Ciba Foundation symposium最新文献_第8页

Health impacts of large releases of radionuclides. Cytogenetic effects as quantitative indicators of radiation exposure. 放射性核素大量释放对健康的影响。作为辐射照射定量指标的细胞遗传学效应。

Ciba Foundation symposium Pub Date : 1997-01-01

M Bauchinger

{"title":"Health impacts of large releases of radionuclides. Cytogenetic effects as quantitative indicators of radiation exposure.","authors":"M Bauchinger","doi":"","DOIUrl":"","url":null,"abstract":"Scoring of dicentrics in metaphase preparations of human T lymphocytes is the method of choice for estimating individual whole-body doses of radiation exposure. A quantification of partial-body exposures or non-uniform distribution of the dose is more complicated but it can be achieved by using specific mathematical approaches. For retrospective biodosimetry, conventional scoring of dicentrics is less precise because these unstable aberrations are eliminated with time post-exposure. Symmetrical translocations are not selected against during mitotic division in the haematopoietic cell reproductive centres, so the frequencies of these stable aberrations are generally assumed to remain constant even for decades. They can now be analysed precisely by fluorescence in situ hybridization using whole chromosome-specific DNA probes (chromosome painting) with an alpha-satellite DNA probe for centromere detection. Based on in vitro calibration curves established with single or multicolour paints covering 4-22% of the total human genomic DNA content, scoring of translocations has been applied for dose reconstruction in smaller groups of atomic bomb survivors and victims of the Chernobyl and Goiania radiation accidents. However, prior to routine use, the method requires further validation. Such work includes the precise evaluation of the unexpectedly high frequency of complex exchanges (> or = 3 breaks in > or = 2 chromosomes) found both at > 2 Gy doses of low linear energy transfer (LET) radiation and generally for high LET alpha-particles. Data on the long-term stability of translocations and the appearance of clonal abberrations, as well as improved measurements of the linear coefficient of standard calibration curves, are also required.","PeriodicalId":10218,"journal":{"name":"Ciba Foundation symposium","volume":"203 ","pages":"188-99; discussion 199-204, 232-4"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20272098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Determinants and mechanisms of enamel fluorosis. 氟牙釉质中毒的决定因素和机制。

Ciba Foundation symposium Pub Date : 1997-01-01 DOI: 10.1002/9780470515303.ch16

G M Whitford

{"title":"Determinants and mechanisms of enamel fluorosis.","authors":"G M Whitford","doi":"10.1002/9780470515303.ch16","DOIUrl":"https://doi.org/10.1002/9780470515303.ch16","url":null,"abstract":"Enamel fluorosis occurs when fluoride concentrations in or in the vicinity of the forming enamel are excessive during its pre-eruptive development. Fluoride concentrations in plasma, enamel and other tissues reflect the difference between intake and excretion, i.e. fluoride balance. In addition to the diet, modern sources of ingested fluoride include a variety of dental products, some of which have been identified as risk factors for fluorosis. Fluoride absorption is inversely related to dietary calcium which, at high concentrations, may cause net fluoride secretion into the gastrointestinal tract. The excretion of absorbed fluoride occurs almost exclusively via the kidneys, a process which is directly related to urinary pH. Thus, fluoride balance and tissue concentrations and the risk of fluorosis are increased by factors such as high protein diets, residence at high altitude, and certain metabolic and respiratory disorders that decrease pH. Factors that increase urinary pH and decrease the balance of fluoride include vegetarian diets, certain drugs and some other medical conditions. Although several other fluoride-induced effects might be involved in the aetiology of fluorosis, it now appears that inhibition of enzymatic degradation of amelogenins, which may delay their removal from the developing enamel and impair crystal growth, may be of critical importance. In addition to the effects of fluoride, disturbances in enamel formation that can be confused with fluorosis are caused by chronic acidosis and hypoxia independently of the level of fluoride exposure.","PeriodicalId":10218,"journal":{"name":"Ciba Foundation symposium","volume":"205 ","pages":"226-41; discussion 241-5"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/9780470515303.ch16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20134685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 64

