Application of sparse linear discriminant analysis and elastic net for diagnosis of IgA nephropathy: statistical and biological viewpoints

Background: IgA nephropathy [IgAN] is the most common primary glomerulonephritis diagnosed based on renal biopsy. Mesangial IgA deposits along with the proliferation of mesangial cells are the histologic hallmark of IgAN. Non-invasive diagnostic tools may help to prompt diagnosis and therapy. The discovery of potential and reliable urinary biomarkers for diagnosis of IgAN depends on applying robust and suitable models. Applying two multivariate modeling methods on a urine proteomic dataset were obtained from IgAN patients, and comparison of the results of these methods were the purpose of this study

Methods: Two models were constructed for urinary protein profiles of 13 patients and 8 healthy individuals, based on sparse linear discriminant analysis [SLDA] and elastic net [EN] regression methods. A panel of selected biomarkers with the best coefficients were proposed and further analyzed for biological relevance using functional annotation and pathway analysis

Results: Transferrin, a1-antitrypsin, and albumin fragments were the most important up-regulated biomarkers, while fibulin-5, YIP1 family member 3, prasoposin, and osteopontin were the most important down-regulated biomarkers. Pathway analysis revealed that complement and coagulation cascades and extracellular matrix-receptor interaction pathways impaired in the pathogenesis of IgAN

Conclusion: SLDA and EN had an equal importance for diagnosis of IgAN and were useful methods for exploring and processing proteomic data. In addition, the suggested biomarkers are reliable candidates for further validation to non-invasive diagnose of IgAN based on urine examination

Seroprevalence of hepatitis a in hemodialysis patient candidate for kidney transplant than forty years

Background: Hepatitis A is a common infection during childhood, especially in developing countries. It can cause severe complications in immunocompromised patients. Due to the increasing number of kidney transplants in the country and epidemiologic shift of HAV which was observed in previous studies, we're going to evaluate the seroprevalence of hepatitis A in hemodialysis patients less than forty years serving kidney transplant candidates to follow vaccination policy for them

Materials and Methods: In a cross sectional study during 2014-2015 hepatitis A antibody levels in hemodialysis patients less than forty years in kidney transplant candidates examined in 12 hospitals in Tehran, Iran. Their serums were tested for anti HAV IgM and IgG by ELISA kits

Results: Hepatitis A virus antibody was positive in 66 [72.5%] of 91 patients. The prevalence of HAV was 0% at the range of younger than 20 and 45% in under 25 years age group. This significantly increased prevalence by increasing the age, and there was according to epidemiological shifts which were shown in other studies

Conclusion: Due to the availability of vaccine and hepatitis severe complications in immunocompromised individuals, as well as a low prevalence of positive serology in individuals under 25 years, it seems the check of antibodies in patients undergoing kidney transplantation and vaccination in seronegative persons is a logical

Evaluating the prevalence of the epidermal growth factor receptor in transitional cell carcinoma of bladder and its relationship with other prognostic factors

Background: The most common malignancy in the urinary system has been bladder cancer and the most predominant histologic subtype has been transitional cell carcinoma [TCC]. There were many molecular risk factors, related with poor prognosis. One of these factors was expression of epidermal growth factor receptor [EGFR]

Objectives: The aim of this study was to evaluate the prevalence of the epidermal growth factor receptor in transitional cell carcinoma of bladder and its relationship with other prognostic factors

Patients and Methods: This analytic descriptive study has performed with 61 patients with TCC of bladder after radical cystectomy whom have been hospitalized in Labbafinejad hospital in Tehran, Iran between 2007 and 2010. We have used Chi-square and t-test to analyze our data samples

Results: Records of 61 patients have studied. Fifty three of the total samples were positive for EGFR expression [86.9%]. Fifty samples of these fifty-three belonged to men and three others were women's samples [P = 0.46]. Among the group with EGFR expression the results were as follows: 25 patients [47.2%] were 60 years old or less and 28 patients [52.8%] were older than 60 [P = 0.023], 16 patients [30.2%] had invasion to lamina properia, and the rest of them had invasion to deeper layers [P = 0.56]. For most patients we could not determine the invasion of tumoral cells into the lymph nodes [Nx] [P = 0.067]. Thirty four patients [64.2%] had not lymphovascular invasion [P = 0.44] and in forty three of patients [81.1%], perineural invasion have not seen [P = 0.23]. Finally, 36 patients [67.9%] were grade 3 [P = 0.27]

Conclusions: In this study we have concluded that most patients had EGFR positive expression. Also, except for the age, there was not any significant relation between expression of EGFR and the other prognostic factors such as, gender, invasion of the tumor into the layers, involving the lymph nodes, lymphovascular or perineural invasion, and grading

Effects of stem cells and granulocyte colony stimulating factor in reperfusion injury

Bone marrow-derived stem cells have a potential capacity to differentiate and accelerate recovery in injured sites of body. Also, factors like granulocyte colony stimulating factor [GCSF] can promote their mobilization to the injured sites. We aimed to investigate the role of GCSF as an alternative therapeutic option instead of mesenchymal stem cells [MSCs] in reperfusion injury. Twenty-nine rats with induced reperfusion injury were divided into 3 groups to receive MSC, GCSF, or nothing [control]. Kidney function was assessed by blood urea nitrogen and serum creatinine levels. Histological grading was performed to evaluate the extent of tubular injury and the rate of recovery. All the rats reached recovery after 14 days. Rats in the MSC group reached early functional and histological recovery compared to the controls on the 7th day of the study [P = .01 and P = .02, respectively]. Compared to the control group, the GCSF group showed a more significant histological recovery on the 7th day [P = .04], but kidney function was ameliorated on the 14th day [P = .04]. Both the GCSF and control groups had a significant number of CD34+ cells, which were detected by flow cytometry on the 7th day after reperfusion injury. We found therapeutic effects following administration of both MSC and GCSF which was more evident with MSC in the setting of reperfusion injury. More investigation is required to find optimal time, dose, and route of administration as well as other possible contributing factors

Expression of survivin and its spliced variants in bladder tumors as a potential prognostic marker

Survivin, a novel inhibitor of apoptosis, is re-expressed in a vast majority of human cancers and is widely considered as a diagnostic marker of cancer. Survivin protein regulates both cell division and apoptosis. There are at least 5 sliced variants of the gene with different subcellular localization and anti-apoptotic property. We examined the expression pattern of survivin and its 2 sliced variants, survivin-delta EX 3 and survivin-2B, and their prognostic values in archival collections of formalin-fixed paraffin-embedded samples of bladder tumors. Total RNA from formalin-fixed paraffin embedded samples [51 samples from 30 patients with bladder cancer and 5-year follow-up] were extracted and analyzed by semiquantitative reverse transcriptase polymerase chain reaction technique. Tissue distribution and subcellular localization of survivin protein in tumor tissues was also examined by immunohistochemistry. The expression of survivin, survivin-delta Ex3, and surviving-2B were detected in 66.6%, 47.8%, and 54.7% of the specimens, respectively. The expression of survivin and survivin-delta Ex3 were preferentially elevated in tumours with higher grades, whereas survivin-2B expression was lower in high-grade tumors [P=.04]. A reverse correlation was observed between survivin-2B expression and high-grade tumors. Immunohistochemistry results also confirmed the nuclear localization of survivin protein within tumoral cells. We were successful in detecting the expression of survivin and its variants in formalin-fixed paraffin-embedded bladder samples. Furthermore, our results showed that overexpression of survivin and survivin-delta Ex3 in bladder tumors correlates with poor prognosis of bladder cancer. We suggest that survivin and its variants are suitable prognostic markers of bladder tumors

established rat model of inducing reversible acute tubular necrosis

Acute tubular necrosis [ATN] is a challenging problem that still requires to be studied in animal models. Our aim was to prepare an established experimental model of inducing reversible ATN in rats by determining the optimum duration of ischemia induction to the kidney. Twenty-four hour after nephrectomy of the right kidney and clamping the pedicle of the left kidney for durations ranging from 10 to 55 minutes, the kidney function and the histologic changes were evaluated. Accordingly, the optimum duration of clamping was determined and in the next step, it was considered for induction of reversible ATN in another group of rats. This group was followed up for 14 days and the pathologic course and function of the kidney were observed. Reversible ATN developed by 47-minute clamping of the renal pedicle. Blood urea nitrogen and serum creatinine levels were elevated up to threefold within 24 hours after the induction of ischemia and they decreased to their reference ranges after 12 and 6 days, respectively. In the histologic study of the kidneys, the least extend of injury was noted by the 14th day following the ATN induction. Even on the 14th day of the follow-up, some signs of ATN remained indicating that the tissue regeneration was not complete yet. To integrate the experimental models of ATN, a rat model with 47-minute clamping of the renal pedicle for induction of ischemia seems appropriate. The resultant ATN remains for a long duration, while kidney function is alleviated

Evaluating the expression of survivin gene as a specific tumor marker for prognosis of bladder cancer

Inhibition of apoptosis may favor the onset and progression of cancer. Survivin is an inhibitor of apoptosis that has been considered as a potential marker for diagnostic and/or prognostic of bladder cancer. The survivin protein regulates both cell division and cell death and its overexpressed in the vast majority of human cancers. In this study, the expression pattern and potential prognostic value of survivin was assessed in Fomalin-Fixed Paraffin-Embedded [FFPE] samples of bladder tumor. FFPE samples, from patients with a well-known five-year survival record, were assessed by semi-quantitative RT-PCR technique. 51 samples from 30 patients were analyzed on the basis of Survivin expression. Tissue distribution and subcellular localization of survivin protein in tumor tissues was also examined by immunohistochemistry [IHC]. The expression of survivin in 66.6% of the samples, with an increase of expression in higher grades of tumor. Furthermore, survivin was overexpressed in 2[nd] and 3[rd] recurrences of the same patients. Also, with the increased malignancy and accordingly increase expression of surviving, the overall 5-year survival rate of patients was significantly declined [P=0.036]. IHC results also localized a nuclear localization for Survivin protein in tumor tissues. In coclusion, we were able to detect the expression of survivin in FFPE samples of bladder tissues, at the level of mRNA and protein and find a correlation between the level of Survivin expression and the degree of malignancy of the tumors. Our findings introduce Survivin as a suitable prognostic marker for predicting the bladder tumors

Correlation between size of renal cell carcinoma and its grade, stage, and histological subtype

The aim of this study was to determine the correlation between histological subtype, size, grade, and stage of the kidney tumors and to investigate whether a correlation exists between the size of the kidney tumor and its behavior. Between 1996 and 2004, we had 212 patients with radical or partial nephrectomy due to a kidney tumor at Shaheed Labbafmejad Medical Center. Their pathologic blocks were re-evaluated with consideration of their tumor size and pathologic features. Of 212 pathologic blocks, 17 [8%] were benign and 195 [92%] were malignant masses including 179 renal cell carcinoma [RCC] tumors. Malignant tumors were slightly greater compared with the benign ones [P = .10]. There was no significant relation between the size of tumor and the histological subtype. Significant relations between the size of the kidney tumor and the nuclear grade [P = .007], clinical symptoms [P = .02], and extracapsular extension [P < .001] were observed. In smaller RCC tumors [< 4 cm], extracapsular extension [stages T3 and T4] was rare [1 in 29]. However, smaller RCC tumors were not significantly different from those larger than 4 cm regarding the nuclear grade, symptoms, and histological subtypes. Tumor size is not an independent predictor for the histological subtype of the tumors; however, larger malignant tumors may have higher grades, higher stages, and clinical symptoms

Prediction of prostatic involvement by transitional cell carcinoma of the bladder using pathologic characteristics of the bladder tumor

The aim of this prospective study is to determine the relationship between the pathologic characteristics of the transitional cell carcinoma [TCC] of the bladder and prostatic involvement. Sixty men with bladder TCC underwent standard radical cystoprostatectomy and were enrolled in this study. Vascular and perineural invasion, maximum diameter of the tumor, presence of carcinoma in situ, distance between the tumor and the bladder neck, and grade and local stage of the tumor were recorded and their relation with prostatic involvement was studied. In addition, hydronephrosis and age of the patients were included in the analysis. The mean age of the patients was 63.9 +/- 11.1 years. Of 60 men included in this study, 15 patients were found to have prostatic involvement with TCC [25%]. Univariate statistical analyses showed that vascular invasion and the distance between the tumor and the bladder neck were significantly related to the prostatic involvement [P = .007; P < .001]. But, in the logistic regression, only the distance between the tumor and the bladder neck was significantly related to the prostatic involvement [P = .001]. This study suggests that the probability of prostatic involvement in patients with bladder TCC tumors near the bladder neck is high. Prostate-sparing or capsule-sparing cystectomy should be avoided in such patients