Search

Immunogenetic diagnostics allows identifying individuals with a high degree of risk of developing certain diseases, and associative connections with the cytokine link of immunity to expand ideas about their immunogenesis to determine prognostic markers and its course. The objective: to evaluate the associative relationships between the HLA-phenotype of patients with pathology of the genitourinary system and the cytokine link in order to determine the role in immunogenesis, improve prognosis and treatment. Materials and methods. The study was carried out within the framework of the NDP "Evaluate the effectiveness and safety of various methods of treatment of men suffering from chronic calculous prostatitis". The distribution of HLA-antigens in 464 patients with chronic cystitis (ChC), including proliferative cystitis (ChPC) and chronic prostatitis (ChP), sclerosis (SP), benign hyperplasia (HP) and prostate cancer (PC) was studied using the standard microlymphocytotoxic test (Terasaki). The reference group consisted of 350 healthy donors. Relative risk (RR≥2) and absolute (attributive) risk of the disease were determined. Levels of TNF-α, IL-18, MCP-1, IL-17, IL-4, VEGF were studied in blood serum by ELISA on the SunRise TouchScreen analyzer (Invitrogen, USA; Vector Best, Ukraine). Results. The connection of the most common diseases of the genitourinary system with certain histocompatibility antigens (RR≥2) is shown. The causal role of HLA with a reliable absolute risk of developing chronic cystitis (including proliferative) (A10, B14, B16), as well as chronic prostatitis (A24, B8, B52), prostate sclerosis (A24, A28), benign hyperplasia (A29, B38) and prostate cancer (A25, A29, B40, B44, B49) was determined. Protective antigens - A25, A26, B5, B14, B16, B17 for chronic prostatitis, as well as A10, B15, B17 for sclerosis, A9, A10, B17 for bening prostatic hyperplasia and A1, B5, B13, B15 for-prostate cancer. Associations of high production of cytokines were found for pro-inflammatory: TNF-α with HLA-A10, A11, A28, B14, B44; IL-18 - A10 and A24; MSR-1 - A28, B8, B41; IL-17 - A24, A28, B14; anti-inflammatory IL-4 - A24 and A28 (A2, B8, B14 are associated with a lower level of the production, and A10 determines the tendency); and VEGF growth factor - A9, A25 and B8. Conclusions. Associations of predictors of pathology and features of cytokines negative for its course determine additional risks for patients and act as markers for prediction and individualization of treatment. [ABSTRACT FROM AUTHOR]

Copyright of Gaceta Médica de Caracas is the property of Academia Nacional de Medicina and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aims: The present study aimed to evaluate and analyze the postoperative complications in patients with open urethroplasty. Instrument & Methods: In this study, the clinical data of the medical histories of 147 patients with long urethral strictures and obliterations were retrospectively evaluated. All patients were male and between 13 and 85 years old. The observation lasted from 6 to 18 months. Patients were examined under the accepted standards of providing urological care. To evaluate the results and postoperative complications of surgical corrections of urethral strictures and obliterations, all patients were divided into three groups. The difference between the mean values was analyzed using the student t-test. Findings: Regardless of the length and etiology of urethral stricture, reconstructive surgeries using a skin-fascial flap were likely to have a higher rate of recurrence (56%) than patients who underwent urethra-urethra- or urethra-prostate anastomosis (27%) and buccal urethral anastomosis. Out of 147 patients who underwent surgery to correct urethral stricture and obstruction, 84% had urethra-urethra- or urethra-prostate anastomosis. Conclusion: During the patient's initial request for medical help, it is important to conduct a maximum examination to choose a rational method of surgical treatment, according to modern standards, with a minimum probability of recurrence. However, early and late postoperative complications and recurrence after surgical treatment are not prevented. [ABSTRACT FROM AUTHOR]

The article dedicate to the problem of failure of extracorporeal shockwave lithotripsy in patients with ureterolithiasis and reveal the changes which appear in the ureter in the location of the stone. The aim. Analysis of the results of treatment in patients, suffering ureteric stones, using the ureterolithotripsy procedure after failure extracorporeal shockwave lithotripsy. Materials and methods. In 137 patients with ureteric stones, whom ureterolithotripsy procedure after failure extracorporeal shockwave lithotripsy was conducted, the symptoms of the disease, the diagnostic methods value, efficacy of surgical treatment and reasons of the failure of previous method of treatment were analyzed. Results. In 135 patients endoscopic removal of stones has been succeeded, in 2 patients because of total obliteration of the ureter, uretero-ureteral anastomosis has been performed. If the symptoms, with are characteristic of ureterolithiasis, persists up to one week stones don't cause significant macroscopic changes to the ureter wall. If the stone persists in the ureter longer than a week we identified local appearing of oedema. Long-term (more than two months) ureteric stone persistence increase the risk of intramucosal «ingrowth» of the calculi greatly. Conclusion. The URS and ESWL are high effective and minimal invasive methods of surgical intervention for patients with ureterolithiasis, guaranteeing high level of postoperative «stone free rate». Prolongation of the stone insertion time in the ureter causes the ureteric wall changes, complicating performance of minimal invasive interventions (ureterolithotripsy and extracorporeal shock-wave lithotripsy) and reduce its efficacy. [ABSTRACT FROM AUTHOR]

During the 25-year period subsequent to the Chernobyl accident, the morbidity of malignant renal tumors in Ukraine has increased from 4.7 to 10.7 per 100,000 of the total population. Recent studies of our group have shown that increases in morbidity, aggressiveness, and proliferative activity of renal cell carcinomas (RCCs), especially clear-cell renal cell carcinoma (CCRCC), in Ukrainian patients continuously inhabiting the radio-contaminated areas could be explained by specific molecular changes influenced by the so-called 'chronic persistent low-dose ionizing radiation' (CPLDIR) exposure. This study aimed to examine the role of angiogenesis in CCRCC carcinogenesis associated with CPLDIR in patients living more than 20 years in cesium 137 (Cs) contaminated areas after the Chernobyl accident in Ukraine. Paraffin-embedded specimens of 106 CCRCs were studied: Control cases were 18 tumors from Spanish patients (group 1), 25 tumors from Ukrainian patients from so-called clean areas without known radio-contamination (group 2), and 63 tumors from Ukrainian patients from radio-contaminated areas (group 3). For intratumoral microvessel density (MVD) determination, anti-CD31 antibody was used. A computerized image analysis program was used to quantitatively calculate the vascular density. Seventy-three percent of group 3 and 72 % of group 2 CCRCCs displayed the highest MVD. A striking increase in MVD was seen in group 3 CCRCCs, in comparison with groups 1 and 2 ( p < 0.001). The majority of the hot spot vessels in group 3 was poorly differentiated. Moreover, MVD values for total vessels as well as for capillaries and tumor grade were strongly correlated. When we compared only tumor-node-metastasis tumor stages I and II, the differences remained statistically significant ( p < 0.1). The ratio of the average total vessels and capillaries in the Ukrainian groups combined was 1.65:1 in comparison to the Spanish group. Our results provide evidence that CPLDIR exposure increases MVD (particularly capillary) in CCRCCs and is associated with a higher histological grade. [ABSTRACT FROM AUTHOR]

We determined whether ubiquitylation and sumoylation processes are involved in conventional renal cell carcinogenesis associated with chronic, long-term, persistent low doses of ionizing radiation (IR) in patients living for more than 20 years in cesium-137 ((137)Cs)-contaminated areas after the Chernobyl accident in Ukraine. To this end, we assessed the immunohistochemical expression of ubiquitin (Ub), SUMO1, SUMO E2 conjugating enzyme Ubc9, and the cell cycle regulators p53, mdm2, and p14(ARF) in 38 conventional renal cell carcinomas from Ukrainian patients with different degrees of radiation exposure after the Chernobyl accident. As control cases, 18 conventional renal carcinoma (cRCC) tissues from a Spanish cohort were analyzed. No significant differences between the Ukrainian and Spanish groups were found regarding Ub overexpression, although being higher in the Ukrainian cases. Furthermore, this expression was inversely associated with SUMO1 and Ubc9, with no correlation with tumor nuclear grade. There was also a direct relationship between Ubc9 and inflammatory response. These findings do not allow us to consider the immunohistochemical expression of ubiquitylation and sumoylation as valuable markers for discriminating the effects of long-term, low-dose IR exposure in cRCC carcinogenesis. [ABSTRACT FROM AUTHOR]

Urinary bladder urothelium as well as cells in the microenvironment of lamina propria (endothelial elements, fibroblasts and lymphocytes) demonstrate a number of responses to chronic persistent long-term, low-dose ionizing radiation (IR). Thus, oxidative stress occurs, accompanied by up-regulation of at least two signaling pathways (p38 mitogen-activated protein kinase and nuclear factor-κB cascades) and activation of growth factor receptors, in the bladder urothelium of people living in Cesium 137-contaminated areas of Ukraine, resulting in chronic inflammation and the development of proliferative atypical cystitis, so-called Chernobyl cystitis, which is considered a possible pre-neoplastic condition in humans. Furthermore, significant alterations in regulation of cell cycle transitions are associated with increased cell proliferation, along with up-regulated ubiquitination and sumoylation processes as well as inefficient DNA repair (base and nucleotide excision repair pathways) in the affected urothelium. The microenvironmental changes induced by chronic long-term, low-dose IR also appear to promote angiogenesis and remodeling of the extracellular matrix that could facilitate invasion as well as progression of pre-existing initiated cells to malignancy. Based on the available findings, new strategies have been developed for predicting and treatment of Chernobyl cystitis—a first step in urinary bladder carcinogenesis in humans. [ABSTRACT FROM PUBLISHER]

The article describes discusses a study on the glucose-induced production of recombinant proteins in Hansenula polymorpha (H. polymorpha) mutants deficient in glucose repression. H. polymorpha is a methyltropic yeast which depends on the regulated promoter for gene encoding peroxisomal enzyme alcohol oxidase (PMOX). The study isolated the H. polymorpha mutants deficient in glucose repression of PMOX because of an impaired HpGCR1 gene. The resulting mutants showed marked defects in PMOX regulation in the hexoses and xylose.

The present study was carried out in order to examine the molecular status of selected growth factor receptors (GFR) in urinary bladder lesions, recently described by our group as representing ‘Chernobyl cystitis’. Fibroblast growth factor receptor 3 (FGFR3), epidermal growth factor receptor 1 (EGFR1), EGFR2 neu (a member of the same family), p53 and Raf-1 serine/threonine kinase expression were evaluated immunohistochemically in urinary bladder biopsies from 22 men with benign prostate hyperplasia (group 1). For comparison, 16 men with benign prostate hyperplasia and five women with chronic cystitis living in non-radio-contaminated areas of the country were also investigated as controls (group 2). Additionally, 14 patients with dysplasia, carcinoma in situ (CIS) and primary urothelial carcinoma (UC) operated before the Chernobyl accident as well as 23 patients with UC living in the radio-contaminated areas were included as pre- and post-Chernobyl UC groups 1 and 2, respectively. Chronic proliferative atypical cystitis (‘Chernobyl cystitis’) was observed in group 1 patients. Foci of dysplasia and CIS were found in 22 (100%) and 19 (86%) of the 22 cases, respectively; moreover, two small UC were also detected. Elevated levels of FGFR3, EGFR2/ neu, p53 and to a lesser extent EGFR1 and Raf-1 expression in the urothelial dysplasia and CIS were evident for patients of group 1. Statistically significant differences in immunohistochemical scores for FGFR3, EGFR1, p53 and Raf-1 were observed between groups 1 and 2 and between group 1 and the post-Chernobyl UC group 2, where a change in expression of EGFR2/ neu was also noted. A significant decrease in FGFR3 expression in additional pre-Chernobyl UC group 1 with dysplasia, CIS and UC compared with group 1 Chernobyl cystitis cases was detected. Our findings suggest that FGFR and EGFR signaling pathways, associated with p53 and Raf-1 activation, may contribute to multistage urothelial carcinogenesis caused by irradiation, through autocrine or paracrine growth stimulation. ( Cancer Sci 2006; 97: 1168–1174) [ABSTRACT FROM AUTHOR]

The present study was carried out in order to examine molecular alterations of extracellular matrix (ECM), associated with cell-cell communication in conventional (clear-cell) renal cell carcinomas (cRCCs) influenced by persistent long-term, low-dose ionizing radiation (IR) exposure to patients living more than 19 years after the Chernobyl accident in Cesium 137 (137Cs)-contaminated areas of Ukraine. The ECM major components such as fibronectin, laminin, E-cadherin/beta-catenin complexes and p53 tumor suppressor gene protein, and transforming growth factor beta 1 (TGF-beta1) were immunohistochemically (IHC) evaluated in cRCCs from 59 Ukrainian patients, which represented 18 patients living in non-contaminated areas and 41 patients from 137Cs-contaminated areas. In contrast, a control group of 19 Spanish patients with analogue tumors were also investigated. For IHC evaluation, a tissue microarray technique was used. Decrease or loss and abnormal distribution of fibronectin, laminin, E-cadherin/beta-catenin complexes accompanied by elevated levels of p53 and TGF-beta1 were detected in the Ukrainian cRCCs from 137Cs-contaminated areas with statistically significant differences. Thus, our study suggests that chronic long-term, low-dose IR exposure might result in global remodeling of ECM components of the cRCCs with disruption in peri-epithelial stroma and epithelial basement membranes. [ABSTRACT FROM AUTHOR]

This study examines the molecular pathways of cell–cell communication in chronic inflammatory processes associated with long-term low-dose urinary bladder exposure to ionizing radiation in people without major disease living more than 19 years in radio-contaminated areas of Ukraine after the Chernobyl accident. Patterns of components of the E-cadherin/β-catenin complex, and transforming growth factor-β1 (TGF-β1) and inducible nitric oxide synthase (iNOS) expression were immunohistochemically evaluated in urinary bladder biopsies from 52 males with benign prostate hyperplasia and 8 females with chronic cystitis (group 1). For comparison, 25 males and 6 females living in non-contaminated areas of Ukraine were also investigated (group 2). Fourteen patients with primary urothelial carcinomas, which were operated on before the Chernobyl accident, were included as a carcinoma group. Chronic proliferative atypical cystitis (‘Chernobyl cystitis’) was observed in group 1 patients. Foci of dysplasia and carcinoma in situ were found in 51 (85%) and 34 (57%) of the 60 cases, respectively. Chronic cystitis with areas of dysplasia was detected in only 4 (13%) cases of 31 group 2 patients. Statistically significant differences in immunohistochemical scores for TGF-β1 in the urothelium and lamina propria, iNOS in the urothelium and both β-catenin and E-cadherin in the cytoplasm were observed between groups 1 and 2 with marked expression in group 1. Furthermore, TGF-β1 overexpression and alteration in E-cadherin/β-catenin complexes in bladder urothelium might play a crucial role in urinary bladder carcinogenesis in humans exposed to long-term low-dose ionizing radiation. ( Cancer Sci 2005) [ABSTRACT FROM AUTHOR]

Previous studies have shown that during the period subsequent to the Chernobyl accident, increases in morbidity, aggressivity and proliferative activity of renal-cell carcinomas (RCCs) in Ukrainian patients were recognized. The present paper describes the molecular alterations of those tumor suppressor genes located on chromosome 9p21 ( INK4a/ARF locus and p15 INK4B) in 26 primary renal-cell epithelial tumors from patients with different degrees of radiation exposure after the Chernobyl accident in Ukraine. Radiometric measurement of Cesium 137 ( 137Cs) was conducted with 1-day urine from all patients before surgery. Our results demonstrate that RCCs from patients living in the radio-contaminated areas showed aberrant hypermethylation of p14 ARF and p16 INK4A genes, associated with increased p38MAPK, p14 ARF, mdm2, cyclinD1 and Ki67 protein expression levels. Present findings show the possibility that chronic long-term low-dose radiation activates the INK4a/ARF locus, targeted by activation of the p38MAPK cascade. These actions could lead to disruptions and loss of cell cycle checkpoints and, thereby, to cellular transformation. [ABSTRACT FROM AUTHOR]

Previous studies have shown that during the period subsequent to the Chernobyl accident, increases in morbidity, aggressivity and proliferative activity of renal-cell carcinomas (RCCs) in Ukrainian patients were recognized. The present paper describes the molecular alterations of those tumor suppressor genes located on chromosome 9p21 ( INK4a/ARF locus and p15(INK4B)) in 26 primary renal-cell epithelial tumors from patients with different degrees of radiation exposure after the Chernobyl accident in Ukraine. Radiometric measurement of Cesium 137 ((137)Cs) was conducted with 1-day urine from all patients before surgery. Our results demonstrate that RCCs from patients living in the radio-contaminated areas showed aberrant hypermethylation of p14(ARF) and p16(INK4A) genes, associated with increased p38MAPK, p14(ARF), mdm2, cyclinD1 and Ki67 protein expression levels. Present findings show the possibility that chronic long-term low-dose radiation activates the INK4a/ARF locus, targeted by activation of the p38MAPK cascade. These actions could lead to disruptions and loss of cell cycle checkpoints and, thereby, to cellular transformation. [ABSTRACT FROM AUTHOR]

After the Chernobyl accident, the morbidity of renal-cell carcinomas in Ukraine increased gradually from 4.7 to 7.5 per 100,000 of the total population. Cesium 137 (137Cs) is responsible for 80-90% of the internal radioactivity in people living in radiocontaminated areas of Ukraine, and 90% of 137Cs is eliminated through the kidneys. Histological and immunohistochemical study of proliferating cell nuclear antigen (PCNA) and K-ras protein was performed in peritumoral kidney tissues of 167 Ukrainian patients (groups I-III, according to varying degrees of internal exposure to radiation), and of 85 analog Spanish patients, as a control group. Our data showed in the majority of Ukrainian patients a radiation sclerosing proliferative atypical nephropathy (RSPAN) in association with an increase in the incidences of tubular epithelial nuclear atypia and carcinoma in situ (CIS). Areas of epithelial nuclear atypia and CIS of the cortex and medulla showed significant PCNA expression with means of extent as 12, 14, and 15% of stained nuclei in groups I, II, and III respectively. K-ras expression of the same areas occurred in 67, 87, and 85% of cases in groups I, II, and III respectively. The present study points to a strong relationship between the long term of low-dose radiation exposure of the Ukrainian population and the development of RSPAN as a possible precursor of malignancy. In addition, it confirms the possible initiator, promoter, or progressor role of chronic low-level radiation of renal human carcinogenesis in Ukraine. [ABSTRACT FROM AUTHOR]