We have analysed the specificity of monoclonal antibodies to human leucocyte subsets by three methods. The distribution of antigen bearing cells has been studied in frozen tissue sections of lymphoid and other tissues by immunofluorescence or immunoenzymatic methods. The cellular distribution of antigen has been compared with existing well established markers and the function of antigen bearing cells has been studied by separation and assay in in vitro model systems. Antibodies characterised in this way may yield useful information when applied to clinical problems.

The study of marine fish diseases has been directly related in its development to the significance of the fisheries or latterly aquaculture systems involved with epizootics. In this respect, Scotland has played a central role because of the importance of specific diseases of salmon which have been especially prevalent in Scotland, and the advanced state of its basic veterinary and medical expertise. This has been particularly important in the past, when very little information was available and extrapolation from higher animal studies was the only relevant approach.

Bracken(Pteridium aquilinum), is one of the most successful plants in the world. It has the ability, by virtue of its underground rhizomes, to spread considerably. One plant alone can occupy a large area and fragment into separate plants which themselves have similar capacity. During the last fanning depression, in the late 1920s to 1930s, when marginal land was abandoned from cultivation and adequate stocking, bracken crept down the hill to invade what had previously been reasonable upland pasture. At that time, the late Professor Stapledon estimated that well in excess of a fifth of the upland of Wales and Scotland was rendered agriculturally of poor value because of bracken encroachment. No-one knows the total area in the world which this plant occupies; it must be many many millions of hectares, much of which could provide a more useful grazing. It is certainly a successful plant.

Herpesviruses and viruses having the typical morphological and replicative characteristics of the genus Herpesvirus from marine animals have been reviewed. These animals include one teleost fish, two reptiles, one pelecypod mollusc and an arthropod. With the exception of the arthropod, all descriptions of virus-related diseases were from animals maintained under artificial culture conditions and a common theme relates temperature, stress and crowding to outbreaks of disease. The significance of these observations in relation to the possible evolution of the herpesvirus group is discussed.

Bracken, Pleridium aquilinum, has long been present in Britain as part of the native flora. Before the arrival of man, Britain was a wooded and forested country, and in this vegetation bracken was an open woodland and forest margin species, which played only a relatively minor vegetational role. Its biology is such, however, that this plant is able to spread rapidly in response to removal of the forest canopy, developing into colonies which are much more ecologically aggressive and dominating than was the original habit of the plant when undisturbed.

In open conditions, bracken also has a far greater spore output than in more shaded ones. It is able to establish anew from spores only in relatively virgin soil conditions, particularly those produced by burning of other vegetation. Burning also benefits established bracken by removal of its competitors, whilst heavy and selective grazing by sheep also slowly reduces the natural vegetation competition in favour of bracken's further spread.

The history of the spread of bracken in Britain from palynological and historical evidence is reviewed in the light of this biology and, in particular, its spread as man has progressively removed the forest canopy,introduced steady heavy grazing pressure, and has burned, and continues to burn, vegetation.

When bone marrow (BM) is taken, cells in suspension are accessible to antibodies. BM transplantation is therefore an ideal situation for using monoclonal antibodies in therapy. These applications include prevention of graft versus host disease by eliminating T cells from allogeneic BM marrow, and the elimination of residual malignant cells from autologous bone marrow. Me Ab-s are currently tested for the removal of residual leukaemic cells in the common form of acute lymphoblastic leukaemia (ALL) and in thymic ALL. Encouraging experiments also indicate that the removal of B leukaemias/lymphomas from the BM will also be feasible.

The review summarises the various ways Ab-s can damage coated ‘unwanted’ cells (opsonisation, complement mediated lysis, and Ab-s coupled to toxins), and the principles for selecting Me Ab-s for BM transplantation.

Viral erythrocytic necrosis (VEN) in fish is prevalent in a wide variety offish species. It has been detected in both wild and captive fish populations. The infection prevalence in wild populations of some fish species is correlated inversely with the age of the fish. VEN is characterised by cytoplasmic inclusions in circulating erythrocytes of infected fish; nuclear necrosis of erythrocytes may also be evident by light microscopy. The stage and degree of infection affect the type of cytology seen in VEN infections of different fish species. By electron microscopy, infected erythrocytes show spherical virions within the cytoplasm and the virion size is characteristic of the host erythrocytes infected. To date, knowledge of VEN viruses in fish is restricted to virus morphology and propagation in vivo, although preliminary studies have indicated the type of blood parameters which VEN can affect. No such virus has been fully isolated and characterised and all of Koch's postulates have not been fulfilled.

The only serious attempt to quantify the area of bracken in Scotland took place in 1957. At that time the Department of Agriculture for Scotland, through the medium of the June Agricultural Census, asked farmers to assess the area of bracken on each holding.

The survey produced a figure of 187,500 ha of bracken-infested land throughout Scotland, of which some 50% was found in the Central, North and West Highland counties of Perth, Inverness and Argyll. One quarter (46,875 ha) of the Scottish total was located on the mainland and islands of Argyll.

Distribution is governed to a great extent by the soil type, exposure and rainfall, with the free-draining slopes of brown soil on the lower hill faces and glen sides providing the ideal habitat for the plant. The poorly drained acid peat as found over much of the Highland areas is an unsuitable medium for bracken growth but thin peat overlying mineral soil may be subject to bracken encroachment.

The crux of the problem lies in the imbalance of brown soils to peat land.

The limited areas of the mineral soils, which are located on the accessible lower slopes, have a marked potential for improved grazing and, by virtue of better drainage, are capable of more complete utilisation in an intensive stocking system.

Bracken control and subsequent grass sward establishment can form the key to greatly increased levels of productivity. This is illustrated by detailed reference to one farm in Argyll where over the past five years an attempt has been made to operate the Hill Farming Research Organization (H.F.R.O.) concept of a Two Pasture System.

By the late 1970s it had become clear that the immunosuppressive effects of conventional anti lymphocyte serum (ALS) were mediated by only a small component of the anti lymphocyte antibodies present. This fact meant that attempts to improve the safety, potency and standardisation of conventional ALS by raising xenosera to single, purified lymphocyte antigens were faced with considerable technical and theoretical problems. Coincidentally and very fortunately, it was at this time that the potential of monoclonal antibodies in the field of ALS were becoming obvious. Their advent has dramatically transformed the situation, from a bleak one with few prospects to one where the early promise of ALS is likely to be realised in the clinic within the next few years. This review looks at why it is that monoclonal antibodies have so changed the situation, and then discusses in detail the optimal properties, in terms of specificity and other characteristics, of immunosuppressive monoclonal antibodies, and finally looks at precisely how they should be used in the clinic.

The production of monoclonal antibodies specifying tumour associated antigens is illustrated by studies with a spontaneously arising rat mammary carcinoma (Sp4). Fusion of spleen cells from tumour-immune rats with mouse myeloma (P3NS1) yielded hybridomas secreting antibody reacting with a tumour specific antigen. These approaches have subsequently been used to produce monoclonal antibodies reacting with human osteogenic sarcoma, although in this case the antigens detected are tumour associated rather than tumour-specific.

The diagnostic applications of these monoclonal antibodies have been explored particularly to evaluate whether radiolabelled preparations can be used for ‘imaging’ tumours. This approach has been validated with the human osteogenic sarcoma xenograft in tests showing that tumours can be detected by y-camera scanning following injection of 131I-labelled antibody when used in conjunction with blood pool labelling using 113MIn and a computerised subtraction technique.

Monoclonal antibodies also have considerable potential for targetting drugs. These approaches are illustrated by studies using anti-rat mammary carcinoma Sp4 monoclonal antibody linked to adriamycin for therapy of subcutaneous tumour. In addition to drug conjugates, monoclonal antibodies are being used for targeting immunomodulating agents. This is illustrated by another series of studies in which the anti-human osteogenic sarcoma monoclonal antibody has been conjugated to human lymphoblastoid cell interferon to produce a reagent for activating host natural killer cells.

