摘要:

Summary1. In several species, partial, or even complete passive immunization of the offspring is achieved through maternal antibodies which are concentrated in the colostrum. Failure to obtain sufficient colostrum renders newborn farm animals highly susceptible to systemic and enteric infection withE. coli.2. A significant number of colostrum‐fed calves nevertheless develop colisepticaemia and many of these animals are hypo‐ or even agammaglobulinaemic. A premature termination of intestinal ability to absorb colostral antibodies (closure) may be responsible for some of these cases.3. Pharmacological doses of certain exogenous corticosteroids are capable of inducing premature closure in rats. It is not certain though whether exogenous corticosterone can induce precocious closure in rat pups or whether exogenous corticosteroids can induce closure in members of other mammalian orders. Corticosteroid levels, however, may influence the efficiency of immunoglobulin absorption. Attempts to delay closure with adrenal suppression in animals with short immunoabsorptive periods have not been effective.4. In piglets, but not in puppies or calves, starvation can postpone closure for several hours and consumption of food may be necessary before closure can occur.5. Closure in the rat and pig apparently takes place by different meth

ISSN:1464-7931    

DOI:10.1111/j.1469-185X.1977.tb00855.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

Summary(1) Cultures of differentiated muscle cells have been grown from diseased human, mouse and chick skeletal muscle, and from cardiac muscle of the myopathic hamster.(2) Methods of culture established for normal embryonic and adult skeletal muscle cells have proved suitable for cultures of diseased muscle cells.(3) Myoblasts obtained fromdy2Jmouse muscle crushed in vivo before explanting fuse in culture and form morphologically normal myotubes. Studies of the effects of innervation bydy2Jspinal cord neurones on the differentiation of normal,dy2Janddymyotubes have been inconclusive but it is probable that innervation does not play a part in the pathogenesis of this disorder.(4) Myoblasts prepared by trypsinization of embryonicdymuscle behave normally in culture and fuse to form myotubes that appear normal. It is not clear if myoblasts that migrate from explants of adult muscle in vitro fuse. Aggregates of non‐fusing cells have been described, but under other culture conditions normal and abnormal forms of myotube have been observed.dymuscle fibres fail to regenerate even when cultured with normal spinal cord explants anddynerves are without effect on regenerating normal muscle fibres. These tissue‐culture studies suggest that thedymouse mutation is a myopathic disorder.(5) Embryonicmdgmyoblasts have a normal cell cycle in vitro and fuse to form well‐differentiated myotubes with cross‐striations.mdgmyotubes have normal electro‐physiological properties but do not contract spontaneously or on depolarization. The defect in the muscle of themdgmutant appears to be a failure of excitation‐contraction coupling.(6) Cells migrate earlier from explants of adult dystrophic chick muscle than from normal muscle but dystrophic chick myotubes appear morphologically normal. Myotubes prepared from embryonic dystrophic chick muscle become vacuolated and degenerate, changes that can be prevented by anti‐proteases such as antipain. Lactic dehydrogenase isozyme subunit M4 is absent from dystrophic muscle in vivo but reappears in cultured myotubes. Dystrophic myotubes innervated in culture by either normal or dystrophic neurones exhibit bi‐directional lcoupling and multiple innervation. These results suggest that there are changes in dystrophic myotubes and that chick muscular dystrophy is a myopathy.(7) Cardiac muscle cells from the cardiomyopathic hamster synthesize less actin and myosin than normal cells, and Z lines in dystrophic cells are irregularly arranged. The beat frequency of myopathic cardiac cells is lower than that of normal cells and declines more rapidly. Tissue‐culture studies have not been made of hamster skeletal muscle.(8) Human dystrophic myotubes do not show degenerative changes in culture and have normal histochemical reactions. RNA synthesis appears normal in dystrophic myotubes but there may be changes in adenyl‐cyclase activity and protein synthesis in dystrophic cells. Morphological and biochemical changes have been found in muscle cells cultured from a case of acid‐maltase deficiency but phosphorylase activity re‐appeared in myotubes cultured from biopsies of phosphorylase‐deficient muscle. Innervation by normal mouse nerves does not induce degenerative changes in dystrophic myotubes.(9) Studies on the origins of myoblasts in explants of muscle fibres in culture suggest that in these conditions myoblasts are derived only from satellite cells and that this process may be the same in n

ISSN:1464-7931    

DOI:10.1111/j.1469-185X.1977.tb00856.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

