bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Attenuated Adenovirus, ONYX-015, As Mouthwash Therapy for Premalignant Oral Dysplasia
Authors: Rudin Charles M. , Cohen Ezra E.W. , Papadimitrakopoulou Vassiliki A. , Silverman Sol , Recant Wendy , El-Naggar Adel K. , Stenson Kirsten , Lippman Scott M. , Hong Waun Ki , Vokes Everett E. 
Published: November 2003

Purpose: Dysplastic lesions of the oral epithelium are known precursors of oral cancer. A significant proportion of oral dysplastic lesions have functional defects in p53 response pathways. The ONYX-015 adenovirus is selectively cytotoxic to cells carrying defects in p53-dependent signaling pathways. The current study sought to establish the feasibility and activity of ONYX-015 administered topically as a mouthwash to patients with clinically apparent and histologically dysplastic lesions of the oral mucosa.Patients and Methods: A total of 22 patients (19 assessable patients) were enrolled onto the study. ONYX-015 was administered on three different schedules to consecutive cohorts. Biopsies of the involved mucosa were performed to evaluate histologic response and changes in expression of putative markers of malignant potential, including p53, cyclin D1, and Ki-67. Serology was performed to measure antiadenoviral titers.Results: Histologic resolution of dysplasia was seen in seven (37%) of 19 patients, and the grade of dysplasia improved in one additional patient. The majority of responses were transient. No toxicity greater than grade 2 (febrile episode in one patient) was observed. Only one of seven patients demonstrated an increase in circulating antiadenoviral antibody titer while on therapy. Although responding and resistant lesions had similar mean p53 staining at baseline, histologic response correlated with a decrease in p53 positivity over time. Significant changes in cyclin D1 or Ki-67 were not observed. Viral replication was confirmed in two of three lesions examined.Conclusion: This novel approach to cancer prevention is tolerable, feasible, and has demonstrable activity.
Agouti-Related Protein Antagonizes Glucocorticoid Production Induced through Melanocortin 4 Receptor Activation in Bovine Adrenal Cells: A Possible Autocrine Control
Authors: Doghman Mabrouka , Delagrange Philippe , Blondet Antonine , Berthelon Marie-Claude , Durand Philippe , Naville Danielle , Bégeot Martine 
Published: November 2003

AbstractAgouti-related protein (Agrp), primarily expressed in the hypothalamus, is an endogenous antagonist of αMSH at the level of melanocortin 3 receptor (MC3-R) and MC4-R, but the adrenal gland represents the second major Agrp-expressing tissue. In adrenal fasciculata cells, the glucocorticoid secretion is under the control of ACTH, which binds specifically MC2-R, the only functional melanocortin receptor described in these cells to date. Nevertheless, using cultured bovine fasciculata adrenal cells, we report that Agrp has no antagonistic properties against ACTH at the level of MC2-R. In our studies, (Nle4, d-Phe7)-αMSH (NDP-αMSH) stimulated the production of cortisol in a dose-dependent manner, and these effects were abolished by Agrp or SHU9119, a synthetic antagonist of MC3-R and MC4-R. Using a more specific antagonist (JKC-363) and RT-PCR analysis, we can postulate that the effects of NDP-αMSH were mediated via MC4-R. These results are suggestive that adrenal glucocorticoid production could be regulated through MC4-R that may have some relevance in the physiology of adrenal cells. Moreover, Agrp might exert an autocrine control on adrenal cells because a protein with biological Agrp-like activity is secreted by these cells. This peptide could then modulate locally the functions of some peripheral tissues such as adrenals.
Galanin Receptor Subtype GalR2 Mediates Apoptosis in SH-SY5Y Neuroblastoma Cells
Authors: Berger Alexandra , Lang Roland , Moritz Kerstin , Santic Radmila , Hermann Anton , Sperl Wolfgang , Kofler Barbara 
Published: November 2003

