Disease Markers - Volume 32, issue 5

Authors: Ju, Chun-Rong | Liu, Wei | Chen, Rong-Chang

Article Type: Research Article

Abstract: Background: Surfactant protein D (SP-D) is a lung-specific protein proposed to predict clinical outcomes in patients with chronic obstructive pulmonary disease (COPD). However, the changes in serum SP-D during acute exacerbation (AECOPD) episodes and the relationship of serum SP-D with the overall severity of the disease in stable COPD (SCOPD) remain unclear. Methods: Serum SP-D levels were analyzed in three groups, including AECOPD (n=40), SCOPD (n=71), and controls (n=60). In AECOPD group, serum SP-D …levels were determined at 1, 5, 14, and 30 days post-exacerbation. In SCOPD group, BODE (body mass index, airflow obstruction, dyspnea, exercise capacity) index was evaluated for severity assessment. Results: Serum SP-D levels were sequentially elevated from the controls to the SCOPD, and then to the AECOPD (p< 0.001). During an AECOPD episode, the raised serum SP-D levels subsided at day 5 (p> 0.05), fell markedly at day 14 (p< 0.001), and continued to decline at day 30 (p< 0.001). Among patients with SCOPD, serum SP-D levels correlated positively with the BODE index (p< 0.01). Conclusions: The longitudinal changes in serum SP-D levels during an AECOPD episode suggest that SP-D may be a potential systemic biomarker for COPD exacerbation. The correlation of serum SP-D levels with the BODE index suggests that circulating SP-Ds can reflect the overall severity of SCOPD. Show more

Keywords: BODE index, COPD, exacerbation, surfactant protein D (SP-D), airflow limitation

DOI: 10.3233/DMA-2011-0887

Citation: Disease Markers, vol. 32, no. 5, pp. 281-287, 2012

Authors: Devanoorkar, Archana | Dwarakanath, C.D. | Gundanavar, Gayatri | Kathariya, Rahul | Patil, Sudhir R

Article Type: Research Article

Abstract: Background: Resistin and adiponectin are the adipokines secreted by adipocytes and various inflammatory cells. These adipokines are known to play an important role in insulin resistance. The aim of this study was to determine the serum resistin levels in periodontal health and disease and also, to determine the effect of nonsurgical periodontal therapy on its levels. Methods: A total of 40 patients (20 Males and 20 Females; age range 20–50 years) participated in the study. Subjects were categorized …as healthy (group 1; Controls) and chronic periodontitis (group 2; Study) groups based on their periodontal status. Periodontal parameters (Plaque index (PI), Gingival index (GI), Bleeding index (BI), Probing pocket depth (PPD), Clinical attachment loss (CAL)) together with serum resistin levels were assessed at baseline and between 6–8 weeks following nonsurgical periodontal therapy for subjects in group~2 and only at baseline in group 1. Sera were tested in duplicate (single run), and the results were averaged. Results: Study group showed higher (1.89 ± 1.83 ng/ml) serum resistin levels, compared to control group (1.35 ± 0.70 ng/ml). However, this difference was not statistically significant (P=0.227). Also, resistin levels decreased following nonsurgical periodontal therapy but, this decrease failed to show any statistical significance, with pretreatment levels being 1.89 ± 1.83 ng/ml and post treatment levels being 1.59 ± 1.01 ng/ml (P=0.386). Conclusion: Observations of the present study revealed that there was not much difference in the serum resistin levels between the cases and the controls. Also the decrease in the resistin levels following nonsurgical periodontal therapy did not show any statistical significance. Show more

Keywords: Biomarkers, adipocytes, resistin, serum, chronic periodontitis, insulin resistance

DOI: 10.3233/DMA-2012-0891

Citation: Disease Markers, vol. 32, no. 5, pp. 289-294, 2012

Authors: Driss, Adel | Wilson, Nana O. | Mason, Karlene | Hyacinth, Hyacinth I. | Hibbert, Jacqueline M. | Serjeant, Graham R. | Stiles, Jonathan K.

