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This report evaluates the pharmacological responses, urinary detection and mass spectral confirmation of ropivacaine in horses. Ropivacaine, a potent local anesthetic (LA) recently introduced in human medicine, has an estimated highest no-effect dose (HNED) of about 0.4 mg/site as determined in our abaxial sesamoid block model. Apparent ropivacaine equivalents were detectable by ELISA screening using a mepivacaine ELISA test after administration of clinically effective doses. Mass spectral examination of postadministration urine samples showed no detectable parent ropivacaine, but a compound indistinguishable from authentic 3-hydroxyropivacaine was recovered from these samples. The study shows that ropivacaine is a potent LA in the horse, that clinically effective doses can be detected in postadministration samples by ELISA-based screening, and that its major post administration urinary metabolite is 3-hydroxyropivacaine.

Mepivacaine is a local anaesthetic drug that is widely used in equine medicine and is classified by the Association of Racing Commissioners International (ARCI) as a Class 2 foreign substance that may cause regulators to impose significant penalties if residues are identified in post-race urine samples. Therefore, an analytical/pharmacological database was developed for this agent and its metabolites. Using an abaxial sesamoid local anaesthetic model, it was determined that the highest no-effect dose (HNED) for its local anaesthetic effect was 2 mg. Using enzyme-linked immunosorbent assay (ELISA) screening, it was determined that subcutaneous (s.c.) administration of the HNED of mepivacaine to eight horses yielded a peak urinary concentration of apparent mepivacaine of 63 ng/mL 2 h after injection. The major identified metabolite recovered from equine urine after dosing with mepivacaine is 3-hydroxymepivacaine. Therefore, 3-hydroxymepivacaine was synthesized, purified and characterized, and a quantitative mass spectrometric method was developed for this metabolite as isolated from horse urine. Following subcutaneous injection of the HNED of mepivacaine, the concentration of 3-hydroxymepivacaine recovered from horse urine reached a peak of about 64.6 ng/mL at 4 h after administration as measured by GC/MS. The concentration of mepivacaine or its metabolites after administration of a HNED dose are detectable by mass spectral techniques. Within the limits of this research, the study suggests that recovery of concentrations less than about 65 ng/mL of 3-hydroxymepivacaine from post-race urine samples may not be associated with a recent LA effect of mepivacaine.

Lidocaine is a local anaesthetic agent that is widely used in equine medicine. It is also an Association of Racing Commissioners International (ARCI) Class 2 foreign substance that may cause regulators to impose substantial penalties if residues are identified in post race urine samples. Therefore, an analytical/pharmacological database was developed for this drug. Using our abaxial sesamoid local anaesthetic model, the highest no-effect dose (HNED) for the local anaesthetic effect of lidocaine was determined to be 4 mg. Using enzyme-linked immunosorbent assay (ELISA) screening, administration of the HNED of lidocaine to eight horses yielded peak serum and urine concentrations of apparent lidocaine of 0.84 ng/mL at 30 min and 72.8 ng/mL at 60 min after injection, respectively. These concentrations of apparent lidocaine are readily detectable by routine ELISA screening tests (LIDOCAINE ELISA, Neogen, Lexington, KY). ELISA screening does not specifically identify lidocaine or its metabolites, which include 3-hydroxylidocaine, dimethylaniline, 4-hydroxydimethylaniline, monoethylglycinexylidine, 3-hydroxymonoethylglycinexylidine, and glycinexylidine. As 3-hydroxylidocaine is the major metabolite recovered from equine urine, it was synthesized, purified and characterized, and a quantitative mass spectrometric method was developed for 3-hydroxylidocaine as recovered from horse urine. Following subcutaneous (s.c.) injection of the HNED of lidocaine, the concentration of 3-hydroxylidocaine recovered from urine reached a peak of about 315 ng/mL at 1 h after administration. The mean pH of the 1 h post dosing urine samples was 7. 7, and there was no apparent effect of pH on the amount of 3-hydroxylidocaine recovered. Within the context of these experiments, the data suggests that recovery of less than 315 ng/mL of 3-hydroxylidocaine from a post race urine sample is unlikely to be associated with a recent local anaesthetic effect of lidocaine. Therefore these data may be of assistance to industry professionals in evaluating the significance of small concentrations of lidocaine or its metabolites in postrace urine samples. It should be noted that the quantitative data are based on analytical methods developed specifically for this study, and that methods used by other laboratories may yield different recoveries of urine 3-hydroxylidocaine.

The raised beach in Church Bay on Rathlin Island, Co. Antrim is shown to be a solitary gravel barrier thai formed around 12000 to 13000 years ago as a result of erosion of the chalk outcrops to the south. The beach sediments exposed in a back barrier gravel pit show the progressive development of a coastal structure under occasional washover. The barrier suggests a sea-level several metres above present, which is consistent with late-Midlandian evidence from elsewhere on the Irish coast, but suggests major land-sea changes must have occurred between Rathlin and the northwest shelf of the British Isles.

