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- Clarke, Robert, et al.
(author)
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Detection of vitamin B12 deficiency in older people by measuring vitamin B12 or the active fraction of vitamin B12, holotranscobalamin.
- 2007
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In: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 53:5, s. 963-970
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Journal article (peer-reviewed)abstract
- BACKGROUND: Impaired vitamin B(12) function and decreased vitamin B(12) status have been associated with neurological and cognitive impairment. Current assays analyze total vitamin B(12) concentration, only a small percentage of which is metabolically active. Concentrations of this active component, carried on holotranscobalamin (holoTC), may be of greater relevance than total vitamin B(12). METHODS: We compared the utility of serum holoTC with conventional vitamin B(12) for detection of vitamin B(12) deficiency in a population-based study of older people, using increased methylmalonic acid (MMA) concentrations as a marker of metabolic vitamin B(12) deficiency in the overall population (n = 2403) and in subsets with normal (n = 1651) and abnormal (n = 752) renal function. RESULTS: Among all participants, 6% had definite (MMA >0.75 micromol/L) and 16% had probable (MMA >0.45 micromol/L) metabolic vitamin B(12) deficiency. In receiver operating characteristic curves for detection of definite vitamin B(12) deficiency, holoTC had a greater area under the curve (AUC) compared with vitamin B(12) in all participants (0.85 vs 0.76; P <0.001) and in subsets with normal (AUC: 0.87 vs 0.79; P <0.001) and abnormal (AUC: 0.85 vs 0.74; P = 0.002) renal function. Similar findings were observed for detection of moderate vitamin B(12) deficiency. Whereas the positive predictive value for both holoTC and vitamin B(12) was greater for detection of probable than definite vitamin B(12) deficiency, both tests were associated with more false-positive than true-positive test results. CONCLUSIONS: HoloTC has a modestly superior diagnostic accuracy compared with conventional vitamin B(12) for the detection of vitamin B(12) deficiency, but neither test can be recommended to screen asymptomatic populations.
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- Hin, Harold, et al.
(author)
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Clinical relevance of low serum vitamin B12 concentrations in older people : the Banbury B12 study
- 2006
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In: Age and Ageing. - London : Oxford University Press. - 0002-0729 .- 1468-2834. ; 35:4, s. 416-422
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Journal article (peer-reviewed)abstract
- Background: low vitamin B12 concentrations are common in older people, but the clinical relevance of biochemical evidence of vitamin B12 deficiency in the absence of anaemia is uncertain. Objective: to examine associations of cognitive impairment, depression and neuropathy with blood measurements of vitamin B12 and folate status in older people. Design: cross-sectional study in general practice in Banbury, England. Participants: a total of 1,000 individuals aged 75 years or older living in the community. Results: low vitamin B12 concentrations were identified in 13% of older people and were associated with memory impairment and depression. After adjustment for age, sex and smoking, individuals with vitamin B12 or holotranscobalamin (holoTC) in the bottom compared with top quartiles had a 2-fold risk (OR = 2.17; 95% CI 1.11-4.27) and a 3-fold risk (OR = 3.02; 95% CI 1.31-6.98) of cognitive impairment, respectively. Low vitamin B12 status was also associated with missing ankle tendon jerks but not with depression. Treatment with vitamin B12 for 3 months corrected the biochemical abnormalities but had no effect on any of the clinical measurements. Conclusions: low vitamin B12 concentrations are associated with cognitive impairment and missing ankle tendon jerks in older people in the absence of anaemia. Large-scale trials of vitamin B12 supplementation are required to assess the clinical significance of these associations.
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- Memon, Ashfaque A., et al.
(author)
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Soluble HER3 predicts survival in bladder cancer patients
- 2018
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In: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 15:2, s. 1783-1788
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Journal article (peer-reviewed)abstract
- The role of soluble human epidermal growth factor receptor (sHER3) in bladder cancer remains unclear. In the present study, an ELISA was developed for the quantification of sHER3 and its role was investigated in patients with bladder cancer (n=82) followed for 10 years. Furthermore, the effects of sHER3 on bladder cancer cell growth and migration were also investigated. The results demonstrated that plasma sHER3 levels were significantly higher in non-invasive tumours (Ta) compared with muscle-invasive tumours (T2-T4). Higher sHER3 levels were associated with a more improved survival rate. However multivariate Cox regression analysis, adjusted for clinical stage, grade, type and size of the tumour, demonstrated that sHER3 was not an independent biomarker of survival. Exogenous sHER3 significantly inhibited bladder cancer cell growth and migration. These results suggest that high sHER3 levels are associated with improved survival rates in patients with bladder cancer, and that sHER3 inhibits bladder cancer cell growth and migration.
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- Riedel, Bettina M., et al.
(author)
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Transcobalamin polymorphism 67A-> G, but not 776C-> G, affects serum holotranscobalamin in a cohort of healthy middle-aged men and women
- 2011
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In: Journal of Nutrition. - Bethesda, Md. : Elsevier BV. - 0022-3166 .- 1541-6100. ; 141:10, s. 1784-1790
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Journal article (peer-reviewed)abstract
- Two polymorphic variants in the gene coding for transcobalamin II (TCN2), TCN2 776C-> G and TCN2 67A-> G, may alter serum holotranscobalamin (holoTC), which in turn may affect cellular uptake of cobalamin (Cbl) and thereby Cbl status indicators. We studied the effects of TCN2 776C- > G and TCN2 67A- > G on blood concentrations of holoTC, Cbl, methylmalonic acid (MMA), and total homocysteine (tHcy) in 2411 individuals (50-64 y) that had been selected on the basis of these TCN2 genotypes from 10601 Norwegian inhabitants. The serum holoTC concentration was lower in TCN2 67AG (55 +/- 0.75 pmol/L) and 67GG (48 +/- 2.14 pmol/L) than in 67AA (62 +/- 0.67 pmol/L) (P < 0.001) but did not differ among TCN2 776C-> G genotypes. The polymorphisms interacted as serum holoTC determinants (P= 0.001) and the presence of TCN2 67AG and GG in strata of 776CC and CG, but not 776GG, increased the risk of having serum holoTC <45.6 pmol/L [tertile 1 vs. tertiles 2 and 3: OR = 2.5(95% CI 1.8-3.5) for 67AG; OR = 5.7 (95% Cl 3.5-9.1) for 67GG in 776CC; OR = 2.1 195% Cl 1.6-2.9) for 67AG; and OR = 4.5 (95% Cl 2.4-8.2) for 67GG in 776CG; all P < 0.0011. Plasma MMA, tHcy, and Cbl were not affected by either polymorphism. In summary, serum holoTC, but not plasma Cbl, MMA, or tHcy, varied according to TCN2 67A-> G genotypes. It remains to be determined whether this polymorphic effect on serum holoTC alters its diagnostic utility as Cbl status indicator.
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- Vinter-Jensen, Lars, et al.
(author)
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Acute contractile effects of epidermal growth factor on bladder smooth muscles. An in vivo and in vitro study in rats
- 1997
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In: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 31:3, s. 231-235
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Journal article (peer-reviewed)abstract
- Chronic treatment with epidermal growth factor (EGF) stimulates growth of all wall layers of the urinary tract in pigs and rats. Herein, we investigated the acute effects of EGF on detrusor smooth muscle activity. For in vivo examination, awake rats received EGF (75 micrograms/kg) intravenously and detrusor smooth muscle activity was monitored cystometrically. The EGF bolus caused no alteration in diuresis but a doubling of the micturition frequency, a 25% increase in micturition pressures, and increased irregular baseline contractile activity. For in vitro examination detrusor smooth muscle strips were exposed to EGF (1 microgram/ml). EGF caused contraction and increase in the spontaneous activity. In conclusion, EGF increases rat detrusor smooth muscle contractile activity in vivo and in vitro. The finding suggests that a direct effect of EGF on bladder smooth muscles is part of the genesis to the growth of the detrusor smooth muscle observed after chronic EGF treatment.
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