Disease Markers - Volume 20, issue 6

Authors: McGlinchey, Paul G. | Spence, Mark S. | Patterson, Chris C. | Allen, Adrian R. | Murphy, Gillian | Fogarty, Damian | Evans, Alun | McKeown, Pascal P.

Article Type: Research Article

Abstract: Matrix metalloproteinase-3 (MMP-3) has been proposed as an important mediator of the atherosclerotic process. The possible role of the functional -1612 5A/6A polymorphism of the MMP-3 gene in the susceptibility to ischaemic heart disease (IHD) was investigated in a well-defined Irish population using two recently described family based tests of association. One thousand and twelve individuals from 386 families with at least one member prematurely affected with IHD were genotyped. Using the combined transmission …disequilibrium test (TDT)/sib-TDT and the pedigree disequilibrium test (PDT), no association between the MMP-3 -1612 5A/6A polymorphism and IHD was found. Our data demonstrate that, in an Irish population, the MMP-3 -1612 5A/6A polymorphism is not associated with IHD. Show more

Keywords: gene polymorphism, ischaemic heart disease, matrix metalloproteinase-3, stromelysin-1

Citation: Disease Markers, vol. 20, no. 6, pp. 289-294, 2004

Authors: Liggett, Walter S. | Barker, Peter E. | Semmes, O. John | Cazares, Lisa H.

Article Type: Research Article

Abstract: Biomarker discovery and development requires measurement reproducibility studies in addition to case-control studies. Parallel pursuit of reproducibility studies is especially important for emerging technologies such as protein biomarkers based on time-of-flight mass spectrometry, the case considered in this paper. For parallel studies, a way to improve reproducibility prior to identification of protein species is necessary. One approach is use of functional principal components analysis (PCA) as the basis for assessing measurement reproducibility. …Reproducibility studies involve repeated measurement of a reference material such as a human serum standard. Measurement in our example is by SELDI-TOF (surface-enhanced laser desorption and ionization time-of-flight) mass spectrometry. Reproducibility is defined in reference to a source of variation, which in our example is associated with a type of commercially available protein biochip. We obtained spectra for 8 spots on each 11 chips. Two spectra are generally more alike when obtained from the same chip rather than different chips. Thus, our experiment indicates potential improvements from reducing variation in chip manufacture and chip handling during measurement. Our analysis involves careful registration of the spectra and characterization of the spectral differences. As shown by our example, a metrological analysis may enhance case-control studies by guiding optimization of the measurements underlying the biomarker. Show more

Citation: Disease Markers, vol. 20, no. 6, pp. 295-307, 2004

Authors: Oguz, Fatma Savran | Ocal, Lale | Diler, Ali Sarper | Ozkul, Hilmi | Asicioglu, Faruk | Kasapoglu, Esen | Bozkurt, Gokay | Konice, Meral | Carin, Mahmut

Article Type: Research Article

Abstract: The frequency and the distribution of HLA-B27 subtypes in spondylarthropathy (SpA) patients and controls were investigated in a sample Turkish population. B27 subtyping was performed by PCR-SSP method in two groups: 49 unrelated HLA-B27 positive Turkish patients with the diagnosis of SpA according to the European Spondyloarthropathy Study Group Criteria, and 55 HLA-B27 positive healthy controls. The frequency of HLA-B*27 was 2.6% in the Turkish population, and B*2705 was the predominant allele among patients with …SpA. The difference was mainly between male patients and male controls The proportion of B*2705 among B27-positive patients and controls was significantly different (P = 0.02). Our study supports other reports from different populations which showed that B*2705 and B*2702 were more frequent in Caucasian patients with SpA. Show more

Keywords: spondyloarthropathy, HLA-B27

Citation: Disease Markers, vol. 20, no. 6, pp. 309-312, 2004

Authors: Aşıcıoǧlu, Faruk | Oguz-Savran, Fatma | Ozbek, Ugur

Article Type: Research Article

Abstract: Paternity tests are carried out by the analysis of hypervariable short tandem repeat DNA loci. These microsatellite sequences mutate at a higher rate than that of bulk DNA. The occurrence of germline mutations at STR loci posses problems in interpretation of resulting genetic profiles. We recently analyzed 59–159 parent/child allele transfers at 13 microsatellite loci. We identified 12 mutations in 7 microsatellite loci. No mutations were occurred in other 6 loci. The highest mutation rate was …observed with 5 mutations at D8S1179 locus at different alleles. The event was always single repeat related. The mutation rate was between 0 and 1.5 × 10^{-2} per locus per gamete per generation. The mutation event is very crucial for forensic DNA testing and accumulation of STR mutation data is extremely important for genetic profile interpretation. Show more

Keywords: STR, mutation, paternity testing, short tandem repeat

Citation: Disease Markers, vol. 20, no. 6, pp. 313-315, 2004

Authors: Doss, Victor A. | Parvathi, S. | Raju, B. Appala | Devi, N. Abitha

Article Type: Research Article

Abstract: Pseudomonas aeruginosa is one of the major causes of infections including the hospital acquired (Nosocomial) infections. Detection of them and their antibiotic resistance profile by conventional method takes about three days. Recently, DNA based diagnostic methods are being used for the identification of the pathogens. Hence we have tested a rapid and sensitive method using DNA sequences as markers for detecting the presence of three genes coding for the enzymes that inactivate the two most commonly …used Anti-pseudomonadal drugs such as β-lactam antibiotics (Penicillin, and its derivatives) and Aminoglycosides such as Gentamicin, Tobramycin, Amikacin, Streptomycin. The internal region of these genes were used for designing and synthesizing primers and these primers were used in Polymerase Chain Reaction (PCR) to screen for the presence of these genes in the clinical isolates and to label them non-radioactively with Biotin. They in turn were used to detect the presence of the antibiotic resistance genes in the clinical isolates by hybridization. The specificity (ratio of positive results obtained in both methods and the sensitivity (the minimum amount of sample DNA and the labeled probe required for the tests) were evaluated. Show more

