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Gareth Roberts

Publications and source records attributed to Gareth Roberts.

7 recordsLinked to original sources

Telomerase subunits expression variation between biopsy samples and cell lines derived from malignant glioma.

Although scientific advances have recognised the prognostic power of telomerase activity in different cancers, as yet there has been no investigation regarding the expression variation of telomerase subunits in glioma tissues and cell lines. In this study, a recurrent anaplastic ependymoma and seven glioblastoma biopsy samples, four cell lines and four controls including two normal brain tissues were analysed for telomerase subunit expression profiles together with telomerase activity. Since telomerase activity is linked to tumourgenesis, the genes were analysed with respect to their expression variation. TEP1 was expressed in all glioma cell lines and 70% of glioblastoma tissues, in addition to the control brain tissues. Tankyrase was expressed in 85% of the glioblastoma tissues and was down-regulated in the recurrent anaplastic ependymoma tissue control cell lines. However, it was expressed in the control tissues. Dyskerin was expressed in all cell lines and tissues apart from U87-MG and NHA cells and the recurrent anaplastic ependymoma tissue. As expected, PARP1 and GAPDH showed constitutive expression throughout all cell lines and tissues since both are known to be housekeeping genes. hTERT was expressed in all glioma cell lines and tissues but was absent in the control cells and tissues. Telomerase activity was absent in IPDDC-A2 cells and 57% of the glioblastoma tissues. These results suggest that hTERT expression and not telomerase activity possibly represents a simple and reliable biological diagnostic tool.

Biomarkers, Tumor↗

Bioelectrical impedance can be used to predict muscle mass and hence improve estimation of glomerular filtration rate in non-diabetic patients with chronic kidney disease.

BACKGROUND: In this article (the second of two companion studies), we report whether bioelectrical impedance analysis (BIA) can be used to predict muscle mass in patients with chronic kidney disease (CKD), and whether using this predicted muscle mass can improve the estimation of glomerular filtration rate (GFR). METHODS: Seventy five non-diabetic patients with CKD (mean age +/- SD, 65.1 +/- 12.0 years; mean GFR 45.9 +/- 28.8 ml/min/1.73 m2) underwent body composition analysis by dual energy X-ray absorptiometry to provide a criterion marker of skeletal muscle mass (appendicular lean mass, ALM). Validity of a published BIA equation to predict ALM was evaluated and a new BIA equation was generated (ALM(BIA)) and cross-validated by the leave-one-out procedure. Renal inulin clearance provided a criterion measure of GFR (GFR(inu)). The performance of the equation including ALM(BIA) to estimate GFR(inu) was compared with demographic variables as used in the modification of diet in renal disease (MDRD) equation, by determining bias, limits of agreement and accuracy. RESULTS: The previously published BIA equation to predict ALM was not valid in these patients with CKD. In contrast, our new ALM(BIA) equation cross-validated successfully. Compared with the MDRD demographic variables, using ALM(BIA) to predict GFR(inu) improved estimation performance, showing reduced bias (4.3 vs 15.6 ml/min) and improved limits of agreement (41.1 vs 59.2 ml/min) and accuracy (69.7 vs 39.4% of patients' predicted GFR did not deviate by more than 30% of GFR(inu)). CONCLUSIONS: ALM(BIA) provides a clinically obtainable and valid method to predict muscle mass in patients with CKD, and using ALM(BIA) improves the estimation of GFR(inu). Researchers developing future GFR estimation equations should consider including ALM(BIA).

Aged↗

The relationship between estimated glomerular filtration rate, demographic and anthropometric variables is mediated by muscle mass in non-diabetic patients with chronic kidney disease.

BACKGROUND: In this study (the first of two related papers), we report whether the relationship between the demographic and anthropometric variables (DA, i.e. age, gender, height and weight) employed in current creatinin (Cr)-based glomerular filtration rate (GFR) estimation equations and actual GFR is mediated by muscle mass. METHODS: We studied 77 patients (mean age +/- SD, 65.1 +/- 11.9 years) with chronic kidney disease (mean GFR 45.7 +/- 28.6 ml/min/1.73 m2). Actual GFR was measured by the renal clearance of inulin (GFR(inu)). Appendicular lean mass (ALM) and its index (ALMI) by dual energy X-ray absorptiometry provided markers of muscle mass. Multiple regression analyses identified variables explaining variance in (i) GFR, (ii) ALM and (iii) Cr. RESULTS: (i) The DA variables used in the abbreviated modification of diet in renal disease (MDRD) equation accounted for only 59.6% (P < 0.001) of the variance in GFR(inu), whilst adding ALMI explained an additional 10.4% variance (P < 0.001). If ALMI was entered first, the relationship between DA variables and GFR(inu) was reduced (for weight) or completely abolished (for age, gender and height). (ii) After inputting all the commonly used DA variables, 17.2% of the variance in ALM was unexplained. (iii) All the DA variables explained only 60.6% (P < 0.001) of the variance in Cr, whilst adding ALM explained an additional 4.2% variance (P < 0.005). CONCLUSIONS: Muscle mass explained more variance in GFR(inu) than MDRD DA variables and mediated the relationship between GFR(inu) and DA variables. Furthermore, DA variables failed to account for individual differences in muscle mass or Cr. Consequently, there is a need to validate simpler, clinically obtainable measures of muscle mass and determine whether these measures will improve GFR estimation.

Adult↗

Solitary plasmocytoma of frontal bone presenting as an asymptomatic forehead lump.

Solitary plasmocytoma of bone is a rare type of plasma cell tumor. We present a case of a solitary extramedullary plasmacytoma of the frontal bone presenting as an asymptomatic forehead lump with clinically benign characteristics. This case highlights the need for a high index of suspicion when dealing with enlarging subcutaneous lumps of the forehead and scalp. The significance of this lies in the appropriate sequencing of investigations and the implementation of the necessary treatment regimen.

Aged↗

GFR estimation using cystatin C is not independent of body composition.

BACKGROUND: Cystatin C (CysC) is an endogenous marker of glomerular filtration rate (GFR) that is claimed to be unaffected by body composition. In this study, we tested this speculation. METHODS: In 77 patients with chronic kidney disease (mean age, 65.1 +/- 11.9 [SD] years; mean indexed GFR, 45.7 +/- 28.6 mL/min/1.73 m(2) [0.76 +/- 0.48 mL/s]), we evaluated kidney function (GFR) by means of inulin clearance. CysC level was determined by using a particle-enhanced turbidimetric immunoassay. Total lean (LM) and fat masses were measured by means of dual-energy x-ray absorptiometry. Multiple regression was used to analyze relationships between absolute GFR, LM, fat mass, demographic and anthropometric variables (age, sex, height, and weight), and CysC levels. Then prediction equations were built that included only CysC level or CysC level and LM. Their performance to predict absolute GFR was evaluated in a subset of patients with extreme body composition (LM or fat mass > +/-1 SD of the entire sample). RESULTS: Only absolute GFR and LM significantly explained variance in CysC levels, and an equation including LM explained more variance in absolute GFR than an equation including CysC level alone. Consequently, the equation including LM performed better than the equation with only CysC level, especially in patients with extreme body composition, showing reduced bias and improved limits of agreement and accuracy (71.4% versus 51.4% of patients' predicted GFR did not deviate by >30% of GFR). CONCLUSION: LM is a previously unrecognized, but important, factor affecting CysC level, and GFR estimation improves when including LM. CysC level is not independent of body composition, as previously assumed, and hence accounting for body composition improves CysC-based GFR estimation.

Aged↗

Apolipoprotein(A) expression in intracranial aneurysms.

OBJECTIVE: Elevated serum levels of lipoprotein(a), a risk factor for atherosclerosis (AS), are also associated with the presence of asymptomatic intracranial aneurysms. AS is present in some aneurysms, but its contribution to aneurysm formation and growth is unclear. Apolipoprotein(a) [apo(a)], the active moiety of lipoprotein(a), is present in atherosclerotic circle of Willis vessels but not in normal circle of Willis vessels. We wished to determine whether apo(a) is present in intracranial aneurysms independently of AS. METHODS: With a purified anti-apo(a) monoclonal antibody, aneurysms (n = 25) and feeding vessels (n = 23) were examined for apo(a) expression by immunohistochemical analysis. Circle of Willis arteries with and without AS (n = 19), cavernous angiomas (n = 5), and arteriovenous malformations (n = 6) acted as control samples. RESULTS: AS was present in 32% of aneurysms, and all of those aneurysms demonstrated mural immunopositivity for apo(a). However, aneurysms devoid of AS also demonstrated apo(a) immunopositivity. Apo(a) was demonstrated in 86% of available feeding vessels. Apo(a) deposition was not observed in cavernous angiomas but was present in arteriovenous malformations. Eleven Circle of Willis arteries (57.9%) were devoid of AS and demonstrated no apo(a) immunostaining, whereas the eight (42.1%) with AS were immunopositive for apo(a). CONCLUSION: Apo(a) expression in intracranial aneurysms may occur independently of AS. Apo(a) in feeding vessels suggests a possible role for apo(a) in early events leading to aneurysm formation. Multilayered transmural apo(a) deposition in established aneurysms suggests apo(a) involvement in aneurysm growth, possibly via cycles of injury and repair. The absence of apo(a) in cavernous angiomas suggests that such injury might be pressure-mediated.

Adolescent↗