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J M Thomas

Publications and source records attributed to J M Thomas.

At least 19 recordsLinked to original sources
PubMed2003

Molecular classification of synovial sarcomas, leiomyosarcomas and malignant fibrous histiocytomas by gene expression profiling.

In this study, we have used genome-wide expression profiling to categorise synovial sarcomas, leiomyosarcomas and malignant fibrous histiocytomas (MFHs). Following hierarchical clustering analysis of the expression data, the best match between tumour clusters and conventional diagnosis was observed for synovial sarcomas. Eight of nine synovial sarcomas examined formed a cluster that was characterised by higher expression of a set of 48 genes. In contrast, sarcomas conventionally classified as leiomyosarcomas and MFHs did not match the clusters defined by hierarchical clustering analysis. One major cluster contained a mixture of both leiomyosarcomas and MFHs and was defined by the lower expression of a set of 202 genes. A cluster containing a subgroup of MFHs was also detected. These results may have implications for the classification of soft tissue sarcomas, and are consistent with the view that sarcomas conventionally defined as MFHs do not represent a separate diagnostic category.

Cluster Analysis↗
PubMed2003

Major amputation for soft-tissue sarcoma.

BACKGROUND: Advances in oncological practice have reduced the number of major amputations performed for soft-tissue sarcoma, but this remains a valuable, if infrequent, option for both curative and palliative indications. METHODS: A review of patients and case-notes was carried out from the prospective sarcoma database at the Royal Marsden Hospital. RESULTS: Over a 10-year interval, 40 major amputations (18 forequarter, 17 hindquarter and five through hip) were performed, predominantly for disease recurring after previous limb-conserving surgery (31 of 40). A wide variety of soft-tissue sarcoma subtypes was seen; they were often large (more than 10 cm; 18 of 40) or multifocal (six), usually high grade (25), and frequently proximal or involving neurovascular structures such that limb salvage was precluded. Median range age of the patients was 59 (17-87) years. The operative 30-day mortality rate was zero. Hospital stay was a median of 10.5 days for forequarter amputation, and 19 days for hindquarter and through-hip amputation. Local recurrence occurred in ten patients, six of whom had concurrent distant metastases. Twenty-seven patients were alive (20 disease free) at a median follow-up of 12 months, nine of whom were alive without evidence of disease beyond 2 years. Ten patients died after a median of 7.5 months; three survived more than 2 years. CONCLUSION: Major amputation is a useful procedure in carefully selected patients with soft-tissue sarcoma.

Adolescent↗
PubMed2003

The role of ultrasound-guided cytology of groin lymph nodes in the management of squamous cell carcinoma of the vulva: 5-year experience in 44 patients.

AIM: To assess the accuracy of ultrasound combined with fine-needle aspiration cytology (FNAC) in the detection of lymph node metastasis in patients with squamous cell carcinoma of the vulva. MATERIALS AND METHODS: The groin nodes of 44 consecutive patients with primary squamous cell carcinoma of the vulva undergoing groin node dissection were assessed with ultrasound and FNAC. The results were compared with histology from subsequent inguinofemoral lymph node dissection. Twenty-nine patients underwent bilateral groin node dissections and 15 unilateral providing comparable data for 73 groins. RESULTS: Histology demonstrated metastatic disease in 28 groins and no evidence of metastatic disease in 45. Ultrasound agreed with the histology in 67 of the 73 groins (92%), with two false-positives, four false-negatives and two indeterminate appearances. Cytology agreed with the histology in 65 of 72 FNAC samples obtained (90%), with six false-negatives, and one indeterminate result. No false-positive cytology results were seen. Ultrasound and FNAC together failed to detect metastatic disease in four groins, one with an indeterminate ultrasound appearance, another with indeterminate cytology, the two others each having a single positive inguinal node despite a negative ultrasound and FNAC. CONCLUSION: The combination of ultrasound and FNAC provides a sensitive and specific tool for pre-operative assessment and may prevent unnecessary groin dissection and the attendant morbidity in selected patients with vulval cancer.

Biopsy, Needle↗
PubMed2003

'Aggressive' angiomyxoma: a distinct clinical entity.