Abstract
Recently we have shown that galanin binding significantly correlates with survival in neuroblastoma patients, indicating a possible modulatory role of galanin receptors in neuroblastic tumor biology. However, the molecular mechanisms beyond this correlation have not been elucidated. Here, the cellular effects on activation of specific galanin receptor subtypes in human SH-SY5Y neuroblastoma cells were analyzed using a tetracycline-controlled expression system. Pharmacological studies confirmed the inducible expression of high affinity binding sites for galanin in SH-SY5Y cells transfected with the galanin receptors GalR1 (SY5Y/GalR1) and GalR2 (SY5Y/GalR2). Microphysiometry revealed that both receptor subtypes were able to mediate an intracellular signal upon galanin application. Interestingly, induction of receptor expression and treatment with 100 nm galanin resulted in a dramatic decrease in cell viability in SY5Y/GalR2 cells (93 ± 3%) compared with a less pronounced effect in SY5Y/GalR1 cells (19 ± 10%). The antiproliferative potency of galanin was 100-fold higher in SY5Y/GalR2 (50% effective concentration, 1.1 nm) than in SY5Y/GalR1 cells (50% effective concentration, 190 nm). Furthermore, activation of receptor expression and exposure to galanin resulted in apparent morphological changes indicative of apoptosis in SY5Y/GalR2 cells only. Induction of cell death by the apoptotic process was confirmed by poly-(ADP-ribose)-polymerase cleavage, caspase-3 activation, and the typical laddering of DNA. This study indicates that a high level of GalR2 expression is able to inhibit cell proliferation and induce apoptosis in neuroblastoma cells and therefore identifies GalR2 as a possible target for pharmacological intervention in neuroblastoma.
The Promoter of the Rat Gonadotropin-Releasing Hormone Receptor Gene Directs the Expression of the Human Placental Alkaline Phosphatase Reporter Gene in Gonadotrope Cells in the Anterior Pituitary Gland as well as in Multiple Extrapituitary Tissues
Authors: Granger Anne , Ngô-Muller Valérie , Bleux Christian , Guigon Céline , Pincas Hanna , Magre Solange , Daegelen Dominique , Tixier-Vidal Andrée , Counis Raymond , Laverrière Jean-Noël 
Published: November 2003

AbstractPrevious studies dealing with the mechanisms underlying the tissue-specific and regulated expression of the GnRH receptor (GnRH-R) gene led us to define several cis-acting regulatory sequences in the rat GnRH-R gene promoter. These include functional sites for steroidogenic factor 1, activator protein 1, and motifs related to GATA and LIM homeodomain response elements as demonstrated primarily in transient transfection assays in mouse gonadotrope-derived cell lines. To understand these mechanisms in more depth, we generated transgenic mice bearing the 3.3-kb rat GnRH-R promoter linked to the human placental alkaline phosphatase reporter gene. Here we show that the rat GnRH-R promoter drives the expression of the reporter gene in pituitary cells expressing the LHβ and/or FSHβ subunit but not in TSHβ- or GH-positive cells. Furthermore, the spatial and temporal pattern of the transgene expression during the development of the pituitary was compatible with that characterizing the emergence of the gonadotrope lineage. In particular, transgene expression is colocalized with the expression of the glycoprotein hormone α-subunit at embryonic day 13.5 and with that of steroidogenic factor 1 at later stages of pituitary development. Transgene expression was also found in specific brain areas, such as the lateral septum and the hippocampus. A single promoter is thus capable of directing transcription in highly diverse tissues, raising the question of the different combinations of transcription factors that lead to such a multiple, but nevertheless cell-specific, expressions of the GnRH-R gene.
Novel Action of Activin and Bone Morphogenetic Protein in Regulating Aldosterone Production by Human Adrenocortical Cells
Authors: Suzuki Jiro , Otsuka Fumio , Inagaki Kenichi , Takeda Masaya , Ogura Toshio , Makino Hirofumi 
Published: November 2003