Epiligrin, the major component of human keratinocyte extracellular matrix, serves as the preferred integrin ligand for alpha 3 beta 1 in plasma membranes and focal adhesions, and colocalizes with alpha 6 beta 4 in hemidesmosomes. In human skin, epiligrin is found in the lamina lucida subregion of epidermal basement membrane, where it is thought to be associated with anchoring filaments. We have identified three patients with an acquired mucosal predominant subepidermal blistering disease who have IgG anti-basement membrane autoantibodies that bind the lamina lucida/lamina densa interface of epidermal basement membrane, stain cultured human keratinocyte extracellular matrix, and immunoprecipitate disulfide linked polypeptides of 170, 145, 125, and 95 kD in human keratinocyte culture media in a pattern identical to that of P1E1, a murine monoclonal antiepiligrin antibody. Comparative immunoprecipitation studies of patient sera, P1E1, and GB3 monoclonal antibody show that epiligrin is identical to the antigen (i.e., BM600 or GB3 antigen) previously reported to be absent from the skin of patients with lethal junctional epidermolysis bullosa, an inherited subepidermal blistering disease. Moreover, skin from a fetus with this disease shows no evidence of reactivity to patient antiepiligrin autoantibodies or P1E1. These studies show that antiepiligrin autoantibodies are a specific marker for a novel autoimmune blistering disease and that the epidermal basement membrane antigen absent in patients with lethal junctional epidermolysis bullosa is epiligrin.

This paper summarises the erosion of the ‘hard’ coast (cliffs and shore platforms) of northeast Ireland, between Portstewart, Co. Londonderry and Larne. Co. Antrim. Although there is abundant evidence of localised coastal changes, it is not possible to define rates of erosion except on the glacial material cliffs at Portballintrae. where a mean rate of 0.25m/year (1949- 1987) was recorded, although this mean rate appears anomalous in a longer term perspective. Elsewhere, marine erosion is confined to occasional block falls or block dislodgement. Undercutting of cliffs also helps to trigger a variety of sub-aerial slope failures ranging from small superficial slides to large landslips. Patterns of marine erosion are linked to lithological variations in the rock, with the most resistant material (Cretaceous chalk) showing no discernible changes over the last 100 years. The construction of the Antrim Coast Road (A2) in the 1800s has led to the disruption of littoral sediment supplies along stretches of the e...

1. Small scale sand removal (loads of 0.5 to 10 tonnes) is a persistent environmental problem on beaches within Areas of Outstanding Natural Beauty in Northern Ireland. 2. This study provides the first objective assessment of the problem in the British Isles, examining both the physical and biological impacts on the beach and the cultural background. These approaches are combined to indicate possible management strategies. 3. About 5000 to 6000 tonnes of sediment (sand and gravel) was ‘drawn’ from the eleven beaches in the study area during 1990. The rate and magnitude of sediment removal varied between and within sites, by day of the week and by season. 4. There are two direct impacts to the shoreline environment. First, over a long period, the amount of sediment removed is enough to cause serious erosion on some smaller beaches. Up to 80% of shoreline recession can be explained by sand lost through extraction. Second, extraction appears to lead to an impoverished beach fauna. More indirect impacts include the loss of aesthetic quality (important in an area reliant on tourism), disturbance of wildlife, damage to and possible reduction of access provision, and impairing the ability of the shoreline to develop foredunes. 5. The views of the coastal community are quite polarized. One group (about 55%) wish to see sand removal cease, while the remainder (45%) do not. Interviews with people actually taking sand suggest that they do not see their actions as damaging the environment. 6. Several options for future management are discussed. It would appear that a management prescription for each site, backed by legislation, might relieve the problem.

Very little attention has been paid to the impact of global warming, especially sea level rise, on coastal dunescapes, despite the fact that these provide natural protection along many of the world's shorelines. This paper reviews likely responses given the IPCC climate change predictions to 2030AD, which include sea level rise in the order of 0.09 to 0.29m. It is envisaged that coastal dunes will react in a variety of ways dependent both on regional and local factors. Rising water levels will increase susceptibility to erosion, but the fate of released sediment, particularly the onshore/offshore partitioning, must depend on morphodynamic antecedence, and the propensity for periodic domain shifts. The release of material at the shoreline may allow construction of coastal dunes, to the point of progradation in some zones. The response of dune vegetation to a warmer, wetter climate is uncertain. Most of the main temperate dune species are C3 plants which given favourable conditions would respond positively to CO2 enhancement. However local factors may offset such potential gains.

In this report we have studied the mechanism of human B lymphocyte adhesion to fibronectin and to proteolytic fragments of this protein. B cells adhered to fibronectin and to a 38-kDa fragment, derived from the A chain, containing the Hep II domain and most of the type III connecting segment, IIICS, of fibronectin. Cells did not bind to an 80-kDa fragment containing the RGD adhesive sequence of fibronectin. Attachment to fibronectin or to the 38-kDa fragment was not affected by the 80-kDa fragment, the GRGDSPC synthetic peptide, or by a mAb specific for the alpha chain of the RGD-dependent fibronectin receptor, alpha 5 beta 1. However, B cell adhesion to fibronectin was inhibited by the synthetic peptides CS-1, comprising the first 25 amino acids of IIICS and B12, containing the sequence LHGPEILDVPST of CS-1 (residues 14-25). Moreover, this sequence was shown to be sufficient to induce stable cell adhesion when coated on plastic surfaces. A mAb specific for the alpha-subunit of the alpha 4 beta 1 integrin, completely inhibited B cell attachment to B12, CS-1, 38 kDa, and fibronectin coated substrata. These data clearly indicate that adhesion of B lymphocytes to fibronectin is exclusively mediated by the interaction of alpha 4 beta 1 with residues 14-25 of the IIICS region in fibronectin. Therefore this interaction constitutes an alternative pathway of adhesion to fibronectin, independent of RGD and alpha 5 beta 1.

