Expression and polarization of intercellular adhesion molecule-1 on human intestinal epithelia: consequences for CD11b/CD18-mediated interactions with neutrophils.

BACKGROUND: Epithelial dysfunction and patient symptoms in inflammatory intestinal diseases such as ulcerative colitis and Crohn's disease correlate with migration of neutrophils (PMN) across the intestinal epithelium. In vitro modeling of PMN transepithelial migration has revealed distinct differences from transendothelial migration. By using polarized monolayers of human intestinal epithelia (T84), PMN transepithelial migration has been shown to be dependent on the leukocyte integrin CD11b/CD18 (Mac-1), but not on CD11a/CD18 (LFA-1). Since intercellular adhesion molecule-I (ICAM-1) is an important endothelial counterreceptor for these integrins, its expression in intestinal epithelia and role in PMN-intestinal epithelial interactions was investigated. MATERIALS AND METHODS: A panel of antibodies against different domains of ICAM-1, polarized monolayers of human intestinal epithelia (T84), and natural human colonic epithelia were used to examine the polarity of epithelial ICAM-1 surface expression and the functional role of ICAM-1 in neutrophil-intestinal epithelial adhesive interactions. RESULTS: While no surface expression of ICAM-1 was detected on unstimulated T84 cells, interferon-gamma (IFN gamma) elicited a marked expression of ICAM-1 that selectively polarized to the apical epithelial membrane. Similarly, apically restricted surface expression of ICAM-1 was detected in natural human colonic epithelium only in association with active inflammation. With or without IFN gamma pre-exposure, physiologically directed (basolateral-to-apical) transepithelial migration of PMN was unaffected by blocking monoclonal antibodies (mAbs) to ICAM-1. In contrast, PMN migration across IFN gamma-stimulated monolayers in the reverse (apical-to-basolateral) direction was inhibited by anti-ICAM-1 antibodies. Adhesion studies revealed that T84 cells adhered selectively to purified CD11b/CD18 and such adherence, with or without IFN gamma pre-exposure, was unaffected by ICAM-1 mAb. Similarly, freshly isolated epithelial cells from inflamed human intestine bound to CD11b/CD18 in an ICAM-1-independent fashion. CONCLUSIONS: These data indicate that ICAM-1 is strictly polarized in intestinal epithelia and does not represent a counterreceptor for neutrophil CD11b/CD18 during physiologically directed transmigration, but may facilitate apical membrane-PMN interactions after the arrival of PMN in the intestinal lumen.     

The effects of predator presence and shoal size on foraging in bluntnose minnows,Pimephales notatus

Synopsis Shoals of 3, 5, 7, 10, 15, and 20 bluntnose minnows,Pimephales notatus, were allowed to forage in the absence and presence of a fish predator, which was separated from the shoal by a clear plexiglass partition. A typical dilution effect was observed in that individual fish in larger shoals were approached less frequently by the predator. In the absence of a predator, foraging latency decreased significantly and the rate of foraging increased with increasing shoal size. Foraging latency for each shoal size tended to increase in the presence of a predator and foraging rate decreased, significantly for shoals of 7, 15, and 20 fish. Members of larger shoals were safer and enjoyed a greater level of food consumption, perhaps due to decreased individual vigilance for predators and social facilitation. However, foraging effort decreased when a predator was present, as more time was allocated to predator avoidance.     

Territorial behaviour of the male johnny darter,Etheostoma nigrum

Synopsis A field study was undertaken to describe the territorial behaviour of male johnny darters (Etheostoma nigrum) over the reproductive cycle. While defending eggs, males performed fewer Lateral Displays and lost fewer encounters with conspecific males than in the pre-egg phase. As the reproductive cycle progressed males were less responsive to females and performed relatively fewer courtship and more aggressive displays. Nesting males apparently shifted from a sexual to a parental phase shortly after acquiring eggs.Frequency of response, responsiveness (number of responses/number of intrusions x 100) and maximum distance of response (MDR) of male johnny darters were highest early in the reproductive cycle and decreased over the egg-guarding phase. The patterns of territorial defence exhibited by male johnny darters over the reproductive cycle were similar to those of other species of fish with paternal care.     

Paleochemistry of manganese in corals from the Galapagos Islands

Approximately 550 measurements of Mn/Ca ratios in three corals from the western Galapagos Islands have been performed to reconstruct a 380-year history of surface ocean variability with respect to this trace element. The time period studied encompasses 1600 A.D. to 1978. Manganese is inferred to be lattice-bound in coralline aragonite at 10–50% of its seawater proportion to calcium; uncertainty about the distribution coefficient stems from inherent variability of oceanic Mn in nearshore settings. Interannual variations at Urvina Bay, Isabela Island are generally small, with the exception of a few decades during the nineteenth century. A large positive Mn/Ca anomaly found between 1821–1830 is hypothesized to have resulted from a major volcanic eruption on nearby Fernandina Island in 1825. On intrannual timescales a pronounced cycle occurs in response to seasonal upwelling. Quarterly changes in Mn/Ca are six months out-of-phase with Cd/Ca variations-a reflection of the opposite distributions of these metals in the upper waters of the eastern Pacific. High frequency reconstructions over brief time intervals from the 17th, 18th, and 20th century reveal that the seasonal onset of warm and cool phases near Galapagos has persisted for at least 340 years. A quantitative assessment of historical changes in upwelling intensity is complicated by offsets in background Mn levels recorded by different corals. One apparent longterm feature is an overall decline in skeletal Mn concentrations from 1600–1978 which results in a net decrease of 20–30%. Several possible explanations exist for this trend, ranging from accumulation of a persistent diagenetic Mn phase in fossil aragonite to a temporal shift in oceanic/atmospheric Mn fluxes reaching the surface waters of the Galapagos Islands.     

