bluuebunny/crossref_metadata_2025_split huggingface dataset:
2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin receptors regulate transcription of the cytochrome P1‐450 gene
Authors: Durrin Linda K. , Jones Phillip B. C. , Fisher Joan M. , Galeazzi Donna R. , Whitlock James P. 
Published: December 2004

AbstractThe environmental contaminant 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) dioxin, produces a diverse set of biological responses which, in some cases, reflects the altered expression of specific genes. An intracellular receptor protein binds TCDD saturably and with high affinity and mediates several of TCDD's biological effects. In mouse hepatoma cells, TCDD induces aryl hydrocarbon hydroxylase activity by activating the transcription of the cytochrome P1‐450 gene. Studies of receptor‐defective variant cells indicate that the activation of cytochrome P1‐450 gene transcription requires functional TCDD receptors. Analysis of the DNA that flanks the 5′‐end of the mouse cytochrome P1‐450 gene reveals at least three control regions: a promoter, an inhibitory element, and a dioxin‐responsive element (DRE). Therefore, expression of the cytochrome P1‐450 gene represents a balance between negative and positive control. The DRE contains two discrete, non‐overlapping DNA domains that respond to TCDD. Each TCDD‐responsive domain acts independently of the other, each requires TCDD receptors for function, and each has the properties of a transcriptional enhancer. For example, the function of the DREs is relatively independent of both their location and their orientation with respect to the promoter. Together, the DREs and the TCDD‐receptor complex constitute a dioxin‐responsive enhancer system. Exposure of cells to TCDD results in the protection of a specific DNA domain from exonuclease digestion. This protection requires TCDD receptors. The protected domain maps to a DRE. This observation implies that the TCDD‐receptor complex interacts with the DRE to activate the transcription of the cytochrome P1‐450 gene.
Genetic evidence that the steroid‐regulated trafficking of cell surface glycoproteins in rat hepatoma cells is mediated by glucocorticoid‐inducible cellular components
Authors: Firestone Gary L. , John Nancy J. , Haffar Omar K. , Cook Paul W. 
Published: December 2004

AbstractThe biological control of posttranslational maturation and compartmentalization reactions that operate upon proteins during transport to their final cellular desti‐ nations is crucial for normal cellular function. Using the expression of mouse mammary tumor virus (MMTV) glycoproteins as sensitive probes in the viral‐ infected rat hepatoma cell line M1.54, we have discovered and documented a novel glucocorticoid‐regulated trafficking pathway that controls the cell surface localization of MMTV glycoproteins. One complement‐selected derivative of M1.54 cells, CR4, failed to compartmentalize cell surface MMTV glycoproteins in the presence of dexamethasone. To test genetically if this glycoprotein trafficking pathway is mediated by cellular or viral gene products, CR4 cells were fused with uninfected Fu5 rat hepatoma cells. Indirect immunofluorescence of CR4 × Fu5 heterokaryons revealed that Fu5 complemented the defect in CR4 only after exposure to 1 μM dexamethasone. The glucocorticoid inhibition of Fu5 proliferation was exploited to recover the receptor‐deficient uninfected derivative EDR3 that expressed a 100‐fold lower level of [3H]dexamethasone binding activity. Analysis of CR4 × EDR3 cell fusions by indirect immunofluorescence revealed that EDR3 cells complemented CR4 in a dexamethasone‐dependent manner, suggesting that EDR3 supplied a functional trafficking component while CR4 provided a functional glucocorticoid receptor to the heterokaryons. Taken together, our results demonstrate that cellular‐encoded glucocorticoid‐inducible components mediate the regulated trafficking of cell surface MMTV glycoproteins.
Heterogeneity of fibroblast response in host‐tumor cell‐cell interactions in metastatic tumors
Authors: Dabbous Mustafa Kh. , Haney Lena , Carter Lee M. , Paul A. K. , Reger James 
Published: December 2004