AIM: An aggressive angiomyxoma is a mesenchymal tumour arising from connective tissues of the perineum or lower pelvis. They cause very little symptoms despite their large size. METHODS: All patients with a diagnosis of aggressive angiomyxoma were studied retrospectively from a prospective database at the Royal Marsden Hospital between January 1990 and July 2001. RESULTS: There were seven female patients with a diagnosis of aggressive angiomyxoma. Sites of involvement included the soft tissues of the perineum (n=4), vulva (n=2) and inguinal region (n=1). The common presenting feature was a mass. The size of the tumour was larger than 10 cm in three patients. Two patients had an intracapsular excision, two had marginal resection and in two patients wide excision was done. Four patients developed recurrent tumour with an interval ranging from 6 months to 97 months. Recurrence was not observed in the two patients after wide excision at intervals of 8 and 13 months. CONCLUSION: The tumour is aggressive in that it has a propensity for recurrence but usually in the long term. Operation can cure patients with aggressive angiomyxoma, but may result in significant morbidity due to the large size of the tumour at presentation and its frequent occurrence in the lower pelvis and perineum with proximity to genitourinary and anorectal structures. A period of watchful waiting to assess growth rate may be the most appropriate course in most patients. Surgery whenever offered for symptom control should be done with minimal morbidity.

Adult↗
PubMed2003

Imaging features of aggressive angiomyxoma.

AIM: To describe the imaging features of aggressive angiomyxoma in a rare benign mesenchymal tumour most frequently arising from the perineum in young female patients. MATERIALS AND METHODS: We reviewed the computed tomography (CT) and magnetic resonance (MR) imaging features of patients with aggressive angiomyxoma who were referred to our hospital. The imaging features were correlated with clinical information and pathology in all patients. RESULTS: Four CT and five MR studies were available for five patients (all women, mean age 39, range 24-55). Three patients had recurrent tumour at follow-up. CT and MR imaging demonstrated a well-defined mass-displacing adjacent structures. The tumour was of low attenuation relative to muscle on CT. On MR, the tumour was isointense relative to muscle on T1-weighted image, hyperintense on T2-weighted image and enhanced avidly after gadolinium contrast with a characteristic "swirled" internal pattern. MR imaging demonstrates the extent of the tumour and its relation to the pelvic floor. Recurrent tumour has a similar appearance to the primary lesion. CONCLUSION: The MR appearances of aggressive angiomyxomas are characteristic, and the diagnosis should be considered in any young woman presenting with a well-defined mass arising from the perineum.

Adult↗
PubMed2002

The number of amino acid residues mismatches correlates with flow cytometry crossmatching results in high PRA renal patients.

Highly sensitized renal transplant candidates present a group at high risk for acute and chronic rejection. The probability of finding compatible donors for these recipients is significantly lower in comparison to those who have low PRA values. As a consequence, these patients spend longer time on the waiting list and become tethered to dialysis. The results of final cross match (XM) are critical for making a decision about whether such a candidate receives an organ or not. The degree of donor and recipient HLA compatibility predicts the results of XM. The goal of this study was to expand a variety of acceptable HLA-AB mismatches (MM) for high PRA kidney recipients using the HLAMATCHMAKER algorithm. This strategy focuses on the fine structural features of HLA polymorphism comprising amino acid residues or triplets (AAT), which are located in alpha-helical coils of HLA molecules and are available to antibodies. We analyzed serum samples from thirty-nine highly alloimmunized recipients (PRA > or = 85%). The level of sensitization was detected using FlowPRA Class I Screening Test. This group of transplant candidates included thirteen recipients who demonstrated negative results of final T/B FCXM and twenty-six, who were FCXM positive. The application of the HLAMATCHMAKER algorithm based on the HLA class I donor and recipient typing allowed us to detect the total number of AATMM as well as the number of immunogenic AAT in both FCXM negative and FCXM positive groups of recipients. Significantly greater numbers of both total and highly immunogenic AATMM have been emerged in the group of FCXM positive patients. Furthermore, the results of this analysis have shown a high degree of probability of positive FCXM if the number of highly immunogenic AATMM was > or = 1 (chi(2) = 22.9 Yate's correction; p = 0.000001). We did not observe overlapping between antibody specificity and permissible HLA-AB MM detected using the HLAMATCHMAKER strategy. Thus, the number of highly immunogenic AATMM can serve as a reliable predictive value for final FCXM results in highly sensitized renal transplant candidates. The HLAMATCHMAKER algorithm appears to be the proper strategy to find donors for high PRA recipients.

Adolescent↗
PubMed2002

Association of cytokine single nucleotide polymorphisms with B7 costimulatory molecules in kidney allograft recipients.

