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author:("mcmurtry, A.")
1.  A three-step technique to correctly identify the trapezium without the need for fluoroscopic imaging 
Hand (New York, N.Y.)  2012;7(4):461-463.
Thumb pain secondary to degenerative arthritis of the carpometacarpal joint of the thumb is a common disabling condition. The key principles of successful basal joint arthroplasty involve trapezial excision, which is required for pain relief, with or without some form of ligament reconstruction. The majority of basal joint reconstructive procedures include partial or complete trapeziectomy, with and without some types of tendon transfer and ligament reconstruction and with or without tendon interposition and/or temporary wire stabilisation. When performing a trapeziectomy, it is important to identify the trapezium correctly before excising it. Excision of the incorrect bone during trapeziectomy for basal joint arthritis of the thumb has been reported within the NHS Litigation Authority database. We describe the senior author’s routinely used three-step technique to confirm the identity of the trapezium before excision. This technique has been reliably used in over 300 cases with successful excision of the trapezium without intraoperative fluoroscopy.
PMCID: PMC3508022  PMID: 24294173
Trapeziectomy; Carpometacarpal; Fluoroscopy; Technique; Identification
2.  A simple aid to fracture reduction in the digit 
PMCID: PMC3954397  PMID: 22943251
3.  Plant root distributions and nitrogen uptake predicted by a hypothesis of optimal root foraging 
Ecology and Evolution  2012;2(6):1235-1250.
CO2-enrichment experiments consistently show that rooting depth increases when trees are grown at elevated CO2 (eCO2), leading in some experiments to increased capture of available soil nitrogen (N) from deeper soil. However, the link between N uptake and root distributions remains poorly represented in forest ecosystem and global land-surface models. Here, this link is modeled and analyzed using a new optimization hypothesis (MaxNup) for root foraging in relation to the spatial variability of soil N, according to which a given total root mass is distributed vertically in order to maximize annual N uptake. MaxNup leads to analytical predictions for the optimal vertical profile of root biomass, maximum rooting depth, and N-uptake fraction (i.e., the proportion of plant-available soil N taken up annually by roots). We use these predictions to gain new insight into the behavior of the N-uptake fraction in trees growing at the Oak Ridge National Laboratory free-air CO2-enrichment experiment. We also compare MaxNup with empirical equations previously fitted to root-distribution data from all the world's plant biomes, and find that the empirical equations underestimate the capacity of root systems to take up N.
PMCID: PMC3402197  PMID: 22833797
Elevated CO2; nitrogen-uptake efficiency; nitrogen-uptake fraction; nitrogen-uptake model; nitrogen-use efficiency; optimal foraging by roots; optimal rooting depth; root distributions; root strategies
4.  MCM3AP Is Transcribed from a Promoter within an Intron of the Overlapping Gene for GANP 
Journal of Molecular Biology  2011;406(3):355-361.
MCM3 acetylase (MCM3AP) and germinal-centre associated nuclear protein (GANP) are transcribed from the same locus and are therefore confused in databases because the MCM3 acetylase DNA sequence is contained entirely within the much larger GANP sequence and the entire MCM3AP sequence is identical to the carboxy terminus of GANP. Thus, the MCM3AP and GANP genes are read in the same reading frame and MCM3AP is an N-terminally truncated region of GANP. However, we show here that MCM3AP and GANP are different proteins, occupying different locations in the cell and transcribed from different promoters. Intriguingly, a promoter for MCM3AP lies within an intron of GANP. This report is an interesting example in nature of two separate gene products from the same locus that perform two entirely different functions in the cell. Therefore, to avoid further confusion, they should now be referred to as separate but overlapping genes.
PMCID: PMC3121959  PMID: 21195085
MCM3AP, MCM3 acetylating protein; TNFα, tumour necrosis factor α; 5′RACE, 5′ rapid amplification of cDNA ends; IL6, interleukin-6; gene structure; organisation
5.  Polyfunctional T-Cell Responses Are Disrupted by the Ovarian Cancer Ascites Environment and Only Partially Restored by Clinically Relevant Cytokines 
PLoS ONE  2010;5(12):e15625.
Host T-cell responses are associated with favorable outcomes in epithelial ovarian cancer (EOC), but it remains unclear how best to promote these responses in patients. Toward this goal, we evaluated a panel of clinically relevant cytokines for the ability to enhance multiple T-cell effector functions (polyfunctionality) in the native tumor environment.