AbstractThe spread and invasion of tumor cells into host tissues are associated with the release of elevated levels of collagenolytic activity of both host and tumor cell origins. However, the mechanisms of regulation of the enzyme activity is still unresolved. Histological examination of human and animal tumors revealed morphological changes in stromal fibroblasts and mast cells at the tumor periphery. Numerous mast cells appeared at microfoci along the tumor: host tissue junction and mast cell degranulation were associated with collagenolysis. In vitro studies, using rat mammary adenocarcinoma and human lung adenocarcinoma cells, showed that both tumor cells and host fibroblasts participate in matrix degradation. Tumor‐associated stromal fibroblasts released higher levels of enzyme activity than normal fibroblasts and were more responsive to stimulation by tumor‐conditioned media and soluble mast cell products. Host fibroblasts appear to be heterogeneous populations of responsive and nonresponsive subpopulations based on their response to tumor‐ or mast‐cell‐mediated stimulation of collagenase release. Fibroblast subpopulations were obtained by density fractionation of serum‐deprived, synchronized confluent fibroblasts on discontinuous Percoll gradient. Density‐fractionated fibroblast subpopulations differed in their response to stimulation by mast cell products and tumor‐cell‐conditioned media. The stimulatory activity of tumor‐cell‐conditioned media also varied as a function of the metastatic potential of the tumor cells. The data suggest that cellular interactions between tumor cells and select subpopulations of host fibroblasts at the tumor periphery play a key role in host tissue degradation. However, heterogeneity of stromal fibroblasts may determine the site and extent of the tissue damage at foci of tumor invasion.
Developmentally regulated expression of cell surface carbohydrates during mouse embryogenesis
Authors: Muramatsu Takashi 
Published: December 2004

AbstractCell surface carbohydrates undergo marked alterations during mouse embryogenesis. In preimplantation embryos, many carbohydrate markers show stage‐specific expression in diverse ways. In early postimplantation embryos, certain carbohydrate markers are localized in defined regions in the embryo. Important carriers of stage‐specific carbohydrates are the lactoseries structure (Galβ1→4GlcNAc) and the globoseries structure (Galα1→4Gal). Notably, the glycoprotein‐bound large carbohydrate of poly‐N‐acetyllactosamine‐type ([Galβ1→4GlcNAcβ1 → 3]n) carries a number of markers preferentially expressed in early embryonic cells. These markers are of practical value in analyzing embryogenesis and cell differentiation. For example, in order to monitor in vitro differentiation of multipotential embryonal carcinoma cells, stage‐specific embryonic antigen‐1 (SSEA‐1) and the Lotus agglutinin receptor have been used as markers of the undifferentiated cells, and the Dolichos agglutinin receptor has been used as a marker of extraembryonic endoderm cells. Developmental control of cell surface carbohydrates is attained by controlled expression of activities of key glycosyltransferases; for example, the activity of N‐acetylglucosaminide αl → 3 fucosyltransferase is lost during in vitro differentiation of embryonal carcinoma cells to parietal endoderm cells, in parallel to the disappearance of SSEA‐1. Accumulating evidence suggests that poly‐N‐acetyllactosamine‐type glycans that are abundant in early embryonic cells are involved in cell surface recognition of these cells.
Inhibition of endocytosis from coated pits by acidification of the cytosol
Authors: Sandvig Kirsten , Olsnes Sjur , Petersen Ole W. , van Deurs Bo 
Published: December 2004

