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Biomedical subjects

P Moss

Publications and source records attributed to P Moss.

At least 37 records · Page 2Linked to original sources

Negotiating spaces in home environments: older women living with arthritis.

Within medical geography there has been a surge of interest in applying critical concepts in social theory to empirical settings, including those for persons with disabilities. The ways through which persons with disabilities negotiate space vary widely according to material and social experiences of being disabled. For older women, chronic illness as a type of disability shapes the way in which they approach their daily lives with respect to both the physical and social aspects of their home environments. In the first half of the paper, conceptually, I take a relational view of space and argue that household, as a narrow reading of domestic space, needs to be replaced by home environment which incorporates more fully age- and ablement-sensitive readings of the spaces constitutive of domestic space. This lays the basis for a contextualized socio-spatial understanding of the ways older women with chronic illness negotiate the spaces in home environments because it accounts for the disadvantaged positionings of access to power and resources as well as the uneven distributions of income based on gender, age, and (dis)ability. It also takes into account the material and social aspects of being disabled. In the second half of the paper, I present case studies of three older women diagnosed with rheumatoid arthritis to illustrate these arguments.

Activities of Daily Living↗

The repertoire of T cell antigen receptor beta-chain variable regions associated with psoriasis vulgaris.

We investigated whether the pattern of T-cell receptors expressed by T cells in inflamed psoriatic skin differed substantially from the pattern seen in T cells from the peripheral blood. A bias or restriction in the repertoire of T-cell receptors found in the lesional skin of different patients might imply that specific subsets of T cells were causally associated with initiating or maintaining the lesions. By using a polymerase chain reaction-based assay of T-cell receptor beta-chain variable region mRNA, we found that the patterns of beta-chain mRNAs displayed in 14 samples of lesional skin or six samples of noninvolved skin were not significantly less diverse than the patterns found in matched peripheral blood samples. There was no evidence that the active lesions of multiple patients showed overexpression of T cells expressing one or a few T-cell receptor forms. The pattern of T-cell receptors displayed in clinically normal skin from normal control individuals showed about the same diversity as normal blood. While these results may not exclude either classical antigen or superantigen-based T-cell activation mechanisms in active plaques, the absence of a simple pattern of Vbeta usage in different patients suggests than other aspects of T-cell biology including trafficking, proliferation, co-stimulation, or responses to cytokines must also be considered.

DNA Primers↗

Clonal populations of CD4+ and CD8+ T cells in patients with multiple myeloma and paraproteinemia.

Patients with paraproteinemia have abnormalities in their T-cell subsets including inversion of the CD4:CD8 ratio and increased expression of activation markers. Recently, distortions in T-cell receptor (TCR) TCRAV and TCRBV gene segment expression have been reported, although the significance of these observations is unclear given the finding of clonal populations of CD8+ T cells in healthy elderly individuals. We have used an extensive range of TCR V-region-specific monoclonal antibodies to assess TCRAV and TCRBV expression in patients with myeloma and paraproteinemia. TCR sequence analysis was used to assess the clonality of expansions and 3-color fluorescence-activated cell sorting analysis determined the phenotype of the expanded populations. The patients show novel oligoclonal expansions within the CD4+ subset and show an increased frequency of CD8+ expansions. Oligoclonal CD4+ T cells belong to the rare CD4+CD28- T-cell subset, a phenotype associated with granular morphology. CD45RA and CD11b are expressed on many of the CD8 T-cell expansions. Comparison of T-cell receptor sequences from two T-cell clones in one patient suggests a possible role for a common peptide antigen in the generation of the expansions. Further work is needed to identify the relevance of such T cells to the B-cell proliferation.

Aged↗

Responses to reduced water intake, including dehydration natriuresis, in sheep excreting sodium predominantly in urine or in faeces.

