The Peyer's patch high endothelial receptor for lymphocytes, the mucosal vascular addressin, is induced on a murine endothelial cell line by tumor necrosis factor-alpha and IL-1

The specificity of lymphocyte homing from the blood into a tissue is determined in part by complementary pairs of adhesion receptors on lymphocytes and endothelial cells termed homing receptors and vascular addressins, respectively. The mucosal vascular addressin involved in lymphocyte homing to Peyer's patches is a 66-kDa glycoprotein, MAdCAM-1. Investigation of the regulation and molecular genetics of MAdCAM-1 have been hampered by the lack of a murine cell line expressing this adhesion molecule. We show herein using indirect immunofluorescence studies that MAdCAM-1 can be induced on a murine endothelial cell line, bEnd.3, by cytokines and LPS. Western blot analysis of MAdCAM-1 purified by affinity column chromatography from TNF-alpha-treated bEnd.3 cells demonstrates a 66-kDa protein that comigrates in SDS-PAGE with the MAdCAM-1 constitutively found on high endothelial venules in murine mesenteric lymph nodes. Comparison of MAdCAM-1 expression on the bEnd.3 cells was made to the expression of adhesion molecules ICAM-1 and VCAM-1. MAdCAM-1 and VCAM-1 are not constitutively expressed on the bEND.3 surface but can be induced in a concentration-dependent manner by LPS, TNF-alpha, and IL-1. ICAM-1 is constitutively expressed on the endothelioma surface and expression is increased by TNF-alpha, IL-1, LPS, and IFN-gamma. Surface expression of MAdCAM-1 peaks 12 to 18 h after exposure to TNF-alpha and remains elevated at 48 h, whereas expression of VCAM-1 peaks at 4 h and inducible ICAM-1 peaks between 4 and 18 h. Interestingly, IFN-gamma has differential effects on expression of these three adhesion receptors. IFN-gamma alone induces VCAM-1 and enhances ICAM-1 expression, but does not induce MAdCAM-1. Furthermore, although, preincubation of bEND.3 cells with IFN-gamma modestly increases the induction of ICAM-1 and VCAM-1 in response to TNF-alpha and IL-1, it dramatically reduces the TNF-alpha, IL-1, and LPS-induced expression of MAdCAM-1. MAdCAM-1 on bEnd.3 cells is functional as the murine T lymphoma TK1, known to bind MAdCAM-1, also binds to TNF-alpha-stimulated endothelioma but not to unstimulated cells. This binding is blocked by the antibodies against MAdCAM-1 and against the alpha 4-chain of its integrin receptor, alpha 4 beta 7, on TK1 cells.(ABSTRACT TRUNCATED AT 400 WORDS)     

Physicochemical characterization of sahti,an ‘ancient’ beer style indigenous to Finland

Sahti, a strong, unhopped farmhouse beer flavoured with juniper, is still actively brewed in rural areas in Finland. Presented here is the first comprehensive analysis of the physical and chemical properties of this unique beer style. Twelve sahti samples from the southwest of Finland were analysed and, while properties varied, the beers generally had high levels of alcohol (mean = 7.9% ABV) and high residual extract (mean = 9.5°P). Foam stability was negligible, as is typical for the style, and glycerol concentrations at 3.1 – 4.7 g L^?1 were higher than in reference beers (commercial lager, wheat beer and porter). These features may be attributed to the very high gravity conditions employed in brewing sahti beers. Bitterness levels were relatively low (3–13 IBU) owing to the absence or moderate use of hops. All samples contained detectable levels of the clove‐like compound 4‐vinylguaiacol owing to the use of baker's rather than brewer's yeast for brewing. Concentrations of higher alcohols and esters were high, with many individual aroma compounds being above the normal flavour thresholds. Results have highlighted the uniqueness of this style of beer in comparison to commercially available beers and have contributed to our understanding of the reasons for the particular sensorial properties of this traditional beer style. Copyright © 2015 The Institute of Brewing & Distilling     

Sperm storage in females of the smooth newt (Triturus v. vulgaris L.): I. Ultrastructure of the spermathecae during the breeding season

Sperm storage in cloacal spermathecae was studied in females of Triturus v. vulgaris collected early in the breeding season in southern England. Females collected in terrestrial situations, presumably unmated, were mated in the laboratory, and the ultrastructure of the transferred sperm and the spermathecae was observed at various intervals after mating. Sperm from a spermatophore cap lodged in a female's cloacal orifice can migrate into spermathecae within 1 hr after mating. Spherical structures on the axial fibers of some sperm in the cap could indicate immaturity. Disorderly clusters of sperm from the cap are still present in the cloacal chamber 12 hr after mating but are absent 24 hr after mating. During storage, sperm often are in tangled masses in the spermathecal tubules. The sperm are coated with spermathecal secretions, and some sperm nuclei were observed embedded in the spermathecal epithelium. Little evidence for spermiophagy early in the breeding season was found. During oviposition, mazes of sperm occur external to the spermathecal orifices, and sperm may be released in this condition onto eggs as they pass through the cloaca. The tangled clusters in which sperm are found from pick-up to oviposition are hypothesized as an adaptation to reduce the effectiveness of sperm competition from the ejaculates of rival males. Additional studies, using the same protocol and covering the entire cycle of sperm storage, are necessary to enable interspecific comparisons leading to phylogenetic hypotheses.     

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Systemic methotrexate toxicity. A pharmacological study of its occurrence after intrathecal administration in a patient with renal failure

Methotrexate pharmacokinetic studies, performed on a patient with renal impairment who had toxic effects following 20 mg/sq m of intrathecally administered methotrexate, demonstrated prolonged serum concentrations of the drug, which accounted for the condition. After the return of normal renal function, pharmacokinetic studies were repeated following the same dose and route of administration of methotrexate. On this occasion there was a rapid clearance of serum methotrexate below toxic levels.