摘要:

SummaryOur present knowledge of the cell structure, which is largely based on electron microscopy, is compared with what was known a few decades ago, when only light microscopy was available to the cytologist. The importance of cytochemical methods for the detection and localization of macromolecules (nucleic acids, proteins) is stressed. But it is pointed out that further analysis, with biochemical techniques, was required in order to understand the actual mechanisms of macromolecule synthesis in the cell (in particular, the relationships existing between nucleic acids and protein synthesis).The importance of genetical analysis in simple systems such as viruses and bacteria for the development of ‘molecular’ biology is then emphasized: in particular, the work of Avery identifying the ‘transforming principle’ with DNA, of Beadle leading to the ‘one gene, one enzyme’ theory, of the virologists who demonstrated that it is the nucleic acid component of viruses which carries the genetical information, have been of fundamental importance for the development of modern biology. No less important has been the work of the X‐ray crystallographers (Crick and Watson, Perutz, Kendrew, etc.) who established the fine structure of nucleic acids and of proteins.A brief review and a schematic representation of present ideas regarding the control exerted by DNA on the synthesis of specific proteins are then given: the main characteristics of the different kinds of RNA's, their interactions for the formation of polysomes, the role of the latter in protein synthesis, the main principles of the genetic codes, are briefly summarized.But cells are, in many respects, more complicated than bacteria. The concepts of molecular biology cannot be applied to cell differentiation without a recognition of the greater complexity of animal and plant cells. They represent, however, a most useful and powerful guide for research in that area: for instance, many aspects of morphogenesis in the unicellular algaAcetabulariaand in amphibian eggs can be explained on the assumption that messenger RNA's are produced by the nucleus and stored, in a stabilized form, in the cytoplasm during days or even weeks. This stability of messenger RNA's in eggs and algae is at variance with their short life in bacteria. The behaviour of non‐nucleate fragments ofAcetabulariais surprising in many respects: they are the site, not only of the synthesis of specific proteins, but even of RNA and DNA net synthesis. Such a synthesis of macromolecules, in the absence of the nucleus is probably linked to the presence of the chloroplasts in this alga: they contain DNA, can synthesize RNA and proteins, and can even increase in number in the absence of the nucleus. The presence of large amounts of DNA in the cytoplasm of many animal eggs raises a number of questions and might account for the extremely important role of the cytoplasm in the very early stages of embryonic development.It is concluded that none of the great problems of cell biology will be solved without the help of the techniques and the theoretical ideas which have been so fruitful for the simpler systems used by the molec

ISSN:1464-7931    

DOI:10.1111/j.1469-185X.1968.tb01106.x

出版商:Blackwell Publishing Ltd    

年代:1968

数据来源: WILEY

ISSN:1464-7931    

DOI:10.1111/j.1469-185X.1968.tb01107.x

出版商:Blackwell Publishing Ltd    

年代:1968

数据来源: WILEY

ISSN:1464-7931    

DOI:10.1111/j.1469-185X.1968.tb01108.x

出版商:Blackwell Publishing Ltd    

年代:1968

数据来源: WILEY

摘要:

SummaryThis review of connective tissue repair has attempted to place into historical perspective information obtained by newer approaches. The literature review is incomplete, as it was unfortunately necessary to leave many interesting studies out of the discussion. Emphasis has been placed upon what is known of the inflammatory response, the fine structure of the connective tissue cells in healing wounds and with correlated chemical findings in these tissues.An optimal inflammatory response appears to be an important, rapid, non‐specific stimulus for fibroplasia. It is not clear how inflammation exerts this effect. The inflammatory cells and their enzymes markedly alter the extracellular matrix of injured tissue. The matrix of connective tissue may itself participate in the control of its own synthesis and degradation. It is possible that modification of this environment by injury and/or inflammation with ensuing matrix alteration may provide a stimulus for cell migration and protein synthesis. The converse may also be true, that is, a given level of matrix concentration may have an inhibitory effect upon the connective tissue cells. The inter‐relationships between the connective tissue matrix and the cells, and the possibilities of feedback mechanisms playing a role in maintaining a balance between these two are important areas for future investigation. In this regard, additional questions may be asked concerning the role of the fibroblast in remodelling and degradation of connective tissue. It is not yet clear how important a balance between collagenolytic enzymes and the solubility states, or stability, of collagen are in each connective tissue. It will be interesting to determine which cells make collagenolytic and/or proteolytic enzymes upon appropriate stimulus.It is possible to distinguish between the fibroblast and the monocyte, or potential macrophage with the electron microscope. The rough endoplasmic reticulum with its large numbers of attached ribosomes is extensively developed in the fibroblast in contrast to the monocyte. The endoplasmic reticulum sequesters collagen precursors and other secretory proteins for transport either directly to the extracellular space, as appears to be the case for collagen, or to the Golgi complex as is the case for other exportable proteins. Collagen precursors are secreted into the environment and are not shed from within the cell surface.A number of cytoplasmic alterations have been described for fibroblasts and other cells during various pathological states. The significance of these alterations is not clear. It will be important to distinguish between specific and non‐specific responses to injury, if these alterations are to aid us in understanding the various cellular responses.The source of the fibroblasts in granulation tissue appears to be mesenchymal cells from adjacent tissues rather than blood‐borne precursors. Although contact inhibition can be demonstratedin vitro, it is not clear how important this phenomenon isin vivo, nor are the reasons for the ability of some tissues to heal by regeneration rather than by scar tissue formation understood.These and many other questions remain to be answered. The healing wound is multifaceted and presents the opportunity for systematic investigation into the problems of cell proliferation, cell and matrix interactions, and protein synthesisin vivoand it also can help to further our understanding of the ubiquitous fibroblast and its complex extracellular

