Marian Danilewicz

Expression of arachidonate metabolism enzymes and receptors in nasal polyps of aspirin-hypersensitive asthmatics.

Background: The pathogenesis of rhinosinusitis in aspirin-exacerbated airway disease is closely linked to the disequilibrium in arachidonic acid metabolism. Although considerable amounts of data concerning impaired eicosanoid production are available, the precise mechanism and pathogenesis of the disease are still unknown. The aim of the present study was to assess the expression of enzymes belonging to the arachidonic acid cascade and receptors for arachidonate derivative metabolites in nasal polyps from aspirin- hypersensitive (AH) and aspirin-tolerant (AT) patients with rhinosinusitis. Methods: Cells expressing cysteinyl leukotriene (CysLT) receptors (CysLT1 and CysLT2), arachidonate 5-lipoxygenase, leukotriene B4 receptor type 1, E-prostanoid receptors (EP2 and EP4), cyclooxygenase (COX)-1 and COX-2 were detected by immunocytochemistry in nasal polyps obtained from 10 AH patients and 18 AT patients. Results: There was a significantly higher density of cells expressing CysLT1 and CysLT2 receptors in nasal polyps from AH patients than from AT patients (p < 0.001). In contrast, the density of cells expressing EP2 receptor and COX-2 was significantly lower in AH patients than in AT patients (p < 0.02). The number of COX-2-positive epithelial cells was significantly reduced in AH polyps (p < 0.04). Conclusions: The elevated number of nasal polyp cells expressing CysLT receptors and lack of cells expressing EP2 receptor and COX-2 may be related to a more severe course of hyperplastic rhinosinusitis in aspirin hypersensitivity.

Rabbit supraspinatus tendon detachment: Effects of size and time after tenotomy on morphometric changes in the muscle

We studied the effects of size and time after rabbit supraspinatus tenotomy (group A - small tenotomy, group B - large tenotomy) on muscle morphometric changes in 48 rabbits. Animals were killed 6 (subgroups A1 and B1), 12 (subgroups A2 and B2) and 24 weeks (subgroups A3 and B3) after tendon detachment. Statistically significantly greater increases in interstitium volume were noted in subgroups A1-A3 and B1-B3 than in controls. Reductions in type I and II fiber diameters were mainly due to the length of observation. However, statistically significant differences in comparison with controls appeared earlier after large tenotomy. The size of the tenotomy primarily affected muscle fiber composition. Our results suggest that these changes were caused by fiber transformation from type I to type II and vice versa. These findings indicate that the interdigitations between the supraspinatus and infraspinatus and between the supraspinatus and subscapularis tendons are important in dynamics and the degree of morphometric changes in the rabbit supraspinatus after tenotomy.

Transforming growth factor beta 1 and metalloproteinase-9 overexpression in colorectal cancer (CC) and adenoma.

Background and aimsAlthough the role of transforming growth factor beta (TGFbeta) 1 and metalloproteinase-9 (MMP-9) is well documented in colorectal cancer (CC), there is a little evidence supporting its role in early carcinogenesis. The aim of the study was to determine the pattern of immunohistochemical expression of TGFbeta1, MMP-9, and Ki-67 in CC and adenomatous polyps.Patient/methodsThe study group comprised 50 patients with colorectal polyps and 33 patients with CC. Endoscopically removed polyps and CC biopsies had been evaluated with histopatologic examination and immunohistochemistry. The biopsies from 30 healthy objects served as a control group. For all antibodies labeling indices (LI) had been calculated.ResultsAmong 62 adenomas, 33 high-grade dysplasia (HGD) and 29 low-grade dysplasia (LGD) had been detected. Mean TGFbeta1, MMP-9, and Ki-67 LI in CC were significantly higher (p < 0.01, 0.01, and 0.01, respectively) than in HGD polyps. Mean TGFbeta1, MMP-9, and Ki-67 LI in HGD polyps were significantly higher than in LGD polyps (p < 0.01, 0.01, and 0.01, respectively). There had been no statistical difference in TGFbeta1, MMP-9, and Ki-67 LI between LGD and the control group (p > 0.05, 0.05, and 0.05, respectively). There was a positive correlation between TGFbeta1 and MMP-9 (r = 0.898), Ki-67 and MMP-9 (r = 0.938), and TGFbeta1 and Ki-67 (r = 0.913). We did not observe any correlation between TGFbeta1, MMP-9, Ki-67 LI and the clinical parameters evaluated.ConclusionThe increased expression of TGFbeta1, MMP-9 observed in colorectal adenomas seems to be related to the grade of dysplasia. We assume that overexpression of TGFbeta1, MMP-9 represent an early event in colorectal carcinogenesis and may possibly have the prognostic value.

