摘要:

Summary1. Amniotic fluid surrounds the human fetus and is separated from the uterus by the amnion, chorion and placenta. The ability to obtain samples of amniotic fluid from women by a simple procedure has encouraged studies on the nature and origin of the fluid, and on its use for the diagnosis of a variety of clinical conditions. The fluid contains cells, which are of fetal origin, and can be grown in a tissue culture. Cyto‐genetic and biochemical analyses can therefore be used to detect chromosomal aberrations and inborn errors of metabolism in the fetus.2. The supernatant of amniotic fluid contains many of the solutes typical of extracellular fluid. In particular, it contains a wide range of proteins and those which are of fetal origin are likely to be of use in the prenatal diagnosis of fetal disease. This review examines the nature and origin of the soluble protein in amniotic fluid, and discusses the diagnostic uses of the proteins which are of fetal origin.3. In other mammals, the arrangement of the fetal membranes is different from that in man, and these differences are reflected by changes in the nature of the amniotic fluid. Thus data from other animals have little applicability to man.4. Electrophoresis and immunoelectrophoresis have established that the major proteins in amniotic fluid are also present in maternal and fetal sera. Their concentrations in the fluid are influenced by their molecular weight and proteins larger than about 2.5 times 106may be excluded. Towards term, phenotyping studies show that a number of serum proteins in amniotic fluid are of maternal origin. In the case of group‐specific component (Gc) this has been shown to be so throughout pregnancy. Such proteins must enter the fluid by diffusing across either the chorion or the chorionic plate and then the amnion.5. It has been previously claimed that various serum proteins in amniotic fluid are of fetal origin. For albumin and IgG there are data that strongly support a maternal origin. The evidence on the origin of insulin is inconclusive. The concentration of β2‐microglobulin in amniotic fluid exceeds that in maternal serum and is probably too high also for fetal serum to be its major source. It has a wide tissue distribution and probably enters the fluid from surrounding structures.6. Alpha‐fetoprotein in amniotic fluid is of fetal origin as it is present in maternal serum at far lower concentrations. It is found in fetal serum, urine and yolk sac, but it is not clear how it enters the amniotic fluid of normal fetuses. The concentrations of Gc and alpha‐fetoprotein have been measured in amniotic fluid and in their sera of origin. The relative concentration of Gc in amniotic fluid was found to be much greater than that of alpha‐fetoprotein and the concentration gradients of these marker proteins can be compared with data for other proteins. In this way further evidence has been obtained that the albumin, α1,‐antitrypsin and transferrin in amniotic fluid are mainly of maternal origin throughout pregnancy.7. Immunological studies have shown that at least three proteins of non‐serum origin are present in amniotic fluid and they have also been located in the amnion and uterine decidua.8. The enzymes present in amniotic fluid are summarized. Many lysosomal enzymes are clearly of fetal origin since they show altered specific activities in the appropriate cases where the fetus is affected with an inborn error of metabolism. For other enzymes, analysis of specific activity gradients can help to decide the extent to which an enzyme is of serum origin, although this will not exclude the possibility of a maternal (uterine) contribution. The results of such analyses suggest that, relative to the serum protein in amniotic fluid, the greatest concentrations of the minor non‐serum proteins in the fluid occurs between thirteen and eighteen weeks of pregnancy and also towards term.9. Some inborn errors of metabolism may be diagnosed prenatally by measuring the specific activity of the respective enzyme in amniotic fluid. However, the presence of different enzymes with similar substrate specificities has prevented this in Pompe's disease.10. In cases where the fetus is affected with anencephaly or spina bifida there is an increase in the concentration of alpha‐fetoprotein in the amniotic fluid. This has provided a way of detecting these diseases early enough to allow termination of pregnancy.11. The discovery of new proteins in fetal serum and in the tissues surrounding the amniotic cavity would seem to provide the best chance of extending the uses of amniotic fluid into the other areas

ISSN:1464-7931    

DOI:10.1111/j.1469-185X.1975.tb00988.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