AbstractWe have uncovered a functional bone morphogenetic protein (BMP) and activin system complete with ligands (BMP-6 and activin βA/βB), receptors (activin receptor-like kinase receptors 2, 3, and 4; activin type-II receptor; and BMP type-II receptor), and the binding protein follistatin in the human adrenocortical cell line H295R. Administration of activin and BMP-6 to cultures of H295R cells caused concentration-responsive increases in aldosterone production. The mRNA levels of steroidogenic acute regulatory protein or P450 steroid side-chain cleavage enzyme, the rate-limiting steps of adrenocortical steroidogenesis, were enhanced by activin and BMP-6. Activin and BMP-6 also activated the transcription of steroidogenic acute regulatory protein as well as the late-step steriodogenic enzyme CYP11B2. Activin enhanced ACTH-, forskolin-, or dibutyryl-cAMP- but not angiotensin II (Ang II)-induced aldosterone production, whereas BMP-6 specifically augmented Ang II-induced aldosterone production. Activin and ACTH but not BMP-6 increased cAMP production. Follistatin, which inhibits activin actions by binding, suppressed basal and ACTH-induced aldosterone secretion but failed to affect the Ang II-induced aldosterone level. Furthermore, MAPK signaling appeared to be involved in aldosterone production induced by Ang II and BMP-6 because an inhibitor of MAPK activation, U0126, reduced the level of aldosterone synthesis stimulated by Ang II and BMP-6 but not activin. In addition, Ang II reduced the expression levels of BMP-6 but increased that of activin βB, whereas ACTH had no effect on these levels. Collectively, the present data suggest that activin acts to regulate adrenal aldosterone synthesis predominantly by modulating the ACTH-cAMP-protein kinase A signaling cascade, whereas BMP-6 works primarily by modulating the Ang II-MAPK cascade in human adrenal cortex in an autocrine/paracrine fashion.
Regulation of the Human Cholesterol 7α-Hydroxylase Gene (CYP7A1) by Thyroid Hormone in Transgenic Mice
Authors: Drover Victor A. B. , Agellon Luis B. 
Published: November 2003

AbstractThyroid hormones exert significant changes in the metabolism of bile acids. However, in humans, the effect of thyroid hormone on cholesterol 7α-hydroxylase (cyp7a), the rate- controlling enzyme in the classical bile acid biosynthetic pathway, remains poorly understood and has been difficult to study directly in vivo. Previous studies from our laboratory have shown that the activity of the human cholesterol 7α-hydroxylase gene promoter is repressed by T3 in cultured cells. Accordingly, we hypothesized that T3 would negatively regulate human CYP7A1 gene expression in vivo. We tested this hypothesis by inducing hypo- and hyperthyroidism in transgenic mice expressing the human CYP7A1 gene. Hypothyroidism did not affect the abundance of human cyp7a mRNA in transgenic mice. In hyperthyroid male mice, human cyp7a mRNA abundance was decreased. No significant change in cyp7a mRNA abundance was observed in hyperthyroid female mice. Gender differences in the amount of cholesterol and bile acids in gallbladder bile were also observed. The data indicate that thyroid hormone can repress the human CYP7A1 gene in transgenic mice, but this effect is dependent on gender in this in vivo model.
Urocortin II Is Expressed in Human Pregnant Myometrial Cells and Regulates Myosin Light Chain Phosphorylation: Potential Role of the Type-2 Corticotropin-Releasing Hormone Receptor in the Control of Myometrial Contractility
Authors: Karteris Emmanouil , Hillhouse Edward W. , Grammatopoulos Dimitris 
Published: November 2003