Article Type: Research Article

Abstract: Acute splenic sequestration (ASS) and chronic hypersplenism are common features of homozygous sickle cell (SS) disease in the first 5 years of life affecting one-third of subjects in the Jamaican Cohort Study. The risk factors are largely unknown and the current study explores a possible role of genetic factors. We have explored these in subjects who received splenectomy in the management of ASS (n=8) or chronic hypersplenism (n=9) along with age, gender, and genotype matched controls …using Luminex Technology to assess 42 human cytokines/chemokines, including IL-1α and CXCL10 (IP-10). Levels of IL-1α (p=0.008) and CXCL10 (p=0.009) were significantly elevated in patients treated by splenectomy compared with the control group. Levels of IL-1α were significantly higher in those with a history of ASS compared with matched normal controls (p=0.028) but not in those treated for hypersplenism (p=0.093). Furthermore, several significant differences were found in the median ratios of some cytokine biomarkers between the splenectomized group and the normal controls. These observations are consistent with acute splenic sequestration having a distinct phenotype which may be helpful in predicting those at risk of this complication and suggest that the mechanism of these differences merit further study. Show more

Keywords: Sickle cell anemia, biomarkers, splenectomy, spleen, interleukins, cytokine, acute splenic sequestration, chronic hypersplenism

DOI: 10.3233/DMA-2011-0888

Citation: Disease Markers, vol. 32, no. 5, pp. 295-300, 2012

Authors: Birbian, Niti | Singh, Jagtar | Jindal, Surinder Kumar | Joshi, Amit | Batra, Navneet | Singla, Neha

Article Type: Research Article

Abstract: Background: High serum MBL level as well as polymorphisms in the mannose-binding lectin 2 (MBL2) gene resulting in MBL deficiency are involved in the mechanism of a number of non-infectious diseases such as asthma, conferring either risk or protection in different population studies. MBL being the first reactant of the MBL pathway is also a major determinant of the fate of the anaphylatoxins such as C3a and C5a, which are also pro-inflammatory mediators. The MBL2 gene …polymorphisms thus control the serum levels of MBL as well as C3a and C5a. Objective: This is the first case-control study conducted in India, investigating the role of MBL2 codon 54 A/B polymorphism in asthma pathogenesis. Methods: A case-control study was performed with a total of 992 adult subjects, including 410 adult asthmatics and 582 healthy controls from regions of North India. The MBL2 codon 54 A/B polymorphism was genotyped by PCR-RFLP. Results: Statistical analysis for the codon 54 polymorphism revealed that the wild (A) allele was significantly associated with asthma with OR=1.9, 95% CI (1.4–2.4), and p< 0.001. Conclusion: The MBL2 codon 54 A/B polymorphism is significantly associated with asthma and its phenotypic traits as the wild (A/A) genotype confers a significant risk towards the disease in the studied North Indian population. Show more

Keywords: Asthma, mannose-binding lectin 2 (MBL2), anaphylatoxins, C3a, C5a, MBL2 codon 54 A/B polymorphism, North Indian population

DOI: 10.3233/DMA-2012-0892

Citation: Disease Markers, vol. 32, no. 5, pp. 301-308, 2012

Authors: Javidroozi, Mazyar | Zucker, Stanley | Chen, Wen-Tien

Article Type: Research Article

Abstract: Seprase (fibroblast activation protein α) has been examined as an invasion biomarker for various types of solid tumors. We studied whether plasma levels of seprase and homologous protease, DPP4 in cancer might serve as tumor biomarkers. We developed sensitive and specific Enzyme-Linked Immunosorbent Assays (ELISAs) to measure these proteases. In 747 plasma samples (from 139 healthy volunteers and 561 cancer patients), mean seprase and DPP4 levels were 0.51 ± 0.30 and 4.65 ± 6.37 μg/mL, respectively, …and they were correlated with each other (R^{2} = 0.382). Plasma DPP4 and seprase levels were significantly lower in cancer patients compared with healthy subjects (4.38 versus 5.65 μg/mL, p< 0.001 for DPP4; 0.46 versus 0.66 μg/mL, p< 0.001 for seprase). Higher DPP4 was associated with better survival in all cancers combined (n=346) as well as in head and neck malignancies (n=38). Higher seprase was associated with better survival in all non-metastatic cancers combined (n=151) as well as head and neck malignancies, but worse survival in colorectal cancers (n=47). This study demonstrates that in contrast to the high expression in solid tumors, plasma concentrations of seprase and DPP4 are reduced and correlate inversely with survival in most types of cancer, suggesting that these circulating proteases represent useful tumor markers. Show more

