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Diagnostic Potential (diagnostic + potential)
Selected AbstractsDiagnostic potential of serum protein pattern in Type 2 diabetic nephropathyDIABETIC MEDICINE, Issue 12 2007Y-H. Yang Abstract Aims Microalbuminuria is the earliest clinical sign of diabetic nephropathy (DN). However, the multifactorial nature of DN supports the application of combined markers as a diagnostic tool. Thus, another screening approach, such as protein profiling, is required for accurate diagnosis. Surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) is a novel method for biomarker discovery. We aimed to use SELDI and bioinformatics to define and validate a DN-specific protein pattern in serum. Methods SELDI was used to obtain protein or polypeptide patterns from serum samples of 65 patients with DN and 65 non-DN subjects. From signatures of protein/polypeptide mass, a decision tree model was established for diagnosing the presence of DN. We estimated the proportion of correct classifications from the model by applying it to a masked group of 22 patients with DN and 28 non-DN subjects. The weak cationic exchange (CM10) ProteinChip arrays were performed on a ProteinChip PBS IIC reader. Results The intensities of 22 detected peaks appeared up-regulated, whereas 24 peaks were down-regulated more than twofold (P < 0.01) in the DN group compared with the non-DN groups. The algorithm identified a diagnostic DN pattern of six protein/polypeptide masses. On masked assessment, prediction models based on these protein/polypeptides achieved a sensitivity of 90.9% and specificity of 89.3%. Conclusion These observations suggest that DN patients have a unique cluster of molecular components in serum, which are present in their SELDI profile. Identification and characterization of these molecular components will help in the understanding of the pathogenesis of DN. The serum protein signature, combined with a tree analysis pattern, may provide a novel clinical diagnostic approach for DN. [source] Phonation threshold flow measurements in normal and pathological phonationTHE LARYNGOSCOPE, Issue 4 2009Peiyun Zhuang MD Abstract Objectives/Hypothesis: Phonation threshold flow (PTF) may provide a tool to assess laryngeal function and could differentiate between normal and pathological voices. Both polyps and nodules contribute to an increased PTF by creating an incomplete glottal closure and increased vocal fold mass and thickness. Study Design: Prospective study. Methods: The Kay Elemetrics Phonatory Aerodynamic System (PAS) (Kay Elemetrics Corp., Lincoln Park, NJ) was used to collect mean flow rate (MFR) and PTF measurements from 40 normal subjects, 21 patients with vocal fold nodules, and 23 patients with vocal fold polyps. Gender-based differences were assessed using a t test. The effect of vocal pathology on PTF and MFR was determined with an ANOVA. Diagnostic potential was evaluated using a receiver operation characteristics (ROC) analysis. Results: Both PTF (P = .047) and MFR (P = .008) were significantly affected by gender. Using a two-way ANOVA and correcting for gender differences, the influence of pathology on PTF was determined to be significant (P < .001). Post hoc tests found a significant difference between normal and polyp subjects (P < .001) but not normal and nodule subjects (P = .177) or nodule and polyp subjects (P = .246). ROC analysis found that PTF (area under the curve [AUC] = 0.691) and MFR (AUC = 0.684) had a similar diagnostic utility. Conclusions: PTF can be used to differentiate between normal and pathological voices. As a parameter that is experimentally sensitive to the biomechanical parameters providing its theoretical basis, it could be used clinically to analyze laryngeal functionality. Future research could focus on measuring PTF in other pathologies, such as paralysis or scarring, which would also affect the effort required to produce voice. Laryngoscope, 2009 [source] Magnetic resonance imaging features of an extranodal T cell rich B cell lymphoma in the pharyngeal mucosa in a horseEQUINE VETERINARY EDUCATION, Issue 6 2008V. Jakesova Summary An 11-year-old Warmblood gelding was presented for inspiratory stridor and dysphagia. Based on history and clinical examination, a solitary mass localised in the oropharynx was suspected. Due to its inaccessibility and defensive behaviour of the horse, it was difficult to visualise this mass either by upper airway endoscopy or by oral examination and the conventional imaging methods (radiology and ultrasound) provided only limited information. Fine needle aspiration cytology was suggestive of lymphoma, but the exact localisation and the extent of tissue infiltration of the tumour could only be defined by magnetic resonance imaging (MRI). MRI has proved to be a very useful diagnostic tool in equine lameness investigation and, as this case illustrates, it has considerable diagnostic potential for soft tissue examination of the equine head. [source] H intragenic polymorphisms and haplotype analysis in the ornithine transcarbamylase (OTC) gene and their relevance for tracking the inheritance of OTC deficiency,,HUMAN MUTATION, Issue 5 2002Consuelo Climent Abstract