Lead differentially modifies cytokine production in vitro and in vivo

An imbalance between helper T cell type 1 (Th1) and helper T cell type 2 (Th2) activation can result in immunodysregulations leading to impaired cell-mediated immunity with an increased incidence of infectious disease or cancer and/or aberrant humoral immunity that may culminate with an autoimmune disease. Mercury, a heavy-metal toxicant, is known to induce renal autoimmunity characterized by a predominant Th2 response. Lead, another metal toxicant, causes enhanced B cell activities and impairs host resistance to several bacterial and viral infections. In addition, Pb was reported to enhance Th2 proliferation and inhibit Th1 proliferation. The differential effects of Pb on Th subset activation have been further investigated. In vitro IL-4 production by a Th2 clone was significantly increased by the addition of PbCl2, whereas IFN gamma production by a Th1 clone was decreased by the addition of PbCl2. When BALB/c mice were subcutaneously exposed to PbCl2, ex vivo Il-4 production by anti-CD3-stimulated splenic T cells was enhanced, but IFN gamma production was inhibited. Additionally, the plasma IL-4 and IgE levels of Pb-exposed mice were increased, and the plasma IFN gamma levels were significantly lowered in the absence of any additional exogenous antigen. In vitro, ex vivo, and in vivo treatment with HgCl2 produced similar findings. This study is the first report of the preferential activation of a Th2 response by Pb in vivo and suggests that PB, like Hg, may induce autoimmune responses by upsetting the balance between Th1- and Th2-like cells, which could enhance production of antibodies to self antigens.     

Non-amphetaminic mechanism of stimulant locomotor effect of modafinil in mice

Previously established dose-response curves indicated that modafinil 20-40 mg/kg i.p. elicited in mice an obvious stimulation of locomotor activity roughly similar to that induced by (+)amphetamine 2-4 mg/kg. The effects of various agents modifying dopamine transmission were compared on the locomotor response to both drugs. The preferential D2 dopamine receptor antagonist haloperidol 37.5-150 micrograms/kg i.p. suppressed the stimulant effect of (+)amphetamine in a dose dependent manner, but not that of modafinil. The D1 dopamine receptor antagonist SCH 23390 (7.5-30 micrograms/kg s.c.) reversed the (+)amphetamine but not the modafinil induced hyperactivity. The tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (200 mg/kg) suppressed the hyperactivity induced by 4 mg/kg dexamphetamine but not that induced by 20 mg/kg modafinil. Associating L-DOPA 150 mg/kg and benserazide 37.5 mg/kg with (+)amphetamine 2 mg/kg resulted in stereotyped climbing behavior, that was not observed with modafinil 10-80 mg/kg. The profound akinesia induced by reserpine (4 mg/kg s.c.; 5 h before testing) was reversed by (+)amphetamine 2 mg/kg but not by modafinil 40 mg/kg. Finally, on synaptosomes prepared from mouse striata preloaded with [3H]dopamine, modafinil 10(-5) M did not increase the spontaneous [3H]dopamine release whereas (+)amphetamine, at the same concentration, doubled it. From all these differences between the two drugs, it is concluded that the mechanism underlying the modafinil induced stimulant locomotor effect differs completely from that of (+)amphetamine.     

Efficient generation of a reshaped human mAb specific for the {alpha} toxin of Clostridium perfringens

We have used the technique of antibody reshaping to producea humanized antibody specific for the a toxin of Clostridiumperfringens. The starting antibody was from a mouse hybridomafrom which variable (V) region nucleo-tide sequences were determined.The complementarity-determining regions (CDRs) from these Vregions were then inserted into human heavy and light chainV region genes with human constant region gene fragments subsequentlyadded. The insertion of CDRs alone into human frameworks didnot produce a functional reshaped antibody and modificationsto the V region framework were required. With minor frameworkmodifications, the affinity of the original murine mAb was restoredand even exceeded. Where affinity was increased, an alteredbinding profile to overlapping peptides was observed. Computermodelling of the reshaped heavy chain V regions suggested thatamino acids adjacent to CDRs can either contribute to, or distort,CDR loop conformation and must be adjusted to achieve high bindingaffinity.     

Recovery from work shifts: How long does it take?