Methodology/Principal Findings
Experiments were performed with resident CD8+ and CD4+ T cells in bulk ascites cell preparations from high-grade serous EOC patients. T cells were stimulated with α-CD3 in the presence of 100% autologous ascites fluid with or without exogenous IL-2, IL-12, IL-18 or IL-21, alone or in combination. T-cell proliferation (Ki-67) and function (IFN-γ, TNF-α, IL-2, CCL4, and CD107a expression) were assessed by multi-parameter flow cytometry. In parallel, 27 cytokines were measured in culture supernatants. While ascites fluid had variable effects on CD8+ and CD4+ T-cell proliferation, it inhibited T-cell function in most patient samples, with CD107a, IFN-γ, and CCL4 showing the greatest inhibition. This was accompanied by reduced levels of IL-1β, IL-1ra, IL-9, IL-17, G-CSF, GM-CSF, Mip-1α, PDGF-bb, and bFGF in culture supernatants. T-cell proliferation was enhanced by exogenous IL-2, but other T-cell functions were largely unaffected by single cytokines. The combination of IL-2 with cytokines engaging complementary signaling pathways, in particular IL-12 and IL-18, enhanced expression of IFN-γ, TNF-α, and CCL4 in all patient samples by promoting polyfunctional T-cell responses. Despite this, other functional parameters generally remained inhibited.
The EOC ascites environment disrupts multiple T-cell functions, and exogenous cytokines engaging diverse signaling pathways only partially reverse these effects. Our results may explain the limited efficacy of cytokine therapies for EOC to date. Full restoration of T-cell function will require activation of signaling pathways beyond those engaged by IL-2, IL-12, IL-18, and IL-21.
PMCID: PMC3008736  PMID: 21203522
6.  Bis[cis-bis­(diphenyl­phosphino)ethene]copper(I) dichloridocuprate(I) 
The crystal structure of the title compound, [Cu(C26H22P2)2][CuCl2], is composed of discrete Cu(dppey)2]+ cations [dppey is cis-bis­(diphenyl­phosphino)ethene] and [CuCl2]− anions. The tetra­hedral Cu(P—P)2 core of the [Cu(dppey)2]+ cation is distorted, with Cu—P bond lengths ranging from 2.269 (1) to 2.366 (1) Å. The five-membered –Cu—P—CH=CH—P– rings adopt envelope conformations, with the Cu atom lying 0.38 and 0.65 Å out of the P—C=C—P planes. The Cu—Cl distances in the [CuCl2]− anion are 2.094 (2) and 2.096 (2) Å, with a Cl—Cu—Cl angle of 176.81 (7)°.
PMCID: PMC2979187  PMID: 21578996
7.  mRNA Export from Mammalian Cell Nuclei Is Dependent on GANP 
Current Biology  2010;20(1):25-31.
Bulk nuclear export of messenger ribonucleoproteins (mRNPs) through nuclear pore complexes (NPCs) is mediated by NXF1. It binds mRNPs through adaptor proteins such as ALY [1, 2] and SR splicing factors [3] and mediates translocation through the central NPC transport channel via transient interactions with FG nucleoporins [4–10]. Here, we show that mammalian cells require GANP (germinal center-associated nuclear protein) for efficient mRNP nuclear export and for efficient recruitment of NXF1 to NPCs. Separate regions of GANP show local homology to FG nucleoporins, the yeast mRNA export factor Sac3p, and the mammalian MCM3 acetyltransferase. GANP interacts with both NXF1 and NPCs and partitions between NPCs and the nuclear interior. GANP depletion inhibits mRNA export, with retention of mRNPs and NXF1 in punctate foci within the nucleus. The GANP N-terminal region that contains FG motifs interacts with the NXF1 FG-binding domain. Overexpression of this GANP fragment leads to nuclear accumulation of both poly(A)+RNA and NXF1. Treatment with transcription inhibitors redistributes GANP from NPCs into foci throughout the nucleus. These results establish GANP as an integral component of the mammalian mRNA export machinery and suggest a model whereby GANP facilitates the transfer of NXF1-containing mRNPs to NPCs.
PMCID: PMC2869303  PMID: 20005110
8.  2-(2-Methyl-1,3-dioxolan-2-yl)-1,1-diphenyl­ethanol 
The mol­ecules of the title compound, C18H20O3, display an intra­molecular O—H⋯O hydrogen bond between the hydr­oxy donor and a ketal O-atom acceptor. In the crystal, inter­molecular C—H⋯π inter­actions connect adjacent mol­ecules into chains parallel to the b axis.
PMCID: PMC2980271  PMID: 21580107
9.  Tumor-Infiltrating T Cells Correlate with NY-ESO-1-Specific Autoantibodies in Ovarian Cancer 
PLoS ONE  2008;3(10):e3409.
Tumor-infiltrating CD8+ T cells are correlated with prolonged progression-free and overall survival in epithelial ovarian cancer (EOC). A significant fraction of EOC patients mount autoantibody responses to various tumor antigens, however the relationship between autoantibodies and tumor-infiltrating T cells has not been investigated in EOC or any other human cancer. We hypothesized that autoantibody and T cell responses may be correlated in EOC and directed toward the same antigens.
