bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokines: Molecular keys to homeostasis, development, and pathophysiology
Authors: Evans Charles H. 
Published: May 2005

AbstractIdentification and definition of the role and diversity of action of cytokines, the regulatory proteins including lymphokines, monokines, interleukins, interferons, and a variety of other growth factors produced by virtually every nucleated cell into the body and having pleiotropic regulatory effects on hematopoietic and many other cell types [Thompson, 1991], are in the forefront of biomedical research. The explosive development of cytokine research is reflected by the inclusion of “cytokine,” first introduced as a term in 1974 to recognize that lymphokines could be produced by other than lymphoid cells in 4,267 biomedical articles published by the end of 1992. From the initial reference to cytokines in 1974 to inclusion in 45 articles in 1985, the doubling of citations each succeeding year, together with 45% of all the citations since 1974 occurring in 1992 alone, attests to the continued rapid expansion of this area of biological research. The important roles of cytokines in many physiological processes and pathophysiological conditions, although largely descriptive in nature, were recognized during the early development of this field of investigation [Balkwill and Burke, 1989; Cohen et al., 1974]. Current and future directions, as highlighted by the series of Prospect articles featuring areas as diverse as embryologic, extracellular matrix, bone, hematologic, and neurologic development and function as well as in the organism's response to foreign organisms in this issue of the journal, are focused on broadening our understanding of the positive and negative influence of cytokines in normal and abnormal differentiation and development and on the molecular pathways underlying cytokine action. The broad areas of cellular biochemistry represented by the Prospects, moreover, emphasize the synthesis and convergence of cytokine research towards an understanding of the critical controls in development and homeostatsis.
Cytokines in the differentiation of Th1/Th2 CD4+ subsets in leishmaniasis
Authors: Reiner Steven L. , Locksley Richard M. 
Published: May 2005

AbstractLeishmania major infect only macrophages in the host, where they reside in endolysosomal compartments into which MHC class II molecules co‐localize. Experimental infection in mice has provided a useful model for the differentiation of Th1 CD4+ effector lymphocytes that are required for the generation of IFN‐γ that activates the macrophage to a microbicidal state. Genetically susceptible BALB/c mice aberrantly activate Th2 CD4+ effector cells that are ineffective in arresting infection. Increasing evidence suggests that, rather than discrete parasite antigens or MHC molecules, cytokines mediate the critical decision in the developmental switch to either the Th1 or Th2 effector phenotype.
Modulation of human microvascular endothelial cell bioenergetic status and glutathione levels during proliferative and differentiated growth
Authors: Mallery S. R. , Lantry L. E. , Laufman H. B. , Stephens R. E. , Brierley G. P. 
Published: May 2005

AbstractDuring angiogenesis, formerly differentiated human microvascular endothelial cells (HMECs) return to a proliferative growth state. Many fundamental questions regarding HMEC function, such as how HMECs adapt to changes in bioenergetic requirements upon return to proliferative growth, remained unanswered. In this study, we evaluated whether modifications in HMEC bioenergetic profiles and glutathione (GSH) levels accompanied the cellular transition between differentiated and proliferative growth. To provide insight into the continuum of cellular adaptations that occur during this transition, we used a method recently developed in our laboratory that induces a state of morphological and functional predifferentiation in HMECs. Cellular morphology, in conjunction with flow cytometric DNA analyses and HMEC functional assays (the directed migration and intercellular association involved in microtubule formation) were employed to validate the HMEC culture state of growth. Analysis of the HPLC nucleotide profiles disclosed several findings common to all culture growth states. These uniform findings, e.g., cellular energy charges > 0.90, and highly reduced redox states, revealed that cultured HMECs maintain high rates of oxidative metabolism. However, there were also significant, culture growth state related differences in the nucleotide profiles. Proliferative HMECs were shown to possess significantly higher (relative to both large vessel endothelial cells, and differentiated HMECs) levels of GSH and specific nucleotides which were related with a return to the active cell cycle‐ATP, GTP, UTP, and CTP, and NADPH. Further, the nucleotide profiles and GSH levels of the predifferentiated HMECs were determined to be intermediate between levels obtained for the proliferative and differentiated HMECs. The results of this study demonstrate that the capacity to modulate their cellular bioenergetic status during growth state transitions is one of the adaptations that enable HMECs to retain a growth state reciprocity. In addition, our findings also show that HMECs, especially during the proliferative growth state, are biochemically distinct from endothelial cells harvested from large vessels, and therefore suggest that HMECs are the cells of choice to employ when studying diseases that affect the human microvasculature.
Organization and expression of H1 histone and H1 replacement histone genes
Authors: Doenecke D. , Albig W. , Bouterfa H. , Drabent B. 
Published: May 2005