Sheep which were predominantly urinary excretors (U) or faecal excretors (F) of sodium were exposed to a 75% reduction of water intake for 72 h. The experiment was performed on moderate, low or high sodium intakes (0.4, 0.05 or 1.2 mmol kg-1 day-1) to test the hypothesis that dehydration natriuresis was not a cause of sodium depletion but a defence against hypernatraemia. Dehydration caused elevation of plasma sodium concentration, osmolality, antidiuretic hormone (ADH) and oxytocin but, as in other experiments, a fall in haematocrit. The two higher levels of sodium intake were associated with dehydration natriuresis but also a smaller increase in faecal sodium excretion in both U and F sheep. On low sodium intake, however, neither urinary nor faecal sodium excretion increased in either group of sheep although the rise in plasma sodium concentration caused by dehydration was similar. Thus, when there is a risk of sodium depletion, due to low sodium intake, dehydration natriuresis does not occur, consistent with the hypothesis. Active sodium transport inhibitor (ASTI) and atrial natriuretic peptide (ANP) fell rather than rose during dehydration. Since aldosterone is suppressed by the higher levels of sodium intake, none of these hormones is likely to mediate dehydration natriuresis in sheep. F sheep showed more effective renal and faecal water conservation when dehydrated. During water restriction, the urinary potassium excretion of U sheep was significantly reduced, unlike that of F sheep; moreover, the latter maintained an identical plasma potassium concentration between baseline and restriction period, whereas in U sheep it was 0.3 mmol l-1 higher during water restriction. Increased drinking rather than reduced urine output was the basis of rehydration when ad lib. water intake was restored.

Animals↗

Recognition of viral antigens at the cell surface.

There is now a very good understanding of the way in which epitope peptides are generated from virus proteins and how the peptides bind to the class I MHC molecules. This gives a framework in which to analyse the potentially protective cytotoxic T lymphocyte response in human immunodeficiency virus infection. A detailed understanding of the specificity of the responding T cells, the clonality of these T cells and the effects of virus variation on the CTL gives a possible explanation for the ultimate failure of the CTL response to control this virus infection.

Acquired Immunodeficiency Syndrome↗

Systematic study of human alpha beta T cell receptor V segments shows allelic variations resulting in a large number of distinct T cell receptor haplotypes.

The variation of the alpha beta T cell receptor (TCR) results mainly from rearrangements of germ-line V, D and J elements combined with the processes of N- and P-region addition. In addition to this extensive diversity, diallelic polymorphism is also recognized in V regions of beta loci. Four such polymorphisms have previously been defined, but the full extent of such variation has not yet been established. To investigate allelic polymorphism, we used a strategy based V locus-specific polymerase chain reaction and single-strand conformation polymorphisms. Studying the two V beta 2 loci and the V alpha 8.1 locus, we found that all exhibited a coding polymorphism. One of the V beta 2 loci proved to be the first multiallele segment to be recognized, with three common variants. The second V beta 2 locus, for which none of the two alleles has been identified in cDNA, appeared in fact to be a V beta orphon, in abnormal location on the chromosome 9. A yeast artificial chromosome containing part of the TCRB locus allowed us to place the first V beta 2 segment on the known map to define haplotypes with two other polymorphic segments: V beta 1 and V beta 6.7. Multiple distinct haplotypes result from combinations between these polymorphic loci, showing that V beta regions are highly variable between individuals. Two alleles exist at the V alpha 8.1 segment and both are expressed. This represents the first example of a frequent coding polymorphism for TCRA gene. The distribution of allele frequencies for these segments suggest the action of balancing selection. These data add a further dimension to TCR polymorphism and suggest new candidates to explore TCR-encoded susceptibility to autoimmune diseases.

Alleles↗

Differences between sheep excreting sodium predominantly in their urine or in their faeces: the effect of changes in sodium intake.

Sheep receiving a total of about 31 mmol day-1 (0.5 mmol kg-1) of sodium were classified according to the predominant route of sodium excretion; urinary (U) or faecal (F). U sheep had a greater water turnover than F sheep; their intake was 41% higher and they produced 133% more urine but there was little difference in faecal water loss. Most faecal sodium was readily exchangeable with water in both groups. When sodium intake was reduced by 80% (to 6 mmol day-1; 0.1 mmol kg-1), the reduction in total sodium excretion was equally effective in F sheep and U sheep after 48 h and after 2 weeks the overall losses of sodium were smaller in F sheep. On sodium intakes close to requirement (0.1 mmol kg-1 or less) the majority of the sheep excreted most of their sodium in faeces and did so on intakes up to 0.5 mmol kg-1 day-1. Excess dietary sodium is mainly excreted renally. When sodium intake is increased abruptly (by 20 mmol day-1, 0.3 mmol kg-1), total sodium excretion only increases gradually but after about 3 days it 'overshoots' as in humans.

Animals↗

Salt appetite during pregnancy in sheep.