Methodology and Principal Findings
We obtained matched serum and tumor tissue from 35 patients with high-grade serous ovarian cancer. Serum samples were assessed by ELISA for autoantibodies to the common tumor antigen NY-ESO-1. Tumor tissue was examined by immunohistochemistry for expression of NY-ESO-1, various T cell markers (CD3, CD4, CD8, CD25, FoxP3, TIA-1 and Granzyme B) and other immunological markers (CD20, MHC class I and MHC class II). Lymphocytic infiltrates varied widely among tumors and included cells positive for CD3, CD8, TIA-1, CD25, FoxP3 and CD4. Twenty-six percent (9/35) of patients demonstrated serum IgG autoantibodies to NY-ESO-1, which were positively correlated with expression of NY-ESO-1 antigen by tumor cells (r = 0.57, p = 0.0004). Autoantibodies to NY-ESO-1 were associated with increased tumor-infiltrating CD8+, CD4+ and FoxP3+ cells. In an individual HLA-A2+ patient with autoantibodies to NY-ESO-1, CD8+ T cells isolated from solid tumor and ascites were reactive to NY-ESO-1 by IFN-γ ELISPOT and MHC class I pentamer staining.
Conclusion and Significance
We demonstrate that tumor-specific autoantibodies and tumor-infiltrating T cells are correlated in human cancer and can be directed against the same target antigen. This implies that autoantibodies may collaborate with tumor-infiltrating T cells to influence clinical outcomes in EOC. Furthermore, serological screening methods may prove useful for identifying clinically relevant T cell antigens for immunotherapy.
PMCID: PMC2561074  PMID: 18923710
11.  4-Hydr­oxy-4,4-diphenyl­butan-2-one 
The mol­ecules of the title compound, C16H16O2, display an intra­molecular O—H⋯O hydrogen bond between the hydroxyl donor and the ketone acceptor. Inter­molecular C—H⋯π inter­actions connect adjacent mol­ecules into chains that propagate parallel to the ac diagonal. The chains are arranged in sheets, and mol­ecules in adjacent sheets inter­act via inter­molecular O—H⋯O hydrogen bonds.
PMCID: PMC2962095  PMID: 21203179
12.  Rapidly destructive osteoarthritis of the hip joint: a case series 
Rapidly destructive arthrosis of the hip is a rare and incompletely understood disorder with scarce literature about variations in natural history within a population.
A series of cases from North Wales with rapid progressive joint destruction and extensive subchondral bone loss in the femoral head and acetabulum are presented. Radiographic findings mimicked those of other disorders such as septic arthritis, rheumatoid and seronegative arthritis, primary osteonecrosis with secondary osteoarthritis, or neuropathic osteoarthropathy, but none of the patients had clinical, pathologic, or laboratory evidence of these entities.
Rapid progression of hip pain and disability was a consistent clinical feature. The average duration of symptoms was 1.4 years. Radiographs obtained at various intervals before surgery (average 14 months) in 18 patients documented rapid hip destruction, involvement being unilateral in 13 cases. All patients underwent total hip arthroplasty, and osteoarthritis was confirmed at pathologic examination.
The authors postulate that these cases represent an uncommon subset of osteoarthritis and regular review, both clinically and radiologically, are required to assess speed of progression and prevent rapid loss of bone stock without the surgeon being aware. These cases are unsuitable for being placed on long waiting list due to technical difficulties in delayed surgery and compromised outcome following surgery.
PMCID: PMC2248167  PMID: 18190689
14.  Safety of a new conjugate meningococcal C vaccine in infants 
Archives of Disease in Childhood  2001;85(5):391-397.
BACKGROUND—Group C conjugate meningococcal vaccines (Men C) were introduced into the UK primary immunisation schedule in November 1999.There has been extensive professional and public interest in their efficacy and safety.
AIM—To determine the occurrence of at least one uncommon adverse event in infants related to the administration of the Chiron Men C vaccine.
METHODS—A total of 2796 infants aged approximately 2 months were recruited into the study from areas in and around Sheffield and from Scotland. They were vaccinated with the Chiron Men C vaccine at 2, 3, and 4 months along with routine immunisations. Data on adverse events occurring one month after each dose were collected actively and prospectively and reviewed for possible relation to the vaccine.
RESULTS—There were no deaths. There were no serious adverse events considered definitely or probably caused by the vaccine. Four infants developed serious adverse events (hypotonia, screaming syndrome, maculopapular rash, and agitation, respectively) that were considered possibly related to the vaccine. All recovered completely. Adverse events were seen in 1804 children but were considered possibly related to the vaccine in only 49 (1.8%). On subsequent immunisation there were no recurrences of adverse events considered to be possibly related to the vaccine.

PMCID: PMC1718967  PMID: 11668101

Results 1-18 (18)