Abstract
The family of CRH-related peptides are suggested to play important roles in the control of myometrial contractility during pregnancy and labor. In this study we investigated the expression of urocortin II (UCN II) in human myometrium and its ability to phosphorylate intracellular components that can be involved in modulating myometrial contractility. Using RT-PCR and fluorescent in situ hybridization, we demonstrated that UCN II and type-2 CRH receptor (CRH-R2) mRNAs were expressed in human nonpregnant and pregnant myometrium. Immunofluorescent studies confirmed protein expression of UCN II in human pregnant myometrial cells, whereas chemical cross-linking studies with radiolabeled UCN II confirmed the presence of CRH-R2 sites with an apparent molecular mass of 50 kDa. Treatment of primary human myometrial cells with UCN II to specifically activate CRH-R2 resulted in a dose-dependent increase of myosin light chain (MLC20) phosphorylation. Activation of protein kinase C (PKC) and ERK1/2 was required for the UCN II-induced activation of MLC20, because treatment of myometrial cells with inhibitors of MAPK kinase 1 (U0126) and PKC (bisindolylmaleimide) inhibited the UCN II-induced phosphorylation of MLC20. Furthermore, the UCN II effect on MLC20 was dependent on RhoA translocation to the membrane and subsequent activation of RhoA-associated kinase, as shown by the use of the specific inhibitors exoenzyme C3 and Y27632. Collectively, our data suggest a distinctive role for CRH-R2- specific agonists like UCN II in the control of myometrial contractility during human pregnancy involving sequential activation of PKC, MAPK kinase 1, ERK1/2, RhoA, and RhoA-associated kinase, leading to the MLC20 phosphorylation.
Self-assembled Monolayers of Spironaphthoxazine–Thioether for UV-controlled Complexation
Authors: Chen Huan , Li Yapeng , Huo Fengwei , Wang Zhiqiang , Zhang Xi 
Published: November 2003

Abstract
We have demonstrated that the self-assembled monolayer (SAM) of spironaphthoxazine-thioether (SNOTE) can complex metal ions based on the complexation property of the open ring form of spironaphthoxazine induced by UV irradiation, and the well-isolated sensing species in SAMs show a kinetic advantage over the closely packed ones.
Efficient Method for the Preparation of Primary, Inverted Secondary and Tertiary Alkyl Carboxylates from Alcohols and Carboxylic Acids by a New Type of Oxidation–Reduction Condensation Using Simple 1,4-Benzoquinone
Authors: Shintou Taichi , Mukaiyama Teruaki 
Published: November 2003

Abstract
A new type of oxidation–reduction condensation using in situ formed alkoxydiphenylphosphines (i.e., diphenylphosphinite esters), easily available 1,4-benzoquionone and carboxylic acids provides a new and efficient method for the preparation of alkyl carboxylates from the corresponding alcohols under mild and neutral conditions. Further, the yields of the corresponding inverted carboxylates were equally high in the case of chiral secondary or tertiary alcohols.
Secondary Prevention of Coronary Heart Disease in the Elderly
Authors: Dornbrook-Lavender Kimberly A , Roth Mary T , Pieper John A 
Published: November 2003

OBJECTIVE: To review relevant literature supporting the use of aspirin, β-blockers, lipid-lowering agents, and angiotensin-converting enzyme (ACE) inhibitors for the secondary prevention of coronary heart disease (CHD) in an elderly patient population aged ≥65 years. DATA SOURCES: A MEDLINE search (1990–May 2003) was conducted using the key terms coronary heart disease, secondary prevention and elderly. STUDY SELECTION AND DATA EXTRACTION: Primary and tertiary literature relating to the use of aspirin, β-blockers, lipid-lowering agents, and ACE inhibitors in the elderly were reviewed. DATA SYNTHESIS: CHD is the leading cause of morbidity and mortality in persons ≥65 years of age, and the use of pharmacologic agents has created a considerable opportunity for reducing recurrent events in those with established disease. This, combined with the aging of the US population, is creating an increase in the number of older adults eligible for secondary prevention. In 2002, the American Heart Association issued a scientific statement on the benefits of specific secondary prevention risk factor interventions in older adults. This article reviews pertinent findings from this statement, along with additional data supporting the use of pharmacologic agents for the secondary prevention of CHD in the elderly. CONCLUSIONS: Data suggest that use of aspirin, β-blockers, lipid-lowering agents, and ACE inhibitors are effective in secondary prevention of CHD in individuals aged ≥65 years. This benefit is similar to, and often greater than, that observed in younger patients. We believe that these agents should be prescribed for all elderly patients without contraindications. Ongoing studies and future clinical trials will more clearly elucidate the benefits of secondary prevention of CHD, particularly in persons ≥75 years of age, to determine the magnitude of benefits that can be achieved in this population.
Relationship of Atypical Antipsychotics with Development of Diabetes Mellitus
Authors: Citrome Leslie L , Jaffe Ari B 
Published: November 2003