African-American race is associated with an increased risk of allograft loss, suggesting that African-American patients may form an immunologically higher risk group. Previously, we demonstrated that immune cell costimulatory molecule expression is significantly higher in African-Americans than in Caucasians. Polymorphic variations in the genes for cytokines have been associated with a number of immunological conditions, and with transplant rejection. This study was performed to determine the distribution, in African-American and Caucasian renal transplant recipients, of single nucleotide polymorphisms (SNPs) in the following cytokine genes: tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin (IL)-6, IL-10, and transforming growth factor-beta (TGF-beta). Cytokine production from blood cells was determined, and cell-surface B7 (CD80, CD86) expression was measured. There was a significant link between IL-10 genotype and acute rejection episodes, but only in African-American patients (p < 0.01). Also, African-American patients had a significantly higher probability of having the IL-6 G-allele (p < 0.0001), which is associated with a high production of IL-6 protein. Incubation of blood cells with IL-6 resulted in increased expression of surface CD80 and CD86, while IL-10 decreased CD80 expression. This study demonstrated a clear correlation of the IL-6 G-allele with increased cellular CD80 expression and the IL-10 G-allele with decreased CD80 expression. These data raise the possibility that specific genotypes are associated with local cytokine regulation of cell-surface costimulatory molecule expression. African-American patients may have a genetically determined, quantitatively different immune response than Caucasian patients, contributing to adverse transplant outcomes.

Adult↗
PubMed2002

Coxsackievirus-adenovirus receptor genetically fused to anti-human CD40 scFv enhances adenoviral transduction of dendritic cells.

A promising approach to immunotherapy involves the loading of dendritic cells (DCs) with genetic material to facilitate sustained expression of a relevant antigen in this population of potent antigen presenting cells (APC). Viral vectors such as adenovirus (Ad) have been used for this purpose. Existing methods for DC infection are limited by lack of specificity and a requirement for DC exposure to high viral doses. Targeting of Ad to DCs with bispecific antibodies has significantly augmented levels of transgene expression. Genetic fusion of the extracellular portion of coxsackievirus-adenovirus receptor (CAR) to cell-specific ligands has also proved successful in targeting Ad to cells of interest. We report here the production and primary characterization of a new fusion protein comprising the ecto-domain of CAR connected to a single chain antibody (scFv) G28-5 against human CD40 present on the surface of DCs. We demonstrate that the fusion protein (CAR/G28) specifically interacts with both recombinant Ad fiber knob and the ecto-domain of human CD40 in a binding assay (ELISA). Finally, we show that the CAR/G28 fusion protein promotes highly efficient transduction of DCs of both rhesus monkey and human origin.

Adenoviridae↗
PubMed2002

Soft-tissue tumours of the perineum.

AIM: Primary perineal tumours in adults are rare entities that have been infrequently reported (one clinical series of nine patients with sarcoma and isolated case reports). We present our experience of perineal tumours better to characterize and define the natural history of this condition. METHODS: Perineal tumours occurring in adults (>18 years) from January 1990 were identified from the Royal Marsden Hospital's Sarcoma Unit prospective database. RESULTS: Nineteen perineal soft-tissue tumours (12 malignant and seven benign) were evaluated and treated at the Royal Marsden Hospital during this period. Liposarcoma (n=3) and aggressive angiomyxoma (n=4) were the most frequent histological subtypes. Three malignant and four benign tumours were larger than 10 cm. Most tumours were located deep to the deep fascia. Local recurrence in those with sarcoma occurred in one of five patients with negative microscopic margins and in one of two patients who had positive microscopic margins. One patient each with aggressive angiomyxoma and fibromatosis recurred locally. CONCLUSION: Aggressive treatment in the form of wide local excision is associated with fewer local recurrences in adults with primary perineal soft-tissue tumours. The aim of surgical treatment should be to obtain negative resection margins without causing disturbance to urinary or anorectal function.

Adolescent↗
PubMed2001

Predictions and associations of fatigue syndromes and mood disorders that occur after infectious mononucleosis.

BACKGROUND: Certain infections can trigger chronic fatigue syndromes (CFS) in a minority of people infected, but the reason is unknown. We describe some factors that predict or are associated with prolonged fatigue after infectious mononucleosis and contrast these factors with those that predicted mood disorders after the same infection. METHODS: We prospectively studied a cohort of 250 primary-care patients with infectious mononucleosis or ordinary upper-respiratory-tract infections until 6 months after clinical onset. We sought predictors of both acute and chronic fatigue syndromes and mood disorders from clinical, laboratory, and psychosocial measures. FINDINGS: An empirically defined fatigue syndrome 6 months after onset, which excluded comorbid psychiatric disorders, was most reliably predicted by a positive Monospot test at onset (odds ratio 2.1 [95% CI 1.4-3.3]) and lower physical fitness (0.35 [0.15-0.8]). Cervical lymphadenopathy and initial bed rest were associated with, or predicted, a fatigue syndrome up to 2 months after onset. By contrast, mood disorders were predicted by a premorbid psychiatric history (2.3 [1.4-3.9]), an emotional personality score (1.21 [1.11-1.35]), and social adversity (1.7 [1.0-2.9]). Definitions of CFS that included comorbid mood disorders were predicted by a mixture of those factors that predicted either the empirically defined fatigue syndrome or mood disorders. INTERPRETATION: The predictors of a prolonged fatigue syndrome after an infection differ with both definition and time, depending particularly on the presence or absence of comorbid mood disorders. The particular infection and its consequent immune reaction may have an early role, but physical deconditioning may also be important. By contrast, mood disorders are predicted by factors that predict mood disorders in general.