AbstractBinding and endocytosis of the ligands transferrin, epidermal growth factor (EGF), and ricin were measured in a number of different cell lines after treatment of cells with compounds that react with SH‐groups and under conditions where the cytosolic pH was lowered. N‐ethylmalemide and diamide irreversibly inhibited endocytosis of all ligands tested, whereas low pH in the cytosol strongly inhibited endocytosis of transferrin and EGF. Data obtained by electron microscopy indicated that the formation of coated vesicles from coated pits is inhibited in acidified cells. Entry of ricin was much less affected, and ricin endocytosed under these conditions was able to intoxicate the cells. At low pH in the cytosol there was a calcium‐dependent increase in the number of transferrin receptors at the cell surface. The increase was even larger in the presence of the calcium ionophore A23187, whereas it was completely blocked by the calmodulin antagonists trifluoperazine and W7. The results show that endocytosis from coated pits can be inhibited in a reversible way by acidification of the cytosol and they suggest that a second pathway of endocytosis exists, possibly involving formation of vesicles from uncoated areas of the membrane.
ERV3 Human endogenous provirus mRNAs are expressed in normal and malignant tissues and cells, but not in choriocarcinoma tumor cells
Authors: Cohen Maurice , Kato Nobuyuki , Larsson Erik 
Published: December 2004

AbstractMessenger RNA expression of a human endogenous provirus, ERV3, has been characterized in 170 specimens of normal and malignant human tissues and cells. In contrast to the high expression in first‐trimester and full‐term placental chorionic villi, most other human tissues expressed ERV3 mRNAs at a level of 2–30% of placenta. However, ERV3 mRNAs were not detected in choriocarcinoma tumor cell lines. These studies suggest that the ERV3 provirus may have been preempted for a biological function and disruption of its mRNA expression results in choriocarcinoma.
Heparanases and tumor metastasis
Authors: Nakajima Motowo , Irimura Tatsuro , Nicolson Garth L. 
Published: December 2004

AbstractThe successful penetration of endothelial basement membranes is an important process in the formation of hematogenous tumor metastases. Heparan sulfate (HS) proteoglycan is a major constituent of endothelial basement membranes, and we have found that HS‐degradative activities of metastatic B16 melanoma sublines correlate with their lung‐colonizing potentials. The melanoma HS‐degrading enzyme is a unique endo‐β‐D‐glucuronidase (heparanase) that cleaves HS at specific intrachain sites and is detectable in a variety of cultured human malignant melanomas. The treatment of B16 melanoma cells with heparanase inhibitors that have few other biological activities, such as N‐acetylated N‐desulfated heparin, results in significant reductions in the numbers of experimental lung metastases in syngeneic mice, indicating that heparanase plays an important role in melanoma metastasis. HS‐degrading endoglycosidases are not tumor‐specific and have been found in several normal tissues and cells. There are at least three types of endo‐β‐D‐glucuronidases based on their substrate specificities. Melanoma heparanase, an Mr ∼96,000 enzyme with specificity for β‐D‐glucuronosyl‐N‐acetylglucosaminyl linkages in HS, is different from platelet and mastocytoma endoglucuronidases. Elevated levels of heparanase have been detected in sera from metastatic tumor‐bearing animals and malignant melanoma patients, and a correlation exists between serum heparanase activity and extent of metastases. The results suggest that heparanase is potentially a useful marker for tumor metastasis.
Assessment of biological activity of synthetic fragments of transforming growth factor‐alpha
Authors: Darlak Krzysztof , Franklin Glen , Woost Philip , Sonnenfeld Elaine , Twardzik Daniel , Spatola Arno , Schultz Gregory 
Published: December 2004