Shoreline erosion is an environmental issue in main parts of Ireland. This paper reports on a detailed study of shoreline change at sixteen beach sites from the mouth of Lough Foyle (Magilligan) in Co. Londonderry to Larne in Co. Antrim, a distance of 135km. Apart from a short stretch of coast (c. 4km) around the mouth of the River Bann. the entire coast is receding, although the rates of change and the reasons for such changes vary considerably. The most rapid erosion (up to 3.5 in/year) is occurring on the northwest coast of Magilligan. probably as part of a lone-term natural adjustment of the shoreline to secular climate and sea-level changes. Elsewhere, average erosion rates are much longer, often less than 0.25 in year, although this rate approaches I m year on those beaches (Cushendall and Cushendun) that are. or have been, used for sand and gravel extraction. In many places shoreline changes have resulted from human activities, including the building of seawalls, jetties and piers. At Portrush and ...

The effects of interleukin 1 (IL-1) are mediated by the activation of protein kinase signalling pathways, which have been well characterized in cultured cells. We have investigated the activation of these pathways in rabbit liver and other tissues after the systemic administration of IL-1alpha. In liver there was 30-40-fold activation of c-Jun N-terminal kinase (JNK) and 5-fold activation of both JNK kinases, mitogen-activated protein kinase (MAPK) kinase (MKK)4 and MKK7. IL-1alpha also caused 2-3-fold activation of p38 MAPK and degradation of the inhibitor of nuclear factor kappaB ('IkappaB'), although no activation of extracellular signal-regulated protein kinase (ERK) (p42/44 MAPK) was observed. The use of antibodies against specific JNK isoforms showed that, in liver, short (p46) JNK1 and long (p54) JNK2 are the predominant forms activated, with smaller amounts of long JNK1 and short JNK2. No active JNK3 was detected. A similar pattern of JNK activation was seen in lung, spleen, skeletal muscle and kidney. Significant JNK3 activity was detectable only in the brain, although little activation of the JNK pathway in response to IL-1alpha was observed in this tissue. This distribution of active JNK isoforms probably results from a different expression of JNKs within the tissues, rather than from a selective activation of isoforms. We conclude that IL-1alpha might activate a more restricted set of signalling pathways in tissues in vivo than it does in cultured cells, where ERK and JNK3 activation are often observed. Cultured cells might represent a 'repair' phenotype that undergoes a broader set of responses to the cytokine.

Lidocaine is a local anesthetic drug that is widely used in equine medicine. It has the advantage of giving good local anesthesia and a longer duration of action than procaine. Although approved for use in horses in training by the American Association of Equine Practitioners (AAEP), lidocaine is also an Association of Racing Commissioners International (ARCI) Class 2 drug and its detection in forensic samples can result in significant penalties. Lidocaine was observed as a monoprotonated ion at m/z 235 by ESI+ MS/MS (electrospray ionization-positive ion mode) analysis. The base peak ion at m/z 86, representing the postulated methylenediethylamino fragment [CH2N(CH2CH3)2]+, was characteristic of lidocaine and 3-hydroxylidocaine in both ESI+ and EI (electron impact-positive ion mode) mass spectrometry. In addition, we identified an ion at m/z 427 as the principal parent ion of the ion at m/z 86, consistent with the presence of a protonated analog of 3-hydroxylidocaine-glucuronide. We also sought to establish post-administration ELISA-based 'detection times' for lidocaine and lidocaine-related compounds in urine following single subcutaneous injections of various doses (10, 40, 400 mg). Our findings suggest relatively long ELISA based 'detection times' for lidocaine following higher doses of this drug.

Diclazuril (4-chlorophenyl [2,6-dichloro-4-(4,5-dihydro-3H-3,5-dioxo-1,2,4-triazin-2-yl)pheny l] acetonitrile), is a benzeneacetonitrile antiprotozoal agent (Janssen Research Compound R 64433) marketed as Clinacox . Diclazuril may have clinical application in the treatment of Equine Protozoal Myeloencephalitis (EPM). To evaluate its bioavailability and preliminary pharmacokinetics in the horse we developed a sensitive quantitative high-pressure liquid chromatography (HPLC) method for diclazuril in equine biological fluids. MS/MS analysis of diclazuril in our HPLC solvent yielded mass spectral data consistent with the presence of diclazuril. After a single oral dose of diclazuril at 2.5 g/450 kg (as 500 g Clinacox), plasma samples from four horses showed good plasma concentrations of diclazuril which peaked at 1.077 +/- 0.174 microg/mL (mean +/- SEM) with an apparent plasma half-life of about 43 h. When this dose of Clinacox was administered daily for 21 days to two horses, mean steady state plasma concentrations of 7-9 microg/mL were attained. Steady-state levels in the CSF ranged between 100 and 250 ng/mL. There was no detectable parent diclazuril in the urine samples of dosed horses by HPLC or by routine postrace thin layer chromatography (TLC). These results show that diclazuril is absorbed after oral administration and attains steady-state concentrations in plasma and CSF. The steady state concentrations attained in CSF are more than sufficient to interfere with Sarcocystis neurona, whose proliferation is reportedly 95% inhibited by concentrations of diclazuril as low as 1 ng/mL. These results are therefore entirely consistent with and support the reported clinical efficacy of diclazuril in the treatment of clinical cases of EPM.

Bupivacaine is a potent local anaesthetic used in equine medicine. It is also classified as a Class 2 foreign substance by the Association of Racing Commissioners International (ARCI). The identification of residues in postrace urine samples may cause regulators to impose significant penalties. Therefore, an analytical/pharmacological database was developed for this medication. The highest no-effect dose (HNED) for the local anaesthetic effect of bupivacaine was determined to be 0.25 mg by using an abaxial sesamoid local anaesthetic model. Administration of the HNED of bupivacaine to eight horses yielded a peak urine concentration of apparent bupivacaine of 23.3 ng/mL 2 h after injection as determined with enzyme-linked immunosorbent assay (ELISA) screening. The major metabolite recovered from beta-glucuronidase-treated equine urine after dosing with bupivacaine is a hydroxybupivacaine, either 3-hydroxybupivacaine, 4-hydroxybupivacaine, or a mixture of the two. To determine which positional isomer occurs in the horse, 4-hydroxybupivacaine was obtained from Maxxam Analytics, Inc., and 3-hydroxybupivacaine was synthesized, purified, and characterized. Furthermore, a quantitative mass spectrometric method was developed for the metabolite as recovered from horse urine. Following subcutaneous injection of the HNED of bupivacaine, the concentration of the hydroxybupivacaine recovered from horse urine reached a peak of 27.4 ng/mL at 4 h after administration as measured by gas chromatography/mass spectrometry (GC/MS). It was also unequivocally demonstrated with ion chromatography that the hydroxybupivacaine metabolite found in horse urine is exclusively 3-hydroxybupivacaine and not 4-hydroxybupivacaine. The mean pH of the 4-h urine samples was 7.21; the mean urine creatinine was 209.5 mg/dL; and the mean urine specific gravity was 1.028. There was no apparent effect of pH, urine creatinine concentration, or specific gravity on the concentration of 3-hydroxybupivacaine recovered. The concentration of bupivacaine or its metabolites after administration of a HNED dose are detectable by mass spectrometric techniques. This study also suggests that recovery of concentrations less than approximately 30 ng/mL of 3-hydroxybupivacaine from postrace urine samples is unlikely to be associated with a recent local anaesthetic effect of bupivacaine.

The shoreline is a rapidly changing interface between the land and the sea, where much of the world's population lives. Coasts are under threat from a variety of natural and anthropogenic impacts, such as climate or sea-level change. This 1995 book assesses how coastlines change, and how they have evolved over the last few thousand years. It introduces concepts in coastal morphodynamics, recognising that coasts develop through co-adjustment of process and form. Particular types of coast, such as deltas, estuaries, reefs, lagoons and polar coasts, are examined in detail with conceptual models developed on the basis of well-studied examples. Coastal Evolution is written for undergraduates who are studying coastal geomorphology, geologists who are mapping coastal sedimentary sequences and environmental scientists, engineers, planners and coastal managers who need to understand the natural processes of change which occur on shorelines.

We have isolated cDNA clones encoding the entire 170-kDa chain of epiligrin (alpha 3Ep) and a genomic clone encoding the alpha 3Ep gene (LamA3). Analysis of multiple cDNA clones revealed two distinct transcripts (alpha 3EpA and alpha 3EpB). Sequencing of the alpha 3EpA transcript indicated sequence and structural homology to laminin alpha 1 and alpha 2 chains that extend from domain IIIa through the carboxyl-terminal G domain. The alpha 3EpB transcript encodes a larger amino-terminal domain and contains additional epidermal growth factor repeats and sequences corresponding to domain IV of alpha 1 laminin. Fluorescence in situ hybridization indicated that the LamA3 gene is located on chromosome 18q11.2, a locus distinct from the LamA1 gene (18p11.3). The G domain of the epiligrin alpha 3 chain contains five subdomains that are individually related to the G subdomains reported for Drosophila and vertebrate laminin alpha chains. Sequence divergence within the G domain of alpha 3 epiligrin suggests that it is functionally distinct from laminin, consistent with our previous report showing that epiligrin interacts with different integrin adhesion receptors. Analysis of RNA from human foreskin keratinocytes (HFKs) identified multiple epiligrin transcripts that were down-regulated by viral transformation and differentiation. In contrast, epiligrin expression was up-regulated in wound sites of human skin.

The Costa del Sol is one of the world’s most developed coasts. Over the past 40 years much of the natural coastline has been destroyed and replaced with tourist-related urban facilities, including high rise apartments, condominiums and hotels. The urban shorefront has become a zone of conflict, as engineers have tried to stem progressive erosion through the construction of seawalls, bulkheads, groynes and breakwaters. The performance of these structures has ranged from satisfactory to poor, in some places exacerbating beach loss and shoreline recession. At Estepona and Marbella, groynes built in the 1960s have recently been removed to assist in stabilising the beach. The environmental stress on the physical resources of the coast may be traced to spiralling demands for water and aggregates. Low seasonal rainfall leads to large-scale water regulation in order to guarantee supplies for agriculture and the urban areas, and this in turn has reduced coastal stream discharge to the point where many rivers are dry for seven to nine months a year. Consequently, sediment delivery to the coast is minimised, and this has resulted in beach erosion, especially along the flanks of deltas. An additional problem arises from the extraction of sand and gravel for construction and agricultural purposes, further depleting beach levels. Also, the recent construction of marinas along the coast has encouraged remobilisation of beach sediment and facilitated its transport onto the shelf. The current phase of large-scale beach nourishment is serving to recycle these materials. There is growing awareness and, inevitably, concern about the future of the Costa del Sol environment, as embodied in recent national and regional directives aimed at reducing stress.