Keywords: gene marker, DNA probes, antibiotic resistance, drug-modifying enzymes, non-radioactive labelling, anti-biogram, culture and sensitivity test

Citation: Disease Markers, vol. 20, no. 6, pp. 317-323, 2004

Authors: Shawky, R.M. | Sayed, N.S. | Elhawary, N.A.

Article Type: Research Article

Abstract: Autosomal recessive congenital ichthyosis (ARCI) is a rare heterogeneous keratinization disorder of the skin. It is clinically divided into 2 subtypes, lamellar ichthyosis (LI) and congenital ichthyosiformis erythroderma (CIE). We investigated forty-three ARCI Egyptian individuals in 16 severe LI, and 10 CIE families. We identified 5 alleles in two Egyptian families as having intron-5/exon-6 splice acceptor mutation recognized by the MspI restriction endonuclease. This promoted to a frequency of 9.6% for this …mutation (5 splice-mutation alleles/52 alleles tested). We extended our previous dataset to update the detection of R142H mutation in 4 CIE Egyptian families and one LI phenotype (frequency of 28.8%; 15/52), whereas we still had no R141H among our Egyptian population. There was no correlation between phenotype and genotype in our study. Surprisingly, the mutant alleles detected in intron-5 acceptor splice-site were associated with the other extreme of CIE phenotypes rather than the severe LI form. We clearly demonstrated that the ARCI Egyptian families in Upper Egypt was ethnically pure and had a tendency not to be a hybrid with other populations in Lower Egypt, Delta zone and Cairo city. Show more

Citation: Disease Markers, vol. 20, no. 6, pp. 325-332, 2004

Authors: Ahmed, Maha Imam | Salahy, Eman-El | Tawfiq, Hassan | Khalifa, Ali | Hassan, Manal M.

Article Type: Research Article

Abstract: Matrix metalloproteinases (MMPs), a family of proteolytic enzymes produced by both stromal and tumor cells, appear to have a key role in the events leading to local invasion and metastasis by malignant neoplasms. In the present study, we evaluated the role of MMP-2, squamous cell carcinoma antigen (SCCA), and tissue polypeptide – specific antigen (TPS) in cervical neoplasia. Using Western blotting and enzyme immunoassay (EIA), we analyzed 50 patients with cervical carcinoma (CC) and 25 normal …controls for expression of MMP-2 in tissue cell lysates. We also quantified SCCA and TPS with microparticle immunoassay and EIA, respectively. The results were correlated with human papilloma virus (HPV) infection, clinicopathological findings, and disease outcome. The cutoff point for each marker was estimated from receiver operating characteristic curves. Logistic regression analysis was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) for each marker. MMP-2, SCCA, and TPS protein expression were significantly higher in patients with CC than in normal controls. While TPS was the best marker for discriminating between patients and controls, MMP-2 was associated with an advanced tumor stage (OR, 13.9 [95% CI, 1.4-133.9]) and poor histological grade (OR, 10.2 [95% CI, 1.7-60.5]). Moreover, independent of the effect of an advanced CC stage and grade, the patients' age, and the presence of HPV infection, MMP-2 was considered a strong predictor for CC recurrence (OR, 8.1 [95% CI, 1.3- 49.1]). Tissue markers may be used to select high-risk patients for early detection of and adjuvant therapy for recurrence. Our MMP-2 findings are particularly relevant to the development of protease inhibitors as a new cancer therapy approach. Show more

Keywords: cervical carcinoma, metalloproteinases, polypeptide – specific antigen, cervical neoplasms, recurrence

Citation: Disease Markers, vol. 20, no. 6, pp. 333-343, 2004

Authors: Celi, Alessandro | Lorenzet, Roberto | Furie, Barbara C. | Furie, Bruce

Article Type: Research Article

Citation: Disease Markers, vol. 20, no. 6, pp. 347-352, 2004

Authors: Mumford, Andrew D. | McVey, John H.

Article Type: Research Article

Abstract: The interaction between cell-surface tissue factor (TF) and the plasma coagulation factor VII (FVII) initiates the coagulation network that leads to the generation of thrombin and the formation of a fibrin clot. Thrombin also activates cellular protease activated receptors (PARs) through which it activates components of the inflammatory pathway. TF is expressed constitutively by cardiomyocytes and evidence from mice transgenic for a human TF mini-gene that express very low levels of human TF suggests that the …TF-FVII interaction is critical for haemostasis within the heart. Pathological contact between TF and FVII may occur in the heart during ischaemia-reperfusion (I-R) injury and this may lead to activation of coagulation and thrombin generation. Evidence from animal models now suggests that thrombin is an important mediator of inflammation in I-R injury. The coagulation pathway therefore represents a novel therapeutic target for intervention in the prevention of I-R injury. Show more

Keywords: tissue factor, blood coagulation, inflammation, cardiomyocytes, ischaemia-reperfusion injury

Citation: Disease Markers, vol. 20, no. 6, pp. 353-358, 2004