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Biomedical subjects

M J Winter

Publications and source records attributed to M J Winter.

10 recordsLinked to original sources

Acute and chronic effects of carrier solvents in aquatic organisms: a critical review.

Recognising the scientific and regulatory need for testing relatively hydrophobic or 'difficult substances', the OECD currently recommends that selected organic solvents may be used in aquatic toxicity testing in order to help achieve more effective dispersion of the toxicant. The OECD recommends a maximum solvent concentration of 100 microl l(-1) (with specific gravity equivalents to 100 microl l(-1) in parentheses) for acetone (79 mg l(-1)), dimethylformamide (95 mg l(-1)), dimethylsulfoxide (1.10 mg l(-1)), ethanol (78.9 mg l(-1)), methanol (79.2 mg l(-1)) and triethylene glycol (1.12 mg l(-1)). While this recommendation is supported by historical data, we have recently observed evidence that some solvents may affect the reproduction of certain fish species, and also impact biomarkers of endocrine disruption. This review presents available data on the effects of solvents in aquatic organisms, supplemented by relevant information from mammalian studies (e.g. effects on liver enzyme induction potentially altering the metabolism of sex hormones). In conclusion, it is recommended that maximum effort should be given to avoiding the use of carrier solvents wherever possible, for example through the use of saturation columns or other physical methods (e.g. stirring or ultrasonification). Where solvent use is necessary, however, it is recommended that in reproduction studies with aquatic organisms, the maximum solvent concentration should not exceed 20 microl l(-1) of dilution water.

Amphibians↗

Plasma concentrations of arginine vasotocin and urotensin II are reduced following transfer of the euryhaline flounder (Platichthys flesus) from seawater to fresh water.

Plasma concentrations and stored levels of the neuroendocrine peptides arginine vasotocin (AVT) and urotensin II (UII) were measured in the euryhaline flounder (Platichthys flesus) following the acute hypo-osmotic challenge of direct seawater (SW) to fresh water (FW) transfer. Hormone measures, plasma osmolality, and ion concentrations and tissue water content were determined 1, 4, 8, 24, 72, and 144 h after transfer. Plasma AVT concentration fell initially following FW transfer but then returned toward pretransfer levels by day 6. Plasma UII concentration decreased while urophysial UII content was increased following hypo-osmotic challenge relative to SW time-matched controls, suggesting down regulation of the UII system during the initial stages after FW transfer. These changes in neuroendocrine activity were associated with a significant fall in plasma osmolality and major plasma ions. Positive correlations were observed between plasma AVT and osmolality and Cl- and Mg2+ concentrations, suggesting functional association of these plasma parameters with AVT action and/or control of AVT secretion. The initial response to hypotonic challenge involves reduced plasma AVT and UII levels consistent with the proposed role for these hormones, supporting flounder osmoregulation in hypertonic media.

Animals↗

The caudal neurosecretory system: control and function of a novel neuroendocrine system in fish.

The caudal neurosecretory system (CNSS) of fish was first defined over 70 years ago yet despite much investigation, a clear physiological role has yet to be elucidated. Although the CNSS structure is as yet thought to be confined to piscine species, the secreted peptides, urotensins I and II (UI and UII), have been detected in a number of vertebrate species, most recently illustrated by the isolation of UII in humans. The apparent importance of these peptides, suggested by their relative phylogenetic conservation, is further supported by the complex control mechanisms associated with their secretion. The CNSS in teleosts is known to receive extensive and diverse innervation from the higher central nervous system, with evidence for the presence of cholinergic, noradrenergic, serotonergic, and peptidergic descending inputs. Recent observations also suggest the presence of glucocorticoid receptors in the flounder CNSS, supporting previous evidence for a possible role as a pituitary-independent mechanism controlling cortisol secretion. The most convincing evidence as to a physiological role for the CNSS in fish has stemmed from the direct and indirect influence of the urotensins on osmoregulatory function. Recent advances allowing the measurement of circulating levels of UII in the flounder have supported this. In addition, there is evidence to suggest some seasonal variation in peptide levels supporting the notion that the CNSS may have an integrative role in the control of coordinated changes in the reproductive, osmoregulatory and nutritional systems of migratory euryhaline species.

Amino Acid Sequence↗

A homologous radioimmunoassay for the measurement of urotensin II in the euryhaline flounder, Platichthys flesus.

A sensitive and specific homologous radioimmunoassay (RIA) has been developed to measure tissue and circulating levels of the fish caudal neurosecretory system neuropeptide, urotensin II (UII), in the euryhaline flounder Platichthys flesus. A polyclonal antiserum was raised against flounder UII in rabbit; UII-125I was produced by the iodogen method and purified by HPLC. Antiserum specificity to flounder UII was demonstrated through lack of cross-reactivity with several small peptides and parallelism with standard curves for serial dilutions of UII in plasma and urophysial extracts. Biological activity of the peptide measured by UII RIA was confirmed by bioassay. Plasma intra- and interassay coefficients of variation were 9 and 18% (n = 5 and n = 3), respectively, nonspecific binding constituted 4.6% (+/-1.42%, n = 8) of total counts, and the limit of RIA detectability was estimated as 1.5 x 10(-16) M UII/assay tube. Plasma samples were subject to a reversed-phase liquid chromatography purification protocol which had an extraction efficiency of 63% (+/-10%, n = 6) and showed consistent recovery of UII over a range of plasma volumes and peptide concentrations. Plasma UII concentrations in seawater (SW)-adapted flounder (3.80 +/- 0.77 x 10(-11) M, n = 7) were significantly higher than those in freshwater (FW)-adapted fish (1.10 +/- 0.15 x 10(-11) M, n = 7). This variation coincided with differences in plasma osmolality and Na+ levels. No differences were found, however, between urophysial UII concentrations in SW-adapted (3.71 +/- 1.78 x 10(-10) M UII/gland, n = 7) and FW-adapted (2.53 +/- 1.33 x 10(-10) M UII/gland, n = 7) flounder.

Adaptation, Physiological↗

The biology of the 17-1A antigen (Ep-CAM).

The glycoprotein recognized by the monoclonal antibody (mAb) 17-1A is present on most carcinomas, which makes it an attractive target for immunotherapy. Indeed, adjuvant treatment with mAb 17-1A did successfully reduce the 5 years mortality among colorectal cancer patients with minimal residual disease. Currently the antibody is approved for clinical use in Germany, and is on its way to approval in a number of other countries. New immunotherapeutic strategies targeting the 17-1A antigen are in development or even in early-phase clinical trials. Therefore, a better understanding of the biology of the 17-1A antigen may result in improved strategies for the treatment and diagnosis of human carcinomas. In this review the properties of the 17-1A antigen are discussed concerning tumor biology and the function of the molecule. This 40-kDa glycoprotein functions as an Epithelial Cell Adhesion Molecule, therefore the name Ep-CAM was suggested. Ep-CAM mediates Ca2+-independent homotypic cell-cell adhesions. Formation of Ep-CAM-mediated adhesions has a negative regulatory effect on adhesions mediated by classic cadherins, which may have strong effects on the differentiation and growth of epithelial cells. Indeed, in vivo expression of Ep-CAM is related to increased epithelial proliferation and negatively correlates with cell differentiation. A regulatory function of Ep-CAM in the morphogenesis of epithelial tissue has been demonstrated for a number of tissues, in particular pancreas and mammary gland. The function of Ep-CAM should be taken into consideration when developing new therapeutic approaches targeting this molecule.

Adult↗

Epithelial cell adhesion molecule (Ep-CAM) modulates cell-cell interactions mediated by classic cadherins.

The contribution of noncadherin-type, Ca2+-independent cell-cell adhesion molecules to the organization of epithelial tissues is, as yet, unclear. A homophilic, epithelial Ca2+-independent adhesion molecule (Ep-CAM) is expressed in most epithelia, benign or malignant proliferative lesions, or during embryogenesis. Here we demonstrate that ectopic Ep-CAM, when expressed in cells interconnected by classic cadherins (E- or N-cadherin), induces segregation of the transfectants from the parental cell type in coaggregation assays and in cultured mixed aggregates, respectively. In the latter assay, Ep-CAM-positive transfectants behave like cells with a decreased strength of cell-cell adhesion as compared to the parental cells. Using transfectants with an inducible Ep-CAM-cDNA construct, we demonstrate that increasing expression of Ep-CAM in cadherin-positive cells leads to the gradual abrogation of adherens junctions. Overexpression of Ep-CAM has no influence on the total amount of cellular cadherin, but affects the interaction of cadherins with the cytoskeleton since a substantial decrease in the detergent-insoluble fraction of cadherin molecules was observed. Similarly, the detergent-insoluble fractions of alpha- and beta-catenins decreased in cells overexpressing Ep-CAM. While the total beta-catenin content remains unchanged, a reduction in total cellular alpha-catenin is observed as Ep-CAM expression increases. As the cadherin-mediated cell-cell adhesions diminish, Ep-CAM-mediated intercellular connections become predominant. An adhesion-defective mutant of Ep-CAM lacking the cytoplasmic domain has no effect on the cadherin-mediated cell-cell adhesions. The ability of Ep-CAM to modulate the cadherin-mediated cell-cell interactions, as demonstrated in the present study, suggests a role for this molecule in development of the proliferative, and probably malignant, phenotype of epithelial cells, since an increase of Ep-CAM expression was observed in vivo in association with hyperplastic and malignant proliferation of epithelial cells.

Animals↗

Music reduces stress and anxiety of patients in the surgical holding area.

Many patients in the Surgical Holding Area become stressed and anxious. In a hospital setting music reduces patients' anxiety. This study determined that music can reduce the anxiety and stress of patients in the Surgical Holding Area. In this study, one group of subjects listed to music while a second group did not. Subjects who listened to music while in the Surgical Holding Area had significantly less stress and anxiety than did those who did not listen to music. Both groups spent similar lengths of time in the Surgical Holding Area. The results strongly suggest that if music were available to all patients in the Surgical Holding Area, most would select this option, and they would experience less anxiety.

Adult↗