Summary1. The cyst‐nematodes, which belong to the genusHeteroderaSchmidt, are obligate plant parasites. Several species cause crop diseases of economic importance. These nematodes differ greatly in structure from the other, vermiform, plant‐parasitic and soil‐inhabiting nematodes, for although the migrant larval phase of cyst‐nematodes is vermiform, this phase is only transient. The principal phases are the sedentary female, which feeds upon the plant root, and the cyst, which derives from the female and consists of the eggs surrounded by mucilage within the dead female cuticle. The term ‘egg’ includes the contents within the shell, which at maturity is usually a coiled, second stage, larva.2. The migrant larva may be parasitized by many species of predacious and endozoic fungi which have been much studied, but these do not parasitize the females or cysts. Until 1974 only one parasite of the females was known, and that imperfectly. On the other hand, many fungi have been cited as parasites of eggs inside cysts, notably the species now known asPhialophora malorumandCylindrocarpon destructans.Insect‐pathogenic fungi have also been cited as egg parasites but evidence is now against their pathogenicity toHeterodera.No other classes of organism are known to parasitize the females or cysts, although Collembola have been reported as predators.3. Studies published since 1973, including the present, show a total of seven (or eight) pathogenic fungi. There are two (or three) pathogens of the females, two major and three minor pathogens of the eggs. The former compriseCatenaria auxiliarisand twoEntomophthora‐likefungi, possibly the same species but both imperfectly known. The major egg pathogens areVerticillium chlamydosporiumand an incompletely known species termed the ‘contortion fungus’ from the symptoms on infected larvae newly hatched from eggs. The minor egg pathogens are a ‘black yeast’ taxonomically fairly similar to but not identical withPhialophora malorum; a sterile ‘crystal‐forming fungus’ andCylindrocarpon destructans.The main features of these pathogens are described and illustrated.4. Mycorrhizal fungi belonging toGlomusTulasne&Tulasne are sometimes associated with cysts. They ordinarily sporulate inside empty cysts, but in one remarkable example fromHeterodera schachtiigrowing on tomato host in glasshouse culture aGlomusapparently behaved as a pathogen.Pythiumspecies may invade cysts maintained under unfavourable conditions. Miscellaneous other fungi are also found occasionally in eggs.5. In addition to undergoing disease caused by fungi, eggs sometimes undergo oily degeneration. This disorder is not of numerical significance, but a high proportion of cysts are diseased through apparently non‐specific causes whose symptoms can be summarized as ‘lysed, shrivelled, coagulated or decayed’. Although the majority of diseased females are killed by fungal pathogens, some 25–40% of diseased cysts are destroyed through non‐specific causes. Overall disease in ten populations ofHeterodera schachtiiexamined from roots was 9% of females and 26% of young cysts; in 76 populations sieved from soils a mean of 14% of older cysts were diseased. Where the cyst‐nematode host had been grown in monoculture for 11 years higher proportions of cysts were diseased although few pathogens of females were present.Heterodera avenuecysts were parasitized to a similar extent.6. Of the pathogens of females,Catenaria auxiliariswas widespread inH. schachtiiand uncommon inH. avenue, whereasEntomophthora‐likefungi were widespread inH. avenueand rare inH. schachtii.Of egg pathogens,Verticillium chlamydosporiumand the ‘contortion fungus’ were common inH. schachtiiandH. avenae, and the ‘contortion fungus’ was also found inH. gly

ISSN:1464-7931    

DOI:10.1111/j.1469-185X.1977.tb00857.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

