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Biomedical subjects

C Fisher

Publications and source records attributed to C Fisher.

At least 37 records · Page 2Linked to original sources
PubMed2004

Structural features of the low-density lipoprotein receptor facilitating ligand binding and release.

The LDLR (low-density lipoprotein receptor) is a modular protein built from several distinct structural units: LA (LDLR type-A), epidermal growth factor-like and beta-propeller modules. The low pH X-ray structure of the LDLR revealed long-range intramolecular contacts between the propeller domain and the central LA repeats of the ligand-binding domain, suggesting that the receptor changes its overall shape from extended to closed, in response to pH. Here we discuss how the LDLR uses flexibility and rigidity of linkers between modules to facilitate ligand binding and low-pH ligand release.

Animals↗
PubMed2004

Intra-abdominal synovial sarcoma: a clinicopathological study.

AIMS: To evaluate a series of synovial sarcomas arising in the abdomen, pelvic cavity, or retroperitoneum. Synovial sarcoma is rare within the abdomen. In this location, it can be confused with other biphasic tumours and with other spindle and round cell sarcomas. METHODS AND RESULTS: Cases were retrieved from archives. There were 11 intra-abdominal tumours among 300 synovial sarcomas in two referral practices (3.7%). Three were pelvic (two midline, one sidewall) and eight were retroperitoneal. They occurred in six males and five females aged from 25 to 75 years (mean 49 years, median 46 years), and ranged in diameter from 65 to 470 mm (mean 210 mm, median 150 mm). Six examples were biphasic, five were monophasic and seven had poorly differentiated areas. Monophasic tumours displayed at least one epithelial marker. One biphasic tumour had a SYT-SSX2 fusion gene. Seven sarcomas were high-grade and four of intermediate grade malignancy. Follow-up data were available in 10 patients. In all but one case, tumour recurred or metastasized within the abdomen. The pelvic sarcomas also metastasized outside the abdomen. Eight of 10 patients (80%) died of disease with survival from 4 to 36 months (mean 17 months, median 18 months). Two patients were alive with disease at 43 and 48 months. CONCLUSIONS: Synovial sarcomas rarely arise within the abdomen and pelvis. They occur mainly in middle age, attain a large size, are difficult to excise and recur locally. Pelvic tumours metastasize distantly. Retroperitoneal tumours remain confined to the abdomen and, unlike synovial sarcomas elsewhere, do not metastasize remotely, although mortality is high.

12E7 Antigen↗
PubMed2004

Imaging features of primary nonurachal adenocarcinoma of the bladder.

OBJECTIVE: Our aim was to describe the imaging appearances of primary nonurachal adenocarcinoma of the bladder. CONCLUSION: A diffusely thickened bladder wall with stranding in the surrounding fat is a frequent finding of primary bladder adenocarcinoma. These malignancies are classified at a high stage at presentation with locally advanced disease, and a large proportion of patients have distant metastases, with the peritoneum, lymph nodes, and lung appearing to be favored sites.

Adenocarcinoma↗
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

Pharmacologic pre-conditioning and controlled reperfusion prevent ischemia-reperfusion injury after 30 minutes of hypoxia/ischemia in porcine hearts.

BACKGROUND: Hearts from non-heart-beating organ donors are not transplanted because of risk of ischemia-reperfusion injury. We tested whether pharmacologic pre-conditioning with adenosine and the Na(+)/H(+) exchanger inhibitor, cariporide, combined with controlled reperfusion, would prevent injury in porcine hearts that had sustained 30 minutes of hypoxia/ischemia in closed-chest animals. METHODS: Hearts from Yorkshire pigs (100 kg) were studied in 3 groups. Group 1 (control) hearts were surgically removed while beating. Group 2 hearts were harvested from animals made hypoxic by discontinuing mechanical ventilation for 30 minutes. Group 3 hearts were hypoxic as in Group 2, but these animals received adenosine (40 mg) and cariporide (400 mg) 10 minutes before stopping ventilation. Cardiac function in all groups was assessed ex vivo in a working heart apparatus in which pressure and flow measurements were made over 3 hours. Controlled reperfusion in Group 3 hearts used leukocyte-depleted blood perfusate containing free radical scavengers. Myocardial injury was assessed on the basis of perfusate creatine phosphokinase activity and histopathologically determined injury score. RESULTS: Groups 1 and 3 hearts could be resuscitated to perform work equivalently during the entire reperfusion period and showed positive responses to increases in pre-load and norepinephrine. Group 2 hearts could not perform work. After 3 hours, Group 2 hearts showed significantly higher creatine phosphokinase and histopathologic injury scores compared to with Groups 1 and 3, which were not significantly different from each other. CONCLUSIONS: Pharmacologic pre-conditioning and controlled reperfusion effectively protect non-beating porcine hearts from injury after 30 minutes of hypoxia/ischemia in situ.

Adenosine↗
PubMed2003

Tumour thickness predicts cervical nodal metastases and survival in early oral tongue cancer.

Squamous cell carcinoma (SCC) of the oral tongue is characterized by a high propensity for cervical nodal metastasis, which affects the probability of regional control and survival. Until now, elective treatment of the clinically negative neck in early lesions (T(1-2)) of the oral tongue cancer remains controversial. This study attempted to identify predictive factor(s) for cervical nodal metastasis and treatment outcomes in patients with early stage SCC of the oral tongue treated primarily by surgery. Fifty patients with previously untreated Stage I/II primary tongue carcinomas with available archival specimens treated at the Royal Marsden Hospital between 1981 and 1998 were reviewed. Clinico-pathological features including age, gender, alcohol and tobacco consumption, tumour location, histological grade, tumour-stromal border, growth pattern, tumour thickness, and clinical stage were evaluated and the correlations with cervical metastases and outcome analysis were determined. The overall occult nodal metastatic rate was 40% (20/50). Tumour thickness exceeding 5 mm was statistically significantly correlated with cervical metastases (P = 0.003; relative risk = 2.429). No statistical correlation was observed between other clinico-pathological parameters and nodal metastasis. With a median follow-up of 98 months, 5-year actuarial overall, disease-specific (DSS), and relapse-free survival were 65.71, 67.77, and 68.18%, respectively. Univariate analysis for DSS showed poorer outcomes for patients with age > 60 years (P = 0.0423) and tumour thickness > 5 mm (P = 0.0067). The effect of tumour thickness was maintained (P = 0.005) on multivariate analysis. The present study indicates that the thickness of primary tumour has a strong predictive value for occult cervical metastasis and poor outcomes in patients with Stage I/II oral tongue SCC. Thus, elective neck treatment (surgery or irradiation) is indicated for tumours exceeding 5 mm thickness.

Adult↗
PubMed2003

Calponin and h-caldesmon expression in synovial sarcoma; the use of calponin in diagnosis.

AIMS: To assess the frequency of expression and potential diagnostic utility of calponin and caldesmon in synovial sarcomas. METHODS AND RESULTS: Immunohistochemistry with antibodies to calponin and h-caldesmon was undertaken in paraffin sections from 50 synovial sarcomas (19 biphasic and 31 monophasic, of which one biphasic and eight monophasic tumours had poorly differentiated areas), 10 each of malignant peripheral nerve sheath tumour (MPNST), solitary fibrous tumour (SFT), dermatofibrosarcoma (DFSP), Ewing's sarcoma (ES/PNET), and neuroblastoma, eight alveolar rhabdomyosarcomas, five adult fibrosarcomas and five carcinosarcomas. Nine of 19 biphasic synovial sarcomas were positive for calponin in spindle and glandular areas, nine in spindle cells only, and one in glands only. All monophasic synovial sarcomas and poorly differentiated areas expressed calponin; in monophasic tumours this was focally (29% of cases), moderately (39%), or diffusely (32%) positive and the poorly differentiated areas were usually moderately or diffusely positive. Four synovial sarcomas showed focal reactivity for h-caldesmon. Calponin was found in 4/10 MPNST, 7/10 SFT, 4/10 DFSP, 3/5 fibrosarcomas and the spindle component of the carcinosarcomas. H-caldesmon was weakly positive in 1/10 MPNST, 4/10 SFT, 0/10 DFSP, 0/5 fibrosarcomas and 1/5 carcinosarcomas (glands only). Both markers were negative in the other small round cell tumours. CONCLUSIONS: Calponin can be used as an additional marker for synovial sarcoma. Its absence argues against the diagnosis. The presence of calponin might be useful in distinguishing poorly differentiated synovial sarcoma from other small round cell tumours. H-caldesmon is not helpful in diagnosis of synovial sarcoma.

Biomarkers, Tumor↗
PubMed2003

Broadening the criteria for avoiding staging bone scans in prostate cancer: a retrospective study of patients at the Royal Marsden Hospital.

OBJECTIVE: To determine if it is possible to exclude staging bone scans in a greater proportion of patients if more consideration is given to T stage and Gleason score, as recent guidelines from the National Institute of Clinical Excellence state that routine staging bone scans for prostate cancer are unnecessary in patients with a prostate specific antigen level (PSA) of < 10 ng/mL and Gleason scores of < 8. PATIENTS AND METHODS: We identified a cohort of consecutive patients with untreated prostate cancer who had a staging isotope bone scan between 1 January 1995 and 31 December 2000, who were not on hormone therapy, who had their PSA estimated within 30 days of the scan, and who had histologically confirmed prostate cancer on biopsy reviewed at the Royal Marsden. Data were analysed according to Gleason score, major Gleason grade, clinical T-stage and PSA level. RESULTS: In all, 420 patients were identified who fulfilled the criteria for inclusion; 67 scans (16%, 95% confidence interval, CI, 13-20%) were positive. Of the 187 scans taken in patients with a PSA level of <or= 20 ng/mL, stage < T4 and Gleason < 8 (with major Gleason grade < 4), two (1%, 0.3-4%) were reported as positive, giving a negative predictive value of 99% (95% CI 98.5-99.5%) for these criteria for avoiding the need for staging bone scans. In 116 patients (28%) with Gleason score 7, of whom 28 (24%) had positive scans, there was a statistically significant association between positive scans and a major Gleason pattern of 4 compared with 3. CONCLUSIONS: Isotope bone scans are an unnecessary part of staging of prostate cancer if the PSA level is <or= 20 ng/mL, stage < T4 and Gleason score < 8, and should be omitted unless the major Gleason pattern is 4. The present results suggest that by considering the Gleason score and T stage, a larger proportion of patients with prostate cancer than previously thought could avoid a staging bone scan.