Increased tissue immunoexpression of YKL-40 protein in high grade serous ovarian cancers

YKL-40 is a glycoprotein secreted by numerous human cells, such as cartilage, synovial, and endothelial cells. The biological role of YKL-40 has not yet been fully unveiled, however, its participation is perceived in angiogenesis, growth, proliferation, differentiation, and remodeling processes. The primary goal of our study was to evaluate possible differences in tissue immunoexpression of YKL-40, assumed between high grade and low-grade ovarian cancers and between the above-mentioned cancer types and benign lesions. Another purpose was to find out whether immunoexpression of the studied protein could correlate with the tumor proliferation process, evaluated by Ki-67 immunoexpression. The analysis comprised 45 women, diagnosed and treated for epithelial ovarian tumors at the Medical University of Lodz between 1997 and 2002. YKL-40 protein immunoexpression was semiquantitatively assessed, whereas immunoexpression of Ki-67 was evaluated using a computer image analysis system. Significantly higher immunoexpression values of both examined proteins were observed in high-grade serous ovarian cancers vs. low-grade and benign tumors. Moreover, a significant positive correlation was identified between the immunoexpressions of YKL-40 and Ki-67 proteins in the studied groups of tumors. In conclusion, the obtained data suggest an overt prominence of TKL-40 tissue immunoexpression of YKL-40 in high-grade serous ovarian tumors, which could then be approached as a helpful, additional marker to identify more aggressive ovarian cancers.

HLA‐DR expression is a significant prognostic factor in laryngeal cancer

HLA‐DR antigen expression in tumour cells was investigated in 68 laryngeal carcinomas. The tissue sections were studied by a morphometric method using a computer image analysis system. Although the highest number of HLA‐DR‐positive cells was observed in the groups with the lowest clinical stage, these differences did not reach statistical significance. Analysis of survival showed a significantly different survival time of patients classified as HLA‐DR positive (10% and more HLA‐DR+tumour cells) compared to those classified as HLA‐DR negative. There were no significant differences in survival times between patients with glottic and extraglottic cancers, or between patients with various grades of histological malignancy.

Trends in the Incidence of Biopsy-Proven Glomerular Diseases in the Adult Population in Central Poland in the Years 1990-2010

Background: There is a paucity of epidemiological data on biopsy-proven glomerulonephritis (GN) in Poland. The aim of this study was to assess the epidemiology of renal diseases based on histological diagnosis in the region of Central Poland over the last two decades. Methods: Retrospective analysis of the results of 746 consecutive native kidney biopsies performed in the Caucasian adults from 1990 to 2010 in a single tertiary nephrology center serving an area of Central Poland. Results: Primary GN was found in 81.4% of all biopsies. The mesangioproliferative GN including IgA nephropathy was the most frequent type of primary GN (51.2%). Membranoproliferative GN was diagnosed between 1990 and 2000 more frequently than in the following decade (26.7 vs. 7.3%, p < 0.001). There was a significant increase in the incidence of FSGS (4.8 vs. 17.3%, p < 0.001) and MCD (5.1 vs. 11.2%, p < 0.001) over time. Secondary GN was documented in 18.6% of biopsies and lupus nephritis was the most frequent cause (34.5%). Conclusion: Our analysis showed the decrease in the incidence of membranoproliferative GN with the parallel increase of FSGS and MCD over the last twenty years. Mesangioproliferative GN including IgA nephropathy remains the most frequent type of GN observed in our region.

IL-17 Expression in Dermatitis Herpetiformis and Bullous Pemphigoid

Dermatitis herpetiformis (DH) and bullous pemphigoid (BP) are skin diseases associated with eosinophilic and neutrophilic infiltrations. Although cytokines are critical for the inflammatory process, there are single findings concerning concentration of IL-17 in bullous diseases. The goal of this study was to assess IL-17 expression in DH and BP patients. Skin biopsies were taken from 10 DH, 14 BP patients and from 10 healthy subjects. The localization and expression of IL-17 was studied by immunohistochemistry and the serum concentration was measured by immunoassays. Expression of IL-17 in the epidermis and in influxed cells in dermis was detected in skin biopsies. Expression of IL-17 was statistically higher in epidermis and infiltration cells in specimens from BP than from DH patients. Examined interleukin expression was detected in perilesional skin of all patients but it was much lower than in lesional skin. The expression of IL-17 was not observed in biopsies from healthy people. Serum level of IL-17 was statistically higher in BP and DH groups as compared to control group. Our results provide the evidence that IL-17 may play an essential role in activating and recruiting eosinophils and neutrophils, which ultimately contribute to the tissue damage in DH and BP.

Differential glomerular immunoexpression of matrix metalloproteinases MMP-2 and MMP-9 in idiopathic IgA nephropathy and Schoenlein-Henoch nephritis.

Both idiopathic IgA nephropathy (IgAN) and Schoenlein-Henoch nephritis (SHN) are characterized by cell proliferation and abnormal extracellular matrix (ECM) remodeling by mesangial cells leading to fibrosis, sclerosis and end-stage renal disease. Matrix metalloproteinases MMP-2 and MMP-9 are reported as the most important proteolytic enzymes involved in remodeling of ECM. Therefore, the aim of the present study was to determine glomerular immunoexpression of MMP-2 and MMP-9 in IgAN and SHN. Another purpose of this study was to examine the relationship between expression of MMPs and mesangial cells, a-smooth muscle actin (alpha-SMA) staining, and monocytes/macrophages. Fifteen patients with idiopathic IgAN and 12 with SHN were examined by percutaneous renal biopsy. Glomerular staining intensity of MMP-2 and MMP-9 was recorded semiquantitatively, whereas mesangial cells, glomerular alpha-SMA staining and glomerular CD 68+ cells were assessed quantitatively using computer image analysis system. Our study revealed that the mean values of glomerular immunoexpression of MMP-2, mesangial cells, alpha-SMA staining and glomerular CD 68+ cells were in SHN patients significantly increased as compared to IgAN cases whereas glomerular staining for MMP-9 did not differ in these groups. Moreover, a glomerular staining of MMP-2 was significantly positively correlated with mesangial cells as well as glomerular alpha-SMA staining in both SHN and IgAN. A positive significant correlation between glomerular MMP-2 staining and glomerular CD68+ cells was noted only in SHN group. The correlations of glomerular MMP-9 and these parameters were weak and not significant. In conclusion, our results confirm increased glomerular staining of MMP-2 but not MMP-9 in SHN patients. A suggestion that augmented mesangial cells proliferation in these cases depends on MMP-2, alpha-SMA and monocytes/macrophages needs further investigations including double staining study.

Intercellular adhesion molecule-1 (ICAM-1), leucocyte function-associated antigen-1 (LFA-1) and leucocyte infiltration in proliferative human glomerulonephritis.

The expression of the intercellular adhesion molecule-1 (ICAM-1), infiltrating cells positive for its ligand leucocyte adhesion molecule-1(LFA-1), and the markers of total leucocytes (CD45RB), T cells (CD45RO), and monocytes/macrophages (CD68) were examined by an indirect immunoperoxidase method on renal biopsy specimens from 20 patients with mesangial proliferative glomerulonephritis-IgA negative (MesProGN) and 20 with IgA nephropathy (IgAN). Histologically, normal portions of the kidney tissue (n = 15) obtained from patients with renal trauma or renal tumours were used as controls. The expression of ICAM-1 was evident and extended in mesangium, on endothelial cells of peritubular capillaries, interstitial cells, several infiltrating immune cells and on tubular epithelial cells, particularly on atrophic tubuli in renal biopsies of MesProGN and IgAN. In both types of glomerulopathies a significant increase in the number of glomerular and interstitial LFA-1-positive cells correlated positively with the expression of ICAM-1. The number of glomerular and interstitial LFA-1-positive cells correlated positively with the number of monocytes/macrophages in glomeruli and interstitium. The strong correlation between expression of ICAM-1 and LFA-1 and between LFA-1-positive cells and immune cells makes these adhesion molecules useful markers of activity and suggest that they are involved in recruitment of leucocytes in the studied types of proliferative glomerulopathies.

Assessment of apoptosis and MMP-1, MMP-3 and TIMP-2 expression in tibial hyaline cartilage after viable medial meniscus transplantation in the rabbit.

Introduction The porpuse of this animal study was to assess chondrocyte apoptosis and MMP-1, MMP-3 and TIMP-2 expression in rabbit tibial cartilage 6 months after viable medial meniscal autografts and allografts. Material and methods Twenty white male New Zealand rabbits were chosen for the study. The medial meniscus was excised from 14 animals and stored under tissue culture conditions for 2 weeks, following which t of them were implantated as autografts and 7 as allografts. The control group consisted of 6 animals which underwent arthtrotomy. When the animals were eutanized, the tibial cartilage was used for immunohisochemical examination. Apoptosis (TUNEL method) and MMP-1, MMP-3 and TIMP-2 expression were estimated semiquantatively. Results An increased level of chodrocyte apoptosis in the tibail cartilage was observed after both kinds of transplants (p < 0.05), allografts (1.43 ±0.98) and autografts (0.86 ±0.69); no statistical diferences existed between them. An increased level of metalloproteinases and TIMP-2 expression was obreved only after allografts with statistical differences among the allograft group, the autograft group nad the control group (p < 0.05). Conclusions Our findings suggest that the meniscal graft does not protect the hyaline cartilage against excessive apoptosis. The results of experimantal studies on humans indicate the need to device a method of apoptosis inhibition in the hyaline cartilage to improve long-term results of meniscal transplantation.