bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apoptosis‐ and cell cycle‐associated gene expression profiling of histiocytic necrotising lymphadenitis
Authors: Ohshima Koichi , Karube Kennosuke , Hamasaki Makoto , Makimoto Yoshifumi , Fujii Akira , Kawano Riko , Tutiya Takeshi , Yamaguchi Takahiro , Suzumiya Junji , Kikuchi Masahiro 
Published: April 2004

Abstract:Cell death is of two types; necrosis and apoptosis. In histiocytic necrotising lymphadenitis (HNL), apoptosis is the main form of cell death. Apoptosis results in the formation of nuclear debris, which is one of the characteristic features of HNL. We previously reported that in HNL it is predominantly CD8‐positive cytotoxic T cells that undergo apoptosis; however, the majority of proliferating cells are also CD8‐positive T cells. Recent advances in technical and analytical methods have facilitated the parallel quantitation of expression of numerous genes using DNA microarrays. The technology is particularly well suited to compare differences in gene expression between normal tissues and inflammatory disease. To investigate the apoptosis‐ and cell cycle‐associated gene expression in HNL, we analysed five cases each of HNL and non‐specific lymphadenitis (NSL), using ready‐made microarrays, including cyclins and caspases, and immunohistochemical staining of caspase‐3, ssDNA, bcl‐2 and NF‐κB. Caspase‐3‐ and ssDNA‐positive apoptotic cells were frequently detected in HNL, but were rare in NSL. However, bcl‐2‐ and NF‐κB‐positive cells were rare in HNL. Gene expression tree analysis of DNA microarrays showed different clustering of HNL and NSL. In comparison with NSL, HNL exhibited diffuse upregulation of these gene profiles, particularly of cyclins and caspases (ratio; cyclin A2, 2.72; caspase‐6, 2.43; caspase‐3, 2.02); whereas, Mcl‐1, which has been shown to delay apoptosis, was downregulated (ratio, 0.71), as confirmed by reverse transcriptase‐polymerase chain reaction (RT‐PCR). Almost all apoptosis‐associated genes, especially caspases, were upregulated, and apoptosis inhibitory genes, including bcl‐2 by immunohistochemistry, were downregulated in all five cases with HNL. In addition, cell cycle‐associated genes were upregulated in all. These findings confirm that both apoptosis and proliferation are simultaneously present in HNL lesions.
Molecular characterization of three novel Fanconi anemia mutations in Israeli Arabs
Authors: Tamary Hannah , Dgany Orly , Toledano Helen , Shalev Zvi , Krasnov Tatyana , Shalmon Lea , Schechter Tali , Bercovich Dani , Attias Dina , Laor Ruth , Koren Ariel , Yaniv Isaac 
Published: April 2004

Abstract:Objectives:  In a previous study, we investigated the molecular basis of Fanconi anemia (FA) in 13 unrelated Israeli Jewish FA patients and identified four ethnicity specific mutations. In the present study we extended our study to Israeli Arab patients.Methods:  We studied three consanguineous families with nine FA patients and an additional unrelated patient. DNA single‐strand conformation polymorphism of each exon of the FANCA and FANCG genes was followed by sequence analysis of the aberrantly migrating fragments and by reverse transcriptase‐polymerase chain reaction (RT‐PCR) analysis of the splice‐site mutations identified.Results:  Three unique disease‐causing mutations were identified: (i) FANCA gross deletion of exons 6–31; (ii) FANCA splice‐site mutation IVS 42‐2A>C; (iii) FANCG splice‐site mutation IVS4+3A>G. Sequence analysis of the FANCA gross deletion revealed recombination between two highly homologous Alu elements. cDNA analysis of the two splice mutations suggested intron 42 retention in FANCA IVS 42‐2A>C and exon 4 skipping in FANCG IVS4+3A>G. The clinical condition of eight patients with FANCA mutations was severe.Conclusions:  Two unique FANCA mutations and one FANCG mutation were identified in Israeli Arab FA patients. Deletion of FANCA exon 6–31 as in previously described gross deletions was within introns rich in Alu repeats. To the best of our knowledge, the FANCA IVS 42‐2A>C mutation is the first in this gene to result in intron retention. Further analysis of FA mutations will enable prenatal diagnosis and a rational therapeutic approach including frequent monitoring and early bone marrow transplantation.
Patterns and distribution of tobacco consumption in India: cross sectional multilevel evidence from the 1998-9 national family health survey
Authors: Subramanian S V , Nandy Shailen , Kelly Michelle , Gordon Dave , Smith George Davey 
Published: April 2004