AbstractTransforming growth factor‐alpha (TGF‐α) is a single chain polypeptide hormone of 50 amino acids that stimulates growth of some human cancer cells via an autocrine mechanism. The domain(s) of TGF‐α that bind and activate its receptor have not been reported. Hydrophilicity plots of TGF‐α indicate three discrete sequences that are theoretically exposed on the hormone's surface and thus potentially able to interact with the TGF‐α receptor. Fragments of TGF‐α encompassing these hydrophilic domains were prepared by using solid‐phase peptide synthesis (SPPS) techniques and purified by use of high performance liquid chromotography (HPLC). Assessment of biological activity of the TGF‐α fragments indicated that none of the fragments significantly inhibited binding of EOF to the receptor, stimulated DNA synthesis of cells, inhibited EGF‐induced DNA synthesis of cells, stimualted growth of cells in soft agar, or induced phosphorylation of the receptor or p35 protein. These results indicate that the receptor binding domain of TGF‐α is not totally encompassed by any of the separate fragments tested and probably is formed by multiple separate regions of TGF‐α.
Human cytokines, tumor necrosis factor, and interferons: Gene cloning, animal studies, and clinical trials
Authors: Bollon Arthur P. , Berent Susan L. , Torczynski Richard M. , Hill Norwood O. , Lemeshev Yuri , Hill Joseph M. , Jia Feng Lan , Joher Anwar , Pichyangkul Sathit , Khan Amanullah 
Published: December 2004

AbstractPresented is a comprehensive program designed to isolate human cytokine genes and investigate their relative induction, and to analyze cytokine activities in cell culture, animal tumor models, and human clinical trials. Human cytokine cDNAs have been isolated from a cDNA library made from normal human peripheral blood leukocytes (PBLs) treated with Sendai virus and the relative induction of tumor necrosis factor (TNF), alpha and gamma interferons (IFN‐α, IFN‐γ), and interleukin‐1 beta IL‐1β genes has been analyzed. In the Sendai virus‐induced PBL system, IL‐1β mRNA was shown to be approximately twofold higher than TNF or IFN‐α mRNA whereas IFN‐γ mRNA was 50–100‐fold lower than TNF or IFN‐α mRNA. The cytotoxic activity of TNF was analyzed on several cell lines and IFN‐α and IFN‐γ were shown to potentiate TNF cytotoxicity about 2–200‐fold depending on cell lines. The LD50 for recombinant TNF in BALB/c mice was determined to be 6 × 107 U/kg and the therapeutic dose of recombinant TNF in sarcoma 180 bearing BALB/c mice was 3 × 105 U/kg, indicating a wide therapeutic index. Phase I clinical trials of recombinant TNF given I.V. indicated a tolerated dose of 150,000 U/kg with biphasic half‐life (T‐1/2) of 2 and 31 min following TNF injection. Phase II trials of TNF and trials of TNF combined with IFN‐α are in progress. These studies indicate that cytokines such as TNF and IFN‐α are subject to similar induction systems, potentiate each other's activities, and can be tolerated at specific doses for potential therapeutic use.
Calmodulin plays a dominant role in determining neurotransmitter regulation of neuronal adenylate cyclase
Authors: Cooper Dermot M. F. , Ahlijanian Michael K. , Perez‐Reyes Edward 
Published: December 2004

AbstractCa2+, through the mediation of calmodulin, stimulates the activity of brain adenylate cyclase. The growing awareness that fluctuating Ca2+, concentrations play a major role in intracellular signalling prompted the present study, which aimed to investigate the implications for neurotransmitter (receptor) regulation of enzymatic activity of this calmodulin regulation. The role of Ca2+/calmodulin in regulating neurotransmitter‐mediated inhibition and stimulation was assessed in a number of rat brain areas. Ca2+/calmodulin stimulated adenylate cyclase activity in EGTA‐washed plasma preparations from each region studied—from 1.3‐fold (in striatum) to 3.4‐fold (in cerebral cortex). The fold‐stimulation produced by Ca2+/calmodulin was decreased in the presence of GTP, forskolin, or Mn2+. In EGTA‐washed membranes, receptor‐mediated inhibition of adenylate cyclase was strictly dependent upon Ca2+/calmodulin stimulation in all regions, except striatum. A requirement for Mg2+ in combination with Ca2+/calmodulin to observe neurotransmitter‐mediated inhibition was also observed. In contrast, receptor‐mediated stimulation of activity was much greater in the absence of Ca2+/calmodulin. The findings demonstrate that ambient Ca2+ concentrations, in concert with endogenous calmodulin, may play a central role in dictating whether inhibition or stimulation of adenylate cyclase by neurotransmitters may proceed.
Detection of GD3 ganglioside in childhood acute lymphoblastic leukemia with monoclonal antibody to GD3: Restriction to immunophenotypically defined T‐cell disease
Authors: Merritt William D. , Sztein Marcelo B. , Reaman Gregory H. 
Published: December 2004