The "private" nature of most mutations causing ornithine transcarbamylase (OTC) deficiency makes mutation identification in the patients difficult. Further, the PCR-amplification technology generally used for the genetic diagnosis of the deficiency misses large deletions in carrier females. Intragenic OTC polymorphisms may allow detection of these deletions and may represent an alternative to mutation detection for prenatal diagnosis and carrier identification in families with a history of inherited OTC deficiency. A new highly informative polymorphism (allele frequencies, 0.66/0.34) in intron 3 of the OTC gene (IVS3-39_40insT) is reported here, and allelic frequencies of 16 additional intragenic OTC polymorphisms are determined in 133-35 (average per polymorphism, 72) unrelated chromosomes. In addition to the novel polymorphism, only three of the studied polymorphisms (Lys46Arg, allelic frequency 0.68/0.32; IVS3-8A>T, 0.34/0.66; Gln270Arg, 0.97/0.03) are confirmed to be informative. These provide, together with another reported polymorphism (IVS4-7A>G; reported allelic frequency 0.71/0.29; Plante and Tuchman, 1998), a set of highly valuable markers of the OTC gene. Nevertheless, the combined informativity of the studied polymorphisms is limited by their distribution in only four haplotypes with one of them predominating (65% of the sampled chromosomes). Although this haplotype composition may be restricted to the Iberian peninsula (the origin of the samples), more informative polymorphisms are required to increase the diagnostic potential and, particularly, to identify large deletions affecting OTC gene exons 5-10, where only one polymorphism of weak diagnostic value is known. © 2002 Wiley-Liss, Inc. [source] Quantitative evaluation of DNA hypermethylation in malignant and benign breast tissue and fluidsINTERNATIONAL JOURNAL OF CANCER, Issue 2 2010Weizhu Zhu Abstract The assessment of DNA had demonstrated altered methylation in malignant compared to benign breast tissue. The purpose of our study was to (i) confirm the predictive ability of methylation assessment in breast tissue, and (ii) use the genes found to be cancer predictive in tissue to evaluate the diagnostic potential of hypermethylation assessment in nipple aspirate fluid (NAF) and mammary ductoscopic (MD) samples. Quantitative methylation specific (qMS)-PCR was conducted on three specimen sets: 44 malignant (CA) and 34 normal (NL) tissue specimens, 18 matched CA, adjacent normal (ANL) tissue and NAF specimens, and 119 MD specimens. Training and validation tissue sets were analyzed to determine the optimal group of cancer predictive genes for NAF and MD analysis. NAF and MD cytologic review were also performed. Methylation of CCND -2, p16, RAR -, and RASSF-1a was significantly more prevalent in tumor than in normal tissue specimens. Receiver operating characteristic curve analysis demonstrated an area under the curve of 0.96. For the 18 matched CA, ANL and NAF specimens, the four predictive genes identified in cancer tissue contained increased methylation in CA vs. ANL tissue; NAF samples had higher methylation than ANL specimens. Methylation frequency was higher in MD specimens from breasts with cancer than benign samples for p16 and RASSF-1a. In summary, i) routine quantitative DNA methylation assessment in NAF and MD samples is possible, and ii) genes hypermethylated in malignant breast tissue are also altered in matched NAF and in MD samples, and may be useful to assist in early breast cancer detection. [source] Development of recombinant OmpA and OmpB proteins as diagnostic antigens for rickettsial diseaseMICROBIOLOGY AND IMMUNOLOGY, Issue 7 2009Eun-Ju Do ABSTRACT In this study the diagnostic potential of Rickettsia conorii recombinant antigens was analyzed. For this, site-specific PCR primers were used to clone the OmpA and OmpB genes of R. conorii into pMAL-c2X plasmids. Six fragments of OmpA and four of OmpB were expressed as fusion proteins with maltose-binding protein in Escherichia coli. OmpA1350-1784, OmpB801-1269, and OmpB1227-1634 regions from truncated proteins were selected as diagnostic candidate antigens by ELISA using control sera. ELISA results of three antigens were compared to the results obtained by using a commercial ELISA kit which contained whole OmpA and OmpB antigens from R. conorii. For this analysis, 40 serum samples taken from febrile patients and uninfected controls were tested. Of the 20 R. conorii test results which were positive with the commercial kit, 18 were shown to be positive by ELISA using OmpA1350-1784 (a sensitivity of 90%). The specificity of the ELISA was 100%; all of the 20 samples shown to be negative using the commercial kit were also negative in our assay. The sensitivities of the ELISA using the OmpB801-1269 and OmpB1227-1634 were 90% and 95%, respectively. The specificities of the OmpB801-1269 and the OmpB1227-1634 were 100% and 95%, respectively. These results suggest that specific regions of OmpA and OmpB effectively detect antibodies against R. conorii, and the truncated recombinant antigens could be used for development of diagnostic tools for rickettsial disease. [source] Transport characteristics of L -citrulline in renal