Environmental stress and blood glucose change in insulin-dependent diabetes mellitus.

Investigated blood glucose (BG) response to psychological stress in 14 22–65 yr old insulin-dependent diabetes mellitus patients. Ss were exposed to 2 sessions (12 wks apart) of 2 20-min standardized stressors (active and passive) and a control condition administered in counterbalanced order. BG response was measured, and mood checklist measures were obtained at prestressor, poststressor, and recovery periods. During the 1st session of testing, the active stressor was associated with significantly more absolute change in BG response than the passive stressor. Ss' BG response to this active stressor was idiosyncratic but significantly reliable over time. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Structure and stability of an immunoglobulin superfamily domain from twitchin, a muscle protein of the nematode Caenorhabditis elegans

The NMR solution structure of an immunoglobulin superfamily module of twitchin (Ig 18') has been determined and the kinetic and equilibrium folding behaviour characterised. Thirty molecular coordinates were calculated using a hybrid distance geometry-simulated annealing protocol based on 1207 distance and 48 dihedral restraints. The atomic rms distributions about the mean coordinate for the ensemble of structures is 0.55( +/- 0.09) A for backbone atoms and 1.10( +/- 0.08) A for all heavy atoms. The protein has a topology very similar to that of telokin and the titin Ig domains and thus it falls into the I set of the immunoglobulin superfamily. The close agreement between the predicted and observed structures of Ig 18' demonstrates clearly that the I set profile can be applied in the structure prediction of immunoglobulin-like domains of diverse modular proteins. Folding studies reveal that the protein has relatively low thermodynamic stability, deltaG(H2O)U-F = 4.0 kcal mol(-1) at physiological pH. Unfolding studies suggest that the protein has considerable kinetic stability, the half life of the unfolding is greater than 40 minutes in the absence of denaturant.     

Cytosolic and nuclear distribution of PPARgamma2 in differentiating 3T3-L1 preadipocytes

In light of the pivotal role that PPARgamma2 plays in the expression of fat specific genes (e.g., A-FABP), we have examined the hypothesis that a rise in PPARgamma2 protein is required for the expression of A-FABP, and that the acceleration of fat cell differentiation by the thiazolidinedione agent, pioglitazone (PIOG), reflects an increase in the abundance of PPARgamma2 mRNA and protein. Western analyses surprisingly revealed that undifferentiated 3T3-L1 fibroblasts contained significant levels of PPARgamma2 protein; that the amount of total cellular PPARgamma2 only increased 2-fold during differentiation; and that the levels of PPARgamma2 protein and mRNA were not increased by PIOG even though fat cell differentiation was accelerated by PIOG as revealed by a 20-fold increase in A-FABP expression. Cell fractionation studies revealed that PPARgamma2 was evenly distributed between the cytosolic and nuclear compartments in both undifferentiated and differentiating 3T3-L1 cells. Immunocytochemical studies with a PPARgamma2-specific antibody indicated that PPARgamma2 was diffusely distributed throughout the cytosol of undifferentiated 3T3-L1 cells, but as the differentiation progressed, the PPARgamma2 became focused around the developing lipid droplets. In contrast to PPARgamma2, undifferentiated 3T3-L1 cells contained no measurable quantities of RXRalpha, but once fat cell differentiation was initiated by treatment with IBMX and dexamethasone, the cellular content of RXRalpha increased several fold. The rise in RXRalpha content paralleled the induction of A-FABP, but the expression of RXRalpha was not enhanced by PIOG. Although the amount of PPARgamma2 and RXRalpha was unaffected by PIOG, gel shift assays revealed that PIOG stimulated PPARgamma2/RXRalpha binding to the adipose response element of A-FABP by 5-fold in less than 12 h. Apparently, RXRalpha rather than PPARgamma2 is the pivotal trans-factor essential for the initiation of terminal fat cell differentiation. However, the high cytsolic content of PPARgamma2 and its association with the lipid droplet of differentiating 3T3-L1 cells suggests PPARgamma2 may possess a cytosolic function in the developing fat cell.     

Effectiveness of single and coastal superposphates applied either in autumn or spring

Phosphorus (P) is known to leach laterally in water flowing during winter over pasture growing on flat soils that are shallow sands over slowly permeable lateritic ironstone gravel or clay soils in the high rainfall (> 800 mm annual average) areas of south-western Australia. The climate is Mediterranean, with hot dry December to March and cool wet April to November growing season, with excess water flowing over the surface from June to early-August. Fertilizer P is presently applied at about mid-March, near the start of the growing season. Single superphosphate has been applied for many years, which has a good residual value, and so the soils are no longer acutely P deficient. Consequently, a better method may be to apply the fertilizer at mid-August, after waterlogging and P leaching have usually receded, and radiation and temperature are rising, so pasture growth is increasing. The field experiment reported here was on a shallow sand over lateritic ironstone gravel where lateral leaching of P occurs. The experiment compared from 1990 to 1994 the effectiveness of single superphosphate (SSP), the fertilizer used at present, and coastal superphosphate (CSP), a partially acidulated rock phosphate containing about half the total P and one third the water-soluble P initially present in SSP. The fertilizers were applied annually either at mid-March or at mid-August. SSP applied at mid-March was the most effective treatment studied in the years when pasture plants had emerged before fertilizer was applied at mid-March. This is attributed to pasture plants being able to take up P from SSP applied at mid-March before leaching of P occurred, so that relative to SSP applied at mid-March, the other P fertilizer treatments (CSP applied at mid-march and mid-August, SSP applied at mid-August) were about equally or less effective. However, in years when the growing season had yet to start before fertilizer was applied at mid-March, then relative to SSP applied at mid-March, the other fertilizer treatments were equally or more effective. This is attributed to extensive leaching of P from SSP applied at mid-March, so that due to P losses from SSP applied at mid-March, the other treatments were equally or more effective. It is therefore concluded that profitable pasture production with reduced leaching is achieved by applying SSP at mid-March if soils are moist and pasture plants are growing at that time. However, if the soils are dry and no pasture plants are growing at mid-March, then CSP should be applied at mid-August.     