Although regulations on work hours usually include a minimum weekly rest period, there is little empirical evidence concerning recovery from work. Shift-working nurses (N?=?61) used a handheld computer for 28 days to complete self-ratings, cognitive-performance tasks, and a sleep diary. Many measures were worse on rest days that followed a night shift rather than a day shift and tended to be worse on 1st rest days compared with subsequent rest days. Alertness was lowest on the 1st rest day following a night shift. Social satisfaction was better on workdays that were preceded by 2 rather than 1 rest day. Reaction time (RT) decreased over consecutive night shifts and tended to increase over rest days following night shifts. The results are interpreted as being consistent with the combined adaptive costs of fatigue and adjustment to and from a nocturnal routine. The practical implications for scheduling rest days are considered. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A kinetic investigation into the removal of carbobenzyloxy group from protected amines via hydrogenolysis reaction

Hydrogenolysis of a carbobenzyloxy group (CBz) was studied utilizing molecular hydrogen in the presence of carbon-supported palladium catalyst. It was demonstrated that the kinetics of the reaction are greatly influenced by the presence of the CO₂ by-product. It was found out that the presence of CO₂ determines whether the reaction is first or zero order since it causes deactivation of the catalyst via inhibition. The effect of potassium carbonate (K₂CO₃) and triethylamine (TEA) as additives was investigated. A considerable solvent effect was also observed that may be explained by the variation of dispersion of the catalyst from one solvent to another.     

Valley floor landscape change following almost 100 years of flood embankment abandonment on a wandering gravel‐bed river

Critical to restoring the nature conservation value of many river corridors is an understanding of how alluvial landscapes will respond to cessation of river management and land use practices that have previously degraded the environment. This paper analyses changes in valley floor landforms and vegetation patch dynamics, in relation to fluvial disturbance, over a period of almost 100 years following flood embankment abandonment on a wandering gravel‐bed river, namely the River Tummel, Scotland. Such rivers were once typical of many draining upland areas of northern maritime Europe. Prior to abandonment the valley floor landscape was agriculturally dominated and the river for the most part was single thread confined between flood embankments. The pattern of landform change and vegetation patch development over time following a decision in 1903 not to maintain embankments was tracked by geomorphic and land cover mapping utilizing successive sets of aerial photography for the period 1946 to 1994. A historical context for these changes was also feasible because the channel planform in 1900 and earlier channel planform changes dating back to 1753 were known due to the availability of old maps and earlier geomorphic studies. The land cover mapping was validated by comparison of results produced from the interpretation work on the 1994 aerial photographs with the field‐based UK National Vegetation Classification protocol. The findings of the study illustrate that bordering the River Tummel fluvial landforms and vegetation patch mosaics, presumably resembling those that occurred before valley floor land use intensification, evolved in less than 50 years after flood embankment abandonment with a resultant increase in habitat diversity. The change relates primarily to flood‐induced channel planform change and moderate levels of fluvial disturbance. The general significance of this change to plant species diversity on the valley floor of the River Tummel and elsewhere is discussed as is possible implications of the upstream impoundment and scenarios for climatically induced changes in flood frequency and magnitude. The overall outcome is the strong possibility that simple changes in river management and land use practices could result in re‐establishment of the nature conservation value of similar river corridors in Europe over the medium term without active restoration efforts. Copyright © 2002 John Wiley & Sons, Ltd.     

Editorial

Ohne Zusammenfassung     

Medicine, population and war

The colonization mechanisms of enteropathogenic Aeromonas strains are poorly characterized, but recent studies indicate that some filamentous structures are intestinal adhesins. This study describes the purification and characterization of a long, flexible pilus from a gastroenteritis-associated strain of Aeromonas veronii biovar sobria. SDS-PAGE analysis (various conditions) of pili preparations yielded a pilin protein band of approximately 21 kDa. Its N-terminal amino acid sequence was unambiguous and homologous with those of type IV pilins. Immunogold electron microscopy with rabbit antisera produced against this pilin protein (SFP) decorated single pili and rope-like bundles of pili on the bacterial surface. These were seen more frequently on strains grown at 22 degrees C compared with 37 degrees C and in liquid rather than on solid medium. SFP was not detected on any of 104 strains of Aeromonas (different species and sources) from our culture collection, although morphologically similar structures were seen on a number of these strains. This finding and differences among other published amino acid sequences show that Aeromonas type IV pili are antigenically diverse. Bundle-forming type IV 'class B' pili are important in the virulence of other enteropathogenic bacteria. The N-terminal amino acid sequence of the Aeromonas SFP, however, showed closer homology to the type IV 'class A' pilins. Studies are in progress to investigate the role of SFP in Aeromonas virulence.     

Management of rhesus isoimmunization by preimplantation genetic diagnosis

Intracranial osteolipomas are rare lesions which occur in the region of the tuber cinereum. All cases reported to date have been incidental autopsy findings. We describe a patient who presented with a variety of neurological symptoms and had a typical osteolipoma surgically removed.