摘要:

AbstractAlongside the numerous applications of NMR spectroscopy to structural elucidation in analytical chemistry, and to biochemical and morphological studies by NMR tomography, NMR microscopy makes possible a whole new range of applications. These include imaging, the investigation of biological objects such as plants and small animals, and also the observation of microscopic structures and structural changes in polymers and ceramics. NMR spectroscopy can also be conducted combinationally as volume‐selective spectroscopy, whereby it is possible to spatially resolve the NMR‐specific parameters: spin density ϱ, chemical shifts δ, and the relaxation timesT1andT2. The numerous well developed methods available make it possible to study dynamic processes by fast imaging with a temporal resolution in milliseconds. This not only allows the imaging of moving objects without incurring movement artefacts but also the measurement of diffusion constants in isotropic and anisotropic diffusion—in the latter case allowing, in principle, the determination of the complete diffusion tensor. The spatially resolved measurement of the relaxation times yields information on molecular mobility and bonding, e. g. the bonding of water, or other solvents, to polymers, the mobility of fluids in polymers or ceramics, or the three‐dimensional evaluation of pore size in porous materials. In biomedicine, NMR microscopy allows the observation of growth on the cellular level, the study of embryos, and the development of therapeutic methods in animal experiments. It can lead to a drastic reduction in the number of animal experiments, and in combination with volume‐selective spectroscopy gives valuable information on in‐vi

ISSN:0570-0833    

DOI:10.1002/anie.199000013

出版商:Hüthig&Wepf Verlag    

年代:1990

数据来源: WILEY

摘要:

AbstractAnimal development starts as a single cell which proliferates into several new cells; these differentiate into highly specialized tissues, organs, and limbs; and the small but functioning organism eventually grows into its full scale. Throughout development the extracellular matrices, which are complex macromolecular networks, also undergo dramatic changes. Matrix transformations occasionally control the much more well‐studied changes in number and type of differentiating cells. Extracellular matrix (ECM) networks are typically broken down enzymatically to oligopeptides and are then resynthesized (remodeled) to form insoluble and nondiffusible macromolecular structures which confer stability of shape to multicellular systems. Mature ECM, such as skin, tendon, cartilage, and blood vessels, provides stiffness and strength to tissues and organs. Remodeling of ECM also occurs in adult organisms, during wound healing. An understanding of the role that ECM plays during development or wound healing can be obtained by use of synthetic ECM analogues. Several simple chemical ECM analogues have been synthesized and a few have been found to possess remarkable biological activity. One of these analogues has induced the partial regeneration of skin in an adult guinea pig wound model as well as in man. Peripheral nerve has been regenerated in another animal model by use of a similar ECM analogue. In all these mammalian lesions it is well‐known that regeneration does not occur spontaneously. These analogues are graft copolymers of collagen and chondroitin 6‐sulfate (a glycosaminoglycan) in the state of highly hydrated and covalently cross‐linked gels. Procedures are summarized for synthesis of copolymers with adjusted physicochemical properties, such as the rate at which they degrade enzymatically when implanted, the elements of their pore structure, and the degree of collagen crystallinity. ECM analogues have provided a novel window into the complexities of morphogenesis and regeneration and they have pointed towards entirely new directions in the medical treatment of serious organ dysfunction and organ loss. An ECM analogue has already become the basis of a new clinical treatment for massively burned patients. An interpretation of the results leads to a hypothesis about the nature of ECM during development. Since biological activity appears only when the physicochemical parameters fall within very narrow limits, it is intriguing to speculate that these experiments describe a single insoluble growth factor which is specific for skin synthesis. Such an insoluble growth factor appears to be just as essential to skin development as are the much more well‐known soluble growth factors. A different ECM analogue appears to induce nerve regeneration, possibly because each tissue requires its own developmentally a

ISSN:0570-0833    

DOI:10.1002/anie.199000201

出版商:Hüthig&Wepf Verlag    

年代:1990

数据来源: WILEY

摘要:

AbstractThe principles governing the replication fidelity of genomes are not fully understood yet.WatsonandCrick'sbase‐pairing principle for matched deoxyribonucleotide (DNA) bases can explain why the guanine–cytosine and adenine‐thymine base pairs are approximately one hundred times more stable thermodynamically than mismatched combinations. In vitro, DNA polymerases reduce the number of mismatched base pairs to about 10−6per Watson–Crick base pair. Replication fidelity can further be enhanced to a mutation probability of 10−10or less in vivo if optimal conditions for DNA synthesis are provided by polymerase–assisting proteins and DNA‐repairing enzymes. The precise reasons for the formation of mismatched base pairs (mispairs), which are responsible for a substantial part of DNA mutations, are still in debate. Although it is agreed that a template‐directed “reading” of the hydrogen‐substitution pattern in the heterocyclic bases is crucial for proper base pairing during DNA synthesis, it is not clear which type of “misreading” leads to mispairs. Misreading may be due to a non‐Watson–Crick base pairing as well as to a change in the hydrogen‐substitution pattern, leading to Watson‐Crick‐like mispairs. The surprising discovery of the selective and quantitative DNA‐polymerase‐catalyzed formation of a pyridine‐pyrimidine base pair (involving a nucleotide base analogue) indicated that rare tautomeric forms in template DNA strands can lead to Watson‐Crick‐like mispairings that are hardly recognized by the polymerase's proofreading activity. This reveals new pathways for substitution mutations (replication‐dependent DNA point muta

ISSN:0570-0833    

DOI:10.1002/anie.199000361

出版商:Hüthig&Wepf Verlag    

年代:1990

数据来源: WILEY

ISSN:0570-0833    

DOI:10.1002/anie.199000581

出版商:Hüthig&Wepf Verlag    

年代:1990

数据来源: WILEY

ISSN:0570-0833    

DOI:10.1002/anie.199000591

出版商:Hüthig&Wepf Verlag    

年代:1990

数据来源: WILEY

ISSN:0570-0833    

DOI:10.1002/anie.199000601

出版商:Hüthig&Wepf Verlag    

年代:1990

数据来源: WILEY

ISSN:0570-0833    

DOI:10.1002/anie.199000611

出版商:Hüthig&Wepf Verlag    

年代:1990

数据来源: WILEY

ISSN:0570-0833    

DOI:10.1002/anie.199000631

出版商:Hüthig&Wepf Verlag    

年代:1990

数据来源: WILEY

ISSN:0570-0833    

DOI:10.1002/anie.199000641

出版商:Hüthig&Wepf Verlag    

年代:1990

数据来源: WILEY

ISSN:0570-0833    

DOI:10.1002/anie.199000651

出版商:Hüthig&Wepf Verlag    

年代:1990

数据来源: WILEY