The aims of this chapter are twofold, to provide a background for the remainder of this volume on Lough Neagh, and to cover some of those aspects of the physical environment e.g. geological history, lake sedimentation and drainage, which would not otherwise be examined but which are germane to an understanding of the Lough Neagh ecosystem. In defence of the first aim it must be emphasised that many of the topics are dealt with more fully in other chapters, so that the inadequate interpretations here are merely signposts to better things. The second aim is to provide a reasonably balanced and integrated account of environmental conditions both in and around Lough Neagh. The somewhat ‘fuller’ sections are designed to supply basic information for the later, more specialised accounts to refer to. Throughout a regional approach has been adopted, mainly for the sake of brevity.

Over the last 5000 years man has formed a subtle, but discernible relationship with the coast of Ireland. Initially confined to sensitive environments such as dunes and marshes, the impact has, over the last two centuries, increased markedly and spread to encompass cliffs, estuaries and the beach/nearshore system. Major impact has been felt through the disruption of the sediment budget caused by the construction of seawalls, bulkheads, jetties and harbours, often deflecting and perturbing local material circulations, the reclamation of land, the removal of beach sand and gravel, and more indirectly, through tourism and recreation. It is suggested this will continue to accelerate as long as planning and policy procedures fail to recognise the inherent, underlying coastal process systems.

As with Chapter 2, this chapter provides some of the essential physical background to the functional ecology of Lough Neagh. The interaction of the water depth and exposure of the lake to mixing forces clearly has a profound influence on the horizontal and vertical homogeneity of the water, and many of the chapters that follow contain explicit or implicit reference to the shallow, well-mixed waters of Lough Neagh, and the effects this has on such processes as photosynthesis and respiration, oxygen distribution and nutrient cycling. Equally the depth of water column turbulence winnows and sorts sediments, producing rocky shores, nearshore sands and deep water silts and clays, which in turn influence, for example, the distribution of shore vegetation or benthic invertebrates. The palaeolimnological ‘story’ rests on a coherent sedimentary process, retention times are an important component in nutrient budgets, and lough levels and fluctuations have implications for the establishment of fen vegetation, bird breeding and access.

The State of Florida possesses one of the world’s most heavily developed recreational shorelines. Much of this development has taken place on low barrier island coasts, well known for their morphological and ecological fragility. The history of recreational development in Florida has been largely interventionist, geared to speculative demand and quick profit, without due regard for the environment. In the mid-1960s it became clear that development could not continue unchecked. The environment, particularly in southern Florida, showed all the symptoms of stress, and even the business community were concerned lest ‘pollution’ should lead to falling demand (Carter, 1974; Blake, 1980).

1. Introduction 2. European Economic Policies and Ireland Frank Convery, University College Dublin 3. Partition, Politics and Social Conflict Dennis Pringle, St Patrick's College, Maynooth 4. Irish Population Problems John Coward, University of Ulster, Coleraine 5. Crime in Geographical Perspective David Rottman, Economic and Social Research Institute, Dublin 6. The Historical Legacy in Modern Ireland Stephen A. Royle, The Queen's University, Belfast 7. The Problems of Rural Ireland Mary Cawley, University College, Galway 8. Agricultural Development Desmond A. Gillmor, Trinity College, Dublin 9. The New Industrialisation of Ireland Barry Brunt, University College, Cork 10. The Changing Nature of Irish Retailing Tony Parker, University College, Dublin 11. Transportation James Killen, Trinity College, Dublin and Austin Smyth, Strategic Planning Consultant with Northern Ireland Railways 12. Patterns in Irish Tourism John Pollard, University of Ulster, Coleraine 13. Irish Energy: Problems and Prospects Palmer Newbould, University of Ulster, Coleraine 14. Water Resource Management David Wilcock, University of Ulster 15. Resources and Management of Irish Coastal Waters and Adjacent Coasts Bill Carter, University of Ulster, Coleraine 16. Air Pollution Problems in Ireland John Sweeney, St. Patrick's College, Maynooth 17. Regional Development Strategies James A. Walsh, St Patrick's College, Maynooth.

Magilligan Point is a recurved cuspate foreland at the mouth of Lough Foyle. Two wave regimes intersect in the estuary mouth and the manner of their interplay controls shoreline changes. Ocean swell waves from the N and NE are refracted around the recurve, losing both height and energy longshore. Width of the surf zone decreases and waves tend to steepen, although both these changes and wave refraction owe something to nearshore geometry. Angle of wave approach becomes more acute and a westerly flowing longshore current moves sand S and SW along the beach. Estuary waves from the S and SW are wind-driven with high-frequencies and steepnesses. They generate a northeasterly current which returns material N, but dies out as the waves become obliterated by nearshore attenuation and breaking of swell. It is possible to identify a time-averaged null-point where shoreline wave power is balanced, although this tends to shift over short periods causing rapid morphological changes. The existence of two independent, but counteractive cells ensures the long-term maintenance of the foreland, without requiring major or continuous supplies of fresh sediment.