Physiological roles for ecto-5’-nucleotidase (CD73)

Nucleotides and nucleosides influence nearly every aspect of physiology and pathophysiology. Extracellular nucleotides are metabolized through regulated phosphohydrolysis by a series of ecto-nucleotidases. The formation of extracellular adenosine from adenosine 5′-monophosphate is accomplished primarily through ecto-5′-nucleotidase (CD73), a glycosyl phosphatidylinositol-linked membrane protein found on the surface of a variety of cell types. Recent in vivo studies implicating CD73 in a number of tissue protective mechanisms have provided new insight into its regulation and function and have generated considerable interest. Here, we review contributions of CD73 to cell and tissue stress responses, with a particular emphasis on physiologic responses to regulated CD73 expression and function, as well as new findings utilizing Cd73-deficient animals.     

Reduced inflammation and tissue damage in transgenic rabbits overexpressing 15-lipoxygenase and endogenous anti-inflammatory lipid mediators

PGs and leukotrienes (LTs) mediate cardinal signs of inflammation; hence, their enzymes are targets of current anti-inflammatory therapies. Products of arachidonate 15-lipoxygenases (LO) types I and II display both beneficial roles, such as lipoxins (LXs) that stereoselectively signal counterregulation, as well as potential deleterious actions (i.e., nonspecific phospholipid degradation). In this study, we examined transgenic (TG) rabbits overexpressing 15-LO type I and their response to inflammatory challenge. Skin challenges with either LTB(4) or IL-8 showed that 15-LO TG rabbits give markedly reduced neutrophil (PMN) recruitment and plasma leakage at dermal sites with LTB(4). PMN from TG rabbits also exhibited a dramatic reduction in LTB(4)-stimulated granular mobilization that was not evident with peptide chemoattractants. Leukocytes from 15-LO TG rabbits gave enhanced LX production, underscoring differences in lipid mediator profiles compared with non-TG rabbits. Microbe-associated inflammation and leukocyte-mediated bone destruction were assessed by initiating acute periodontitis. 15-LO TG rabbits exhibited markedly reduced bone loss and local inflammation. Because enhanced LX production was associated with an increased anti-inflammatory status of 15-LO TG rabbits, a stable analog of 5S,6R,15S-trihydroxyeicosa-7E,9E,11Z,13E-tetraenoic acid (LXA(4)) was applied to the gingival crevice subject to periodontitis. Topical application with the 15-epi-16-phenoxy-para-fluoro-LXA(4) stable analog (ATLa) dramatically reduced leukocyte infiltration, ensuing bone loss as well as inflammation. These results indicate that overexpression of 15-LO type I and LXA(4) is associated with dampened PMN-mediated tissue degradation and bone loss, suggesting that enhanced anti-inflammation status is an active process. Moreover, they suggest that LXs can be targets for novel approaches to diseases, e.g., periodontitis and arthritis, where inflammation and bone destruction are features.     

The Southwest of Scotland Structural Chromosomal Abnormalities Database: an assessment of its contribution to genetic counselling in affected families

AIM: To assess the effect of establishing a genetic database on the provision of genetic counselling to individuals and families with structural chromosomal abnormalities. METHOD: For the four year period 1997-2000, we compared all cytogenetics laboratory records with entries on the database to determine its completeness. We assessed the extent to which families had been followed up, compared these findings with a previous four year period (1977-1980) and sought to discover why some families were not followed up. RESULTS: Of 215 probands identified during 1997-2000, 19 (9%) were not recorded on the register. Approximately one third of families were followed up completely, one third were partially followed up and one third had had no follow-up, for a variety of reasons. In this last group, there was evidence that some had received inadequate or incorrect genetic advice. There was no evidence that the database improved follow-up in families with structural chromosome abnormalities. Over 20 years, there has been a downward trend in the proportion of cases referred to the genetic clinic. CONCLUSIONS: Our register can be used to monitor trends in clinical practice but has had no direct effect on the service provided to patients and their families.     

Behavioural Response of Juvenile Bluegill Sunfish to Variation in Predation Risk and Food Level

The behavioural response of juvenile bluegill sunfish (Lepomis macrochirus) to predation risk when selecting between patches of artificial vegetation differing in food and stem density was investigated. Bluegill foraging activity was significantly affected by all three factors. Regardless of patch stem density or risk of predation bluegills preferred patches with the highest prey number. During each trial bluegill foraging activity was clearly divided into a between- and within-patch component. In the presence of a predator bluegills reduced their between-patch foraging activity by an equivalent amount regardless of patch stem density or food level, apparently showing a risk-adjusting behavioural response to predation risk. Within patches, however, foraging activity was affected by both food level and patch stem density. When foraging in a patch offering a refuge from predation, the presence of a predator had no effect on bluegill foraging activity within this patch. However, if foraging in a patch with only limited refuge potential, bluegill foraging activity was reduced significantly in the presence of a predator. Further, this reduction was significantly greater if the patch contained a low versus a high food level, indicating a risk-balancing response to predation with respect to within-patch foraging activity. Both these responses differ from the risk-avoidance response to predation demonstrated by juvenile bluegills when selecting among habitats. Therefore, our results demonstrate the flexibility of juvenile bluegill foraging behaviour.