Chi-Square Distribution↗
PubMed2001

Pharmacological characterization of the putative cADP-ribose receptor.

cADP-ribose (cADPR), a naturally occurring metabolite of NAD(+), has been shown to be an important regulator of intracellular Ca(2+) release. Considerable evidence suggests that cADPR is the endogenous modulator of the ryanodine receptor (RyR), which mediates Ca(2+)-induced Ca(2+) release (CICR). Indeed, cADPR-mediated Ca(2+) release is subject to functional regulation by other modulators of CICR, including Ca(2+), caffeine and calmodulin. However, the underlying basis behind the effect of such agents on cADPR activity (in particular whether they regulate cADPR binding), as well as the precise nature of the cADPR receptor remains unclear. In the present study, use of (32)P-radiolabelled cADPR has enabled a detailed pharmacological characterization of cADPR-binding sites in sea urchin egg homogenates. We report that cADPR binds specifically to a single class of high affinity receptor. Retainment of binding to membranes after a high-salt wash suggests the involvement of either an integral membrane protein (possibly the RyR itself) or a peripheral protein tightly associated to the membrane. Insensitivity of [(32)P]cADPR binding to either FK506 or rapamycin suggests that this does not concern the FK506-binding protein. Significantly, binding is highly robust, being relatively insensitive to both endogenous and pharmacological modulators of RyR-mediated CICR. In turn, this suggests that such agents modulate cADPR-mediated Ca(2+) release primarily by tuning the 'gain' of the CICR system, upon which cADPR acts, rather than influencing the interaction of cADPR with its target receptor. The exception to this is calmodulin, for which our results indicate an additional role in facilitating cADPR binding.

Adenosine Diphosphate Ribose↗
PubMed2001

An essential role for natural killer cells in augmentation of allograft survival mediated by donor spleen cells.

BACKGROUND: Previous studies have shown that skin allograft survival can be augmented by the administration of donor spleen or donor bone marrow in antithymocyte serum (ATS) treated recipients. Because natural killer cells (NK) have been reported to possess immunoregulatory properties, we investigated whether the ability of donor spleen or bone marrow cells to enhance allograft survival was dependent on the presence of donor NK cells. METHODS: Recipient (C57BL/6 x A/J)F1 strain mice (H2 haplotypes Kb/k, Ab/k, E-/k, Db/d) were treated with ATS on days -1 and +2 relative transplantation of a C3H (H-2k) skin allograft. On day +7, each recipient was randomly assigned to one of the following groups that received i.v. donor C3H cell infusions via the tail vein: 1) 5.0x10(7) wild-type donor spleen cells (SPC); 2) 5.0x10(7) spleen cells from C3H/HeJ-Lystbg-2J/+ mice (commonly called beige mice and have selectively impaired NK cell function); 3) 2.5x10(7) wild-type donor bone marrow cells (BMC); 4) 2.5x10(7)beige C3H bone marrow cells; and 5) no donor cell infusion (ATS controls). In another experiment, each recipient was randomly assigned to one of the following groups that received injections of: 1) 4.75x10(7) spleen cells depleted of NK cells; 2) 2.5x10(6) purified splenic NK cells; 3) a coinfusion of 5.0x10(7) beige spleen cells and 2.5x10(6) purified wild-type splenic NK cells. RESULTS: Recipients infused with wild-type SPC exhibited significant augmentation of allograft survival compared with ATS controls. However, graft survival was reduced in recipients that were infused with spleen cells from beige mice compared with recipients infused with wild-type SPC (median survival time (MST): 38 vs. 92 days, P=0.02). In contrast, infusions of beige BMC augmented allograft survival as well as wild-type BMC (MST: 47 vs. 49 days, P=0.76). Furthermore, the ability of wild-type SPC to augment allograft survival was abrogated by the depletion of NK cells (MST=92 vs. 34 days, respectively, P=0.005). The co-infusion of beige SPC and purified splenic NK cells enhanced allograft survival as well as wild-type SPC (MST=56 days, P=0.65). Finally, recipients infused with purified NK cells did not experience increased graft survival compared to recipients that received no infusion (MST=29 vs. 33 days, respectively, P=0.6). CONCLUSIONS: Donor splenic NK cells are necessary, but not sufficient, for the extension of graft survival by infusion of donor splenocytes, suggesting that they may work in concert with another cell-type. In contrast, the extension of graft survival by donor bone marrow does not depend on the presence of donor NK cells.