Recent overwashing, and to a more limited extent overtopping, has occurred on a gravel-dominated beach just west of Carnsore Point in south-east Ireland. At relatively low points swash excursions have breached the duneline and extensive gravel fans have formed on landward-facing slopes. Also, at interbreach positions, swash ramps have been built-up in front of previously eroding dune cliffs, allowing overtopping at heights of up to 5 m above MHWOST, spreading a veneer of sediment over the adjacent dune ridge. In both cases events appear to be preceded by erosion and backbeach sand and gravel deposition. Stratigraphic, textural and fabric analyses assist in identifying environmental conditions that prevailed during overwash throat and fan, and overtopping ramp, sedimentation.

The extent and the specificity of the initial cell attachment induced by various proteins coated on plastic surfaces have been studied with the following results: (a) Cell adhesion on the surfaces coated with sialidase and beta-galactosidase was as strong as on concanavalin A and limulus lectin-coated surfaces and the reactions were strongly inhibited by glycosidase inhibitors or by competitive substrates. The adhesion on sialidase was inhibited by 2-deoxy-2,3-dehydro-N-acetylneuraminic acid and by polysialoganglioside (GT1b) at low concentration (0.05-0.1 mM). The cell adhesion on beta-galactosidase coat was inhibited by 1,4-D-galactonolactone and beta-methylgalactoside but not by alpha-methylgalactoside. Thus, the initiation of cell adhesion on glycosidase surfaces could be mediated through the interactions of the specific binding sites of the enzyme surface with the cell surface substrates under physiological conditions. (b) Cell adhesion on various lectins could be blocked by various competing monosaccharides at the concentrations similar to the inhibitory concentrations for binding of lectins from solution to the cells. (c) Cell adhesion on fibronectin surfaces as well as on gelatin-coated surfaces was equally inhibited by GT1b at relatively high concentrations (0.25-0.5 mM). Lower concentrations of GT1b (0.05-0.1 mM) inhibited the cell adhesion on surfaces of Limulus lectin and sialidase. It is suggested that the cell adhesion mediated by fibronectin is based on yet unknown interactions in contrast to a specific cell adhesion through glycosidases and lectins.

SummaryStructures formed during wind deflation of poorly sorted beach sediments have rarely been described in the literature. However, a number of distinct forms exist including capped pedestals, asymmetrical ‘tear’ structures and scoured or impacted crusts. All these phenomena result from differential spatial erosion of the beach surface by wind, caused by textural or compositional variations. Ephemeral structures are indicative of rapidly changing geomorphological conditions and their presence may also exert control over continuing aeolian processes.

A monoclonal antibody, P1H5, to the human fibroblast class II extracellular matrix receptor (ECMR II) specifically inhibits human fibroblast adhesion to collagen and immunoprecipitates a cell surface receptor containing an alpha and beta subunit of approximately 140 kilodaltons each (Wayner, E. A., and Carter, W. G. (1987) J. Cell Biol. 105, 1873-1884). We report here that P1H5 also specifically inhibits adhesion of unactivated human platelets to type I and III collagens, but not to fibronectin. Immunoprecipitation of the class II ECMR from Triton X-100 detergent lysates of platelets, after cell surface iodination, identified the platelet collagen receptor. Peptide mapping confirmed that the II alpha and II beta subunits immunoprecipitated from platelets are structurally homologous with those derived from fibroblasts. The platelet ECMR II alpha and -beta subunits comigrate with platelet membrane glycoproteins Ia and IIa, respectively, on two-dimensional nonreduced-reduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels. These results indicate that platelet and fibroblast adhesion to collagen are both mediated by a similar receptor and that the alpha and beta subunits of this receptor are identical to platelet membrane glycoproteins Ia and IIa, respectively. Although glycoprotein Ia has been previously implicated as a collagen binding protein, our results are the first direct evidence that platelet glycoprotein Ia is associated with glycoprotein IIa in a heterodimer complex and that this complex, by mediating platelet attachment, is an actual receptor for platelet adhesion to collagen.

The detergent-insoluble matrix of cultured human fibroblasts contains cytoskeletal and nuclear components, as well as two major, noncollagenous glycoproteins, fibronectin and GP140. These glycoproteins are stabilized by extensive intermolecular disulfide bonding. GP140, in contrast to fibronectin, is resistant to digestion with trypsin and is not cross-reactive with antisera prepared against fibronectin (Carter, W. G., and Hakomori, S. (1981) J. Biol. Chem. 256, 6953-6960). GP140 was partially purified, under nonreducing conditions, by differential extraction of trypsinized cells with sodium trichloroacetate. Alternatively, a higher yield of GP140 could be obtained under reducing conditions by extraction with urea-dithiothreitol followed by molecular sieve chromatography in the presence of sodium dodecyl sulfate and dithiothreitol. The purified GP140 contained mannose, galactose, and N-acetylglucosamine residues, totaling 2.7% of the molecule. In addition, mild periodate oxidation of GP140 followed by reduction with NaB3H4 under conditions designed to label sialic acid also labeled the peptide portion of the molecule. Amino acid analysis of GP140 detected periodate-sensitive hydroxylysine residues, as well as hydroxylproline, accounting for the periodate/NaB3H4-induced label in the peptide. These hydroxylated amino acids are major components of collagens and collagen-like proteins. The GP140 isolated under nonreducing conditions was found to induce stable cell attachment and cell spreading when coated on plastic surfaces. The cell attachment could not be inhibited with affinity purified anti-fibronectin antibodies. However, trypsinization of cells under conditions that removed surface fibronectin reduced the ability of the cells to bind to the GP140-coated surface. Metabolic labeling of cells with radioactive glucosamine during 1-h cell attachment experiments incorporated label into both fibronectin and GP140, as well as four other carbohydrate-containing components as part of a stable detergent-insoluble matrix, indicating that the cells rapidly glycosylate both fibronectin and GP140 and incorporate them into the matrix. Long term labeling and chase experiments indicated that fibronectin and GP140 in the matrix are subject to very slow turnover. Neither fibronectin nor GP140 were detectable in the detergent-insoluble matrix of SV40-transformed human fibroblasts by either metabolic or cell surface labeling. These results are consistent with the conclusion that fibronectin and GP140 may function in a cooperative manner in cell adhesion and spreading.

Although a number of programmes for the visual estimation of breaking wave height have been, or are being, operated in different parts of the world (USA-LEO, Australia-COPE), there has been little investigation of the reliability of such data to make precise evaluations of breaking wave height. Using a combination of field data for simultaneous visual estimations and measurements of breaking wave height, it can be shown that experienced observers are able to estimate mean height with only a 20% error. Also the moments of the breaking wave spectrum may be calculated, allowing quick and cheap measurements of extreme waves. LEO records from Florida and California indicate that almost 50% of the data are redundant as frequency of observation could be halved without loss. However, records appear to be filtered, inasmuch as extreme waves are underestimated.

(1982). COASTAL CARAVAN SITES IN NORTHERN IRELAND 1960–1980. Irish Geography: Vol. 15, No. 1, pp. 107-111.

The Dolichos biflorus lectin was isolated from seed homogenates by adsorption onto insoluble polyleucyl hog blood group A + H substance and subsequent elution with N-acetyl-D-galactosamine. Although the lectin was homogeneous as determined by discontinuous polyacrylamide gel electrophoresis, isoelectric focusing, sedimentation equilibrium, and immunodiffusion against rabbit antisera prepared against the crude seed extract, the lectin was fractionated into at least two electrophoretically distinquishable forms (A and B) by chromatography on concanavalin A-Sepharose. Approximately 12% of the original lectin sample did not bind to the concanavalin A and contains the B form. The bound lectin was eluted specifically and quantitatively as a biphasic peak from the concanavalin A-Sepharose with a gradient of methyl alpha-D-glucopyranoside. Carbohydrate analyses of lectin fractions obtained from different portions of the elution profile showed variation in the amount of mannose and N-acetylglucosamine, thus confirming the heterogeneity of the electrophoretic A form. Both the A and B forms of the lectin are active and are apparently present in the dry seeds. Once separated, the two electrophoretic forms of the D. biflorus lectin are distinguishable by electrophoresis. The separated A and B forms show a high degree of similarity in molecular weights (113,000 and 109,000, respectively), antigenic character, and amino acid compositions. Both forms have alanine as NH2-terminal residues and either leucine or valine as the only detectable COOH-terminal residues. The A and B forms specifically agglutinate and have similar titers for type A human red blood cells. They gave similar precipitin curves with hog blood group A + H substance and show similar inhibition curves with methyl alpha-N-acetyl-D-galactosamine and N-acetyl-D-galactosamine. Discontinuous polyacrylamide gel electrophoresis of the unfractionated D. biflorus lectin in 0.1% sodium dodecyl sulfate-8.0 M urea produced two major bands, corresponding to subunits IA and IIA of the A form of the lectin and two minor bands corresponding to subunits IB and IIB of the B form. Subunit molecular weight determinations by electrophoresis in 0.1% sodium dodecyl sulfate gels showed molecular weights of 26,500 for subunits IA and IIA and 26,000 for subunits IB and IIB, Thus indicating that each form of the lectin is composed of four subunits.

Production of GP140, a major component of the extracellular matrix of cultured fibroblasts, is markedly decreased in SV40 transformed cells as compared with normal cells (Carter, W. G., 1982, J. Biol. Chem., 257:13805-13815). To determine at what step the biosynthesis is inhibited, we compared the levels of functional mRNA for GP140 in normal and transformed fibroblasts. Translation of total RNA from W138 cells in a reticulocyte lysate, followed by immunoprecipitation with affinity-purified antibodies to GP140, yielded a single polypeptide with an Mr of 125,000. This polypeptide was identified as GP140 based on its immunoreactivity, collagenase sensitivity, and comigration on polyacrylamide gels with GP140 synthesized by cells in the presence of tunicamycin and 2,2'-bipyridyl. No cell-free synthesis of GP140 was observed with total RNA from SV40 transformed W138 cells, indicating that these cells contain very low levels of GP140-specific mRNA. The biosynthesis of GP140 might therefore be blocked at the transcriptional level.

On Magilligan Strand the formation of an unusual form of rhythmic shoreline ‐ termed a stationary sand wave ‐ has had a profound effect on erosion rates of the dune cliffs. The sand wave has expanded laterally to c. 1200 m since its formation in 1968/69, but its centre has remained in one place. Examination of maps, charts and photographs suggests that similar features have formed in the past, but reasons for their eventual decay can only be speculated upon.