Summary1. The pituitary hormones can be divided into 4 families; within each the members are structurally related and have probably evolved from a common ancestor by a process of gene duplication and divergence.2. Recent structural studies have revealed much about the evolution of proteins. The roles of point mutation, gene duplication and partial gene duplication in molecular evolution have been highlighted, and the nature of the evolutionary forces involved has been extensively debated. The information available about the evolution of proteins in general provides a background for consideration of pituitary hormone evolution.3. The structure and function of the mammalian neurohypophysial hormones (oxytocin and vasopressin) has been studied in detail. Related (structurally similar) peptides have been found in the neurohypophyses of lower vertebrates and have been Characterized in many instances. Several schemes have been proposed for the evolution of these hormones.4. The vasopressins of the pig and its relatives show a genetic polymorphism. The roles of neurohypophysial hormones in lower vertebrates are very varied and not fully understood.5. The ACTHs and MSHs are members of a second family of pituitary hormones. They are polypeptides of moderate size. Studies on amino‐acid sequences have been carried out for ACTHs and MSHs from several mammals. α‐MSH is identical in all cases studied in detail, but β‐MSH and ACTH vary to some extent. There is considerable sequence homology between the hormones in this family ‐ indicating a common phylogenetic origin and several gene duplications.6. Dogfish MSH is the only non‐mammalian hormone of the ACTH‐MSH family to have been studied in detail. Two MSHs have been isolated from this species; both resemble the a‐MSH of mammals in amino‐acid sequence. ACTH‐like and MSH‐like hormones exist in many other vertebrate groups, but have not been characterized fully.7. Structure‐function relationships have been widely studied in the ACTH‐MSH family, and have some interesting evolutionary implications. Polymorphism of P‐MSHs is found in some mammals.8. A third family of protein hormones includes pituitary prolactin and growth hormone, and placental lactogen. These are proteins of moderate size which have been shown to be widely distributed among the vertebrates. Species specificity can be recognized with regard to biological, immunological and structural properties.9. Amino‐acid sequences have been determined for growth hormones and prolactins from several mammals. There is sequence homology between growth hormone and prolactin. Human placental lactogen closely resembles human growth hormone. A phylogenetic tree has been constructed for this protein family. Rates of evolution within the group are rather variable.10. The fourth family of pituitary hormones (FSH, LH, TSH and some related placental hormones) are all glycoproteins and have a subunit structure. Extensive sequence studies have been carried out on the hormones from some mammals, and show that there is considerable homology between the various subunits. The α‐subunits of human TSH, LH and HCG (and probably FSH) are very similar. The β‐subunits are different, but homologous. Evolution of this family clearly took place by a series of gene duplications followed by gene divergence. Schemes whereby this could have occurred have been discussed. Related hormones occur in lower vertebrates, but have not been fully characterized. Some lower vertebrates may possess only one gonado‐trophin.11. The pituitary hormones provide an interesting range of evolutionary problems, and are useful models for the study of molecular evolution. The evolutionary processes involved in their diversification have been discussed, with particular reference to the co‐evolution of hormones and their receptors. Neutral mutations and gene duplications may have played a role in providing co‐existing variation of hormones and receptors.12. A speculative model for the evolution of neurohypophysial hormones is proposed, as an example of how molecular evolution may have operated in this and other hormone groups.13. Homologies have been proposed between the various families of pituitary hormones, and between pituitary proteins and other entero‐secretory proteins. The pituitary protein hormones were probably elaborated from smaller molecul

ISSN:1464-7931    

DOI:10.1111/j.1469-185X.1975.tb00989.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SummaryMitotic homeostasis:Mitotic control is maintained by the interaction of a tissue‐specific mitosis‐inhibiting chalone, which permeates the whole tissue, and a non‐tissue‐specific mitosis‐promoting mesenchymal factor, which originates in the connective tissue and acts only on connective‐tissue‐adjacent cells.In the basal layer of the epidermis the mitotic rate is determined by the relative concentrations of these two substances; in the distal layers the chalone is dominant so that all cells must become post‐mitotic, age, and die. Thus the perfect balance between cell gain and cell loss that is maintained equally in hypoplasia, normality, and hyperplasia is ensured by the fact that all cells forced distally by mitotic pressure enter a chalone concentration that is high enough to direct them into post‐mitosis and so to their deaths.The mitotic rate of the basal epidermal cells and the ageing rate of the distal cells are both inversely related to the chalone concentration. A change in the mitotic rate is matched by an equal change in the ageing rate so that, within limits, epidermal thickness (or mass) remains constant. Epidermal thickness is determined by the tissue‐specific ratio, mitotic rate: ageing rate; it is influenced by the mitotic rate only when this exceeds a certain critical level.Evidently all epithelial tissues, even when these form solid masses (e.g. liver hepato‐cytes), have a similar control mechanism, the ‘basal cells’ being those that are connective‐tissue‐adjacent and the ‘distal cells' those that are not. Tissues that are not connective‐tissue‐based (e.g. erythrocytes and granulocytes) have specialized mechanisms involving differentiation from relatively undifferentiated stem cell populations, as also do the connective tissues themselves.Local tissue damage leads via local chalone loss to a temporarily and locally increased mitotic rate; chronic damage leads via chronic chalone loss to hyperplasia, the increase in tissue mass being limited by the reduced life‐span of the post‐mitotic cells.Compensatory hypertrophyWhen a tissue mass is so large (e.g. the hepatocytes) in relation to the total body mass that the escaping chalone forms a significant systemic concentration, extensive damage leads to compensatory hypertrophy. The reduced tissue mass (e.g. after partial hepatectomy) produces less chalone, leading to a reduced systemic concentration, and therefore a higher chalone loss from the surviving tissue. This results in a general mitotic response in that tissue, as the relative power of the mesenchymal factor increases, and thus to an increase in tissue mass. Growth ceases when the normal tissue mass is attained.When a large tissue suffers chronic damage (e.g. liver cirrhosis) the chronic chalone lack results in hypertrophy, which is limited by the reduced life‐span of the post‐mitotic cells.Tumour growthMitotic control is lost when the chalone concentration falls so low that the ‘distal cells’ remain mitotic; cell gain then exceeds cell loss and a tumour appears. Such chalone loss is related to permanent membrane damage, which may be the central event in carcinogenesis.The evidence is that a tumour continues to produce and to respond to the chalone of its tissue of origin. As a tumour grows the systemic concentration of its chalone rises steadily so that there is an increasing mitotic inhibition, first, in the parent tissue, and second, in the tumour itself. Thus tumour growth may be described as an exponential process limited by an exponential retardation. This means that, if the host survives, the tumour growth will cease and the tumour mass will reach a plateau.This is a negative feedback mechanism which differs from compensatory hypertrophy only in that, at the plateau, the mass attained is greater than normal, and also in that, at any time, further cell damage may cause the tumour to ‘progress’. When this happens the new and higher plateau may be unattainable before the host is killed.Tumour growth is normally slower than would be expected if the mitotic advantage were the only factor involved; clearly tumour growth is usually inhibited by factors other than the chalone, in particular perhaps by the immune response to the altered cell membrane.It is an especial pleasure to acknowledge the constant help and enco

ISSN:1464-7931    

DOI:10.1111/j.1469-185X.1975.tb00990.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY