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D Orhan

Publications and source records attributed to D Orhan.

At least 19 recordsLinked to original sources

The role of nitric oxide in mediating nonadrenergic, noncholinergic relaxation in rat pulmonary artery.

Experiments were undertaken to investigate the existence of inhibitory nonadrenergic, noncholinergic (i-NANC) nerve activity by using in vitro functional and immunohistochemical techniques in rat main pulmonary arterial rings. Vessels precontracted with phenylephrine (3 microM) relaxed in response to electrical field stimulation (EFS) (50 V, 0.2 ms, 0.1-10 Hz for 5 s) in the presence of atropine (1 microM) and guanethidine (1 microM). Tetrodotoxin (0.3 microM) abolished this response, indicating that it is neuronal in origin. l-NAME (30 microM), methylene blue (10 microM), and removal of endothelium significantly reduced the EFS-induced relaxations. The inhibitory action of l-NAME was completely reversed by l-arginine (1 mM) but not by d-arginine (1 mM). Moreover l-arginine alone potentiated the magnitude of the relaxations elicited by EFS. On the other hand, immunohistochemical work clearly demonstrated the existence of neuronal nitric oxide synthase in the pulmonary artery vessel wall. All these results are consistent with the suggestion that nitric oxide is the likely mediator of this vasodilatation. However, the incomplete blockade of the responses by l-NAME gives evidence of an additional inhibitory NANC neurotransmitter(s) mediating the residual relaxation, which requires further experiments to clarify its nature.

Animals↗

Proximal bronchial extension with special reference to tumor localization in non-small cell lung cancer.

OBJECTIVE: Surgery is the optimal treatment in patients with non-small cell lung cancer (NSCLC) and tumor-negative bronchial resection margins should be maintained for a curative resection. The epidemiology of NSCLC, including the aspects of tumor localization, has been changing during the recent decades. The aim of this study was to evaluate microscopic proximal bronchial extension with special reference to the site of the tumor. METHODS: Surgical specimens of 70 NSCLC cases were examined histologically for proximal bronchial extension of the tumor. The entire bronchial tree with the tumor was extracted from the specimen and serially cut at a thickness of 5 mm in the transverse plane of the bronchus. Microscopic proximal extension of the tumor was classified as either endobronchial or peribronchial. RESULTS: Thirty-three (47.1%) tumors had central and 37 (52.9%) had peripheral localization. Among the central and peripheral tumors, 10 (30.3%) and seven (18.9%) had microscopic proximal extension, respectively. In total, the mean length of proximal extension was 10.94 +/- 7.07 mm. The mean length of extension for peripheral tumors was 15.71 +/- 8.38 mm, significantly greater than that of central tumors, which was 7.60 +/- 3.47 mm (P = 0.026). Peripheral tumors showed a significant peribronchial extension (P = 0.024). CONCLUSIONS: A greater percentage of central tumors show microscopic proximal bronchial extension, whereas the length of microscopic proximal bronchial extension is significantly greater in peripheral tumors. Peripheral tumors preferentially have a peribronchial extension pattern.

Adenocarcinoma↗

P53, bcl-2 and bax immunoreactivity as predictors of response and outcome after chemotherapy for metastatic germ cell testicular tumours.

OBJECTIVE: To evaluate the roles of p53, bcl-2 and bax as determinants of chemosensitivity in testicular cancers and to assess whether immunohistochemical expression of these proteins in testicular germ cell tumours (GCTs) could be used to predict the outcome in patients with metastatic testicular GCTs. PATIENTS AND METHODS: Immunoreactivity for p53, bcl-2 and bax were examined in primary testicular tumours from 24 patients with metastatic GCTs who were treated with bleomycin, etoposide and cisplatin chemotherapy. All immunostaining results were scored for the appropriate percentage of positive tumour cells and relative immunostaining intensity (score range 0-15) and compared with the response of the patients to chemotherapy. RESULTS: Overall, 20 (83%), 13 (54%) and 24 of the 24 GCTs showed > or = 1% immunoreactivity with p53, bcl-2 and bax, respectively. Only the bax immunostaining intensity and score had statistically higher mean values in the nonseminoma than in seminoma GCTs (P = 0.047 and P = 0.027, respectively). Only p53 immunostaining intensity, percentage of p53 immunopositive cells and p53 staining score were sig-nificantly different among the response groups. The median survival after chemotherapy was 30.5 months; however, taking the median values of the immunostaining scores as threshold values for the survival analysis, none of the three proteins were associated with significant differences in survival. CONCLUSIONS: The incidence of p53 and bax immuno-reactivity in testicular GCTs is higher than that of bcl-2 immunoreactivity. However, only p53 immuno-reactivity could be used to predict the response to chemotherapy. P53, bcl-2 and bax scores were not significant prognostic factors for survival after chemotherapy.

Adolescent↗

Inducible nitric oxide synthase expression in benign prostatic hyperplasia, low- and high-grade prostatic intraepithelial neoplasia and prostatic carcinoma.

OBJECTIVE: To elucidate the incidence of inducible nitric oxide synthase (iNOS) expression in benign prostatic hyperplasia (BPH), low- and high-grade prostatic intraepithelial neoplasia (PIN) and prostatic carcinoma lesions, and to explore the role of iNOS in prostate tumorigenesis. MATERIALS AND METHODS: Immunoreactivity for iNOS was examined in 20 samples each of BPH, high-grade PIN, low-grade PIN and prostatic carcinoma. RESULTS: Positive iNOS immunostaining was detected in all samples from all patients; iNOS was detected in both basal epithelial cells and secretory cells of the glandular epithelium. High-grade PIN and prostatic carcinoma samples had more intense iNOS immunostaining than low-grade PIN and BPH samples. In all samples, smooth muscle cells showed weak or moderate iNOS immunoreactivity and endothelial cells showed moderate immunostaining. CONCLUSIONS: Nitric oxide generated by iNOS may be involved in prostate tumorigenesis and further studies with immunohistochemical and molecular biology are needed to determine the exact role of iNOS in the pathogenesis of prostatic carcinoma.

Adenocarcinoma↗

Association of nitric oxide production and apoptosis in a model of experimental nephropathy.

BACKGROUND: In recent studies increased amounts of nitric oxide (NO) and apoptosis have been implicated in various pathological conditions in the kidney. We have studied the role of NO and its association with apoptosis in an experimental model of nephrotic syndrome induced by a single injection of adriamycin (ADR). METHODS: The alteration in the NO pathway was assessed by measuring nitrite levels in serum/urine and by evaluating the changes in vascular reactivity of the isolated perfused rat kidney (IPRK) system. Rats were stratified into control groups and ADR-induced nephropathy groups. These two groups were then divided into: group 1, animals receiving saline; and group 2, animals receiving aminoguanidine (AG) which is a specific inhibitor of inducible-NO synthase. On day 21, rats were sacrificed after obtaining material for biochemical analysis. RESULTS: Histopathological examination of the kidneys of rats treated with ADR revealed focal areas of mesangial proliferation and mild tubulointerstitial inflammation. They also had significantly higher levels of proteinuria compared with control and treatment groups (P < 0.05). Urine nitrite levels were significantly increased in the ADR-nephropathy group (P < 0.05). In the IPRK phenylephrine and acetylcholine related responses were significantly impaired in the ADR-nephropathy group. Apoptosis was not detected in controls. However, in the ADR-nephropathy group, numerous apoptotic cells were identified in the tubulointerstitial areas. Double staining revealed numerous interstitial apoptotic cells to stain for ED1, a marker for monocytes/macrophages. Treatment with AG prevented the impairment of renal vascular bed responses and reduced both urine nitrite levels and apoptosis to control levels. CONCLUSION: We suggest that interactions between NO and apoptosis are important in the pathogenesis of the ADR-induced nephrosis.

Animals↗

Collecting duct carcinoma.

Collecting duct carcinoma of the kidney is a rare variant of renal cell carcinoma. Hematuria is the most common presenting symptom. This tubulopapillary tumor arises from or differentiates forward to medullary collecting tubules. It is typically centered on the medulla of the kidney and extends into the cortex with a desmoplastic reaction. There are few reports documenting the clinical presentation and long-term prognosis. We describe a case of this uncommon tumor with clinical, histological and immunohistochemical features and review the literature.

Aged↗

Changing patterns of lung cancer; (3/4 in.) 1.9 cm; still a safe length for bronchial resection margin?

BACKGROUND: Surgical resection is the best treatment modality in non-small cell lung cancer (NSCLC). As a guideline, it is suggested that at least a bronchial resection margin of 1.9 cm from the macroscopic tumor might provide a tumor-free margin in lung cancer. In some recent reports, there is great emphasis on the changing histopathological patterns of lung cancer, but no concern for the proximal extension of lung cancer. The aim of this study was to determine the validity of this guideline in the current time. METHODS: Surgically resected specimens of NSCLC cases (n = 70) were examined. The bronchial tree including tumor was dissected and beginning from the edge of the visible tumor, the bronchus were cut into serials in its transverse plane, 5 mm apart from each other. Cut sections were examined for proximal extension of tumor at different levels. RESULTS: Microscopic proximal extension was observed in 24.2% (n = 17/70) of all the cases. Peribronchial extension (n = 9/17) (52.9%) was more predominant compared with bronchial extension (n = 8/17) (47.0%). Squamous cell carcinoma (n = 11/38) (28.9%) showed proximal extension more than adenocarcinoma (n = 5/23) (21.7%). Adenocarcinoma showed more peribronchial extension (n = 4/5) (80.0%) whereas squamous cell carcinoma (n = 7/11) (63.6%) showed more bronchial extension. The farthest extension was 3.0 cm for adenocarcinoma and 2.0 cm for squamous cell carcinoma. Excluding tumor positive specimens beyond 1.5 cm level to the bronchial resection margin, all tumors accounted for 96% of the whole series. CONCLUSIONS: Microscopic proximal extension of lung cancer occurs in 24.2% of NSCLC cases. Squamous cell carcinoma extends more proximally compared with adenocarcinoma in ratio whereas adenocarcinoma extends more in length. A bronchial resection of 1.5 cm in length from the macroscopic tumor will provide clear margins in 93% of NSCLC cases.

Adult↗

Remission of nephrotic syndrome after removal of localized Castleman's disease.

Renal complications of Castleman's disease are uncommon. Among the various renal disorders, including mesangial proliferative glomerulonephritis, membranous glomerulonephritis, and minimal change disease, nephrotic syndrome attributable to renal amyloidosis is very rarely reported. We report a case of mixed type of localized Castleman's disease complicated with nephrotic syndrome. Renal biopsy was performed. The deposition of AA amyloidosis was shown. After the removal of two mesenteric lymphoid masses, the proteinuria was gradually decreased and disappeared. Renal biopsy was repeated after 14 months, and, despite complete remission of nephrotic syndrome, no regression in amyloid deposition was found.

Adult↗

Leiomyoma of the epididymis.

Tumours of the epididymis, both primary and secondary, whether benign or malignant are very rare. We report a case of leiomyoma of the epididymis and discuss the treatment of this tumour.

Epididymis↗

Bcl-2 proto-oncogene expression in low- and high-grade prostatic intraepithelial neoplasia.

OBJECTIVE: To determine the incidence of bcl-2 protein expression in low- and high-grade prostatic intra-epithelial neoplasia (PIN) lesions, and to explore the role of bcl-2 in prostatic tumorigenesis. Materials and methods Immunoreactivity for bcl-2 was examined in 10 samples of benign prostatic hyperplasia (BPH), 13 of primary prostatic adenocarcinoma, 15 of high-grade PIN and 18 of low-grade PIN. All immunostaining results were scored for the approximate percentage of positive tumour cells and relative immunostaining intensity (score range 0-12). RESULTS: In all BPH samples, bcl-2 staining was detected consistently in the basal cell layer of the ducts and acini, but no staining was ever apparent in luminal cells. The immunoreactivity for bcl-2 was heterogeneous in the prostatic carcinomas and bcl-2 protein expression was present in six samples. In these six bcl-2-positive tumours, the mean (range) staining score was 1.15 (1-6). There was detectable expression of bcl-2 in low- and high-grade PIN in all cell layers; immunoreactivity was present in 10 of 15 high-grade PIN lesions, with a mean (range) score of 1.14 (1-4), and in 12 of 18 samples of low-grade PIN, with a mean (range) score of 1.77 (1-6). CONCLUSIONS: The high incidence of bcl-2 protein expression in low- and high-grade PIN lesions suggests that bcl-2 protein expression is associated with early prostate tumorigenesis.

Gene Expression↗

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Journal Article↗

Renomedullary interstitial cell tumor.

Renomedullary interstitial cell tumor was first introduced by Lerman and co-workers. These lesions have been referred to as medullary fibromas. The ultrastructural studies showed that the spindle cells throughout the stroma have the features of medullary interstitial cells. These benign tumors with specific histology are rare since they are incidental findings at autopsies. We report here a case of renomedullary interstitial cell tumor in a 55-year-old woman.

Female↗

Influence of tumor stage, size, grade, vascular involvement, histological cell type and histological pattern on multifocality of renal cell carcinoma.

PURPOSE: We assessed the influence of clinical and pathological factors on multifocality of renal cell carcinoma. MATERIALS AND METHODS: Between June 1995 and September 1999 radical nephrectomy was performed in 71 men and 32 women with a mean age of 56.5 years. The 103 removed kidneys with renal cell carcinoma were sectioned at 3 mm. intervals and inspected microscopically for satellite carcinomas. We evaluated pathological stage, grade, cell type, histological pattern, vascular involvement, tumor size and the incidence of multifocality. To determine cell type we used several classification systems. RESULTS: The primary tumor was 2 to 20 cm. (mean plus or minus standard deviation 7.10 +/- 3.48). Overall satellite carcinomas were present in 22 of the 103 cases (21.4%). When the predominant lesion was 5 cm. or smaller, the incidence of multifocality was 19%. The incidence of multifocality was statistically higher in patients with stage pT3 than in those with stage pT1 or pT2 disease (p = 0.022). Multiple logistic regression analysis demonstrated that only primary tumor pathological stage was a significant predictor of renal cell carcinoma multifocality in stages T3 versus T1 and T3 versus T2 cancer (odds ratio 3.45, 95% confidence interval 1.15 to 10.39 and 5.75, 1.31 to 25.29, respectively). Other parameters, such as tumor size, grade, vascular invasion, cell type and histological pattern, did not correlate with multifocality. CONCLUSIONS: Our results imply that primary tumor stage is a significant factor for multifocal disease. Therefore, more precise preoperative staging of the primary lesion is required if nephron sparing surgery is indicated.

Adult↗

Histological evaluation of colonic anastomotic healing in the rat following preoperative 5-fluorouracil, fractionated irradiation, and combined treatment.

There is a growing interest in neoadjuvant chemo- and radiotherapy as a treatment modality for colorectal cancer which could affect mechanical and biochemical parameters of anastomotic healing. This study investigated the effect of such protocols on colonic anastomotic healing by evaluating the histopathological parameters. One hundred and sixty male Wistar rats were divided into six groups: a control group (I, n = 20), a saline group (II, n = 30) which received 1 ml NaC1 intraperitoneally, a sham-irradiated group (III, n = 20), a 5-fluorouracil (5-FU) group (IV, n = 30), which received 5-FU (20 mg/kg) intraperitoneally for 5 consecutive days, an irradiated group (V, n = 40) which received fractionated irradiation to the whole pelvis to a total dose of 22 Gy, 5.5 Gy per fraction on 4 consecutive days, and a concomitant 5-FU + irradiation group (VI, n = 20) which received 5-FU as in group IV and irradiated as in group V. All groups underwent left colonic resection with primary anastomosis, and the last fraction of irradiation and the last injection were given 4 and 3 days before the operation, respectively. Within each group one half of the animals were killed on the third postoperative day and the other half on the seventh postoperative day. After the resection of the anastomotic segments, histopathological examination was evaluated. Apposition of the wound edges of the mucosa and the muscularis were not affected by the therapy. The level of granulocytes was high, inflammatory exudate and necrosis persisted, granulation tissue formation was delayed, and the levels of macrophages and fibroblasts were low. We conclude that colonic anastomotic healing can be affected by the administration of preoperative chemotherapy, irradiation, and chemoirradiation.

Anastomosis, Surgical↗

Immunohistochemical determination of p53 protein in prostatic cancer and prostatic intraepithelial neoplasms.

A role of genetic alterations in the p53 tumor suppressor gene has been implicated in many types of human malignancies. In this study, we examined the prevalence of immunohistochemically detectable p53 accumulation in prostatic tissues obtained from patients with prostatic adenocarcinoma, benign prostate hyperplasia and prostatic intraepithelial neoplasms. Six of 36 (16.7%) cancer cases and 2 of 11 (18.2%) cases of high-grade prostatic intraepithelial neoplasms showed p53 expression while no nuclear staining was observed in normal and hyperplastic prostatic tissues. Correlation of p53 expression with cancer stage, Gleason score and serum prostate-specific antigen level demonstrated that there was no statistically significant relationship between p53 expression and these clinicopathological parameters. Also, no significant association between p53 expression and prognosis was observed.

Adenocarcinoma↗

Carcinosarcoma of the prostate. A case report and a possible evidence on the role of hormonal therapy.

A case of prostatic carcinosarcoma is presented with histopathologic and immunohistochemical characteristics. A 70-year-old man presented with a history of anti-androgen (cyproterone acetate) therapy for prostatic adenocarcinoma. Diffuse and strong staining for progesterone receptor was observed in the carcinosarcoma specimen although it was completely negative in the previous adenocarcinoma specimen. It may be speculated that hormonal therapy might have facilitated the selection of a progesterone-dependent subclone of tumor cells with the ability of mesenchymal differentiation and that genetic instability due to p53 inactivation might have played a role in this process.

Adenocarcinoma↗