Human umbilical vein endothelial cells attach and spread on laminin-coated substrates. Affinity chromatography was used to identify the attachment receptor. Fractionation of extracts from surface-iodinated endothelial cells on human laminin-Sepharose yielded a heterodimeric complex, the subunits of which migrated with molecular sizes corresponding to 160/120 kD and 160/140 kD under nonreducing and reducing conditions, respectively. The purified receptor bound to laminin and slightly less to fibronectin and type IV collagen in a radioreceptor assay. This endothelial cell laminin receptor was classified as an alpha 2 beta 1 integrin because monoclonal and polyclonal antibodies directed against the alpha 2 and bet 1 subunits immunoprecipitated the receptor. Cytofluorometric analysis and immunoprecipitation showed that the alpha 2 subunit is an abundant integrin alpha subunit in the endothelial cells and that the alpha subunits associated with laminin binding in other types of cells are expressed in these cells only at low levels. The alpha 2 beta 1 integrin appears to be a major receptor for laminin in the endothelial cells, because an anti-alpha 2 monoclonal antibody inhibited the attachment of the endothelial cells to human laminin. These results define a new role for the alpha 2 subunit in laminin binding and suggest that the ligand specificity of the alpha 2 beta 1 integrin, which is known as a collagen receptor in other types of cells, can be modulated by cell type-specific factors to include laminin binding.

The extracellular matrix, prepared by extraction of confluent cultures of human lung WI-38 fibroblasts with a dipolar tonic detergent, contains four major glycoproteins: fibronectin, GP250, GP170, and GP140. All the glycoproteins can be surface-labeled; however, only fibronectin and GP170 can be readily removed by digestion with trypsin (Carter, W. G., and Hakomori, S. (1981) J. Biol. Chem. 256, 6953-6960). Most of the noncovalently bound GP250, GP170, and GP190, an additional minor glycoprotein, can be dissociated from the matrix by extraction with 8 M urea. The remaining insoluble matrix is stabilized by extensive intermolecular disulfide bonds and contains primarily GP140 and fibronectin (Carter, W. G. (1982) J. Biol. Chem. 257, 3249-3257). Affinity-purified, monospecific antibodies were prepared against GP[140 and fibronectin and utilized for detection of GP140 and fibronectin in extracts and conditioned media of WI-38, WI-38 VA13, WI-26, WI-26 VA4, and HT-1080 cells. Additional affinity-purified, polyspecific antibodies that react with GP250, GP190 GP170, and GP140 were also utilized. Fibronectin, GP250, GP190, GP170, and GP140 were all absent from transformed cells. With the exception of GP140, the absence of these glycoproteins from the matrix of transformed cells was paralleled by their accumulation in the conditioned culture media. Incubation of conditioned culture media with collagenase indicated that GP190, GP170, and GP140, as well as other glycoproteins, were digested. Antibodies to GP140 did not react with any other cellular component indicating that it is not a processing product of other matrix glycoproteins. GP140 has characteristics unlike all reported collagen types and appears to be a new collagen-like glycoprotein. In contrast, neither Gp250 nor fibronectin were sensitive to digestion with collagenase. Antibodies that react with GP250 did not react with fibronectin and vice versa, suggesting that GP250 and fibronectin do not share antigenic determinants. The interaction of labeled fibronectin and the labeled, gelatin-binding domain of fibronectin with cells after fractionation on polyacrylamide gels indicated that GP170 is the primary procollagen receptor for fibronectin in the extracellular matrix. GP140 also bound fibronectin but to a lesser degree. Soluble GP170 and GP190 present in the conditioned medium of cultured cells also bound to insolubilized fronectin, confirming the association of GP170 and GP190 with fibronectin. The interaction of the glycoprotein components in the matrix are discussed in relation to their potential cooperative function in cell attachment and their failure to adhere to the surface of transformed cells.

A tidal power barrage on Strangford Lough, would supply about 10% of Northern Ireland's energy requirements in the year 2000. However, the Droject will have serious environmental consequences for the largely unpolluted estuary which contains rare floral and faunal elements, provides a major bird feeding ground and has considerable recreation potential. This article reviews the likely environmental impact of the project.

A major extracellular matrix glycoprotein, GP140 , synthesized by WI-38 human lung fibroblasts has previously been shown to be collagen-like. A form of GP140 that is related to extracellular matrix GP140 both antigenically and in apparent molecular mass was isolated from human placenta. Types I-VI collagen were isolated from human tissues by limited pepsin digestion, selective salt precipitation, and chromatography. Immunoblot analysis of the collagens and GP140 utilizing affinity-purified polyclonal antiserum directed against extracellular matrix GP140 demonstrated cross-reactivity of antibodies with type VI collagen. Both type VI collagen and matrix GP140 could be digested with bacterial collagenase following reduction with dithiothreitol but were collagenase insensitive under nonreducing conditions, unlike types I-V collagen. Placental and matrix GP140 and type VI collagen were shown to have receptors for 125I-labeled Lens culinaris lectin. Pepsin digestion of WI-38 extracellular matrix GP140 yielded a 64,000-dalton band which co-migrated with subunits of reduced type VI collagen on Coomassie-stained sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels, reacted with anti- GP140 antiserum and 125I-labeled L. culinaris lectin, and was collagenase-sensitive only under reducing conditions. CNBr fragmentation of extracellular matrix GP140 , the 64,000-dalton pepsin-resistant peptide of GP140 and type VI collagen followed by immunoblot analysis using anti- GP140 revealed similarities in peptide maps of GP140 and type VI collagen. Our data strongly suggest that GP140 and type VI collagen share characteristics that differ from those of other collagen types and that intermolecular disulfide bonding appears to stabilize these molecules in their native unreduced form, thus conferring collagenase resistance. Finally, the SC1 and SC2 subunits of type VI collagen appear to be generated by pepsin digestion of GP140 .