OBJECTIVE: To review the pharmacoepidemiologic evidence for the link between exposure to atypical antipsychotics and the development of diabetes mellitus. DATA SOURCES: A MEDLINE search (1990–March 2003) was conducted. STUDY SELECTION AND DATA EXTRACTION: The search was limited to articles that described findings from analyses of large databases and used the words diabetes or hyperglycemia, and antipsychotic or clozapine or olanzapine or risperidone or quetiapine or ziprasidone or aripiprazole in the title or abstract. The odds ratio or relative risk, together with their corresponding confidence interval, was extracted. DATA SYNTHESIS: Results are conflicting, and this variability may be due to the different populations studied, different study designs, and the possibility of publication bias related to funding by the pharmaceutical industry. Nevertheless, an increased risk for diabetes mellitus appears to be present for patients receiving atypical antipsychotics. However, differential risk among the atypical antipsychotics is difficult to ascertain. CONCLUSIONS: Clinicians are urged to manage risk by regularly monitoring all patients receiving atypical antipsychotics for the emergence of diabetes mellitus. Future studies should carefully control for confounding variables such as age, diagnosis, change in weight, activity level, family history, and ethnicity.
Biosafety concerns for shared flow cytometry core facilities
Authors: Schmid Ingrid , Merlin Steven , Perfetto Stephen P. 
Published: November 2003

AbstractMany researchers who need flow cytometry for their projects have neither sufficient funds nor the work volume to justify the purchase of an analytic cytometer or cell sorter. In shared flow cytometry facilities, costs for instrument purchases, cytometer maintenance, and personnel are pooled to provide economic services for a multitude of users when they are required. Owing to the diverse nature of the samples that are submitted to core facilities, the biohazard potential of the samples can vary dramatically. For the safety of facility personnel and users, it is critical that information about hazards contained in the samples be transmitted to instrument operators before flow cytometry experiments are started. During 1999 the former Biosafety Committee of the International Society for Analytical Cytology formulated a framework biosafety questionnaire for shared facilities designed to request information about the hazard potential of experimental samples from investigators who wish to use the facility. In this report we review safety issues that are pertinent to flow cytometry core facilities by discussing the individual components of this biosafety questionnaire. Cytometry Part A 56A:113–119, 2003. © 2003 Wiley‐Liss, Inc.
Lectinocytochemical detection of apoptotic murine leukemia L1210 cells
Authors: Bilyy R. O. , Stoika R. S. 
Published: November 2003