Summary1. Death in several infectious diseases is caused by protein toxins secreted by invading bacteria. Cholera toxin is a simple protein secreted byVibrio choleraecolonizing the gut; it is responsible for the massive diarrhoea that is cholera.2. The primary action of cholera toxin is an activation of adenylate cyclase, an enzyme found on the inner membrane of eukaryotic cells that catalyses the conversion of ATP to cyclic AMP. Consequent increases in the intracellular concentration of cyclic AMP are responsible for other manifestations of cholera toxin including the diarrhoea. The toxin is active on almost all eukaryotic cells.3. The toxin can be purified from culture filtrates ofV. cholera.It has a molecular weight of 82000; and is composed of one subunit A (itself two polypeptide chains joined by a disulphide bond: AI (22000) and A2 (5000)) and five subunits B (11500). These can be separated in dissociating solvents such as detergents or 6 M guanidine hydrochloride. An amino‐acid sequence of subunit B has been published. The five B subunits (sometimes found by themselves in the filtrate and known as ‘choleragenoid’) are probably arranged in a ring with the subunit A in the middle joined to them non‐covalently by peptide A2.4. The first action of cholera toxin on a cell is to bind to the membrane strongly and irreversibly. Several thousand molecules of toxin bind to each cell and the binding constants are of the order of 10‐10M. The binding is rapid, but is followed by a lag phase of about an hour before the intracellular cyclic AMP concentration begins to increase.5. Ganglioside GM1, a complex amphiphilic lipid found in cell membranes, binds tightly to the toxin which shows an enzyme‐like specificity for this particular ganglioside. Toxin that has already bound ganglioside can no longer bind to cells and is therefore inactive. This and other experiments using cells depleted of endogenous ganglioside suggest that ganglioside GM1is the natural receptor of the toxin on the cell surface. The binding is followed by a lateral movement of the toxin‐ganglioside complex in the cell surface forming a ‘cap’ at one pole of the cell.6. The binding of ganglioside by toxin is a function exclusively of subunit B; Subunit A does not bind and can be eluted with 8 M urea from an insolubilized toxin‐ganglioside complex. Subunit B is not by itself active, and so preincubation with B can protect cells or even whole gut from the action of toxin by occupying all the ganglioside binding sites.7. Subunit A is responsible for activation of adenylate cyclase. Purified subunit A or just peptide AI is active by itself and this activity is not inhibited by ganglioside or by antisera to subunit B. In intact cells the activity is low and shows the characteristic lag phase but in lysed cells the subunit (or the whole toxin) is much more active and there is no lag phase. This suggests that the lag phase represents the time that subunit A takes to cross the cell membrane and get to its target.8. Several cofactors are needed for toxin activity in lysed cells: NAD+, ATP, sulphydryl compounds and another unidentified cytoplasmic component. The activity of the cyclase is altered in a complex way generally rather similarly to the action of hormones such as adrenalin, but it is difficult to draw any general conclusions.9. There are two chief theories of how cholera toxin acts. The first is that subunit A (or just peptide AI) enters the cell and there catalyses some reaction leading to activation of the cyclase. The cleavage of NAD+ into nicotinamide and adenosine diphosphoribose could be such a reaction; it is catalysed by high concentrations of cholera toxin.10. The other theory is that part of the toxin binds directly to the adenylate cyclase or to some other molecule that can then interact with the cyclase, perhaps after the lateral movement of the toxin‐ganglioside complex in the cell surface. This binding may be related to the known action of guanyl nucleotides on the cell surface.11. The entry of peptide AI into the cell and its transport through the membrane is mediated by the binding of subunits B to the cell surface, perhaps just because the binding increases the local concentration of subunit A, or perhaps following specific conformational changes in the subunits and the formation of a tunnel of B subunits through the membrane. An experiment showing that the toxin remains active when the subunits are covalently bonded together suggests that peptide AI does not separate completely from the rest of the molecule.12. There are several other proteins that resemble cholera toxin in structure and function. For example, glycoprotein hormones such as thyrotrophin also activate adenylate cyclase and have an apparently similar subunit structure with one type of subunit that binds to a ganglioside. There may also be analogies between the amino‐acid sequences of toxin and hormones.13. The enterotoxin made by some strains ofEscherichia coliproduces a similar diarrhoea to that of cholera. Several different toxic proteins have been prepared but they all seem to activate adenylate cyclase in the same sort of way as cholera toxin does and also to cross‐react immunologically with it. TheE. colitoxin also reacts with ganglioside G, but the reaction is weak and probably physiologically insignificant.Salmonella typhimuriumsecretes a similar toxin.14. Tetanus toxin also reacts with a ganglioside receptor. This protein has two polypeptide chains of which only one reacts with the ganglioside; but the molecular activity is not yet known.15. Diphtheria toxin has an A fragment that is directly responsible for the toxicity (by catalysing an NAD+ cleavage reaction leading to the total inhibition of protein synthesis) and a B fragment that gets the A fragment into the cells. This structure of active and binding components therefore seems to be common to many toxins.16. The ability to produce toxin may confer some selective advantage onV. cholerae.The toxin may originate from accidental incorporation of DNA from an eukaryotic host, or alternatively from some material involved with the cyclic AMP me

ISSN:1464-7931    

DOI:10.1111/j.1469-185X.1977.tb00858.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY