Ciba Foundation symposium最新文献_第9页

CSF-deficient mice--what have they taught us? csf缺陷小鼠，它们教会了我们什么?

Ciba Foundation symposium Pub Date : 1997-01-01 DOI: 10.1002/9780470515280.ch5

G J Lieschke

{"title":"CSF-deficient mice--what have they taught us?","authors":"G J Lieschke","doi":"10.1002/9780470515280.ch5","DOIUrl":"https://doi.org/10.1002/9780470515280.ch5","url":null,"abstract":"Haemopoietic growth factor-deficient mice have been particularly instructive for defining the usual physiological role of these factors. Mice now exist lacking the granulopoietic factors G-CSF, GM-CSF, M-CSF (CSF-1), SCF, several other factors influencing haemopoiesis (including erythropoietin, interleukins 5 and 6), combinations of these factors (GM- & M-CSF; G- & GM-CSF; G- & GM- & M-CSF) and several CSF receptor components. Most of these mice were generated by targeted gene disruption, others are spontaneously arising mutants. The phenotypes of these mice indicate that the granulopoietic factors have both unique and redundant roles in vivo. Some factors are uniquely important in baseline myelopoiesis. Experimental infection of CSF-deficient mice indicates unique roles for some factors in emergency 'overdrive' haemopoiesis. Recovery from myeloablation evaluates the role of CSFs in emergency 'restoring normality' haemopoiesis. Redundancy also exists in the capacity of CSFs to support complete granulocyte development in vivo. Some factors are not involved in all the in vivo roles suggested by the range of their actions demonstrable in vitro. Some CSFs have indispensable roles in non-haemopoietic tissues. Some factors have in vivo roles not anticipated from previous studies. Mice deficient in several factors have identified compensating roles for factors by revealing exacerbated and additional phenotypic features, and may unmask additional in vivo roles.","PeriodicalId":10218,"journal":{"name":"Ciba Foundation symposium","volume":"204 ","pages":"60-74; discussion 74-7"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20056908","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: 29

Chromatin and ageing in yeast and in mammals. 酵母和哺乳动物的染色质和衰老。

Ciba Foundation symposium Pub Date : 1997-01-01 DOI: 10.1002/9780470515433.ch7

L Guarente

引用次数: 4

Mouse models for the study of telomerase. 端粒酶研究的小鼠模型。

Ciba Foundation symposium Pub Date : 1997-01-01 DOI: 10.1002/9780470515433.ch11

M A Blasco, H W Lee, M Rizen, D Hanahan, R DePinho, C W Greider

{"title":"Mouse models for the study of telomerase.","authors":"M A Blasco, H W Lee, M Rizen, D Hanahan, R DePinho, C W Greider","doi":"10.1002/9780470515433.ch11","DOIUrl":"https://doi.org/10.1002/9780470515433.ch11","url":null,"abstract":"The ends of chromosomes, or telomeres, consist of short repeated sequences that are synthesized by a ribonucleoprotein-DNA polymerase called telomerase. The RNA component of telomerase is essential for enzyme activity. The maintenance of telomere length by telomerase has been proposed to be essential for cellular viability and to play an important role in cellular senescence and immortalization. We are interested in using the mouse as a model system for the study of telomerase. We studied telomerase activity and expression of the mouse telomerase RNA component (mTR) in two different transgenic mouse models of multistage tumorigenesis: models of islet cell carcinoma and squamous cell carcinoma. In both tumour models, telomerase activity was detected only in late-stage tumours, whereas the telomerase RNA was present at higher than normal levels in pre-neoplastic stages and increased further in late-stage tumours. However, the RNA levels did not parallel the amounts of telomerase activity detected, suggesting that regulation of telomerase activity does not correlate with the regulation of its RNA component. These results establish a direct correlation between progression to late-stage tumours and induction of telomerase activity, and suggest that the initial upregulation of telomerase RNA is an early event. To address the role of telomerase during normal mouse development and tumour formation, we have constructed a knockout mouse for the mouse telomerase RNA, mTR-/-. These mice and the cell lines derived from them are telomerase deficient.","PeriodicalId":10218,"journal":{"name":"Ciba Foundation symposium","volume":"211 ","pages":"160-70; discussion 170-6"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20447725","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: 46

The telomere and telomerase: how do they interact? 端粒和端粒酶:它们是如何相互作用的?