AbstractBackgroundVarious cytomorphologic and biochemical markers of apoptosis are found in different compartments (plasma membrane, cytoplasm, nucleus, and mitochondria) of target cells. Although the plasma membrane is an easily accessible cellular compartment, relatively little is known about its changes during apoptosis. We investigated whether specific changes in the expression of plasma membrane glycoproteins take place during apoptosis and whether these changes could be used for a quantitative estimation of apoptosis.MethodsLectin cytochemical study of normal and apoptotic murine leukemia cells of the L1210 line was done. Horseradish peroxidase–labeled Laburnum anagyroides bark agglutinin, Phaseolus vulgaris agglutinin, Pisum sativum lectin (PSL), Ricinus communis agglutinin (RCA‐120; 120 kDa), Solanum tuberosum agglutinin, Triticum vulgaris lectin (wheat germ agglutinin), Viscum album agglutinin, Canavalia ensiformis lectin (concanavalin A), and Helix pomatia lectin were used to compare specific glycoprotein expressions in normal and apoptotic murine leukemia cells of the L1210 line sensitive (L1210) and resistant (L1210R) to apoptosis induction by cisplatin.ResultsThe data demonstrated significantly increased binding of α‐D‐mannose–specific PSL lectin (P < 0.01) and β‐D‐galactose–specific RCA‐120 lectin (P < 0.001) by the apoptotic cells of the L1210 and L1210R lines in comparison with the intact cells. That binding was shown to be specific because it was blocked by the corresponding inhibitory sugars.ConclusionsLectins specific to α‐D‐mannose (PSL) and β‐D‐galactose (RCA‐120) can be used to distinguish between native and apoptotic murine leukemia L1210 cells and to quantitatively estimate apoptosis in a population of these cells. Cytometry Part A 56A:89–95, 2003. © 2003 Wiley‐Liss, Inc.
Stability of the breakoff point in a high‐speed cell sorter
Authors: Petersen Timothy W. , van den Engh Ger 
Published: November 2003

AbstractBackgroundHigh‐speed jet‐in‐air cytometric sorting requires knowledge of the time it takes a particle to travel from the laser to the point where the jet breaks into droplets. Variations in this breakoff time will result in poorer yields and poorer sort purities.MethodsThis work examined the physical mechanisms that lead to the break up of the jet into droplets and calculated the stability of the droplet breakoff time relative to physical parameters, which govern the behavior of the jet.ResultsWe derived the variations in the breakoff time and found that small variations in the drive frequency, temperature, pressure, and drive amplitude can lead to correspondingly large changes in the breakoff time. We found explicitly that the time it takes the jet to break up is not necessarily correlated with the distance to the breakoff point.ConclusionsMany high‐speed cell sorters use active means to control the breakoff time. A common method to monitor the breakoff time is to visually monitor the breakoff point. This technique in fact may decrease the sorting purity and efficiency by inadvertently correcting for breakoff time variations. We show explicitly the breakoff time's dependence on a number of physical parameters that can be monitored to increase the stability of the breakoff time. Cytometry Part A 56A:63–70, 2003. © 2003 Wiley‐Liss, Inc.
Development of a photoaffinity label for respiratory syncytial virus inhibitors
Authors: Dischino Douglas D. , Cianci Christopher W. , Civiello Rita , Krystal Mark , Meanwell Nicholas A. , Morimoto Hiromi , Williams Philip G. , Yu Kuo‐Long 
Published: November 2003

AbstractThe syntheses of tritiated and radio‐iodinated respiratory syncytial virus inhibitor photoaffinity labels are reported. 3H‐1‐Isopropyl‐3‐(1‐[2‐(3‐methyl‐3H‐diazirin‐3‐yl)‐ethyl]‐1H‐benzoimidazol‐2‐yl)methyl)‐1,3‐dihydrobenzoimid‐azol‐2‐one (1), was prepared in two steps by the initial tritiation of N‐isopropenyl‐2‐benzimidazolone followed by coupling to 2‐chloromethyl‐1‐[2‐(3‐methyl‐3H‐diazirin‐3‐yl)ethyl]‐1H‐benzoimidazole. The mono and diiodo‐radio‐iodinated derivatives of 1‐(4‐hydroxybenzyl)‐3‐(1‐[2‐(3‐methyl‐3H‐diazirin‐3‐yl)‐ethyl]‐2,3‐dihydro‐1H‐benzo‐imidazol‐2‐ylmethyl)‐1,3‐dihydro‐benzoimidazol‐2‐one (2, 3), were prepared by the radio‐iodination of the corresponding phenol with Na125I and iodogen. Copyright © 2003 John Wiley & Sons, Ltd.