Aged↗
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↗
PubMed2003

Cystic fibrohistiocytic tumours presenting in the lung: primary or metastatic disease?

AIMS: Cystic fibrohistiocytic tumour of the lung is a rare proliferative process. Its histogenesis is uncertain, but evidence suggests that some cases represent metastatic disease from apparently indolent skin lesions, namely cellular fibrous histiocytomas. This study presents four cases and reviews the literature concerning this pattern of disease and its aetiology. METHODS AND RESULTS: All patients were male (age range 35-54 years). Two presented with recurrent haemoptysis. Two cases had histories of cutaneous fibrohistiocytic lesions in the chest wall, excised 10 and 23 years prior to presentation with lung disease. Imaging data showed multiple bilateral cystic lung lesions in all four patients with nodular cavitating opacities seen on high-resolution computed tomography scans. Microscopy showed variably dilated thin-walled cystic airspaces lined by cuboidal epithelium and an underlying layer of mildly pleomorphic spindle cells with slightly wavy morphology and storiform architecture, admixed with inflammatory cells. Tumour cells stained for CD68 in three of four cases. All cases were negative for CD34. All patients were alive with disease, although one required pneumonectomy for intractable haemoptysis. CONCLUSION: This study and a review of published cases show that the majority of cystic fibrohistiocytic tumours of the lung probably represent metastases from cellular fibrous histiocytomas. However, rare cases may be either primary in origin or the primary site remains occult; the term cystic fibrohistiocytic tumour remains appropriate for such cases.

Adult↗
PubMed2003

N-terminal pro B type natriuretic peptide, but not the new putative cardiac hormone relaxin, predicts prognosis in patients with chronic heart failure.

OBJECTIVE: To determine whether the plasma concentration of the putative new cardiac hormone relaxin is predictive of clinical outcome in patients with chronic heart failure (CHF). DESIGN: Plasma relaxin and N-terminal pro B type natriuretic peptide (NT pro BNP) concentrations were measured in 87 patients admitted in an emergency with CHF caused by left ventricular systolic dysfunction. These were related to death and death or readmission with CHF over the following year. SETTING: Western Infirmary, Glasgow, UK. MAIN OUTCOME MEASURES: Plasma concentrations of relaxin and NT pro BNP; time to death or hospitalisation caused by heart failure. RESULTS: Plasma concentrations of both relaxin and NT pro BNP were greatly increased. Of the 43 patients with NT pro BNP above the group median concentration, 23 (53%) died and 30 (70%) died or were hospitalised with CHF. Among the 44 with concentrations below the median, these numbers were 5 (11%) and 12 (27%), respectively (p < 0.0001 and p < 0.0001, respectively). Plasma NT pro BNP concentration remained an independent predictor of an adverse clinical outcome in a multivariate analysis. Of the 42 patients with a relaxin concentration above the median, 13 (31%) died and 20 (48%) died or were hospitalised. Below the median, these numbers were 15 of 45 (33%) and 22 of 45 (49%) (p = 0.76 and p = 0.84, respectively). CONCLUSIONS: NT pro BNP is a powerful and independent predictor of outcome in CHF, whereas relaxin, also secreted by the heart in increased amounts in CHF, is not.

Aged↗
PubMed2003

Hb Q-India: an uncommon variant diagnosed in three Punjabi patients with diabetes is identified by a novel DNA analysis test.

AIMS: An abnormality in the glycated haemoglobin peak (Hb A1c) on Diastat (Bio-Rad) cation exchange low pressure liquid chromatography (LPLC) was found in three Punjabi patients with diabetes. The aims of this study were to identify the variant by chromatography and electrophoresis and to determine whether a DNA analysis test could be designed for confirmation that could be generally applied for the identification of any unusual abnormal haemoglobin. METHODS: The presence of an Hb variant was confirmed by cellulose acetate electrophoresis at pH 8.6. The variant was characterised further by high performance liquid chromatography (HPLC; Bio-Rad Variant) and isolelectric focusing (IEF) electrophoresis. A novel DNA analysis test based on the amplification refractory mutation system (ARMS) and the polymerase chain reaction (PCR) was developed to confirm the presence of the mutation for the uncommon variant. RESULTS: Comparison of the HPLC retention time and IEF band position determined the presence of the variant Hb Q-India in all three cases. Hb Q-India is caused by the mutation GAC --> CAC at codon 64 of the alpha-1 globin gene and is clinically silent. ARMS-PCR specific primers were designed and used successfully to confirm the presence of the mutation for Hb Q-India. CONCLUSIONS: The results show that the ARMS-PCR technique, developed previously for the diagnosis of beta thalassaemia mutations, can also be adapted to provide a simple, rapid, and inexpensive approach for the identification of abnormal haemoglobins.

Adult↗