Bracken grows on sites very suitable for forest tree growth allowing a wide choice of tree species. However, the trend in afforestation is towards poorer soils and the area of bracken land being planted is declining. Bracken will damage young trees and methods of its control are reviewed. Hand weeding still has a part to play, but most weeding of heavy bracken growth is by herbicides. Experiments using dicamba, chlorthiamid, picloram and more recently asulam and glyphosate demonstrate a gradual improvement in the selectivity and cost effectiveness of herbicides. Dicamba can only be used before planting and its use is limited to sites where control over three years is assured. Picloram and chlorthiamid at the rates necessary to control bracken are damaging to conifers. Asulam is selective and can be applied after planting giving good control of the bracken. Glyphosate is more damaging to trees than asulam but its use may be justified where a wider spectrum of weed control is required.

Furunculosis has caused serious economic losses in some Atlantic salmon farms in Scotland. It is considered that the disease has the potential to be a significant economic problem to the whole industry unless control measures are adopted. When salmon in a farmed population carry the disease agent in non-clinical form the bacterium has low to intermediate virulence, but in stocks with recurring clinical disease, virulence is apparently increased. The significance of these observations is discussed in terms of the major methods of control, namely avoidance, husbandry procedures, chemotherapy, vaccines and statutory controls.

The toxicity of bracken fern (Pteridium aquilinum (L) Kuhn) is complicated because this plant elaborates more than one type of agent potentially harmful to livestock.

When simple-stomached animals are fed a diet containing some green fronds or rhizomes for a few weeks, they develop anorexia and inco-ordination symptoms; this polyneuritic syndrome shows all the characteristics of thiamine deficiency. Thiamine therapy is effective in curing the animal provided it is administered at the onset of clinical symptoms.

Bracken staggers in the horse and rhizome poisoning of pigs are diseases of this nature,i.e. an avitaminosis B1 has been induced. The causative agent in the fern is a steam-labile enzyme, thiaminase I, which destroys thiamine in such a way that it is no longer active in animal nutrition.

Acute cattle bracken poisoning occurs after frequent eating of the fern over a period of weeks.Haemorrhages and fever are the characteristic clinical symptoms, and the animal usually dies within a few days. The fundamental lesion is bone marrow aplasia resulting in a severe leucopenia and thrombocytopenia.Thiaminase I is not involved in this disease. Bracken contains an organic chemical(s) which poisons rapidly dividing cells in the bovine animal. Sheep are less sensitive to this toxic agent, although the condition has been described along with 'bright-blindness* in some parts of Britain (e.g. North York Moors).

Purification of the active principle causing cattle bracken poisoning from green fronds and rhizomes is far advanced; these methods are described, along with calf toxicity tests on each fraction. Chemical investigations are also under way to determine the nature of the components.

Whether the cattle factor, in small doses over an extended period of time (years), is also the agent causing tumours in livestock, is probable but not certain. Some bracken constituents shown to be carcinogenic in small animals, e.g. shikimic acid, quercetin or the tannin fraction, are not capable of producing acute cattle bracken poisoning; neither does safrole or 1-indanone.

Some of the sesquiterpene glycosides—the 'pterosides' and/or their aglycones, the 'pterosins', of which over 30 have been identified in bracken—are likely candidates. On the other hand, the active principle(s) may be something quite different; the search continues.

The general biology and pathology of Lepeophtheirus salmonis and Caligus elongatus and the prevention and treatment of such ‘sea-lice’ infestations on farmed salmonids are described from the literature and original observations. The life-cycle of L. salmonis and probably also that of C. elongatus comprises the egg and 10 stages separated by moults, namely, two nauplius, one infective copepodite, four chalimus, two pre-adult and the adult (male and female) stages. Water temperature greatly affects the rate of development, especially for early larval stages. Heavy infestations of wild fish seem rare, and lice are lost fairly rapidly in freshwater. In Scotland at least L. salmonis shows a succession of generations on farmed salmonids; generation time is about six weeks at 9–12 C. Post-chalimus stages of C. elongatus may exchange between farmed salmonids and wild fish (especially gadoids). Epizootics (particularly with L. salmonis) cause great damage to salmonids in Norwegian and Scottish farms largely through feeding on host skin. The dermis is oedematous and haemorrhaged where lice feed, and blood seeps between scales; deaths probably result from osmoregulatory failure. Whilst prevention of infestation is difficult, a bath treatment for 1 h with 1 ppm of the organophosphorus compound Dichlorvos is effective against post-chalimus stages of L. salmonis on caged salmonids. Side effects are minimal and clearance rates from fish tissues satisfactory, but treatment may be required every 3–4 weeks.