Keywords: Seprase, fibroblast activation protein α (FAP-α), DPP4, prognosis, cancer, tumor marker

DOI: 10.3233/DMA-2011-0889

Citation: Disease Markers, vol. 32, no. 5, pp. 309-320, 2012

Authors: Yu, Fang | Jiang, Qingping | Zhou, Ying | Yang, Zhen | Yu, Xiaoli | Wang, Hao | Liu, Zhen | Wang, Lijing | Fang, Weiyi | Guo, Suiqun

Article Type: Research Article

Abstract: Aims and background: The aim of the present study was to analyze the expression of matrix metalloproteinase-9 (MMP9) in endometrial cancer and its correlation with clinicopathologic features in Chinese patients, including the survival of patients with endometrial cancer. Methods: Using immunohistochemistry analysis, we analyzed MMP9 protein expression in clinicopathologically characterized 128 endometrial cancer (EC) cases with age ranging from 30 to 85 years (median=51.6 years) and 30 endometrial atypical hyperplasia (EAH) and 30 normal …endometrium (NE). Cases with greater than or equal to 6 and less than 6 with the score value of cytoplasmic MMP9 immunostaining were regarded as high expression and low expression, respectively. The relationship between the expression levels of MMP9 and clinical features was analyzed in EC cases. Results: Immunohistochemical analysis revealed that the protein expression of MMP9 detected in EC tissues was higher than that in the EAH tissues and NE tissues (P=0.006). In addition, high levels of MMP9 protein were positively correlated with the status of lymph node metastasis (P=0.044) and the histopathological grade (P<0.05) of EC patients. Patients with higher MMP9 expression did not correlate with EC patients' clinical outcome in China. Multivariate analysis suggested that status of lymph node metastasis and depth of myometrial invasion, but not MMP9 expression level, were significantly correlated with patients' survival. Conclusion: MMP9 is highly expressed in ECs and correlates with the progression of ECs, but not be helpful in predicting the prognosis of EC patients. Show more

Keywords: Matrix metalloproteinase-9, endometrial cancer, Chinese patients

DOI: 10.3233/DMA-2011-0886

Citation: Disease Markers, vol. 32, no. 5, pp. 321-327, 2012

Authors: Ciebiada, Maciej | Górski, Paweł | Antczak, Adam

Article Type: Research Article

Abstract: Although eicosanoids are involved in lung carcinogenesis they were poorly investigated in exhaled breath condensate (EBC) and bronchoalveolar lavage fluid (BALf) in patients with primary lung cancer. In this study 17 patients with diagnosed non-small cell lung cancer, 10 healthy smokers and 12 healthy nonsmokers were included. The levels of cys-LTs, 8-isoprostane, LTB4 and PGE2 were measured before any treatment in the EBC of all patients and in BALf of patients with lung cancer by enzyme …linked immunosorbent assay. 8-isoprostane, LTB4, cys-LTs and PGE2 were detectable in the EBC and BALf. There were no significant differences between healthy smokers and nonsmokers in concentrations of all measured mediators. Compared with both healthy controls, patients with diagnosed lung cancer displayed higher concentrations of cys-LTs (p< 0.05) and LTB4 (p < 0.05) in EBC. In patients with lung cancer, the mean concentrations of all measured mediators were significantly higher in BALf compared with EBC and there was a significant, positive correlation between concentration of cys-LTs, LTB_{4} and 8-isoprostane in BALf and their concentrations in the EBC (r=0.64, p < 0.05, r=0.59, p< 0.05, r=0.53, p< 0.05 respectively). Since cys-LT, LTB4 and 8-isoprostane concentrations in EBC from patients with lung cancer reflect their concentrations in BALf, they may serve as a possible non-invasive method to monitor the disease and to assess the effectiveness of therapy. Show more

Keywords: Exhaled breath condensate, broncholaveolar lavage, lung cancer, leukotrienes, prostaglandins, early detection

DOI: 10.3233/DMA-2011-0890

Citation: Disease Markers, vol. 32, no. 5, pp. 329-335, 2012