ICRF: from mayhem to meltdown. Imperial Cancer Research Fund.
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Biomedical subjects
Publications and source records attributed to R Horton.
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OBJECTIVE: To assess the impact of LupusLine during its pilot phase of operation by determining patterns of utilization and user satisfaction. LupusLine is a peer counseling service designed to provide ongoing emotional support from home to home by telephone appointment. METHODS: One hundred fifty-three respondents were surveyed, using a 72-item structured questionnaire administered over the telephone by interviewers separately trained and hired specifically for this purpose. The questionnaire was pilot tested on 10 volunteers with systemic lupus erythematosus (SLE), and a panel of related health professionals reviewed the questionnaire for face validity. RESULTS: Most users were women (94.5%) who had SLE themselves (87.5%) and who called the service because of recent changes in their physical functioning and reported feelings of depression and anxiety about their illness. Forty-one percent of respondents made 6 or more calls to their assigned peer counselor. Respondents reported high levels of satisfaction across 5 highly correlated measures, with 92% of callers reporting at least moderate satisfaction with the service. Over 60% of respondents who reported a change in 6 "feeling" categories attributed this change to using LupusLine. Fewer users reported a change in 4 specific behaviors since using the service, but more respondents attributed changes, when they occurred, to LupusLine. CONCLUSIONS: Based on these initial findings, we believe that telephone networks similar to the LupusLine model may be able to offer substantial benefit to people coping with the complex, ongoing psychosocial challenges of SLE. Further, the at-home accessibility and low cost of such volunteer-based interventions may play an ever more needed role in the present health care environment.
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The interaction of the human immunodeficiency virus (HIV) Gag protein with the plasma membrane of a cell is a critical event in the assembly of HIV particles. The matrix protein region (MA) of HIV type 1 (HIV-1) Pr55Gag has previously been demonstrated to confer membrane-binding properties on the precursor polyprotein. Both the myristic acid moiety and additional determinants within MA are essential for plasma membrane binding and subsequent particle formation. In this study, we demonstrated the myristylation-dependent membrane interaction of MA in an in vivo membrane-binding assay. When expressed within mammalian cells, MA was found both in association with cellular membranes and in a membrane-free form. In contrast, the intact precursor Pr55Gag molecule analyzed in an identical manner was found almost exclusively bound to membranes. Both membrane-bound and membrane-free forms of MA were myristylated and phosphorylated. Differential membrane binding was not due to the formation of multimers, as dimeric and trimeric forms of MA were also found in both membrane-bound and membrane-free fractions. To define the requirements for membrane binding of MA, we analyzed the membrane binding of a series of MA deletion mutants. Surprisingly, deletions within alpha-helical regions forming the globular head of MA led to a dramatic increase in overall membrane binding. The stability of the MA-membrane interaction was not affected by these deletions, and no deletion eliminated membrane binding of the molecule. These results establish that myristic acid is a primary determinant of the stability of the Gag protein-membrane interaction and provide support for the hypothesis that a significant proportion of HIV-1 MA molecules may adopt a conformation in which myristic acid is hidden and unavailable for membrane interaction.
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Ouabain can block the action of angiotensin II (AII on aldosterone secretion in both rat and human adrenal tissue although its action is much more potent on human zona glomerulosa cells (ZG). Since magnesium can antagonize digitalis action in vivo, we have examined the interaction of both agents on aldosterone secretion in both rat and human adrenal cells. Ouabain itself at high concentration (10(-5) M) in Mg++ buffer blocks AII action on aldosterone secretion on rat ZG cells and at 1000-fold lower concentrations inhibits AII-action in human cells as previously reported by us. When buffer Mg++ is higher (4mM) than normal (0.7 mM) in cultured human adrenal cells it decreases both basal aldosterone secretion (8.6 +/- 0.4 vs. 6.8 +/- 0.2, p < 0.001) and AII action on aldosterone (13.9 +/- 0.6 vs. 9.7 +/- 0.7 ng/10(6) cells/h, p < 0.01). High Mg++ buffer had this effect at both 10(-8) and 10(-7) M concentrations of ouabain (control 8.6 +/- 0.4, AII [10(-9) M] 13.9 +/- 0.7, AII + Ouabain [5 x 10(-8) M] 10.9 +/- 0.6, AII + ouabain [10(-7) M] 7.8 +/- 0.3 ng/10(6) cells/h, both p < 0.01 vs. AII). In contrast, a low Mg++ buffer stimulated both basal (6.9 +/- 0.2 vs. 8.3 +/- 0.4 ng/10(6) cells/h, p < 0.01) and AII stimulation of aldosterone secretion (8.4 +/- 0.2 vs. 9.8 +/- 0.4 ng/10(6) cells/h, p < 0.01). When ouabain was added to low Mg++ buffer there was further inhibition of AII induced aldosterone secretion than with normal Mg++ buffer. However, the effect of ACTH on aldosterone was not altered by changes in Mg++. We conclude that ouabain actions and the effect of angiotensin II on aldosterone is inhibited by an increased level of Mg++ while low levels of Mg++ are stimulatory to both basal and AII action on aldosterone.