AbstractObjective To investigate the demographic, socioeconomic, and geographical distribution of tobacco consumption in India.Design Multilevel cross sectional analysis of the 1998-9 Indian national family health survey of 301 984 individuals in 92 447 households in 3215 villages in 440 districts in 26 states.Setting Indian states.Participants 301 984 adults (≥ 18 years).Main outcome measures Dichotomous variable for smoking and chewing tobacco for each respondent (1 if yes, 0 if no) as well as a combined measure of whether an individual smokes, chews tobacco, or both.Results Smoking and chewing tobacco are systematically associated with socioeconomic markers at the individual and household level. Individuals with no education are 2.69 times more likely to smoke and chew tobacco than those with postgraduate education. Households belonging to the lowest fifth of a standard of living index were 2.54 times more likely to consume tobacco than those in the highest fifth. Scheduled tribes (odds ratio 1.23, 95% confidence interval 1.18 to 1.29) and scheduled castes (1.19, 1.16 to 1.23) were more likely to consume tobacco than other caste groups. The socioeconomic differences are more marked for smoking than for chewing tobacco. Socioeconomic markers and demographic characteristics of individuals and households do not account fully for the differences at the level of state, district, and village in smoking and chewing tobacco, with state accounting for the bulk of the variation in tobacco consumption.Conclusion The distribution of tobacco consumption is likely to maintain, and perhaps increase, the current considerable socioeconomic differentials in health in India. Interventions aimed at influencing change in tobacco consumption should consider the socioeconomic and geographical determinants of people's susceptibility to consume tobacco.
On the Depth and Dynamics of Online Search Behavior
Authors: Johnson Eric J. , Moe Wendy W. , Fader Peter S. , Bellman Steven , Lohse Gerald L. 
Published: April 2004

This paper examines search across competing e-commerce sites. By analyzing panel data from over 10,000 Internet households and three commodity-like products (books, compact discs (CDs), and air travel services), we show that the amount of online search is actually quite limited. On average, households visit only 1.2 book sites, 1.3 CD sites, and 1.8 travel sites during a typical active month in each category. Using probabilistic models, we characterize search behavior at the individual level in terms of (1) depth of search, (2) dynamics of search, and (3) activity of search. We model an individual's tendency to search as a logarithmic process, finding that shoppers search across very few sites in a given shopping month. We extend the logarithmic model of search to allow for time-varying dynamics that may cause the consumer to evolve and, perhaps, learn to search over time. We find that for two of the three product categories studied, search propensity does not change from month to month. However, in the third product category we find mild evidence of time-varying dynamics, where search decreases over time from already low levels. Finally, we model the level of a household's shopping activity and integrate it into our model of search. The results suggest that more-active online shoppers tend also to search across more sites. This consumer characteristic largely drives the dynamics of search that can easily be mistaken as increases from experience at the individual level.
D‐Amino Acid Homopiperazine Amides: Discovery of A‐320436, a Potent and Selective Non‐Imidazole Histamine H3‐Receptor Antagonist
Authors: Curtis Michael P. , Dwight Wesley , Pratt John , Cowart Marlon , Esbenshade Timothy A. , Krueger Kathy M. , Fox Gerard B. , Pan Jia Bao , Pagano Thomas G. , Hancock Arthur A. , Faghih Ramin , Bennani Youssef L. 
Published: April 2004

AbstractStructure‐activity relationships of homopiperazine‐containing alkoxybiaryl nitriles employing various D‐amino acid moieties and their N‐furanoyl analogues were undertaken. This led to A‐320436, a potent and selective non‐imidazole H3‐receptor antagonist possessing balanced affinity for both rat and human H3‐receptors. This compound was shown to demonstrate in vitro and in vivo functional antagonism and is non‐neurotoxic at doses (i.p.) up to 163 mg/kg in a general observation test.
Loading of the Antigen‐Presenting Protein CD1d with Synthetic Glycolipids
Authors: Wallner Fredrik K. , Chen Liying , Moliner Annalena , Jondal Mikael , Elofsson Mikael 
Published: April 2004