AbstractThe H1 family is the most divergent subgroup of the highly conserved class of histone proteins [Cole: Int J Pept Protein Res 30:433–449, 1987]. In several vertebrate species, the H1 complement comprises five or more subtypes, and tissue specific patterns of H1 histones have been described. The diversity of the H1 histone family raises questions about the functions of different H1 subtypes and about the differential control of expression of their genes. The expression of main type H1 genes is coordinated with DNA replication, whereas the regulation of synthesis of replacement H1 subtypes, such as H1° and H5, and the testis specific H1t appears to be more complex. The differential control of H1 gene expression is reflected in the chromosomal organization of the genes and in different promoter structures. This review concentrates on a comparison of the chromosomal organization of main type and replacement H1 histone genes and on the differential regulation of their expression. General structural and functional data, which apply to both H1 and core histone genes and which are covered by recent reviews, will not be discussed in detail.
Microtubular protein in its polymerized or nonpolymerized states differentially modulates in vitro and intracellular fluxes catalyzed by enzymes of carbon metabolism
Authors: Cortassa S. , Aon M. A. , Cáceres A. 
Published: May 2005

AbstractThe fluxes through HK/G6PDH and PK/LDH coupled‐enzymatic reactions were quantified in the presence of physiological concentrations (1–15 μM) of polymerized or non‐polymerized microtubular protein (MTP) from rat brain and in a permeabilized yeast cell system. In vitro enzymatic fluxes were increased by either polymerized or nonpolymerized brain MTP mainly in the lower range of MTP concentration. At fixed MTP concentrations in the flux stimulatory range of HK/G6PDH (1 mg/ml MTP) or PK/LDH (0.4 mg/ml MTP), a hyperbolic and sigmoidal response to NADP and PEP, respectively, was detected. That dependence varied according to the polymeric status of MTP. The specificity of the phenomenon observed in vitro, was tested for the PK/LDH and HK/G6PDH enzymatic couples in the presence of neutral polymers such as glycogen (⩽ 10 mg/ml), poly(ethylene glycol) (up to 10% w/w) or G‐actin (⩽ 1 mg/ml). In permeabilized Saccharomyces cerevisiae cells, the PK‐catalyzed flux was sensitive to microtubule disruption by nocodazole (15 μg/ml). The HK/G6PDH system was not affected by nocodazole showing values of kinetic parameters close to those obtained in vitro in the presence of polymerized brain MTP. Indirect immunofluorescence with specific antibodies against tubulin allowed to confirm the microtubules disruption in the presence of nocodazole in permeabilized yeast cells under the same conditions in which enzymes were assayed intracellularly. The experimental evidence is in agreement with the observed phenomenon of increase in fluxes in the enzymatic reactions assayed to be specifically induced by MTP either in vitro or in situ. The results presented are discussed in terms of the assembly of large supramolecular structures as a supraregulatory mechanism of synchronization of systemic cellular processes such as metabolic fluxes. © 1994 Wiley‐Liss, Inc.
The ubiquitous nature of the progesterone receptor binding factor‐1 (RBF‐1) in avian tissues
Authors: Landers James P. , Subramaniam Malayannan , Gosse Barbara , Weinshilboum Rebecca , Madden Benjamin J. , Spelsberg Thomas C. 
Published: May 2005