Animals↗
PubMed2001

Solvent-free routes to clean technology.

A major aim for the chemical technology of the future is the avoidance of noxious and environmentally unacceptable organic solvents. In this concept article we discuss more environmentally friendly and highly selective alternatives which we have evolved for carrying out a number of important chemical conversions. These entail the use of porous heterogeneous catalysts in which the active sites have been atomically engineered and fully characterized. Such solid catalysts operate under solvent-free conditions and usually entail one-step processes.

Journal Article↗
PubMed2001

Cytoprotection of pancreatic islets before and soon after transplantation by gene transfer of the anti-apoptotic Bcl-2 gene.

Isolated pancreatic islet transplantation is a promising alternative to conventional insulin-dependent diabetes treatment but is not yet a practical clinical therapy. In the first few days after pancreatic islet transplantation, substantial donor pancreatic islet dysfunction and apoptosis commonly occur. Islet apoptosis has been documented after extracellular matrix disruption and exposure to proinflammatory cytokines, and during hypoxia before islet revascularization and rejection. These studies show that targeting the apoptosis pathway by adenoviral-mediated gene transfer of the anti-apoptotic Bcl-2 gene exerts a major cytoprotective effect on isolated macaque pancreatic islets. Bcl-2 transfection ex vivo protects these islets from apoptosis induced by disruption of the islet extracellular matrix during pancreatic digestion. Additionally, overexpression of Bcl-2 confers long-term, stable protection and maintenance of functional islet mass after transplantation of macaque islets into diabetic severe combined immunodeficency mice. Notably, genetic modification of pancreatic islets also reduced the islet mass required to achieve stable euglycemia. Ex vivo gene transfer of anti-apoptotic genes has potential as a therapeutic approach to both minimize loss of functional islet mass after transplant and reduce the high donor islet requirement currently needed for successful stable reversal of insulin-dependent diabetes.

Adenoviridae↗
PubMed2001

The role of XAFS in the in situ and ex situ elucidation of active sites in designed solid catalysts.

New mesoporous and microporous catalysts based on silica, aluminophosphates, or aluminophosphates containing one or other of the heteroatoms Ti, Co, Mn, Fe and Cr, are ideally suited for study by X-ray absorption fine structure (XAFS). The information derived from X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) elucidates the nature of the catalytically active site, generally (but not invariably) under in situ conditions. This, in turn, provides new insights into the mechanism of the catalysis and suggests methods of improving the performance of the original catalyst. In this way, significant advances have recently been made in designing catalysts for the selective oxidation of alkanes, for the epoxidation of alkenes and for the dehydration of alcohols to yield olefins. Combined with density functional theory (DFT) computations, XAFS studies have also yielded fresh insights into the architecture of nanoparticle catalysts, such as Ru12Cu4C2 supported on mesoporous silica.

Journal Article↗
PubMed2001

Effect of Si(IV) substitution on the stability of microporous ZnAPSO-44 solid acid catalysts: a combined XAS/XRD study.

The combined XAS/XRD technique has been used to investigate the stability of the microporous structure during calcination process for a series of ZnAPSO-44 materials. Incorporation of large amounts of Zn is found to produce materials that are unstable upon removal of the structure directing organic template molecule. However, simultaneous incorporation of Si is found to increase the thermal stability of the materials, yielding catalysts that are well suited for acid catalysed reactions.

Journal Article↗
PubMed2001

The architecture of Mg(II) centres in MAPO-36 solid acid catalysts.

The local structure around Mg2+ ions of a Magnesium substituted aluminophosphate, with the ATS structure (MgAPO-36, Mg/P=0.08), in the as-prepared and calcined state has been investigated by Mg K-edge XAS spectroscopy. High quality XAS data were collected using the solid-state fluorescence detector. Mg2+ is found to replace tetrahedrally co-ordinated Al3+ in the as-prepared state and remained intact even after calcination, thus yielding a highly active, solid acid catalyst.

Journal Article↗