005

Abstract:  Little is known about children's ability to assess itch. The present paper aimed to investigate the discriminative capacity of two itch rating scales in children. Sixty healthy children, 4 to 12 years of age, participated. Itch was provoked with three histamine concentrations (0.1, 1.0, and 10 mg/ml). Physiologic saline was the negative control. The test solutions were pricked with a lancet into the skin of the lower arms in random order under coded conditions. The overall itch intensity for each skin prick was rated with a 100‐mm visual analog scale and a four‐stepped verbal rating scale (none, mild, moderate, and severe itch). In addition, the itch duration and flare response were recorded. A significant dose–response relationship was shown for the itch duration and itch intensity as rated with both scales. This was also true for the flare response, indicating a correct skin prick technique. However, children 4 to 5 years of age rated the itch intensity (both scales) less well than those aged 6 to 12 years. The younger age group discriminated between saline and histamine, but not between the different histamine concentrations. In conclusion, children aged 6 to 12 years were able to discriminate between different itch stimulus strengths in a dose‐dependent way with a 100‐mm visual analog scale and a four‐stepped verbal rating scale, indicating the validity of these scales for measurement of experimental itch in children 6 years or older.
Raising Sun Protection and Early Detection Awareness among Florida High Schoolers
Authors: Geller Alan C. , Shamban Jill , O'Riordan David L. , Slygh Carolyn , Kinney John P. , Rosenberg Steven 
Published: March 2005

Abstract:  Changing adolescents’ sun protection behaviors remains a challenge, and the need for effective interventions targeting this group is a priority, particularly in warmer climates where emphasis on appropriate sun protection remains a year‐round concern. However, there has been little prospective research on the effect of school‐based sun protection interventions, particularly on adolescents, especially teens aged 15 to 18. High school science students in Palm Beach County, Florida, received a seven‐lesson sun protection and early detection curriculum preceded by pretests and followed with post‐tests 6 months later. The main outcome measures were student knowledge and sun protection practices, including adherence to sunscreen recommendations. Of 344 students completing the baseline surveys, 184 students completed the postintervention questionnaire. Overall, there were significant improvements from baseline to follow‐up for many of the knowledge questions. Greatest change scores were seen in the children's ability to correctly define the five rules of early detection of skin cancer (27–60%, p < 0.001) with improved change scores by gender and race persisting after 6 months. No significant differences were found in reported use of sunscreen, hat wearing, or sunglasses, although there was a slight decrease in the reported use of always wearing sun protective clothing (p = 0.03). In conclusion, in this study, a skin cancer prevention and detection curriculum integrated into high school biology, resulted in knowledge gains maintained at least 6 months after classroom teaching. For example, procedural knowledge (e.g., knowing ways to identify early malignant moles) obtained in this study improved in 6 months, and may lay the foundation for future behavioral change. Sun protection activities in the United States have met with many challenges and obstacles and thus, further work is needed to better understand what combination of knowledge‐based information, activity‐based education, school‐wide changes, and community efforts, will create a long‐term systemic improvement in sun protection habits in children.
Diffuse Normolipemic Plane Xanthoma in a 9‐year‐old Boy
Authors: Hofmann Maja , Zappel Kristina , Trefzer Uwe , Audring Heike , Albrecht‐Nebe Helga , Sterry Wolfram , Ulrike Blume‐Peytavi  
Published: March 2005

Abstract:  Normolipemic plane xanthoma normally occurs in adults. We report the atypical instance of a 9‐year‐old boy who developed disseminated, flat, yellow‐brown plaques up to 2 to 3 cm without any complaints. The histology showed the hallmarks of xanthoma, including the presence of CD68+ foam cells and Touton giant cells. No systemic involvement or lipid disorders were evident. It is important to perform regular follow‐up of these patients because normolipemic plane xanthoma often precedes myeloproliferative disorders such as leukemia, paraproteinemia, or lymphoma.
Buschke–Ollendorff Syndrome: Three Generations in a Japanese Family
Authors: Kawamura Ai , Ochiai Toyoko , Tan‐Kinoshita Miyuki , Suzuki Hiroyuki 
Published: March 2005