AbstractThe avian oviduct receptor binding factor‐1 (RBF‐1) is a 10 kDa nuclear matrix protein that was originally identified through its ability to effect high affinity interaction of activated progesterone receptor (PR) with chromatin. In the present study, the RBF‐1 is shown to not be restricted to reproductive tissues (e.g., oviduct) but present in all avian tissues examined by Western blot analysis with a monoclonal antibody prepared against purified RBF‐1. The heart and pancreas had the highest and lowest RBF‐1 levels, respectively; the concentration ranging by ∼ 50‐fold in these tissues. The 10 kDa size of the RBF‐1 detected in all tissues suggests no significant tissue‐specific differences in the protein. This was consistent with the finding that purified hepatic and oviductal RBF‐1 have identical amino‐terminal sequence. Using a recently isolated cDNA to RBF‐1, the levels of RBF‐1 mRNA were found to correlate well with the ubiquitous presence of the protein as well as tissue‐specific differences in concentration. The presence of RBF‐1 in non‐progesterone responsive tissues suggests the possibility that RBF‐1 may not be specifically involved in PR‐DNA interactions but may play a more diverse role, possibly involving other steroid receptors such as the glucocorticoid receptor. © 1994 Wiley‐Liss, Inc.
Giant cell tumor of bone: A unique paradigm of stromal–hematopoietic cellular interactions
Authors: Robinson Dror , Einhorn Thomas A. 
Published: May 2005

AbstractGiant cell tumor of bone is a progressive, potentially malignant process which destroys skeletal tissue by virtue of its osteoclast complement. As a biological entity it provides a unique natrual model of bone resorption by osteoclasts whose recruitment and development is controlled by a neoplastic population of fibroblast‐like cells. Understanding of the etiopathogenesis of this tumor could provide new insights into the mechanisms underlying osteoblast–osteoclast interactions in normal and diseased bone. Recent studies have shown that the stromal cell component in giant cell tumors is the only proliferating subpopulation of cells, and the giant cells themselves are nonproliferative and reactive. These stromal cells express several genes associated with the osteoblastic phenotype, synthesize, to a limited degree, certain matrix proteins associated with bone, and express several factors which are presumably involved in the recruitment of osteoclasts. In culture, giant cell tumor–associated stromal cells promote the fusion of monocytes and the proliferation of osteoblasts either by the secretion of factors or cell–cell contact. Hence, giant cell tumor of bone is a self‐contained biosystem in which cells of both the stromal and hematopoietic lineages interact in a fashion similar to that observed in normal skeletal remodeling. The neoplastic nature of the stromal component, however, drives the hematopoietic precursors to undergo fusion, produces aggressive bone resorption, and results in extensive skeletal destruction. Examination of the various components of this system could lead to new directions for investigations aimed at a better understanding of osteoblast–osteoclast interactions. © 1994 Wiley‐Liss, Inc.
Role of active and latent transforming growth factor β in bone formation
Authors: Bonewald L. F. , Dallas S. L. 
Published: May 2005

AbstractAt first reading the statement “TGFβ stimulates bone formation but inhibits mineralization” may appear to be an oxymoron. However, the bone formation process can take weeks to months to complete, and the unique properties of TGFβ allow this factor to be stored in bone matrix in a latent form, ready to be activated and inactivated at key, pivotal stages in this long process. TGFβ may act to trigger the cascade of events that ultimately leads to new bone formation. However, once this process is initiated, TGFβ must then be inactivated or removed because if present in the later stages of bone formation, mineralization will be inhibited. The unique properties of TGFβ and its role in bone remodeling are the subject of this review. © 1994 Wiley‐Liss, Inc.
Stabilization of C5a receptor–G‐protein interactions through ligand binding
Authors: Wennogle Lawrence P. , Conder Lynnette , Winter Cindy , Braunwalder Albert , Vlattas Sid , Kramer Richard , Cioffi Catherine , Hu Shou‐Ih 
Published: May 2005

AbstractBinding of biotin‐C5a to the C5a receptor in membrane fragments followed by detergent solubilization and purification with streptavidin‐agarose affinity chromatography resulted in the isolation of a receptor complex with associated G‐proteins. In contrast, when receptor was detergent‐solubilized in the absence of C5a and purified by affinity chromatography with Affigel‐C5a, G‐proteins did not copurify. Since the results indicate that receptor ligation stabilized the receptor–G‐protein interaction to allow purification of the complex, the findings emphasize the dynamic nature of the C5a receptor–effector interactions. When biotin‐C5a–ligated receptor was purified from a mouse cell line overexpressing recombinant human receptor, both Gialpha2 and Gialpha3 subunits copurified, confirming that multiple transducing systems are linked to the C5a receptor. The method of stabilization of receptor‐transducer complexes offers the opportunity to further elaborate the interactions of the C5a receptor with diverse transducing elements and second messenger systems. © 1994 Wiley‐Liss, Inc.
Regulation of TNF‐α release from bone marrow–derived macrophages by vitamin D
Authors: Abu‐Amer Yousef , Bar‐Shavit Zvi 
Published: May 2005