Ciba Foundation symposium Pub Date : 1997-01-01 DOI: 10.1002/9780470515433.ch2

E Blackburn, A Bhattacharyya, D Gilley, K Kirk, A Krauskopf, M McEachern, J Prescott, T Ware

{"title":"The telomere and telomerase: how do they interact?","authors":"E Blackburn, A Bhattacharyya, D Gilley, K Kirk, A Krauskopf, M McEachern, J Prescott, T Ware","doi":"10.1002/9780470515433.ch2","DOIUrl":"https://doi.org/10.1002/9780470515433.ch2","url":null,"abstract":"The tandemly repeated DNA sequence of telomeres is typically specified by the ribonucleoprotein enzyme telomerase. Telomerase copies part of its intrinsic RNA moiety to make one strand of the telomeric repeat DNA. Recent work has led to the concept of a telomere homeostasis system. We have been studying two key physical components of this system: the telomere itself and telomerase. Mutating the template sequence of telomerase RNA caused various phenotypes: (1) mutating specific residues in the ciliate Tetrahymena and two yeasts showed that they are required for critical aspects of telomerase action; (2) certain mutated telomeric sequences caused a previously unreported phenotype, i.e. a strong anaphase block in Tetrahymena micronuclei; and (3) certain template mutations in the telomerase RNA gene of the yeast Kluyveromyces lactis led to unregulated telomere elongation, which in some cases was directly related to loss of binding to K. lactis Rap1p. Using K. lactis carrying alterations in the genes for Rap1p and other silencing components, we proposed a general model for telomere length homeostasis: namely, that the structure and DNA length of the DNA-protein complex that comprises the telomere are key determinants of telomerase access, and hence the frequency of action of telomerase, at the telomere.","PeriodicalId":10218,"journal":{"name":"Ciba Foundation symposium","volume":"211 ","pages":"2-13; discussion 15-9"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20447779","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: 43

Met-HGF/SF: tumorigenesis, invasion and metastasis. Met-HGF/SF:肿瘤发生、侵袭和转移。

Ciba Foundation symposium Pub Date : 1997-01-01 DOI: 10.1002/9780470515457.ch8

G F Vande Woude, M Jeffers, J Cortner, G Alvord, I Tsarfaty, J Resau

{"title":"Met-HGF/SF: tumorigenesis, invasion and metastasis.","authors":"G F Vande Woude, M Jeffers, J Cortner, G Alvord, I Tsarfaty, J Resau","doi":"10.1002/9780470515457.ch8","DOIUrl":"https://doi.org/10.1002/9780470515457.ch8","url":null,"abstract":"Hepatocyte growth factor/scatter factor (HGF/SF) is synthesized by mesenchymal cells and is a paracrine effector of cells, predominantly epithelial, that express the Met tyrosine kinase receptor. We have demonstrated that autocrine Met-HGF/SF expression in mouse fibroblasts results in transformation and tumorigenesis. HGF/SF-treated cells expressing Met can respond in a variety of ways: mitogenically, by scattering (motility), and by forming branching tubules in gel matrices (branching morphogenesis). HGF/SF also induces in vitro invasiveness and is angiogenic in in vivo assays. A human cell line and several mouse cell lines that we have constructed to express Met-HGF/SF in an autocrine fashion are tumorigenic, invasive and metastatic in athymic nude mice. Thus, the very complex process of invasion and metastasis can be mediated by a ligand-receptor signalling pathway, and the cell lines we have developed provide important model systems for identifying the signalling molecules that mediate these phenotypes: For example Met-HGF/SF signalling activates the urokinase plasminogen proteolysis network, thus coupling this signal transduction pathway to the proteases that mediate dissolution of the extracellular matrix. Branching morphogenesis, mediated by Met-HGF/SF signalling, is dependent on this process, as well as the formation of cell-cell junctions and interaction with the extracellular matrix. We have proposed a hypothesis for the role of Met and downstream signalling molecules in generating normal ducts and lumenal structures, as well as a model for how interruption of this signalling leads to abnormal malignant progression. Is Met involved in human cancer? Human sarcomas often inappropriately express Met, suggesting that it is an important oncogene in these cancers, and an increasing number of reports have implicated Met-HGF/SF signalling in a variety of human cancers.","PeriodicalId":10218,"journal":{"name":"Ciba Foundation symposium","volume":"212 ","pages":"119-30; discussion 130-2, 148-54"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/9780470515457.ch8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20448886","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: 123

GIS support for precision agriculture: problems and possibilities. GIS对精准农业的支持:问题和可能性。

Ciba Foundation symposium Pub Date : 1997-01-01 DOI: 10.1002/9780470515419.ch11

A K Bregt

{"title":"GIS support for precision agriculture: problems and possibilities.","authors":"A K Bregt","doi":"10.1002/9780470515419.ch11","DOIUrl":"https://doi.org/10.1002/9780470515419.ch11","url":null,"abstract":"Precision farming aims to optimize the use of soil resources and external inputs on a site-specific basis. Base ingredients for research in the field of precision farming are spatial data, including a characterization of the spatial variability, and simulation models for the characterization of the processes that take place. Geographical information systems (GIS) are systems for the storage, analysis and presentation of spatial data. A combination of GIS and simulation models is highly relevant for precision farming. Currently only static one- or two-dimensional simulation models can be fully supported by commercial GIS systems. Within precision agriculture an engineering component can be also distinguished, in which the research findings are translated into operational systems for use at farm level. GIS can support this engineering activity by providing a good platform for storage of base data, simple modelling, presentation of results, development of a user interface and, in combination with a global positioning system, controlling the navigation of farm vehicles. On the basis of GIS a decision support system could be developed for operational application of precision agriculture at farm level.","PeriodicalId":10218,"journal":{"name":"Ciba Foundation symposium","volume":"210 ","pages":"173-9; discussion 179-81"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20495249","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: 5

