Cell and region specificity of Aryl hydrocarbon Receptor (AhR) system in the testis and the epididymis.

Aryl hydrocarbon receptor (AhR) plays multiple important functions in adaptive responses. Exposure to AhR ligands may produce an altered metabolic activity controlled by the AhR pathways, and consequently affect drug/toxin responses, hormonal status and cellular homeostasis. This research revealed species-, cell- and region-specific pattern of the AhR system expression in the rat and human testis and epididymis, complementing the existing knowledge, especially within the epididymal segments. The study showed that AhR level in the rat and human epididymis is higher than in the testis. The downregulation of AhR expression after TCDD treatment was revealed in the spermatogenic cells at different stages and the epididymal epithelial cells, but not in the Sertoli and Leydig cells. Hence, this basic research provides information about the AhR function in the testis and epididymis, which may provide an insight into deleterious effects of drugs, hormones and environmental pollutants on male fertility.

The impact of an expanded genetic testing program and selective oophorectomy on the incidence of ovarian cancer in West Pomerania.

The aim of the study was to evaluate the impact of a regional population-based genetic testing program on the incidence of ovarian cancer in West Pomerania. Between 1999 and 2010, a total of 37,552 women ages 35 to 70 were tested for three BRCA1 founder mutations at the outpatient genetics clinic of the Pomeranian Medical University in Szczecin, Poland. A total of 641 women were found to carry a mutation (1.7%) and of these, 220 had a prophylactic oophorectomy (34.3%). A total of 12 women had an occult cancer diagnosed at the time of prophylactic oophorectomy (5.5%). We estimate that 26 more ovarian cancers would have been diagnosed by January 2015 in the absence of these oophorectomies and that an additional 25 cancers will be prevented in the future (total 51). During this period, 1611 ovarian cancers were diagnosed in the region; therefore we estimate that approximately 1.6% of ovarian cancers were prevented between 1999 and 2015 by our genetic testing program. We conclude that the prophylactic oophorectomies performed between 1999 and 2010 as a result of widespread BRCA1 mutation testing have reduced the incidence of ovarian cancer in Pomerania by a small amount (about 1.6%), and that the impact of genetic testing will increase in the coming years.

Gastric hyperplastic polyps coexisting with early gastric cancers, adenoma and neuroendocrine cell hyperplasia.

Gastric hyperplastic polyps (GHP) constitute up to 93% of all benign epithelial polyps of the stomach. The average probability of malignant transformation in GHP is 0.6-22% in large series. The aim of the study was to present the coexistence of GHP with early gastric cancer (EGC), gastric adenoma (GA), neuroendocrine cell hyperplasia (NH) and well-differentiated neuroendocrine tumour (NET G1). Three cases were studied to reveal clinical data and morphological changes and to assess the relationship between GHP and accompanying gastric neoplastic lesions.

Analysis of specificity of anti-human leukocyte antigen antibodies in kidney recipients in reference to clinical outcome.

BACKGROUND: Anti-human leukocyte antigens antibodies (HLA) are not always the main cause of graft injury but can be a marker of immune response to the graft. The aim of this study was to analyze anti-HLA specificities with the use of the most sensitive detection method (Luminex) in reference to clinical condition. METHODS: Sera of 65 kidney recipients (n = 443) were screened with the use of the mixed LABScreen kit, and, for 47 recipients, sera with maximal normalized background ratio (NBG) were subjected to specificity testing. NBG, numbers of specificities, donor-specific antibodies (DSA), and normalized mean fluorescence index (nMFI) of DSA and maximal anti-HLA were analyzed in reference to clinical (acute rejection [AR] diagnosis, immunosuppression), histopathological (C4d staining, chronic allograft nephropathy, AR type), and laboratory parameters (creatinine). RESULTS: We observed 1 to 51 specificities, class I DSA in 26.7%, class II in 10%, and estimated DQ-DSA in 63.3% of tested patients. Patients with AR and humoral AR had significantly higher NBG, number of anti-HLA class I, DQ and DQ-DSA types, and more frequently had anti-HLA and class II DSA-positive sera (P < .052). C4d staining was associated with higher anti-HLA class I (P = .053) and class I DSA (P = .002) type numbers, and maximal anti-HLA nMFI (P = .036) and was more frequent in AR (P = .048) and class II DSA positive patients (P = .046). Patients with chronic allograft nephropathy showed higher DQ-DSA-nMFI (P = .036). DQ-DSA-nMFI and maximal anti-HLA-nMFI correlated with creatinine increase (Spearman range [SR] = 0.64, SR = 0.41). Together with NBG, maximal class I and class II anti-HLA-nMFI correlated with the number of transplantation and maximal panel-reactive antibodies ratio (SR = 0.19-0.40). CONCLUSIONS: Anti-HLA detection allows for humoral AR diagnosis but also for identification of patients with risk of any rejection. However, clear rules of anti-HLA interpretation and studies on their clinical impact are needed.

Histopathologic evaluation of pretransplantation biopsy as a factor influencing graft function after kidney transplantation in 3-year observation.

BACKGROUND: Many factors affect long-term results in kidney transplantation including histologic damage as a independent predictor, eg, chronic allograft dysfunction (CAD) in protocol biopsies and age-dependent lesions. Histopathologic findings correlate with the incidence of delayed graft function, eventual renal function, and allograft survival, allowing a rather precise prediction of graft outcomes. PATIENTS AND METHODS: We analyzed 92 thick-needle preimplantation renal biopsies and 29 from grafts after explantation. They had been preserved in 4% formalin and immersed in paraffin. Evaluable specimens contained ≥10 glomeruli and ≥2 arterial cross-sections. We analyzed tubulitis, intensity of acute tubular necrosis (ATN), inflammatory infiltration, glomerulonephritis, arterial hyalinization, arteritis, fibrosis, tubular atrophy, arterial intimal fibrosis, increased mesangial matrix, and glomerulosclerosis percentage, although for comparative analysis not only optimal ones were taken into consideration. Over postoperative time, we analyzed patient condition, urine output, serum concentrations of creatinine, urea, uric acid, and ions as well as necessity for postoperative dialysis, ie, delayed graft function (DGF). During the 3-year observation we analyzed living recipients, graft loss, death with a functioning graft, incidence of dysfunction (CAD), and acute rejection episodes (ARE). RESULTS: We observed significant correlations between immediate graft function (IGF) and lack of ATN in the pretransplantation biopsy. The presence of ATN significantly correlated with DGF and primary graft non-function. There was no correlation between renal function and arterial hyalinization or fibrosis, inflammatory infiltration, and tubular atrophy. Over postoperative time we observed significant correlations between IGF and the lack of interstitial fibrosis as well as significantly lower levels of creatinine, urea, and potassium as well as greater urine output early after transplantation. IGF correlated with shorter time to reach a creatinine level of 2 mg/dL, lower concentrations of creatinine, urea, and potassium, as well as greater diuresis during the first 5 days. In addition, lower creatinine and urea concentrations after 1 month and of urea at 6 and 36 months were associated with IGF. Female recipients showed lower concentration of creatinine over 3 months, of urea during the 1st day, and of potassium at 1 month; however, thereafter the differences were not significant. Better function of the right kidney was observed. The presence of severe ATN (ATN III) correlated with lower creatinine concentrations at 6 months and urea after 3 years. The presence of hyalinization in biopsies correlated with higher concentrations of urea at 1 year and of borderline significance after 3 years; surprisingly, potassium concentrations were lower after 2 and 3 years. The presence of inflammatory infiltrates correlated with higher creatinine concentrations after 1 and 3 years; similar correlations, albeit of borderline significance, were observed in tubular atrophy. Interstitial fibrosis correlated with creatinine concentrations during 10 days after the operation and after 12 months, also with potassium concentrations 5 days after the operation. Borderline correlations were observed between donor age and creatinine concentration in the first day after the operation, after 6 months, and time to achieve a creatinine concentration of 2 mg/dL. We observed that biopsies with greater numbers of glomeruli correlated with better graft function, namely, lower creatinine concentrations after 5 days as well as at 1 and 6 months, as well as lower urea concentrations after 5 days and 6 months. We also observed differences in renal function depending on gender. The presence of acute tubular necrosis, arterial fibrosis and a lack of inflammatory infiltration in pretransplantation biopsy correlated with worse late renal function. Explantation biopsies showed signs of CAD in 66.4% and histologic features of ARE in 38.51%.

Elastin degradation within the abdominal aortic aneurysm wall--relationship between intramural pH and adjacent thrombus formation.

BACKGROUND: The natural history of abdominal aortic aneurysm (AAA) is wall remodelling potentially leading to a final rupture. The pathogenesis of AAA appears to be multifactorial. The aim of this pilot prospective study was to assess the relationship between the thickness of the thrombus within the abdominal aortic aneurysm, intramural pH and local elastin degradation. MATERIALS AND METHODS: The AAA size, intraluminal thrombus (ILT) morphology and location were evaluated in 206 consecutive patients. Thirty patients with large AAA (aortic diameter > or = 50 mm) and adjacent ILT with the thinnest part < or = 10 mm and thickest > or = 25 mm, measured in the region of the maximum diameter of AAA, were included for further study. During AAA surgery intramural pH measurements were performed and specimens taken from both thin thrombus-covered and thick thrombus-covered wall for computerized morphometric analysis. RESULTS: Mean intramural pH value was 7.21 +/- 0.18 for the wall covered by thick ILT and 7.64 +/- 0.10 for the thin one (P < 0.001). Computerized morphometric analysis demonstrated that elastin fibres in the thin thrombus-covered wall were decreased in size (for width--P < 0.0001, for length--P < 0.13), irregularly orientated (P < 0.000001) and the amount of fibres was reduced when compared to the wall covered by thick ILT (P < 0.0004). CONCLUSION: A strong relationship between intramural pH and elastin net destruction suggests that the local alkaline status within the thin thrombus-covered part of the aneurysm wall is contributing to the elastinolytic process.

Membranous glomerulonephritis may be associated with heavy marijuana abuse.

It is well documented that drug abuse can cause renal diseases. Nephropathy and proteinuria among heroin addicts has been recognized since the early 1970s. The predominant lesions in heroin-associated nephropathy are segmental glomerulosclerosis in African-Americans and membranous glomerulonephritis (MGN) in the Caucasian population. Cocaine may induce kidney damage, predominantly acute renal failure in the course of rhabdomyolysis. However, there are no case reports of nephropathy associated with marijuana smoking. We report a case of a marijuana-addicted 27-year-old Caucasian man after cadaveric kidney transplantation who developed de novo posttransplant MGN. The long period and high level of narcotic intoxication suggested that de novo MGN may have been associated with heavy marijuana abuse.

Histopathologic evaluation of pretransplant biopsy as a factor influencing graft function after kidney transplantation: a 1-year observation.

INTRODUCTION: Many factors affect long-term results in kidney transplantation including histologic damage as a independent predictor, such as chronic allograft/nephropathy in protocol biopsies and age-dependent lesions. Histopathologic findings correlate with the incidence of delayed graft function, renal function, and allograft survival, allowing a rather precise prediction of graft outcome. MATERIALS AND METHODS: We analyzed 92 renal thick needle preimplantation and 29 postexplantation biopsies. Biopsies were preserved in 4% formalin and immersed in paraffin. Optimal biopsies contained at least 10 glomeruli and at least 2 cross-sections of arteries. We analyzed tubulitis, intensity of acute tubular necrosis, inflammatory infiltration, glomerulonephritis, arterial hyalinization, arteritis, fibrosis, tubular atrophy, arterial intimal fibrosis, increase of mesangial matrix, and percentage of glomerulosclerosis. During the postoperative course we analyzed patients condition, exigency of postoperative dialysis, urine output, as well as serum concentrations of creatinine, urea, uric acid, and ions. During a 1-year observation period, we analyzed living recipients, graft loss, death with a functioning graft, incidence of nephropathy (CAN), and acute rejection episodes (ARE). RESULTS: We observed a significant correlation between immediate graft function (IGF) and lack of ATN in the pre-0 biopsy. We observed no correlation between renal function and arterial hyalinization and fibrosis, inflammatory infiltration, tubular atrophy. In the postoperative period, we observed a significant correlation between IGF and lack of interstitial fibrosis with significantly lower levels of creatinine, urea, and potassium and higher urine output early after transplantation. IGF and better function of the right kidney was correlated with shorter time to reach a creatinine level of 2 mg%. In the postoperative periods, we also observed a difference between renal function depending on gender. The presence of acute tubular necrosis, arterial fibrosis, lack of inflammatory infiltration in the pre-0 biopsy correlated with worse late renal function. Among explantation biopsies 65.5% showed signs of CAN, and 37.93%, histologic marks of ARE.