AbstractCD1 proteins present mammalian and microbial lipid and glycolipid antigens to different subsets of T cells. Few such antigens have been identified and the binding of these to CD1 molecules has mainly been studied by using responding T cells in cellular assays or recombinant solid‐phase CD1 proteins. In the present study we use four different glycolipids, some of which contain tumor‐associated carbohydrate antigens, to develop a procedure to easily detect binding of glycolipids to CD1 proteins on viable cells. Two of these glycolipids are novel glycoconjugates containing α‐D‐N‐acetylgalactosamine (α‐GalNAc) that were prepared by a combined solution and solid‐phase approach. The key step, a Fischer glycosylation of 9‐fluorenylmethoxycarbonylaminoethanol with GalNAc, furnished the α‐glycoside 4 in 34 % yield. Cells were incubated with glycolipids and stained with monoclonal antibodies specific for the carbohydrate part. The level of glycolipid bound to cells was then determined by flow cytometry with a secondary antibody labeled with fluorescein isothiocyanate. All four glycolipids were found to bind to CD1d but with different selectivity. The loading was dose dependent and could be inhibited by an established CD1d ligand, α‐galactosylceramide. Through use of this procedure, glycolipids were selectively loaded onto CD1d expressed on professional antigen‐presenting cells for future use as cellular vaccines. Moreover, the glycolipids described in this study represent novel CD1d‐binding ligands that will be useful derivatives in the study of CD1d‐dependent immune responses, for example, against tumors.
Fluorescent Labelled Thiourea‐Bridged Glycodendrons
Authors: Krist Pavel , Vannucci Luca , Kuzma Marek , Man Petr , Sadalapure Kashinath , Patel Anupama , Bezouška Karel , Pospíšil Milan , Petruš Ladislav , Lindhorst Thisbe K. , Křen Vladimír 
Published: April 2004

AbstractGlcNAc‐coated glycodendrimers, which are polyvalent glycomimetics, display strong in vitro affinity for the rat natural killer cell protein‐1A (NKR‐P1A), a C‐type lectin‐like receptor of natural killer (NK) cells in rats, humans and some strains of mice. Administration of these compounds in vivo results in a substantial increase in the antitumour activity with involvement of the natural cell immunity. To clarify the in vitro and in vivo fate of these molecules, we synthesized labelled glycodendron analogues of the previously studied glycodendrimers. Labelling with fluorescent tags enabled the localization of the glycodendrons in white blood cells, tumours and other tissues by using different imaging techniques such as fluorescence and confocal microscopy. These studies are useful for probing the mechanism of action and fate of artificial ligands and the cell receptors involved.
The Molecular Mechanism of Membrane Proteins Probed by Evanescent Infrared Waves
Authors: Nyquist Rebecca M. , Ataka Kenichi , Heberle Joachim 
Published: April 2004

AbstractThe catalytic action of membrane proteins is vital to many cellular processes. Yet the molecular mechanisms remain poorly understood. We describe here the technique of evanescent infrared difference spectroscopy as a tool to decipher the structural changes associated with the enzymatic action of membrane proteins. Functional changes as minute as the protonation state of individual amino acid side chains can be observed and linked to interactions with a ligand, agonist, effector, or redox partner.
Neem—An Omnipotent Plant: A Retrospection
Authors: Brahmachari Goutam 
Published: April 2004

AbstractNeem (Azadirachta indica A. Juss.) has universally been accepted as a wonder tree because of its diverse utility. Multidirectional therapeutic uses of neem have been known in India since the Vedic times. Besides its therapeutic efficacies, neem has already established its potential as a source of naturally occurring insecticide, pesticide and agrochemicals. Safe and economically cheaper uses of different parts of neem in the treatment of various diseases and in agriculture are discussed in this article. It further deals with the active chemical constituents of various neem formulations. Commercially available neem products are also mentioned along with their respective applications. Furthermore, evaluation of safety aspects of different parts of neem and neem compounds along with commercial formulations are also taken into consideration. Systematic scientific knowledge on neem reported so far is thus very useful for the wider interests of the world community.
Autodisplay of Active Sorbitol Dehydrogenase (SDH) Yields a Whole Cell Biocatalyst for the Synthesis of Rare Sugars
Authors: Jose Joachim , von Schwichow Steffen 
Published: April 2004