AbstractWe have recently reported that the disialoganglioside GD3 is found in cellular lipid extracts of T‐cell acute lymphoblastic malignancies (T‐ALL) but is not detectable by resorcinol staining in extracts of non‐T acute lymphoblastic leukemia blasts (non‐T‐ALL). We have now extended this study to assess the detectability of GD3 in T‐ALL vs non‐T‐ALL utilizing an anti‐GD3 antibody, R24. Gangliosides isolated from T‐ALL and non‐T‐ALL blasts by two different methods were separated by thin‐layer chromatography and stained with anti‐GD3 and a control antibody specific for GM3 and sialosylparagloboside (SPG). Anti‐GD3 reactivity was observed in extracts from T‐ALL cells in all cases, whereas GD3 was not detected in any of the non‐T‐ALL samples. The anti‐GM3/SPG antibody stained GM3 in all of the leukemic samples analyzed as well as SPG in the non‐T‐ALL samples. Indirect immunofluorescence was used to assess the expression of GD3 at the surface of leukemic blasts. Fluorescence‐activated cell sorting analysis with R24 showed that whereas T‐ALL blasts were highly reactive with this antibody, non‐T‐ALL blasts were totally unreactive. In an analysis of a larger number of leukemia patients by fluorescence microscopy, 20 out of 28 samples with the T‐ALL phenotype were positive for R24, whereas zero out of 11 non‐T‐ALL samples were reactive. These results confirm our earlier finding of the specificity of GD3 to the T‐ALL subclass of childhood leukemias and furthermore suggest the potential value of anti‐GD3 as an immunological tool for the diagnosis and therapy of T‐cell ALL.
Structures, function, and transformational changes of the sugar chains of glycohormones
Authors: Kobata Akira 
Published: December 2004

AbstractHuman chorionic gonadotropin (hCG), human luteinizing hormone, human thyroid‐stimulating hormone, and human follicle‐stimulating hormone are closely related family of proteins which share a common α‐subunit. However, their sugar moieties are quite different.hCG contains five acidic asparagine‐linked sugar chains. These five sugar chains are derived by sialylation from three neutral oligosaccharides: two biantennary (N‐1 and N‐2) and one monoantennary (N‐3) complex‐type oligosaccharides. Although hCG purified from the urine of pregnant women is more enriched in sialylated sugar chains than that purified from placenta, the molar ratio of N‐1, N‐2, and N‐3 of these two hCGs are the same (1:2:1). Comparative study of the sugar moieties of the α‐ and β‐subunits of hCG revealed that α contains 1 mol each of N‐2 and N‐3, while β contains 1 mol each of N‐l and N‐2. This specific distribution of oligosaccharides at the four asparagine loci of the hCG molecule is now helping us to consider the functional role of the sugar moiety of glycohormones.hCG is produced not only by the trophoblast but also by various trophoblastic diseases. The hCGs purified from the urine of patients with hydatidiform mole contain the same oligosaccharides as normal hCG. However, those from the urine of choriocareinoma patients contain five additional neutral oligosaccharidcs. In contrast, hCGs from invasive‐mole patients contain three of the live oligosaccharidcs, specifically found in choriocarcinoma hCGs.The malignant transformational change of the sugar moiety of hCG can be explained by an increase of a fucosyltransferase, which forms the Fucαl→6GlcNAc group and by ectopic expression and subsequent modification of N‐acetylglucosaminyltransferase IV. The appearance of tumor‐specific sugar chains of hCG has been used to develop a new diagnostic method for invasive mole and choriocarcinoma.
Lymphocyte activation and capping of hormone receptors
Authors: Bourguignon Lilly Y. W. , Jy Wenche , Majercik Mary H. , Bourguignon Gerard J. 
Published: December 2004

