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Biochemical Criteria (biochemical + criterion)
Selected AbstractsValidation of MCADD newborn screeningCLINICAL GENETICS, Issue 2 2009EM Maier Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) represents a potentially fatal fatty acid ,-oxidation disorder. Newborn screening (NBS) by tandem mass spectrometry (MS/MS) has been implemented worldwide, but is associated with unresolved questions regarding population heterogeneity, burden on healthy carriers, cut-off policies, false-positive and negative rates. In a retrospective case-control study, 333 NBS samples showing borderline acylcarnitine patterns but not reaching recall criteria were genotyped for the two most common mutations (c.985A>G/c.199C>T) and compared with genotypes and acylcarnitines of 333 controls, 68 false-positives, and 34 patients. c.985A>G was more frequently identified in the study group and false-positives compared to controls (1:4.3/1:2.3 vs. 1:42), whereas c.199C>T was found more frequently only within the false-positives (1:23). Biochemical criteria were devised to differentiate homozygous (c.985A>G), compound heterozygous (c.985A>G/c.199C>T), and heterozygous individuals. Four false-negatives were identified because our initial algorithm required an elevation of octanoylcarnitine (C8) and three secondary markers in the initial and follow-up sample. The new approach allowed a reduction of false-positives (by defining high cut-offs: 1.4 ,mol/l for C8; 7 for C8/C12) and false-negatives (by sequencing the ACADM gene of few suspicious samples). Our validation strategy is able to differentiate healthy carriers from patients doubling the positive predictive value (42,88%) and to target NBS to MCADD-subsets with potentially higher risk of adverse outcome. It remains controversial, if NBS programs should aim at identifying all subsets of all diseases included. Because the natural course of milder variants cannot be assessed by observational studies, our strategy could serve as a general model for evaluation of MS/MS-based NBS. [source] Diverting a protein from its cellular location by intracellular antibodiesFEBS JOURNAL, Issue 4 2000The case of p21Ras We describe the use of phage libraries to derive new antibodies against p21Ras to be used for intracellular expression in mammalian cells. A panel of single-chain antibody fragments, binding to Ras, were analyzed and characterized for their capacity to interfere in vitro with (a) the intrinsic GTPase activity of Ras and (b) the binding of Ras to its effector Raf, and were found not to neutralize its function, according to these biochemical criteria. When expressed intracellularly in mouse 3T3 K-Ras transformed cells all the anti-Ras single-chain variable fragments (scFv) tested inhibited cell proliferation, as assessed by bromodeoxyuridine incorporation. Double immunofluorescence analysis of transfected cells using confocal microscopy confirmed that anti-Ras antibody fragments colocalize with endogenous Ras, at subcellular locations where the protein Ras is not normally found. These data suggest that the ability of phage-derived anti-Ras scFv fragments to inhibit the function of Ras in vivo is a rather general and frequent property and that the range of antibodies that can be successfully used for intracellular inhibition studies is much greater than anticipated, exploiting the mode of action of diverting protein traffic. [source] Cobalt requirement of beef cattle , feed intake and growth at different levels of cobalt supplyJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 3 2000F. J. Schwarz Summary In a study using a total of 36 German Simmental beef bulls weighing between 236 kg and about 620 kg the question of what constitutes an adequate Co supply was investigated with reference to the performance criteria growth, feed intake, energy intake, nutrient intake and carcass criteria. The bulls received a diet of corn silage ad libitum and 2.5 kg concentrate for a period of 280 days. Ten rations (R) with graduated Co supplements were fed with mean concentrations of 0.07 (R1), 0.09 (R2), 0.11 (R3), 0.15 (R4), 0.18 (R5), 0.26 (R6), 0.33 (R7), 0.42 (R8), 0.59 (R9) and 0.69 (R10) mg Co per kg dry matter (DM) intake. The Co supplement was added as CoSO47H2O. The diets with no or low Co supplementation produced either distinctly lower daily gains of 1045g (R1) and 1130g (R2) or lower daily gains of about 1260 g (R3, R4) than rations R5,R10, where daily gains averaged 1340 g. The mean daily feed intake per animal was also significantly or marginally affected with values of 6.0 kg DM (R1) rising to 7.7 kg DM (R2,R4) versus 7.9 kg DM on average (R5,R10). Calculations using the broken line model and the quadratic model show that the optimal Co supply for maximum growth is 0.12 mg/kg dietary DM and for maximum feed intake, 0.16,0.18 mg Co/kg dietary DM. After taking further biochemical criteria into account (Stangl et al. 2000), a level of 0.20 mg/kg dietary DM is recommended as an adequate Co supply for growing cattle. [source] Novel mutations in the 7-dehydrocholesterol reductase gene of 13 patients with Smith,Lemli,Opitz syndromeANNALS OF HUMAN GENETICS, Issue 3 2001P. E. JIRA Smith,Lemli,Opitz syndrome (SLOS) is caused by mutations in the DHCR7 gene leading to deficient activity of 7-dehydrocholesterol reductase (DHCR7; EC 1.3.1.21), the final enzyme of the cholesterol biosynthetic pathway, resulting in low cholesterol and high concentrations of its direct precursor 7-dehydrocholesterol in plasma and tissues. We here report mutations identified in the DHCR7 gene of 13 children diagnosed with SLOS by clinical and biochemical criteria. We found a high frequency of the previously described IVS8,1 G > C splice acceptor site mutation (two homozygotes, eight compound heterozygotes). In addition, 13 missense mutations and one splice acceptor mutation were detected in eleven patients with a mild to moderate SLOS-phenotype. The mutations include three novel missense mutations (W182L, C183Y, F255L) and one novel splice acceptor site mutation (IVS8,1 G > T). Two patients, homozygous for the IVS8,1 G > C mutation, presented with a severe clinical phenotype and died shortly after birth. Seven patients with a mild to moderate SLOS-phenotype disclosed compound heterozygosity of the IVS8,1 G > C mutation in combination with different novel and known missense mutations. [source] Need for staging laparoscopy in patients with gastric cancerBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 3 2000R. Bhalla Aims: The aim of preoperative staging in gastric cancer is to correctly identify patients with advanced disease who should not be subjected to surgery and to allow the treatment of those who are admitted for operation to be planned accurately. This study assessed the impact of a policy of selective staging laparoscopy in patients deemed suitable for curative or palliative surgery, to ascertain whether the selective approach increased the frequency of abandoned or unplanned surgical procedures. Methods: Fifty consecutive patients with gastric or type III gastro-oesophageal junction cancer staged by computed tomography (CT) alone, in whom surgery was felt to be appropriate for ,cure' or palliative symptom control, were studied. Specific CT, endoscopic and biochemical criteria were applied prospectively to select out a subgroup of 18 patients who also underwent preoperative staging laparoscopy. The overall accuracy of staging and operative outcomes were assessed. Results: Using this selective approach the resection rate was 98 per cent, although three patients in each group had their planned procedure altered to a less radical (two in each group) or more radical (one in each group) resection (P = 0·23). Overall, 41 of 50 patients were staged correctly (accuracy 82 (95 per cent confidence interval 69,90) per cent) and 86 per cent of patients underwent the planned surgical procedure. The only abandoned operation occurred in the staging laparoscopy group. Conclusions: It is possible to plan a patient's operation accurately without the need for a staging laparoscopy in all cases. © 2000 British Journal of Surgery Society Ltd [source] Prediction of cure and risk of hypothyroidism in patients receiving 131I for hyperthyroidismCLINICAL ENDOCRINOLOGY, Issue 1 2009K. Boelaert Summary Context, There is little consensus regarding the most appropriate dose of radioiodine (131I) to be administered to patients with hyperthyroidism. Objective, To compare the efficacy of fixed dose regimens of 131I in curing hyperthyroidism and to define simple clinical and biochemical factors that predict outcome in individual patients. Design, Consecutive series of hyperthyroid subjects treated with 131I. Setting, Single Secondary/Tertiary Care Hospital Clinic. Participants, A total of 1278 patients (1013 females and 262 males, mean age 49·7 years) presenting with hyperthyroidism between 1984 and 2006. Intervention, Treatment with 131I using a fixed dose regimen. Main outcome measures, Probability of cure and risk of development of hypothyroidism following a single dose of 131I. Results, Patients given a single dose of 131I of 600 MBq (n = 485) had a higher cure rate (84·1%) compared with those receiving either 370 MBq (74·9%, P < 0·001) or those given 185 Bq (63%, P < 0·001). An increased incidence of hypothyroidism by 1 year was evident with higher doses (600 MBq: 60·4%; 370 MBq: 49·2%, P = 0·001; 185 Bq: 38·1%, P < 0·001). Binary logistic regression analysis identified a 600 Bq dose of 131I [adjusted odds ratio, AOR 3·33 (2·28,4·85), P < 0·001], female gender [AOR 1·75 (1·23,2·47), P = 0·002], lower presenting serum free T4 concentration [AOR 1·01 (1·01,1·02), P < 0·001] and absence of a palpable goitre [AOR 3·33 (2·00,5·56), P < 0·001] to be independent predictors of cure. Similarly, a 600 MBq dose [AOR 3·79 (2·66,5·38), P < 0·001], female gender [AOR 1·46 (1·05,2·02), P = 0·02], younger age [AOR 1·03 (1·02,1·04), P < 0·001], absence of a palpable goitre [AOR 3·85 (2·38,5·88), P < 0·001] and presence of ophthalmopathy [AOR 1·57 (1·06,2·31), P = 0·02] were identified as independent factors predicting the probability of development of hypothyroidism at one year. Based on these findings, formulae to indicate probability of cure and risk of hypothyroidism for application to individual patients were derived. Conclusions, Simple clinical/biochemical criteria can be used to predict outcome after 131I treatment. These factors determine that males, those with severe biochemical hyperthyroidism, and those with a palpable goitre require larger doses (600 MBq) in order to achieve cure. [source] | |||||||||||||