Health impacts of large releases of radionuclides. Radioactive contamination of the marine environment. 放射性核素大量释放对健康的影响。海洋环境的放射性污染。

Ciba Foundation symposium Pub Date : 1997-01-01

A Aarkrog

引用次数: 0

Pharmacokinetics of oligonucleotides. 寡核苷酸的药代动力学。

Ciba Foundation symposium Pub Date : 1997-01-01 DOI: 10.1002/9780470515396.ch6

S Agrawal, R Zhang

{"title":"Pharmacokinetics of oligonucleotides.","authors":"S Agrawal, R Zhang","doi":"10.1002/9780470515396.ch6","DOIUrl":"https://doi.org/10.1002/9780470515396.ch6","url":null,"abstract":"The effectiveness of antisense oligonucleotides as therapeutic agents depends on their pharmacokinetics, tissue disposition, stability, elimination and safety profile. Pharmacokinetic data allow one to determine the frequency of administration and any potential toxicity associated with chronic administration. Phosphorothioate oligonucleotides degrade from the 3' end, the 5' end, and both the 3' and 5' ends in a time- and tissue-dependent manner. After intravenous administration in mice, rats and monkeys, phosphorothioate oligonucleotides are detected in plasma; they distribute rapidly and are retained in the majority of tissues. The major route of elimination is the urine. The pharmacokinetic profile is similar following subcutaneous, intradermal or intraperitoneal administration, but with lower maximum plasma concentrations. Phosphorothioate oligonucleotides have a short plasma half-life in humans. End-modified, mixed-backbone oligonucleotides (MBOs) contain nuclease-resistant 2'-O-alkylribonucleotides or methylphosphonate internucleotide linkages at both the 3' and 5' ends of phosphorothioate oligonucleotides. These end-modified MBOs have pharmacokinetic profiles similar to those of the parent phosphorothioate oligonucleotides, but they are significantly more stable in vivo and they can be administered orally. Centrally modified MBOs contain modified RNA or DNA in the centre of a phosphorothioate oligonucleotide. They show controlled degradation and elimination following administration in rats. The pharmacokinetics of antisense oligonucleotides depends on the sequence, the nature of the oligonucleotide linkages and the secondary structure.","PeriodicalId":10218,"journal":{"name":"Ciba Foundation symposium","volume":"209 ","pages":"60-75; discussion 75-8"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20312457","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: 30

The genetic basis of human scientific knowledge. 人类科学知识的遗传基础。

Ciba Foundation symposium Pub Date : 1997-01-01 DOI: 10.1002/9780470515372.ch3

R N Shepard

{"title":"The genetic basis of human scientific knowledge.","authors":"R N Shepard","doi":"10.1002/9780470515372.ch3","DOIUrl":"https://doi.org/10.1002/9780470515372.ch3","url":null,"abstract":"The ecologically most significant respect in which humankind now dominates all other terrestrial species is in its scientific understanding and technological manipulation of the world. What psychological adaptation underlies this seemingly discontinuous development? There is reason to believe that natural selection has endowed the perceptual/representational systems not only of humans but also of other perceptually and cognitively advanced animals with an implicit knowledge of pervasive and enduring properties of the world. Perhaps especially in the human species, natural selection has, in addition, favoured a heightened degree of voluntary access to the representational machinery embodying this implicit wisdom, thus facilitating the realistic mental simulation of possible actions in the world before taking the risk of carrying them out physically. This, together with the emergence of an unprecedented motivation toward understanding, seems to have enabled some human individuals to use 'thought experiments' to convert more and more of the implicit knowledge that we all share into a self-consistent set of explicit scientific laws. Although knowledge of the world must ultimately come from the world, as empiricists claim, it can in this way come through one's genes as well as through one's own direct perceptual interactions with the world.","PeriodicalId":10218,"journal":{"name":"Ciba Foundation symposium","volume":"208 ","pages":"23-31; discussion 31-8"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20316874","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: 14

The role of enamel matrix proteins in the development of cementum and periodontal tissues. 牙釉质基质蛋白在牙骨质和牙周组织发育中的作用。

Ciba Foundation symposium Pub Date : 1997-01-01 DOI: 10.1002/9780470515303.ch17

L Hammarström

引用次数: 79