Ramazan Uçak

Renal tubular injury induced by hyperoxaluria: evaluation of apoptotic changes.

Abstract In order to evaluate the injurious effect of hyperoxaluria on renal tubular epithelium, as judged by apoptotic changes in the renal parenchyma, we performed an experimental study in 20 rabbits. In the experimental group animals (n=10) severe hyperoxaluria was induced by continuous ethylene glycol (EG; 0.75%). Histologic alterations, including crystal formation, together with apoptotic changes were evaluated after 7 and 28 days. Control group animals (n=10) received normal distilled drinking water. Following 7- and 28-day periods, tissue sections obtained from kidneys were examined histopathologically under light microscopy for the presence and the degree of crystal deposition in the tubular lumen. Apoptotic changes in renal tubular cells were examined using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP in situ nick and labeling (TUNEL) method during the same follow-up period. Crystal deposition was evident in the tubular lumen of tissue sections obtained during the 7-day examination period. During the 28-day examination period, however, these findings were found to be either limited or to have disappeared. In relation to apoptotic changes, the percentage of positive nuclei stained using the TUNEL method was from 11 to 20% in the experimental group and 5.6% in the control group. Our findings indicate that both calcium oxalate (CaOx) crystals and hyperoxaluria itself may be injurious to renal tubular cells, as indicated by apoptotic changes. These changes may be responsible for the pathologic course of urolithiasis.

Vascular plexus is a differentation criterion for muscularis mucosa from muscularis propria in small biopsies and transurethral resection materials of urinary bladder

Objective: Smooth muscle fibres are found within thesuperficial lamina propria of urinary bladder (Muscularis Mucosa). Thesemuscle fibres of muscularis mucosa should be distinguished from themuscularis propria in cases with urothelial carcinoma, because the depthof infiltration affects prognosis and therapy modalities. The aim of thepresent study was to evaluate whether the presence of vascular plexus isa criterion for muscularis mucosa and to distinguish it from muscularispropria in urinary bladder biopsies and transurethral resectionspecimens. Materials and methods: Hematoxylin-Eosin andMasson-Trichrome stained slides of 54 cases with urothelial carcinomawere reviewed. Results: In all cases (100%), thick walledvessels were observed within the lamina propria of urinary bladder.Smooth muscle layer of lamina propria was seen in 48 of 54 cases(88.8%), and these smooth muscle fibres were co-existed with thickwalled vessels. In invasive urothelial carcinoma; thin smooth musclefibres and thick walled vessels were seen within the lamina propria in22 of 24 cases (91.7%). There were two cases (8.3%)including only vessels in small biopsies of invasive urothelialcarcinoma cases. In cases with non-invasive urothelial carcinoma; musclefibres of muscularis mucosa and vessels were found within the laminapropia in 26 of 30 cases (86.7%). In this group, muscle fibreswere not detected in 4 cases (13.3%). Conclusion:Muscularis mucosa can be detected histologically in urinary bladderbiopsies and TUR materials. We emphasize that the presence of vascularnetwork is a useful criterion to determine muscularis mucosa of urinarybladder, even in the absence of muscle fibres.

Cycline-Dependent Kinase Inhibitor, p27 (KIP1), Is Associated With Cholesteatoma

Objective Cyclin‐dependent kinases (CDKis) can arrest the cell cycle, which in turn inhibits the cell proliferation. P27 (KIP1) is a CDKi and acts as a tumor suppressor gene. In this study, we aimed to investigate the role of p27 CDKi in cholesteatoma, a disease characterized by the presence of hyperproliferative squamous epithelium.

Langerhans cell related inflammatory reaction in laryngeal squamous cell carcinoma.

The major cells involved in cancer cell kill are the T lymphocytes. However, T cells need to be activated upon antigen presentation, which is mediated by the antigen presenting cells, one of which is the Langerhans cell (LC). The purpose of this study was to assess the significance of LC and inflammatory cell infiltration in the laryngeal squamous cell carcinoma (LSCC). Forty-five patients who were operated on for LSCC between 1992 and 1999 were included in the study. The clinical and histopathological features of the patients were reviewed. A semiquantitative estimation of the lymphocyte dominant inflammatory reaction within and around the tumor was performed. Anti S-100 antibodies were used for immunohistochemical detection of LCs. Horseradish peroxidase method was used. LCs were present in almost all of the specimens within and around the tumor tissue. The S-100 results did not associate with grade, T and N stages, tumor stage, laryngeal site of involvement and survival (P>0.05). The S-100 results significantly associated with inflammatory reaction in the tumor tissue (P<0.01). In conclusion, the LC related response is not important to inhibit regional metastasis by cancer cells. The LC is not a reliable tool to determine prognosis of the patients with LSCC in the clinical practice.

Verapamil prevents the apoptotic and hemodynamic changes in response to unilateral ureteral obstruction.

Introduction:  Obstruction of the urinary tract has marked effects on renal blood flow, glomerular filtration rate (GFR), and tubular function. Moreover, ureteral obstruction results in an injury response that can progress to irreversible renal fibrosis and tubular atrophy by apoptosis.

Unilateral Testicular Torsion: Evaluation of bcl-2, p-53 and PCNA Expression in Contralateral Testes

Objectives and Methods: The present study aims to evaluate the histologic as well as apoptotic changes indicated by PCNA, p-53 and bcl-2 expression in the contralateral testes after a period of unilateral testicular torsion of 4 h. Results: Regarding the histologic changes, while some significant alterations such as complete or incomplete spermatocytic arrest as well as sertoli cell only formation have to some extent been noted after the detorsion procedure, reasonably better preserved histology could be demonstrated following the orchiectomy procedure both in the early and late follow-up. Thus, the orchiectomy procedure was found to be limiting enough on the severity of the histologic changes in the contralateral testes after a certain period of time following the torsion procedure. On the other hand, however, in relation to the apoptotic events indicated by the three markers, while PCNA activity was found to be significantly different depending on the procedure performed (detorsion or orchiectomy), p-53 and bcl-2 positivity did not exhibit any difference in this aspect. Increased PCNA activity (especially after the detorsion procedure) together with marked positivity of p-53 both in the early and late follow-up indicated the increased cell turnover in the contralateral testes, which in turn may be accepted as a sign of increased apoptosis in these testes. In addition to these findings, bcl-2 expression has been found to be consistently negative in all specimens evaluated both in the early and late follow-up. Conclusion: Taking into account the strong inhibitory effect of bcl-2 during apoptotic events, these findings again support the likelihood of increased apoptosis in the contralateral testes.

AgNOR/P53 expression compared with different grades in bladder carcinoma

Objective: The aim of this study is to assess the relation betweensilver-strained nucleolar organizer regions (AgNOR)/P53 expression andurothelial neoplasm of the bladder which graded according to the WHO/ISUPtumor grading system.Methods: Transurethral resection materials(TUR) and cystectomy specimens from 52 patients with bladder urothelialcarcinomas were stained by AgNORs and analyzed immunohistochemicallyusing an avidinbiotin peroxidase method for p53 staining and also silver forAgNORs.Results: Nuclear p53 accumulation was determined in two of5 LMP cases (%40), in 10 of 22 LGC (%45.4), and in 8 of 25 HGC (%32).Positivity of p53 accumulation was observed in 20 (%57.7) of all cases.There was no statistically significant relationship between AgNOR score ofp53(+) and p53(−) cases. There was no correlation between LGC and LMP,also between LGC and HGC (p > 0.05), but a meaningful relationship wasfound between LMP and HGC (p = 0.03). Association between P53 and grade,AgNOR value and grade, p53 and AgNOR was found statisticallyinsignificant.Conclusions: Although we found a statistically significant correlationbetween AgNOR count of LMP and HGC, this study did not show a satisfyingcorrelation between AgNOR, p53 and any grade of urothelial carcinoma.

Significance of Fas Protein in Squamous Cell Carcinoma of the Larynx

The purpose was to elucidate the clinical significance of Fas protein in laryngeal squamous cell carcinoma (LSSC). Medical records of 30 patients who were operated for LSCC between 1991 and 1997 were reviewed, and histopathological and immunohistochemical studies of the archival tumor tissues were performed. Conventional histopathology included tumor grading, mitotic counting (MC) and status of the cervical lymph nodes. The monoclonal antibodies to Fas (DAKO M 3554) and nm23 (DAKO A0096 Lot 035) proteins were used for immunohistochemical staining. Streptavidin-Biotin, horseradish method was used. Positive staining for both Fas and nm23 was obtained in 27 (90%) tumor samples. There was no correlation between neck metastasis and Fas positivity (

Expression of the p53 and nm23 genes in cholesteatoma

Objective - To evaluate the roles of p53 and nm23 genes in cholesteatoma. Material and methods - The results of p53 and nm23 immunostainings were compared between 28 cholesteatoma samples and 13 control skin samples obtained from the external acoustic canal. Results - There were no correlations between p53 staining and either gender or type of cholesteatoma ( p <0.05). The mean numbers of p53 -positive cells in the unpaired cholesteatoma and skin specimens were 23.1 - 43.5 and 1 - 1.9, respectively and this difference was not statistically significant ( z =-1.531; p =0.2). The mean numbers of p53 -positive cells in the paired cholesteatoma and skin specimens were 3.8 - 6.1 and 29 - 56.9, respectively and this difference was also not statistically significant ( t =-1.078; p =0.3). Cholesteatoma showed no nm23 positivity. Conclusion - The mechanisms relating to the expression of p53 and nm23 genes are not associated with the occurrence of cholesteatoma.

Verapamil Attenuates Renal Tubular Apoptosis in Response to Partial Unilateral Ureteral Obstruction

Introduction: Partial unilateral ureteral obstruction (PUUO) is the type of obstruction that is most often encountered in pediatric clinical practice. The majority of our knowledge on PUUO has been derived from experimental studies and the effects of PUUO on the kidney have still been a source of continual investigation. Material and Methods: In the present study, renal expression of p53, Fas and PCNA were examined in rabbits with long-term (4 weeks) partial obstruction. Additionally, the effect of calcium channel blocker on pronounced apoptotic changes were evaluated. Results: Immunohistochemistry results revealed that PUUO for 4 weeks caused an upregulation of p53 to 55.2 ± 2% and Fas to 30.1 ± 1.1%, whereas verapamil challenge attenuated the expression of these two apoptotic markers (p53: 15.9 ± 1.8%; Fas: 18.2 ± 1.4%, p < 0.05). Importantly, PCNA activity was also increased in response to PUUO. However, verapamil treatment after onset of obstruction caused a markedly decrease in the expression of PCNA (42.9 ± 10.8% vs. 9.6 ± 2.1%, PUUO, PUUO + verapamil; respectively, p < 0.05). Conclusion: The expression of p53, Fas and PCNA molecules is associated with long-term partial ureteral obstruction, whereas verapamil seems to be a protective agent against apoptotic changes.