Cholesterol and lipoprotein(a) as risk factors for coronary heart disease in elderly subjects

The changes in lipoprotein(a) concentration that occur with age as a result of its association with an increased risk of coronary artery disease were investigated. Lipoprotein(a) concentrations were measured in serum samples from healthy volunteers, individuals with premature coronary artery disease, individuals with hyperlipidaemia but without evidence of premature coronary artery disease, and also in elderly men and women who had hyperlipidaemia. Concentrations in individuals with premature coronary artery disease were the same as those of the healthy volunteers, while in both these groups they were lower than those found in hyperlipidaemic elderly men and women, and those found in hyperlipidaemic women aged 36-68 years. No association between raised lipoprotein(a) concentration and mortality as a result of premature coronary artery disease was demonstrated. Raised lipoprotein(a) levels found in the hyperlipidaemic individuals also suggested that it may not be an independent risk factor.     

Quantum-confined stark effect and ultrafast absorption dynamics in bilayer inas quantum dot waveguide

A Stark shift of 40 nm at 1340 nm in a bilayer InAs/GaAs quantum dot ridge waveguide is reported. Time-resolved measurements indicate absorption recovery times of 7 ps at -8 V. Such favourable properties are desirable for intensity and phase modulators     

Prenatal cocaine delays astroglial maturation: immunodensitometry shows increased markers of immaturity (vimentin and GAP-43) and decreased proliferation and production of the growth factor S-100

Exposure to cocaine during fetal development has been demonstrated to produce a variety of brain and behavioral changes. Cocaine is a potent releaser of a variety of neurotransmitters, such as serotonin, which act as developmental signals. Since serotonin plays an important role in astroglial maturation, migration, and growth factor production (e.g. S-100 beta), we proposed that these properties of astroglial cells will be altered in a brain prenatally exposed to cocaine. To observe cocaine's effects on astroglial development, we performed immunocytochemical analyses of a variety of developmental protein makers including BrdU, Gap-43, vimentin, and S100 beta. Our results demonstrate that prenatal cocaine administration produces decreased cell proliferation as measured by BrdU staining, retarded neurite outgrowth as ascertained by increased Gap-43 immunoreactivity, increased density of vimentin-positive radial glial cells, and diminished tissue S100 beta immunoreactivity. Overall, these results suggest that cocaine delays astroglial development. This delay would have profound effects on neuronal development and outgrowth and, thus, development of the entire brain.     

Degradative transport of cationic amphiphilic drugs across phospholipid bilayers

Drug molecules must cross multiple cell membrane barriers to reach their site of action. We present evidence that one of the largest classes of pharmaceutical drug molecules, the cationic amphiphilic drugs (CADs), does so via a catalytic reaction that degrades the phospholipid fabric of the membrane. We find that CADs partition rapidly to the polar-apolar region of the membrane. At physiological pH, the protonated groups on the CAD catalyse the acid hydrolysis of the ester linkage present in the phospholipid chains, producing a fatty acid and a single-chain lipid. The single-chain lipids rapidly destabilize the membrane, causing membranous fragments to separate and diffuse away from the host. These membrane fragments carry the drug molecules with them. The entire process, from drug adsorption to drug release within micelles, occurs on a time-scale of seconds, compatible with in vivo drug diffusion rates. Given the rate at which the reaction occurs, it is probable that this process is a significant mechanism for drug transport.     

Voluntary risk taking and skill deficits in young driver accidents in the UK

In absolute terms, young drivers have three to four times as many accidents per year as older drivers; and even allowing for their relative numbers in the population, their accident involvement is about 2.5 times higher than older drivers. A sample of 3437 accident reports was considered, including 1296 in detail, from midland police forces in the UK, involving drivers aged 17-25, and covering the years 1994-1996 inclusive. Four types of accident were identified as being of particular concern due to their high frequency: 'cross-flow'-turns; rear-end shunts; loss of control on bends; and accidents in darkness. (The term 'cross-flow' is used in relation to turns to denote an intersection accident where a driver is turning across the path of oncoming traffic, i.e., left turns in the US and continental Europe, but right turns in the UK and other countries where driving on the left side of the road is the norm.) An examination of driver risk taking behaviours as revealed in police interviews gave an insight into some of the motivational factors underlying young driver behaviour. Young driver accidents of all types are found to be frequently the result of 'risk taking' factors as opposed to 'skill deficit' factors. It had previously been thought that one of the main problems that young drivers have is in the area of specific skills needed in the driving task. However, it appears that a large percentage of their accidents are purely the result of two or three failures resulting from voluntary risk taking behaviour, rather than skill deficits per se. It is shown that specific groups of young drivers can even be considered as above average in driving skills, but simultaneously have a higher accident involvement due to their voluntary decisions to take risks.