AbstractThe calcium‐regulating hormone 1,25‐dihydroxyvitamin D3[1,25(OH)2D3] is recognized as an immuno‐modulator affecting the activities of macrophages and lymphocytes. We have shown that macrophages harvested from vitamin D–deficient mice (–D MPs) exhibit impaired phagocytic and tumoricidal activities as compared with control cells (+D MPs), and that bone marrow–derived macrophage (BMDM) differentiation is modulated by 1,25(OH)2D3. The release of tumor necrosis factor–α (TNF‐α) by macrophages is considered a major mechanism by which these cells exert their tumoricidal function. This cytokine was also implicated in modulation of bone resorption. In the present study we examine the role of 1,25(OH)2D3 in TNF‐α synthesis and release. BMDMs were harvested from +D and −D mice, cultured in vitro, and their conditioned media were analyzed for the presence of TNF‐α. BMDMs did not release measurable amounts of TNF‐α without stimulation. Addition of endotoxin (LPS) to the cultures resulted in a marked stimulation of TNF‐α release. 1,25(OH)2D3 increased the stimulatory action of LPS, but failed to elicit a stimulatory effect in the absence of LPS. The use of another macrophage activator, interferon‐γ (IFN‐γ), yielded essentially similar results. +D and −D mice were injected with LPS and TNF‐α levels in the serum were measured. A marked reduction (∼ fourfold) in the TNF‐α levels was observed in the serum of −D mice as compared with +D mice. Western blot and immunoprecipitation analyses suggested that the main effect of 1,25(OH)2D3 is on TNF‐α synthesis. Our findings suggest that 1,25(OH)2D3 plays a role in the regulation of TNF‐α secretion by mononuclear phagocytes. © 1994 Wiley‐Liss, Inc.
Inhibition of bone resrption by selctive inactivators of cysteine proteinases
Authors: Hill Peter A. , Buttle David J. , Jones Sheila J. , Boyde Alan , Murata Mitsuo , Reynolds John J. , Meikle Murary C. 
Published: May 2005

AbstractIncativators of cystein proteinases (CPs) were tested as inhibitors of bone resorption in vitro and in vivo. The following four CP inactivators were tested: Ep453, the membrane‐permeant produrg of Ep475, a compound with low membrane pereability which inhibits cathepsins B, L, S, H, and calpain; Ep453, the membrane‐permeant prodrug of Ep475; CA074, a compound with low membrane permeability which selectivly inactives cathepsin B; and CA07Me, the membrane‐permanent prodrug of CA074. The test systems consisted of (1) monitoring the release of radioisotope from prelabelled mousecalvarial explants and (2) assessing the extene of bone resorption in and isolated osteoclast assay using confocal laser microscopy. Ep453, Ep475, and CA074Me inhebited both stimulated and basal bone resorption in vitro while CA074 WASA without effect; The inhibition was reversible and dose dependent. None of the inhibitors affected protein synthesis, DNA synthesis, the PTH‐enhanced secretion of β‐glucuronised, and N‐acetyle‐β‐glucosaminidase, or the spontaneous release of lactate dehyrogenese. Ep453, Ep475, and CA074Me does‐dependently inhibited the resorption activity of isolated areat osteoclassts cultured on bone slices with a maximal effect at 50 μM. The munber of resorption pits and their mean volume was reduced, whilest the mean administration subcutaneously at a dose of 60 μg/g body weight inhibited bone resorption in vivo as measured by an in vivo/in vitro assay, by about 20%. This study demonestration that cathepsins B,L, and/or S are involved in bone resorpotion in vitro and in vivo. Whilest cathepsin L and/or S act extracellularly, and possibly intractually, cathepsin B mediate its effects intracellularly perpheps through the activation of other proteinases involved in subsosteoclastic collagen degradition.
Two‐dimensional protein crystals (S‐layers): Fundamentals and applications
Authors: Sleytr Uwe B. , Sára Margit , Messner Paul , Pum Dietmar 
Published: May 2005

