Biomedical subjects
J Field
Publications and source records attributed to J Field.
Intrathymic islet allografts prevent hyperglycemia and autoimmune beta-cell destruction in BB rats following transplantation in the prediabetic period.
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Sexual lifestyles and HIV risk.
Britain's first large, national survey of sexual attitudes and lifestyles will allow improved estimates of the magnitude of the HIV epidemic in Britain and should lead to better strategies for prevention.
Radio frequency probe and power amplifier for nuclear magnetic resonance microscopy and microvolume selected 1H spectroscopy at 500 MHz.
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Long-term prognosis of displaced Colles' fracture: a 10-year prospective review.
In all, 85 per cent of Colles' fractures are clinically satisfactory after 10 years. Clinical results improve little after 3 months. Displaced intraarticular fracture, wrist deformity and algodystrophy are associated with an unsatisfactory outcome.
Features of algodystrophy ten years after Colles' fracture.
The long-term outcome of algodystrophy is unknown. Ten years after Colles' fracture, 26% of 55 cases showed features of the syndrome. The finding of poor finger function three months following the fracture correlated significantly with the presence of components of algodystrophy after ten years.
Comparison of three methods of antibiotic prophylaxis in knee arthroplasty.
Prophylactic intravenous cefamandole nafate was administered by the systemic, systemic with probenecid (causing renal tubular blockade of antibiotic excretion), and intravenous regional routes. Bone antibiotic levels were assayed 15 minutes and 12 hours after administration, and hematoma concentrations after 8 hours. Bone concentrations after intravenous regional administration were significantly greater than systemic after 15 minutes, but were not detectable after 12 hours. Probenecid produced inhibitory concentrations in bone after 12 hours and also increased hematoma antibiotic concentrations to three times those achieved by systemic administration. Adequate prophylaxis may be possible with two rather than three doses of cefamandole if probenecid is used.
Genetic and biochemical analysis of the adenylyl cyclase-associated protein, cap, in Schizosaccharomyces pombe.
We have identified, cloned, and studied a gene, cap, encoding a protein that is associated with adenylyl cyclase in the fission yeast Schizosaccharomyces pombe. This protein shares significant sequence homology with the adenylyl cyclase-associated CAP protein in the yeast Saccharomyces cerevisiae. CAP is a bifunctional protein; the N-terminal domain appears to be involved in cellular responsiveness to RAS, whereas loss of the C-terminal portion is associated with morphological and nutritional defects. S. pombe cap can suppress phenotypes associated with deletion of the C-terminal CAP domain in S. cerevisiae but does not suppress phenotypes associated with deletion of the N-terminal domain. Analysis of cap disruptants also mapped the function of cap to two domains. The functional loss of the C-terminal region of S. pombe cap results in abnormal cellular morphology, slow growth, and failure to grow at 37 degrees C. Increases in mating and sporulation were observed when the entire gene was disrupted. Overproduction of both cap and adenylyl cyclase results in highly elongated large cells that are sterile and have measurably higher levels of adenylyl cyclase activity. Our results indicate that cap is required for the proper function of S. pombe adenylyl cyclase but that the C-terminal domain of cap has other functions that are shared with the C-terminal domain of S. cerevisiae CAP.
A comparison of mice and rats as recipients for canine islet xenografts.
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Psychological adjustment of relinquishing mothers before and after reunion with their children.
A main objective of this study was to compare the emotional well-being of mothers who had already experienced a reunion with children relinquished two to four decades ago, with that of mothers who were still awaiting the possibility of such re-contact. A nationwide postal survey was carried out in New Zealand of the relinquishment experiences and subsequent adjustment of 238 women who had been able to re-contact their children and of 206 women who had not as yet made contact. The two subgroups did not differ on two standardised measures of psychological well-being (GHQ-28 and global self esteem). However, the post-reunion women reported significantly greater improvements in their feelings connected with "adoption events", and also reported higher levels of perceived social support than did the pre-reunion women. Women who still lacked any information about their relinquished child showed significantly more negative affect and poorer psychological well-being than those who had at least obtained some non-identifying information.
Evidence for a functional link between profilin and CAP in the yeast S. cerevisiae.