Sodium preference was examined in three groups of sheep which had all sustained two consecutive pregnancies and lactations on either adequate sodium intakes (group C) or low sodium diets (B and C). Group B received a potassium supplement as well as a low sodium diet during the present experiment. No convincing or sustained increase in sodium preference resulted from the reduction in body sodium caused by pregnancy and lactation in group B or C, whether the sodium solutions offered were 40 or 300 mmol/l. In a second experiment, sodium preference (sodium bicarbonate, 40 mmol/l) was studied throughout pregnancy in sheep on low or adequate sodium diets, also non-pregnant controls on low sodium diets. Again, pregnancy on a low sodium intake failed to intensify salt appetite except for a transient (but significant) peak around d90, close to the peak of aldosterone secretion; a similar increase in preference occurred on the adequate sodium diet. However, salt appetite failed to intensify during the period of peak sodium demand (the last third of pregnancy) whereas renal and faecal sodium conservation are appropriately increased.

Animals↗

Altered synthesis of myosin light chains is associated with contractility in cultures of differentiating chick embryo breast muscle.

Cultured chick embryo skeletal muscle cells normally synthesize only the embryonic isoform of mysoin. We have found that aneural muscle cultures that become or are provoked into an extremely contractile state will begin to synthesize a pattern of myosin light chains typical of maturing muscle. Immunoblots with neonatal and adult specific monoclonal antibodies did not reveal a corresponding isozyme transition in myosin heavy chain. These results demonstrate a correlation between contractility and the regulation of myosin light chain maturation, and also suggest that the transitions of heavy and light chain synthesis during development do not appear to be under close coordinate regulation.

Animals↗

Effect of induced hypomagnesaemia on the toxicity of imidocarb in calves.

The hypothesis that the toxic effects of imidocarb mediated by reduced cholinesterase activity might be intensified by hypomagnesaemia was tested in calves. Hypomagnesaemia was induced in 12 males (50 kg) using an artificial milk based on a commercial nondairy coffee creamer. Although plasma magnesium levels reached 0.33 mmol litre-1 in two weeks no clinical signs were detected. In 12 control calves a daily magnesium supplement of 0.6 g was inadequate although the published requirement is 0.45 g; it was raised to 1.2 g to keep plasma magnesium normal. Lighter calves developed hypomagnesaemia more readily and fast-growing calves had lower plasma urea concentrations. Plasma calcium, but not plasma magnesium, showed significant positive correlation with plasma albumin. The only statistically significant effects of hypomagnesaemia were slight elevations of white cell count and plasma sodium. The hypomagnesaemic and normomagnesaemic calves were divided into two equal groups and treated with 3.3 mg kg-1 of imidocarb dipropionate or a placebo. The drug produced the expected clinical signs of mild toxicity and depression of cholinesterase but no other adverse effects. Transient slight depressions of plasma calcium and potassium concentration, a transient rise of plasma sodium and elevation of creatine kinase occurred. None of the effects of imidocarb treatment was intensified by hypomagnesaemia except, perhaps, constriction of the pupils; generally, hypomagnesaemic animals were affected less.

Animals↗

Prolongation of lidocaine spinal anesthesia with phenylephrine.

The effect of added phenylephrine on the duration of sensory analgesia during lidocaine spinal anesthesia was determined in 65 ASA class I-III patients randomly divided into three groups. Group 1 (n = 25) received 62.5 mg lidocaine in 7.5% glucose; group 2 (n = 21) received lidocaine with 2 mg phenylephrine; and group 3 (n = 19) received lidocaine with 5 mg phenylephrine. The level of analgesia to pin prick was assessed by an anesthesiologist unaware of the drug combination used. The mean +/- SD cephalad level of analgesia did not differ among the groups. In group 1, the times for two- and for four-segment regression of the level of analgesia, and the time for regression of analgesia to the T-12 dermatome, were 77 +/- 19 (1 SD), 99 +/- 24, and 109 +/- 26 min, respectively. The corresponding values were 98 +/- 25, 118 +/- 27, and 130 +/- 36 min in group 2 and 124 +/- 32, 142 +/- 31, and 162 +/- 35 min in group 3. All the regression times in group 2 were significantly longer than those in group 1 (P less than 0.05). All the regression times in group 3 were significantly longer than those in group 2 (P less than 0.02). It is concluded that clinically useful prolongation of sensory analgesia may be obtained by addition of phenylephrine to lidocaine during spinal anesthesia.

Aged↗