Cross-species comparisons. 跨物种的比较。

Ciba Foundation symposium Pub Date : 1997-01-01 DOI: 10.1002/9780470515372.ch10

D F Sherry

引用次数: 29

Health impacts of large releases of radionuclides. The fate and impact of radiocontaminants in urban areas. 放射性核素大量释放对健康的影响。放射性污染物在城市地区的命运和影响。

Ciba Foundation symposium Pub Date : 1997-01-01 DOI: 10.1002/9780470515006.ch8

J Roed, K G Andersson, C Lange

引用次数: 1

Repair and processing events at DNA ends. DNA末端的修复和加工过程。

Ciba Foundation symposium Pub Date : 1997-01-01 DOI: 10.1002/9780470515433.ch13

T Lindahl, D E Barnes, A Klungland, V J Mackenney, P Schär

引用次数: 5

Drosophila telomere elongation. 果蝇端粒伸长。

Ciba Foundation symposium Pub Date : 1997-01-01 DOI: 10.1002/9780470515433.ch5

H Biessmann, M F Walter, J M Mason

引用次数: 21

Oligonucleotide therapeutics for human leukaemia. 人类白血病的寡核苷酸疗法。

Ciba Foundation symposium Pub Date : 1997-01-01 DOI: 10.1007/978-3-0348-8946-9_9

A. Gewirtz

引用次数: 5

Controversies in the cellular pharmacology of oligodeoxynucleotides. 寡脱氧核苷酸的细胞药理学争议。

Ciba Foundation symposium Pub Date : 1997-01-01 DOI: 10.1002/9780470515396.ch7

C. Stein

{"title":"Controversies in the cellular pharmacology of oligodeoxynucleotides.","authors":"C. Stein","doi":"10.1002/9780470515396.ch7","DOIUrl":"https://doi.org/10.1002/9780470515396.ch7","url":null,"abstract":"Phosphodiester and phosphorothioate oligodeoxynucleotides are polyanions that cannot passively diffuse across cell membranes. Instead, the processes of adsorbtive endocytosis and pinocytosis probably account for the great majority of oligodeoxynucleotide internalization in most cell types. Oligodeoxynucleotides can adsorb to heparin-binding, cell surface proteins. An example of such a protein is the integrin Mac-1 (alpha M beta 2; CR3; CD11b/CD18), a receptor for fibrinogen which is found on neutrophils, macrophages and natural killer cells. Up-regulation of neutrophil cell surface Mac-1 expression by interleukin 8, arachidonic acid or tumour necrosis factor alpha leads to increased cell surface oligodeoxynucleotide binding and internalization. Binding and internalization can be blocked by both fibrinogen and by anti-Mac-1 monoclonal antibodies. Subsequent to internalization, oligodeoxynucleotides reside in subcellular vesicular structures, i.e. endosomes and lysosomes. However, in the absence of permeabilizing agents, these compartments may be sites of sequestration and the oligomers may be unavailable for antisense activity. At present, controversy surrounds the use of guanosine-rich phosphorothioate oligodeoxynucleotides as antisense agents. We examined the ability of the 24mer antisense rel A (p65) phosphorothioate oligodeoxynucleotide to inhibit nuclear translocation of NF kappa B in K-BALB murine fibroblasts. 7-Deaza-2'-deoxyguanosine substitution in the 5' guanosine quartet region demonstrated that inhibition of nuclear translocation could not be due to a Watson-Crick antisense effect. Rather, we favour the explanation that the parent molecule may be a sequence-specific, apatameric decoy.","PeriodicalId":10218,"journal":{"name":"Ciba Foundation symposium","volume":"8 1","pages":"79-89; discussion 89-93"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81916316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biological aspects of macrophage-stimulating protein (MSP) and its receptor. 巨噬细胞刺激蛋白(MSP)及其受体的生物学特性。