ISSN:1464-7931    

DOI:10.1111/j.1469-185X.1968.tb01109.x

出版商:Blackwell Publishing Ltd    

年代:1968

数据来源: WILEY

ISSN:1464-7931    

DOI:10.1111/j.1469-185X.1968.tb01110.x

出版商:Blackwell Publishing Ltd    

年代:1968

数据来源: WILEY

摘要:

Summary1. The purpose of this review article is to re‐evaluate and integrate many of the observations related to the physiological effects of vitamin D, using as a working hypothesis the concept that the vitamin may be acting analogously to a steroid hormone in terms of its ability to interact with genetic information and ultimately elicit a physiological response. Prior to this time the problem of the mechanism of action of vitamin D has primarily been approached from the point of view that the vitamin was acting as a cofactor for some specific enzymic reaction.2. The physiological activities of vitamin D are integrated with those of parathyroid hormone to provide a homeostatic control for the regulation of primarily calcium and secondarily phosphate metabolism. It is proposed that the role of vitamin D in this homeostatic control mechanism is older and more fundamental than that of parathyroid hormone. The interaction of vitamin D on skeletal calcium metabolism may have evolved before the effects of the vitamin on intestinal calcium absorption.3. There are several physiological defects of calcium metabolism—rickets, osteo‐malacia, vitamin D‐resistant rickets and idiopathic hypercalcaemia—all of which may be a consequence of an aberration in one or another of the interlocking steps of the vitamin D‐dependent and calcium‐dependent homeostatic control mechanism.4. The most thoroughly established action of vitamin Din vivois to promote or facilitate the intestinal absorption of calcium. Although the exact biochemical details of this process are not available, this may involve vitamin D‐mediated synthesis of the appropriate enzyme systems or the alteration of membrane structure necessary for calcium absorption. It is not yet unequivocally established whether calcium absorption is an energy‐dependent active transport process or is a passive carrier‐mediated or simple diffusion process.5. The exact action of vitamin D on bone metabolism is not as well established, but the primary effect of the vitamin is likely to mediate bone resorption. The vitamin D‐dependent activities of the cell in both the intestine and bone are to absorb calcium and transfer it to the blood.6. No direct effects of vitamin D on intestinal absorption of phosphate have been found. Furthermore the validity of a vitamin D‐mediated renal reabsorption of phosphate is questioned, for the major effects of vitamin D are cation oriented. If the renal effects of vitamin D are true, it is postulated that the mechanism of action of the vitamin here on the anion, phosphate, is fundamentally different from its cation oriented mechanism.7. There is a lag in the action of vitamin D on the vitamin mediated: (a) transport of calcium bothin vivoin rats and chicks, andin vitrowith everted intestinal slices;(b) the apparent increased permeability of intestinal mucosa; (c) increased levels of citric acid in serum or bone; (d) the increased incorporation of radioactive inorganic phosphorus into intestinal mucosa phospholipids. As shown by the use of radioactive vitamin D, this lag is not due to a lack of the vitamin in the target organs.8. Whereas large, unphysiological doses of radioactive vitamin D localize in all tissues and all subcellular fractions, small physiological doses of radioactive vitamin D localize predominantly in the nucleus of the intestinal mucosa. The amount of vitamin D localized in the nucleus would appear to be too low for the vitamin to function as a cofactor, and is more indicative of an interaction on or with deoxy‐ribonucleic acid.9. Actinomycin D, an inhibitor of DNA‐directed RNA synthesis, inhibits the action of vitamin D in mediating intestinal calcium absorption and bone resorption. Vitamin D also stimulates messenger‐RNA synthesis in intestinal mucosa within 1/2 hr. of vitamin treatment. Vitamin D may play a crucial role, along with parathyroid hormone and calcium, in a DNA, gene‐dependent, homeostatic control mechanism for cal, ium metabolism. In this system the vitamin D molecule has certain very specific structural requirements which are probably a reflection of the specificity of its receptor molecule, rather than structural requirements for

ISSN:1464-7931    

DOI:10.1111/j.1469-185X.1968.tb01111.x

出版商:Blackwell Publishing Ltd    

年代:1968

数据来源: WILEY

ISSN:1464-7931    

DOI:10.1111/j.1469-185X.1968.tb01112.x

出版商:Blackwell Publishing Ltd    

年代:1968

数据来源: WILEY