AbstractWhole cell biocatalysts are attractive technological tools for the regio‐ and enantioselective synthesis of products, especially from substrates with several identical reactive groups. In the present study, a whole cell biocatalyst for the synthesis of rare sugars from polyalcohols was constructed. For this purpose, sorbitol dehydrogenase (SDH) from Rhodobacter sphaeroides, a member of the short‐chain dehydrogenase/reductase (SDR) family, was expressed on the surface of Escherichia coli using Autodisplay. Autodisplay is an efficient surface display system for Gram‐negative bacteria and is based on the autotransporter secretion pathway. Transport of SDH to the outer membrane was monitored by SDS‐PAGE and Western blotting of different cell fractions. The surface exposure of the enzyme could be verified by immunofluorescence microscopy and fluorescence activated cell sorting (FACS). The activity of whole cells displaying SDH at the surface was determined in an optical test. Specific activities were found to be 12 mU per 3.3×108 cells for the conversion of D‐glucitol (sorbitol) to D‐fructose, 7 mU for the conversion D‐galactitol to D‐tagatose, and 17 mU for the conversion of L‐arabitol to L‐ribulose. The whole cell biocatalyst obtained by surface display of SDH could also produce D‐glucitol from D‐fructose (29 mU per 3.3×108 cells).
Development of Novel 1,2,3,4‐Tetrahydroisoquinoline Derivatives and Closely Related Compounds as Potent and Selective Dopamine D3 Receptor Ligands
Authors: Mach Ulrich R. , Hackling Anneke E. , Perachon Sylvie , Ferry Sandrine , Wermuth Camille G. , Schwartz Jean‐Charles , Sokoloff Pierre , Stark Holger 
Published: April 2004

AbstractBased on N‐alkylated 1,2,3,4‐tetrahydroisoquinoline derivatives, which are structurally related to the partial agonist BP 897, a series of novel, selective dopamine D3 receptor antagonists has been synthesised. Derivatisation included changes in the arylamide moiety and the tetrahydroisoquinoline substructure leading to compounds with markedly improved selectivities and affinities in the low nanomolar concentration range. From the 55 structures presented here, (E)‐3‐(4‐iodophenyl)‐N‐(4‐(1,2,3,4‐tetrahydroisoquinolin‐2‐yl)butyl)acrylamide (51) has high affinity (Ki(hD3)=12 nM) and a 123‐fold preference for the D3 receptor relative to the D2 receptor subtype. Its pharmacological profile offers the prospect of a novel radioligand as a tool for various dopamine D3‐receptor‐related in vitro and in vivo investigations.
Studies on the dehydrative cyclization of epimeric 4‐(L‐xylo and L‐lyxo‐tetritol‐1‐yl)‐2‐phenyl‐2H‐1,2,3‐triazoles. Circular dichroism and NMR assignment of the formed anomeric C‐nucleoside L‐threofuranosyl triazole analogs
Authors: Sallam Mohammed A.E. , Louis Farida F. 
Published: April 2004

AbstractDehydrative cyclization of epimeric 4‐(L‐xylo‐ and L‐lyxo‐tetritol‐1‐yl)‐2‐phenyl‐2H‐1,2,3‐triazoles afforded the anomeric α and β‐L‐threofuranosyl analogs. The anomeric configuration of the formed anomeric C‐nucleoside analogs was determined by circular dichroism and NMR spectroscopy. Chirality 16:331–335, 2004. © 2004 Wiley‐Liss, Inc.
Aluminum chloride‐mediated kinetic resolution of racemic γ‐substituted‐γ‐lactones
Authors: Patil Sudhir T. , Karnik Anil V. 
Published: April 2004

AbstractPreparation of chiral γ‐substituted‐γ‐lactones (1) through kinetic resolution is described. (S)‐(–)‐1‐Phenylethylamine (2) in the presence of anhydrous AlCl3 shows satisfactory levels of enantioselection in reaction with racemic γ‐substituted‐γ‐lactones 1, where (R)‐1 remains unreacted, while (S)‐1 is enantioselectively converted to the ring‐opened amide (S,S)‐4. The enantiopurity of (R)‐(+)‐ γ‐substituted γ‐lactones recovered ranges from 62–98% ee. Chirality 16:336–338, 2004. © 2004 Wiley‐Liss, Inc.
Fibroblast growth factor receptor‐3 is expressed in undifferentiated intestinal epithelial cells during murine crypt morphogenesis
Authors: Vidrich Alda , Buzan Jenny M. , Ilo Chibuzo , Bradley Leigh , Skaar Kirstin , Cohn Steven M. 
Published: April 2004

AbstractPrior studies have demonstrated that fibroblast growth factor receptor‐3 (FGFR‐3) regulates proliferation of undifferentiated intestinal epithelial cells in vitro. However, the function(s) of FGFR‐3–mediated signaling during intestinal development and epithelial differentiation in vivo remain unknown. The goal of this study was to define the temporal, regional, and cell‐specific patterns of FGFR‐3 expression and its ligands during normal intestinal ontogeny and epithelial regeneration. Both the IIIb and IIIc isoforms of FGFR‐3 mRNA, which result from differential splicing of the FGFR‐3 primary transcript, were detected in mouse small intestine as early as embryonic day 16. FGFR‐3 levels peaked in the small intestine from 7 to 21 days after birth and decreased thereafter to reach the low levels observed in adult mice. FGFR‐3 IIIb and IIIc mRNA levels were highest in the duodenum and proximal jejunum with lower levels of both seen in the distal jejunum, ileum, and colon. FGFR‐3 was expressed in a subset of proliferating undifferentiated crypt epithelial cells located in the intervillous epithelium and in the lower half of nascently forming crypts but not in differentiated epithelial cell types. FGFR‐3 IIIb was the dominant isoform expressed in both small intestinal and colonic crypts. Expression of FGF1, FGF2, and FGF9, known ligands of FGFR‐3, paralleled patterns of FGFR‐3 expression during gut development. These data suggest that signaling through FGFR‐3 plays a role in regulating morphogenic events involved in formation of intestinal crypts and/or the fate of epithelial stem cells. Developmental Dynamics 230:114–123, © 2004 Wiley‐Liss, Inc.
Cadherin‐2 function in the cranial ganglia and lateral line system of developing zebrafish
Authors: Kerstetter A.E. , Azodi E. , Marrs J.A. , Liu Q. 
Published: April 2004

AbstractCadherins are cell surface molecules that mediate cell–cell adhesion through homophilic interactions. Cadherin‐2 (also called N‐cadherin), a member of classic cadherin subfamily, has been shown to play important roles in development of a variety of tissues and organs, including the nervous system. We recently reported that cadherin‐2 was strongly expressed by the majority of cranial ganglia and lateral line system of developing zebrafish. To gain insight into cadherin‐2 role in the formation of these structures, we have used several markers to analyze zebrafish embryos injected with a specific cadherin‐2 antisense morpholino oligonucleotide (cdh2MO). We find that development of several cranial ganglia, including the trigeminal, facial, and vagal ganglia, and the lateral line ganglia and neuromasts of the cdh2MO‐injected embryos are severely disrupted. These phenotypes were confirmed by analyzing a cadherin‐2 mutant, glass onion. Our results suggest that cadherin‐2 function is crucial for the normal formation of the zebrafish lateral line system and a subset of cranial ganglia. Developmental Dynamics 230:137–143, 2004. © 2004 Wiley‐Liss, Inc.
Regional expression of L‐type calcium channel subunits during cardiac development
Authors: Acosta Lourdes , Haase Hannelore , Morano Ingo , Moorman Antoon F.M. , Franco Diego 
Published: April 2004

AbstractThe contraction of cardiomyocytes is initiated by the entrance of extracellular calcium through specific calcium channels. Within the myocardium, L‐type calcium channels are most abundant. In the heart, the main pore‐forming subunit is the α1C, although there is a larger heterogeneity on auxiliary β subunits. We have analyzed the distribution pattern of different α1C and β subunits during cardiac development by immunohistochemistry. We observed homogeneous expression of α1C and β subunits within the early tubular heart, whereas regional differences are observed during the late embryogenesis. β2 and β4 show differential expression within the embryonic myocardium. α1CD1 displays only a transient enhanced expression in the ventricular conduction system. In adult heart, the expression of the different calcium channel subunits analyzed is homogeneous along the entire myocardium except for α1CD1 that is practically undetectable. These findings suggest that β subunits might play a major role in conferring calcium handling heterogeneity within the developing embryonic myocardium, while α1C subunits might contribute just transiently. Developmental Dynamics 230:131–136, 2004. © 2004 Wiley‐Liss, Inc.
Expression of chicken slug and snail in mesenchymal components of the developing central nervous system
Authors: Marin Faustino , Nieto M. Angela 
Published: April 2004

AbstractSlug and Snail are members of the Snail family of zinc‐finger transcription factors. They are involved in triggering epithelial–mesenchymal transitions during the development of the neural crest and the mesoderm. We have analyzed by in situ hybridization their expression in the nervous system of chicken embryos at mid‐gestation stages, from 4 to 15 days of incubation. We show that Slug and Snail show specific and nonoverlapping expression patterns in mesenchymal structures associated to the developing central nervous system. While Slug is expressed in the meninges and in the pericytes/vascular smooth muscle cells (vSMCs) of the brain, the spinal cord and other embryonic tissues, Snail is expressed in the stroma of the choroid plexus of both the hindbrain and the forebrain. Developmental Dynamics 230:144–148, 2004. © 2004 Wiley‐Liss, Inc.