AbstractIn this study both a Ligand‐dependent treatment [concanavalin A (Con A)] and a ligand‐independent treatment [high‐voltage pulsed galvanic stimulation (HVPGS)] have been used to initiate lymphocyte activation via a transmembrane signaling process. Our results show that both treatments cause the exposure of two different hormone [insulin and interIeukin‐2 (IL‐2)] receptors within the first 5 min of stimulation. When either insulin or IL‐2 is present in the culture medium, the stimulated lymphocytes undergo the following responses: (1) increased free intra‐cellular Ca2+activity; (2) aggregation of insulin or IL‐2 receptors into patch/cap structures; (3) tyrosine‐kinase‐specific phosphorylation of a 32‐kd membrane protein; and finally (4) induction of DNA synthesis.Further analysis indicates that hormone receptor capping is inhibited by (1) cytochalasin D, suggesting the involvement of microfilaments; (2) sodium azide, indicating a requirement for ATP production; and (3) W‐5, W‐7, and W‐12 drugs, implying a need for Ca2 +/calmodulin activity. Treatment with these metabolic or cytoskeletal inhibitors also prevents both the tyrosine‐kinase‐specific protein phosphorylation and DNA synthesis which normally follow hormone receptor capping. Double immunofluorescence staining shows that actomyosin, Ca2+/calmodulin, and myosin light‐chain kinase are all closely associated with the insulin and IL‐2 receptor cap structures.These findings strongly suggest that an actomyosin‐mediated contractile system (regulated by Ca2+, calmodulin, and myosin light‐chain kinase in an energy‐dependent manner) is required not only for the collection of insulin and IL‐2 receptors into patch and cap structures but also for the subsequent activation of tyrosine kinase and the initiation of DNA synthesis. We, therefore, propose that the exposure and subsequent patching/capping of at least one hormone receptor are required for the activation of mouse splenic T‐Iymphocytes.
Vanadate‐treated baby hamster kidney fibroblasts show cytoskeleton and adhesion patterns similar to their rous sarcoma virus‐transformed counterparts
Authors: Marchisio Pier Carlo , D'Urso Nicoletta , Comoglio Paolo M. , Giancotti Filippo G. , Tarone Guido 
Published: December 2004

AbstractRous sarcoma virus‐trans formed baby hamster kidney fibroblasts (RSV/B4‐BHK) adhere to a fibronectin‐coated substratum by means of dot‐like adhesion sites called podosomes in view of their shape and function as cellular feet (Tarone et al.: Exp Cell Res 159:141, 1985). Podosomes concentrate tyrosine‐phosphorylated proteins, including pp60v‐src, and appear in many cells transformed by oncogenes coding for tyrosine kinases. In this paper we used orthovanadate, an inhibitor of phosphotyrosine phosphatases, in order to increase the cellular concentration of phosphotyrosine and to study whether this treatment induced the cytoskeleton remodeling leading to the formation of podosomes. Indeed, orthovanadate (10–100 μM) induced in a time‐and dose‐dependent manner the redistribution of F‐actin and the formation of podosomes in BHK cells. Cytoskeleton remodeling occurred along with a marked increase of tyrosine phosphorylatcd proteins. The vanadate effect on the cytoskeletal phenotype was enhanced by the simultaneous treatment of cells with a phorbol ester. Under the latter conditions almost all BHK cells showed podosomes. The vanadate effect was reversible insofar as podosomes and tyrosine‐phosphorylated proteins disappeared. Then, vanadate treatment of normal cells induced the cascade of events leading to the cytoskeletal changes typical of transformation and suggested that the transformed cytoskeletal phenotype may he primarily induced by the tyrosine phosphorylation of unknown target(s) operated by endogenous kinases.