Current research into viral monoclonal antibodies is reviewed in the light of their use or potential use as diagnostic reagents. Special attention is paid to influenza, the adenovirus group, herpes virus hominis types 1 and 2, rota viruses, hepatitis and cytomegalovirus. Although monoclonal antibodies have many advantages, particularly as regards specificity, purity, reproducibility, homogeneity and availability in unlimited supplies, certain problems are inherent in their very nature. Their preciseness may in fact be a hindrance to their use in diagnosis necessitating their recombination in pools and the quality assessment of their reactions with their homologous 'wild" types presents large logistic problems. There is no doubt that a powerful new serological tool has become available but their large-scale diagnostic use may be a little premature.

Immunoassays have markedly enlarged the armamentarium of the clinical chemist during the last twenty years. Radioimmunoassays and their variants, in particular, now provide evidence which is central to diagnosis and patient management in endocrinology and certain other disorders. Currently used methods employ labelled antigens in the radioimmunoassay (RIA) method first described for insulin by Yalow and Berson. The advent of monoclonal antibodies seems to remove the one major barrier to the use of methods based upon labelled antibodies–the immunoradiometric (IRMA) method as proposed by Miles and Hales. These procedures offer advantages of speed, sensitivity, working range, specificity and robustness which strongly suggest that they will replace RIA for the microdetermination of specific proteins. Nevertheless, their specificity is based upon the recognition of a single epitope on the antigen and thorough testing on varied patient material will be required before they can safely be adopted for routine use.

Information concerning the carcinogenicity of bracken fern (Pteridium aquilinum) in different species and organs is reviewed. Various methods used in attempts to identify the plant components responsible are described and the results evaluated. Reference is made to recent and current research in this field (University College of North Wales, Bangor) and includes mutagenic and sterility studies, and the introduction of teratogenic screening by injection of Japanese quail eggs. The many problems still challenging bracken workers are indicated, and a final section deals with the potential hazard to human health in an attempt to link experimental work with epidemiological surveys of human cancer incidence. One important result of the study of bracken carcinogenicity is that active components, previously thought to be harmless, can be found in a wide variety of regular dietary items.

The general epidermal morphology of teleost fish is described and comparison made in terms of its vulnerability to ultraviolet radiation (UVR) with that of the human. Whereas human skin has a natural pigmentary photoprotective (tanning) mechanism within its epidermis, in teleosts the protective pigment layer is located primarily within the upper dermis. The potential impact of solar UV on farmed fish is discussed both in relation to water penetration of UVR and the phenomenon of photosensitisation, a condition common in higher animals and which has now been shown to induce skin lesions in fish. The results of recent investigations into photosensitisation in fish are described.

There is a high incidence of cancer in beef cows in certain sharply localised geographic calf-rearing areas in Britain and also in cattle in several other parts of the world. The tumours occur on farms which are highly infested with bracken fern and which have a history of bracken poisoning. Bracken is known to cause intestinal and bladder cancer in rats and recently the flavonol, quercetin, has been shown to be a mitogen and to be carcinogenic in rats. Bracken contains large amounts of quercetin. In addition the animals have a high incidence of papillomas of the alimentary tract and these transform to malignant tumours. A new and unique papilloma virus has been isolated from these tumours. Studies using genetic engineering and DNA hybridisation techniques have shown that both alimentary and urinary bladder tumours contain viral DNA sequences. The relationship between bracken, quercetin and viral DNA sequences is under investigation both in cattle and at the molecular biology level as two possible stages in a multi-stage process in the aetiology of a high incidence naturally occurring cancer.

The development of various secondary sexual characteristics in salmonids is described, together with a method of preventing sexual maturation by surgical gonadectomy. The major problem in the application of this technique is the regeneration of male testicular tissue, and it is suggested that the practical solution is the use of hormonal feminisation techniques prior to gonadectomy.