CAP is a component of the S. cerevisiae adenylyl cyclase complex. The N-terminal domain is required for cellular RAS responsiveness. Loss of the C-terminal domain is associated with morphological and nutritional defects. Here we report that cap- cells bud randomly and are defective in actin distribution. The morphological and nutritional defects associated with loss of the CAP C-terminal domain are suppressed by over-expression of PFY, the gene encoding profilin, an actin- and polyphosphoinositide-binding protein. The phenotype of cells lacking PFY resembles that of cells lacking the CAP C-terminal domain. Study of mutated yeast profilins and profilins from Acanthamoeba suggests that the ability of profilin to suppress cap- cells is dependent upon a property other than, or in addition to, its ability to bind actin. This property may be its ability to bind polyphosphoinositides. We propose that CAP and profilin provide a link between growth signals and remodeling of the cellular cytoskeleton.
Evidence for direct and indirect pathways in the generation of the alloimmune response against pancreatic islets.
The role of the direct and indirect pathways of alloantigen presentation in the generation of the alloimmune response was dissected using the murine mixed lymphocyte-islet coculture system (MLIC). Stimulator DBA/2J (H-2d) pancreatic islet populations consisted of whole islets (MHC class I+, II+) or FACS-purified beta cells (MHC class I+, II-). Responding C57Bl/6 (H-2b) splenocyte populations were either: (1) untreated; (2) depleted of helper T cells with anti-L3T4 monoclonal antibody plus complement; (3) depleted of cytotoxic T lymphocytes with anti-Lyt2 mAb plus complement; or (4) depleted of antigen-presenting cells by passage through a Sephadex G-10 column. Whole islets were capable of stimulating a significant C57Bl/6 anti-DBA cytotoxic T cell response if the responding population was untreated or treated with complement alone. Depletion of responding splenocytes with either anti-Lyt2 or anti-L3T4 mAb plus complement abrogated the generation of allospecific CTL. If the responding splenocyte population was depleted of APCs, the allo-CTL response against whole islets was decreased, but still significant. If, however, the stimulator population consisted of FACS-purified DBA 2J beta cells, APC-depleted C57Bl 6 splenocytes were incapable of generating any CTL response. Adding responder type (C57Bl/6) APCs back to the microwells restored the capacity for both whole islets and purified beta cells to stimulate a strong allo-CTL response. These data demonstrate that both indirect and direct pathways of alloantigen presentation function in the MLIC.
CAP is a bifunctional component of the Saccharomyces cerevisiae adenylyl cyclase complex.
CAP, a protein from Saccharomyces cerevisiae that copurifies with adenylyl cyclase, appears to be required for yeast cells to be fully responsive to RAS proteins. CAP also appears to be required for normal cell morphology and responsiveness to nutrient deprivation and excess. We describe here a molecular and phenotypic analysis of the CAP protein. The N-terminal domain is necessary and sufficient for cellular response to activated RAS protein, while the C-terminal domain is necessary and sufficient for normal cellular morphology and responses to nutrient extremes. Thus, CAP is a novel example of a bifunctional component involved in the regulation of diverse signal transduction pathways.
The alloimmune response against pancreatic islets is generated by both direct and indirect pathways.
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Sexual lifestyles under scrutiny.
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Cloning and characterization of CAP, the S. cerevisiae gene encoding the 70 kd adenylyl cyclase-associated protein.
Adenylyl cyclase from S. cerevisiae contains at least two subunits, a 200 kd catalytic subunit and a subunit with an apparent molecular size of 70 kd, which we now call CAP (cyclase-associated protein). We cloned a cDNA encoding CAP by screening a yeast cDNA expression library in E. coli with antisera raised against the purified protein. The cDNA contained an open reading frame capable of encoding a 526 amino acid protein that is not homologous to any sequences in the current data bases. Adenylyl cyclase activity in membranes from cells that lacked CAP was not stimulated by RAS2 proteins in vitro. These results suggest that CAP is required for at least some aspects of the RAS-responsive signaling system. Mutants lacking CAP had four additional phenotypes that appear to be unrelated to effects of the RAS/adenylyl cyclase pathway: the inability to grow on rich medium (YPD), temperature sensitivity on minimal medium, sensitivity to nitrogen starvation, and a swollen cell morphology.
Mutations of the adenylyl cyclase gene that block RAS function in Saccharomyces cerevisiae.
The interaction between RAS proteins and adenylyl cyclase was studied by using dominant interfering mutations of adenylyl cyclase from the yeast Saccharomyces cerevisiae. RAS proteins activate adenylyl cyclase in this organism. A plasmid expressing a catalytically inactive adenylyl cyclase was found to interfere dominantly with this activation. The interfering region mapped to the leucine-rich repeat region of adenylyl cyclase, which is homologous to domains present in several other proteins and is thought to participate in protein-protein interactions.