apical membrane of proximal tubular cellsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 3 2009Keisuke Mitsuoka Abstract L -Citrulline has diagnostic potential for renal function, because its plasma concentration increases with the progression of renal failure. Although L -citrulline extracted by glomerular filtration in kidney is mostly reabsorbed, the mechanism involved is not clearly understood. The present study was designed to characterize L -citrulline transport across the apical membranes of renal epithelial tubular cells, using primary-cultured rat renal proximal tubular cells, as well as the human kidney proximal tubular cell line HK-2. L -Citrulline was transported in a Na+ -dependent manner from the apical side of both cell types cultured on permeable supports with a microporous membrane. Kinetic analysis indicated that the transport involves two distinct Na+ -dependent saturable systems and one Na+ -independent saturable system in HK-2 cells. The uptake was competitively inhibited by neutral and cationic, but not anionic amino acids. Relatively large cationic and anionic compounds inhibited the uptake, but smaller ones did not. In HK-2 cells, mRNA expression of SLC6A19 and SLC7A9, which encode B0AT1 and b0,+AT, respectively, was detected by RT-PCR. In addition, L -citrulline transport was significantly decreased in HK-2 cells in which either SLC6A19 or SLC7A9 was silenced. Hence, these results suggest that amino acid transporters B0AT1 and b0,+AT are involved in the reabsorption of L -citrulline in the kidney, at least in part, by mediating the apical membrane transport of L -citrulline in renal tubule cells. Copyright © 2009 John Wiley & Sons, Ltd. [source] Diagnosis of Parietaria judaica pollen allergy using natural and recombinant Par j 1 and Par j 2 allergensCLINICAL & EXPERIMENTAL ALLERGY, Issue 2 2007R. González-Rioja Summary Background Parietaria judaica pollen is one of the main causes of allergic diseases in the Mediterranean area and contains two major allergens, called Par j 1 and Par j 2. Objective To evaluate the diagnostic potential of natural and recombinant forms of Par j 1 and Par j 2 in comparison with standardized P. judaica pollen extract. Methods Thirty patients allergic to P. judaica pollen and 15 control patients were investigated. Skin prick tests and determination of specific IgE levels were performed with commercial P. judaica extract, natural Par j 1 and Par j 2, and recombinant forms of both allergens expressed in P. pastoris. Results The whole group of patients with allergy to P. judaica had a positive skin test reaction to purified nPar j 1,Par j 2 and rPar j 2 at 5 ,g/mL, and no false-positive reactions were detected. Natural and recombinant Par j 1 and Par j 2 showed no significantly different responses in skin tests compared with P. judaica extract. A high correlation was found between the serum-specific IgE levels to P. judaica extract vs. natural (R=0.996; P<0.001) and recombinant allergens (R=0.887 and 0.982 for rPar j 1 and rPar j 2, respectively; P<0.001). rPar j 2 displayed a 100% sensitivity and specificity among P. judaica -allergic patients. Conclusions In vivo and in vitro diagnosis of P. judaica pollen allergy could be simplified using rPar j 2. This protein showed comparable IgE response and skin prick reactivity with those produced by P. judaica pollen extract. [source] Simultaneous voiding cystourethrography and voiding urosonography reveals utility of sonographic diagnosis of vesicoureteral reflux in childrenACTA PAEDIATRICA, Issue 12 2003M Nakamura Aim: To evaluate the diagnostic potential of voiding urosonography (VUS) compared with fluoroscopic voiding cystourethrography (VCUG) under identical conditions and to evaluate potential reasons for false-negative VUS results, particularly regarding bladder concentrations of the US contrast agent, Levovist. Methods: Fifty-six paediatric patients (M/F 34/22, mean age 2.3 y, age range 1 mo-14 y) underwent simultaneous VUS and VCUG under identical conditions. The bladder was filled by simultaneous administration of Levovist and the X-ray contrast medium, DIP Conray. Levovist concentrations in bladders were calculated using amounts of Levovist injected and total DIP Conray infused when reflux was first observed in either procedure. Results: Sensitivities of VUS and VCUG for detection of vesicoureteral reflux (VUR) were both 86%, assuming that VUR detected by either method represented a true-positive, and no reflux by either method represented a true-negative. Patients under 24-mo of age displayed a better VUS sensitivity, of 94%. Levovist concentrations in bladders ranged from 1.8% to 23%, with older children tending to demonstrate increased bladder capacity and lower concentration. All VUS false-negative units displayed Levovist bladder concentrations of less than 5%. Conclusion: The present simultaneous study suggests that: 1) the two techniques demonstrate similar sensitivity for detection of reflux; 2) sustained Levovist bladder concentrations of below 5% may not allow detection of reflux on VUS; and 3) VUS represents a suitable technique, particularly for small children whose bladder capacity is not so large. [source] | |||||||||||||