Abstract:  Buschke–Ollendorff syndrome is an autosomal dominant disease characterized by disseminated connective tissue nevi of elastic type and osteopoikilosis. We report a 6‐year‐old Japanese boy with connective tissue nevi that showed slightly grouped yellowish or skin‐colored papules and nodules, distributed from birth over his right thigh, right buttock, and back. Radiologic skeletal survey revealed osteopoikilosis. A skin biopsy specimen obtained from a papule showed that collagen bundles in the dermis were thickened and homogenized. The elastic fibers were not increased but were coarse and clumped. The boy's father, at age 34, has had osteopoikilosis and similar papules and nodules on his left buttock and back for the preceding 18 years. We studied the paternal grandfather, aged 65. He had osteopoikilosis and similar skin lesions on his lumbar region. None of the three had a history of hearing loss or malignant tumor. To our knowledge, this is the first report of three generations of Buschke–Ollendorf syndrome in a Japanese family.
Comparison of the Efficacy and Safety of the 308 nm Excimer Laser for the Treatment of Localized Psoriasis in Adults and in Children: A Pilot Study
Authors: Pahlajani Niraj , Katz Brian J. , Lozano Ann Marie , Murphy Frank , Gottlieb Alice 
Published: March 2005

Abstract:  The 308‐nm excimer laser has been shown to be safe and efficacious in the treatment of localized mild‐to‐moderate plaque‐type psoriasis in adults. However, the laser's safety and efficacy has not yet been demonstrated in children. Four of seven children with a mean age of 11.0 years and 12 of 18 adults with a mean age of 48.8 years completed the full protocol. The most common reason for incompletion was noncompliance unrelated to side effects. Both the children (p = 0.0200) and the adult groups (p = 0.0009) yielded a significant decrease in psoriatic severity scores of their respective target lesions. The children group had a greater reduction (p = 0.008) from a mean baseline target (PSS) of 5.75 ± 1.71 to final of 0.50 ± 0.58 (91.3% reduction) as compared to the adult treatment group from a mean baseline psoriatic severity score of 5.00 ± 1.15 to final of 1.92 ± 1.11 (61.6% reduction). However, there was no statistical difference between the mean total treatments required to achieve this result (p = 0.112). Side effects were common, albeit minor and well tolerated. In conclusion, the 308 nm excimer laser appears to be a safe and effective treatment for localized psoriasis in children as well as in adults.
Efficacy of Listerine® Antiseptic in reducing viral contamination of saliva
Authors: Meiller Timothy F. , Silva Arley , Ferreira Sonia M. , Jabra‐Rizk Mary Ann , Kelley Jacqueline I. , DePaola Louis G. 
Published: March 2005

AbstractAim: The anti‐viral efficacy of oral antimicrobial rinses has not been adequately studied in terms of potential clinical significance. As a follow‐up to an in vitro study on the effect of oral antiseptics on Herpes simplex virus, Type 1, this study was undertaken to evaluate the in vivo effect of an essential oil containing oral antiseptic on the reduction of viral titer in saliva during active viral infection.Method: Patients were recruited and evaluated in a single visit protocol at the onset of a perioral outbreak, consistent historically and clinically with recurrent Herpes labialis. Direct immunofluorescence of cytological smears of the lesions/oral fluids was used to confirm Herpes simplex virus types I or II. Patients were randomly assigned to one of two treatment groups: (1) active ingredient and (2) sterile water control. The viral lesion was evaluated as to clinical stage according to standard protocol. Salivary fluid samples were taken: (1) at baseline; (2) immediately following a 30 s rinse; (3) 30 min. after the 30 s rinse; and (4) on the repeat trial, also at 60 min. after the 30 s rinse. All samples were evaluated for viral titer and results compared.Results: In Trial 1, the sample population consisted of 19 males and 21 females with an average age of 29.2 and in Trial 2, 21 males, 19 females with an average age of 28. In both Trials 1 and 2, recoverable infectious virions were reduced to zero after a 30 s experimental rinse; whereas, the control rinse resulted in a non‐significant (p>0.05) reduction. The experimental group also demonstrated a continued significant (p<0.05) reduction 30 min. post rinse when compared with baseline while the control group returned to baseline levels. In Trial 2, the 60 min. post rinse follow‐up demonstrated a 1–2 log residual reduction from baseline in the experimental group; however, this was not significant.Conclusions: There is clinical efficacy in utilizing an oral rinse with the antimicrobial agent Listerine® Antiseptic in reducing the presence of viral contamination in oral fluids for at least 30 min. after oral rinse. The risk of viral cross contamination generated from these oral fluids in person to person contact or during dental treatment may be reduced.