The ability of the liver to regenerate after resection has been known for many years. Two reports from Germany in the late 1800s probably mark the introduction of the phenomenon into the scientific literature, but in the early 1900s the first reviews of this subject had appeared in the English literature. Predating these early scientific reports the legends from the Greek mythology described the fate of Prometheus. As punishment for defying Zeus and revealing the secret of fire to man, Prometheus was chained to a rock and each day had part of his liver ripped out by an eagle which, returning the following day, repeated the torture because his liver regenerated itself overnight. Although the speed of regeneration in the Greek legend is somewhat greater than that observed either clinically or in the laboratory, the myth does serve to emphasise the remarkable ability of the liver to repeatedly regenerate following repeated resections. This review aims to summarise the more recent literature concerning the early molecular events accompanying liver regeneration and to integrate this with the existing knowledge of this subject.
Metastatic growth is a selective, non-random process, which in the case of colorectal cancer, frequently occurs in the liver and is the major cause of cancer related death in these patients. This review summarises attempts to find biological and molecular markers of metastasis and their role in establishment of secondary tumours. Recent evidence suggests that liver metastases are phenotypically different to the primary from which they were derived and thus represent a separate disease entity.
SUMMARY1. The experiments correlate certain changes in the ultrastructure of cat hypogastric nerves constricted at two points with the distribution of a mitochondrial enzyme (cytochrome oxidase), noradrenaline (stored in some of the vesicles with an electron dense core, i.e. granular vesicles) and adenosine triphosphate (ATP) (present in noradrenaline storage granules, mitochondria and the soluble fraction of the axon).2. Noradrenaline (NA) and granular vesicles accumulated proximal but not distal to both constrictions. The total amount of NA and the concentration of granular vesicles above the first constriction was greater than that present in a similar piece of normal nerve, indicating that the cell body was continuing to produce the transmitter despite injury to its axon. The granular vesicles proximal to the first constriction were found in swollen or distorted axons and in new axonal outgrowths. It was concluded that the movement of NA in these constricted nerves was only centrifugal in direction.3. Mitochondria and cytochrome oxidase accumulated on both sides of the two constrictions, indicating a bi-directional movement of mitochondria in the damaged axons. The possibility that some of the increase in the cytochrome oxidase could be related to an increase in the number of mitochondria in cells other than neurones is considered.4. The adenosine triphosphate content increased on both sides of the two constrictions. This increase developed more slowly and was less marked than that of the other two substances.5. It was concluded that (a) there was a close correlation between the behaviour of noradrenaline and granular vesicles and between cytochrome oxidase and mitochondria, (b) the dense cored vesicles and the mitochondria moved independently of one another and at different rates after P. BANKS, D. MANONALL AND D. MA YOR constriction of non-myelinated axons, (c) while some of the changes may be attributed to an obstruction to the free movement of axoplasm others may be due to an active reaction to axonal injury, and (d) localized intraaxonal synthesis of noradrenaline and cytochrome oxidase did not occur between the two constrictions.
Myoblast cell lines have proved to be valuable model systems for studies of skeletal muscle metabolism and differentiation. In the case of the mouse C2C12 line the cells grow readily as mononucleated myoblasts until the cultures reach a confluent state, when fusion into multinucleated, nondividing, differentiated myotubules begins. These myotubes develop biochemical and morphological properties characteristic of skeletal muscle. Fusion and enlargement continues, and the myotubes may go on to develop cross striations and spontaneously contract.This differentiation and expression of a striated muscle phenotype is accompanied by an increase in specific insulin binding and the development of insulin-sensitive glucose uptake mechanisms.The entry of glucose into cells is mediated by a family of membrane glycoprotein transporters of which GLUT 1 is generally regarded as the constitutive transporter and GLUT 4 as the insulin sensitive transporter characteristic of adipose tissue and skeletal muscle. It is however clear that this is general view is simplistic and that the GLUT 1 transporter, despite its constitutive label, is in fact subject to regulation by a number of mechanisms which include nutrient availability, differentiation, cell cycle and hormones. Glucose is a major regulator of GLUT 1 activity, and glucose deprivation results in a slow increase in the rate of glucose uptake, by a mechanism dependent upon continued protein synthesis. Depending on the cell type this may involve a slowing of GLUT 1 degradation or an increased production of GLUT 1 mRNA and increased transcription.The mouse C2C12 cell line expresses only the GLUT 1 transporter.Isolated rat adipocytes possess a mechanism for the desensitisation of glucose transport which requires glucose, insulin and glutamine for its operation and which is mediated through the hexosamine pathway (1). Adipocyte pyruvate kinase activity also appears to be regulated by a mechanism linked to the hexosamine pathway (2), raising the possibility of a family of insulinresponsive enzymes which are co-ordinately regulated by the hexosamine pathway. It is not yet clear however to what extent this situation is ubiquitous amongst the insulin sensitive tissues.In the present experiments we have examined insulinstimulated glucose uptake by the mouse C2C12 myoblast cell line, and show that these cells, like adipocytes, exhibit decreased glucose uptake in the presence of glucosamine. However the effects of glutamine and azaserine on the C2C12 cells is different from that seen in adipocytes suggesting that if the C2C12 cells do have a hexosamine pathway its interactions with glucose uptake differs from that operating in adipocytes.The C2C12 line grown in low glucose medium (5.5mM) shows little capacity for insulin-stimulated glucose uptake ( lO-7M insulin causes only a 10% increase). However, prolonged exposure to insulin resulted in a gradual increase in glucose uptake, reaching a doubling at around 20-30 h. Thus, despite having only the GLUT 1 transporter, conventionally regarded ...
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