AbstractTwo‐diminsional crystalline surface layers (S‐layers) composed of prtein or glucoprotein subunits are one of the most commonly observed prokaryotic cell envelope structures. lsolated S‐layer Subunits are endowed with the ability to assemble into monomolecular arrays in suspension, on surfaces or interface by an entropy‐driven process. S‐layer lattices are isoporous structures with functional groups located on the surface in an identical position and orientation. These characteristic featupes have alreadu led to applicatioinns of S‐layers as (1) ultrafilration membranes with well‐defiled mmlecular weight cut ‐ooffs and excellent antifouling characteristics, (2) immobilization matrices for functional molecules as required for affiviy and enzyme memberanes, affiniy micricarriers and biosensors, (3) conjugate vaaines, (4) carriers for Langmuir‐Blodgett films and reconstituted biological memberanes, and (5) patterning elements in molecular nanotechnology.
Negative regulatory element in the mammary specific whey acidic protein promoter
Authors: Kolb Andreas F. , Günzburg Walter H. , Albang Richard , Brem Gottfried , Erfle Volkep , Salmons Brian 
Published: May 2005

AbstractExpression of the whey acidic protein (WAP) gene is tightly regulated in a tissue and developmental stage specific manner, in that the WAP gene is exclusively expressed in the mammary gland during pregnancy and lactation. Using both deletion and competition analyses, evidence is provided for the existence of a negative regulatory element (NRE) in the WAP promoter loaated between 413 and 93 with respect to the WAP transcriptional initiation site. This NRE dramatically decreases transcription from linked heterologous promoter‐reporter gene constructs. The activity of NRE requires WAP promoter sequences that are 230 bp apart since subfragments of the NRE fail to inhibit transcription of adjoining reporter genes. Nuclear extracts from different cell types, in whiah the WAP gene is not active, contain a protein or complex that specifically interacts with the entire NRE but not with subfragments of it. The contact points between this protein (NRE binding factor [NBF]) and element have been partially determined. Mutation of the implicated nucleotides severely peduces the ability of NBF to bind, and such promotep fragments dail to alleviate transcpiptional repression in competition experiments. This suggests that NBF binding to the NRE is at least il part responsible for the negative regulation of the WAP promoter. Since NBF is not detectable in the lactating mammary gland, where the WAP gene is expressed, we speculate that it may be a determinant of the expression spectrum of the WAP gene.
Characterization of the major sulfated protein of mouse pancreatic acinar cells: A high molecular weight peripheral membrane glycoprotein of zymogen granules
Authors: De Lisle Robert C. 
Published: May 2005

AbstractThe major sulfated protein of the mouse pancreatic acinar cell, gp300, hsa been identified and characterized with monoclonal and polyclonal antibidies. gp300 is a glycoprotein of Mr = 300,000 which contains ∼40% of metabolically incroporated [35S] sulfate in the acinar cell. Sulfate on gp300 is resistant to hot 1N HCl, but sensitive to alkaline hydrolysis. demonstrating that the sulfate is carbohydrate‐linked rather than tyrosine‐linked. gp300 metabolically labeled with [3H]glucosamine and [35H]sulfate was chemically and enzymaticlly treated followed by Bio‐Gel P‐10 gel filtration. Both labels were resistant to treatments which degrade glycosaminoglycan. Treatment of dual‐labeled gp300 with PNGase F to cleave N‐linked oligosaccharides released ∼17% of [3S]. Mild alkaline borohydride treatment after removal of N‐linked sugar relased the remainder of both labels, indicating the presence of sulfated O‐linked oligosaccharides. Biosynthetic studies and PNGase F digestion indicating the presence of sulfated O‐linked oligosaccharides. Biosunynthetic studies and PNGase digestion F digestion indicate that the core protein is ∼210 KDa, with apparent contrinution of ∼35 KDa N‐linked sugar, and ∼55 KDa O‐linked sugar. Lectin blotting and glycosidase digestion demonstrated the presece of Galβ(1–3)GalNAc and sialic acid α(2–3)Gal in O‐linked oligosaccharide, and Galβ(1–4)GLcNAc in N‐linked oligosaccharide. Immunolocalization and subcellular fractionation showed that gp300 is a peripheral memberane protein localized to the lumenal face of the zymogen granule membrane. gp300 was not secreted in reponse to hormone stimulation ofacini, so it is not a secertroy product. Immunoblot analysis showed that gp300 is present in other gastrointestinal tissues and parotid glands. Localization of this nonsecreted sulfated glycoprotein to exocrine secretory granule membranes suggests that gp300 may have a role in granule bigeneses.