Ciba Foundation symposium Pub Date : 1997-01-01 DOI: 10.1002/9780470515457.CH12

E. Leonard

{"title":"Biological aspects of macrophage-stimulating protein (MSP) and its receptor.","authors":"E. Leonard","doi":"10.1002/9780470515457.CH12","DOIUrl":"https://doi.org/10.1002/9780470515457.CH12","url":null,"abstract":"Macrophage-stimulating protein (MSP; also known as HGF-like protein [HGFl]) is a 78 kDa plasma protein that is secreted by the liver into the circulation as single-chain, biologically inactive pro-MSP. The presence of conserved triple disulfide loops (kringles) places pro-MSP in a family of coagulation system serine protease zymogens that are activated by proteolytic cleavage. Although pro-MSP has lost enzymic activity, it has retained the activation mechanism, in that proteolytic cleavage at a single site yields biologically active disulfide-linked alpha beta-chain heterodimeric MSP. The MSP receptor is a transmembrane protein tyrosine kinase. MSP causes phosphorylation of the receptor cytoplasmic domain, association of phosphatidylinositol (PI)-3 kinase with the receptor, and phosphorylation of receptor-bound PI-3 kinase. Inhibition of PI-3 kinase by wortmannin prevents MSP action on cells. MSP stimulates motility of murine resident peritoneal macrophages. However, it does not act on exudate macrophages or blood monocytes, since these earlier maturational stages of the lineage do not express the receptor. MSP also stimulates keratinocyte cell lines, causing either chemotactic responses or increased cell numbers in culture. We suggest that pro-MSP diffuses into local tissue sites, where proteolytic cleavage to MSP results in stimulation of keratinocytes and macrophages. It possibly plays a role in tissue injury or wound healing.","PeriodicalId":10218,"journal":{"name":"Ciba Foundation symposium","volume":"44 1","pages":"183-91; discussion 192-7"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82051321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 18

Differentiation and functions of T cell subsets. T细胞亚群的分化和功能。

Ciba Foundation symposium Pub Date : 1997-01-01 DOI: 10.1002/9780470515280.ch10

T R Mosmann, L Li, H Hengartner, D Kagi, W Fu, S Sad

{"title":"Differentiation and functions of T cell subsets.","authors":"T R Mosmann, L Li, H Hengartner, D Kagi, W Fu, S Sad","doi":"10.1002/9780470515280.ch10","DOIUrl":"https://doi.org/10.1002/9780470515280.ch10","url":null,"abstract":"The Tc1 and Tc2 subsets of CD8+ T effector cells secrete different patterns of cytokines, but have similar functions, including perforin- and Fas-dependent cytotoxicity, and induction of delayed type hypersensitivity (DTH) reactions involving oedema and granulocytic infiltration. The characteristic cytokines of Tc1 (gamma-interferon) and Tc2 (interleukins 4 and 5) are expressed in vivo during the DTH reaction. Tc1 cells that are deficient in cytokine synthesis also induce similar levels of DTH, supporting the lack of correlation between CD8+ T cell cytokine patterns and DTH. CD8+ T cells often produce lower cytokine levels than CD4 cells because the CD8 cells kill their antigen-presenting cells before full stimulation can occur. This effect can be counteracted by increasing the frequency of stimulation, or using perforin-deficient T cells. A multiparameter analysis of cytokine effects on CD8+ T cell differentiation has been initiated, on the basis of the principle that normal immune responses involve complex cytokine mixtures. All combinations of seven cytokines were tested. In some combinations, the combined effect could not have been predicted from individual cytokine functions. Conditions were identified in which each of interleukins 4, 10 and 12 could have opposite effects on CD8+ T cell differentiation.","PeriodicalId":10218,"journal":{"name":"Ciba Foundation symposium","volume":"204 ","pages":"148-54; discussion 154-8"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20056846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 61