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Biomedical subjects

G Tezel

Publications and source records attributed to G Tezel.

33 records · Page 2Linked to original sources

Different nuclear/cytoplasmic distributions of RET finger protein in different cell types.

The RET finger protein (RFP), which belongs to the B box zinc finger protein family, has a tripartite motif consisting of a Ring finger, a B box finger and a coiled-coil domain. The RET finger protein becomes oncogenic when its tripartite motif is fused with the tyrosine kinase domain of the RET protein. This study examined the RFP expression in normal and tumor tissues by immunohistochemistry. RFP was detected in the nuclei of various cells, including peripheral and central neurones, hepatocytes, adrenal chromaffin cells and male germ cells. Among them, RFP was expressed at high levels in male germ cells such as primary spermatocytes and round spermatids, and formed a perinuclear cap structure in primary spermatocytes. On the other hand, high levels of cytoplasmic expression of RFP were observed in some plasma cells as well as solitary plasmacytoma and multiple myeloma. These results suggested that different nuclear/cytoplasmic distributions of RFP might play a role in the regulation of growth or differentiation of different cell types.

Animals↗

Inhibition of caspase activity in retinal cell apoptosis induced by various stimuli in vitro.

PURPOSE: Although recent work implicates a decisive role for a family of cysteine aspartic acid proteases, termed caspases, as mediators of neuronal apoptosis, little is known about caspase activation that accompanies apoptosis in the retina. The purpose of this study was to investigate caspase activation in retinal cell apoptosis induced by various stimuli, including simulated ischemia, excitotoxicity, and antibody to heat shock protein 27 (hsp27), and to assess whether the inhibition of caspases can block apoptosis in retinal cells induced by different stimuli. METHODS: Apoptotic cell death induced in cultured retinal cells by simulated ischemia, excitotoxicity, or hsp27 antibody was examined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling technique. Changes in the caspase activity were studied using western blot analysis and a fluorometric protease activity assay in the presence or absence of caspase inhibitors. In addition, changes in the expression of bcl-2 and bax were examined by western blot analysis. RESULTS: The authors' in vitro observations revealed that the apoptotic process in retinal cells induced by different stimuli share a common executioner proteolysis cascade, including caspase-3 and poly(ADP ribose) polymerase cleavage. One exception, however, was that caspase-8 activation was only observed during the apoptosis induced by hsp27 antibody. In retinal cells going to apoptosis regardless of the stimulus, bcl-2 expression was decreased and bax expression was increased. Furthermore, the authors observed that treatment of retinal cells with inhibitors of caspases, including B-D-FMK and Z-IETD-FMK, blocked the apoptotic cell death induced by different stimuli. CONCLUSIONS: The authors' observations provide a better understanding of the apoptotic process in retinal cells at molecular level and demonstrate an effective blockade of caspase activation with specific inhibitors. These findings may have therapeutic implications in the treatment of neuroretinal diseases, which are characterized by apoptotic cell death.

Animals↗

Clinical and ocular histopathological findings in a patient with normal-pressure glaucoma.

OBJECTIVE: To study the histopathological changes of eyes from a patient with normal-pressure glaucoma whose clinical and laboratory findings were well documented. METHODS: Postmortem histopathological findings in a patient with normal-pressure glaucoma who had monoclonal gammopathy and serum immunoreactivity to retinal proteins were examined in comparison with those of an age-matched control subject. Clinicopathological correlations to laboratory findings were examined. RESULTS: Clinical and histopathological findings of the patient, including cavernous degeneration of optic nerve and characteristic optic nerve cupping, were similar to those in patients with glaucoma who had high intraocular pressure. In addition, we found immunoglobulin G and immonuglobulin. A deposition in the ganglion cells, inner and outer nuclear layers of the retina, and evidence of apoptotic retinal cell death using terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling technique. CONCLUSIONS: Serum antibodies to retinal proteins and retinal immunoglobulin deposition constitute novel findings in a patient with normal-pressure glaucoma and may contribute to better understanding of the mechanisms underlying glaucomatous optic neuropathy in this disorder.

Aged↗

Anti-Ro/SS-A positivity and heat shock protein antibodies in patients with normal-pressure glaucoma.

PURPOSE: To describe the clinical and laboratory findings in 10 patients with normal-pressure glaucoma and anti-Ro/SS-A positivity by enzyme-linked immunosorbent assay (ELISA) and to determine whether that positivity may be related to an autoimmune mechanism for the optic neuropathy. METHODS: In this prospective study, we evaluated ocular and systemic clinical findings of 10 patients with normal-pressure glaucoma and anti-Ro/SS-A positivity by ELISA, including sicca complex features. Oüchterlony immunodiffusion was performed to confirm the presence of antibodies for Ro/SS-A, and the presence of other serum antibodies and their possible cross-reactivities with Ro/SS-A were investigated. RESULTS: None of the 10 patients with normal-pressure glaucoma and anti-Ro/SS-A positivity (by ELISA) had clinical or laboratory signs of Sjögren syndrome or other connective tissue diseases. Only one of 10 patients had evidence of anti-Ro/SS-A antibodies by Oüchterlony immunodiffusion. All patients demonstrated serum immunoreactivity to bacterial heat shock protein 60 (hsp60) by Western blotting. Cross-reactivity between bacterial hsp60 and Ro/SS-A was demonstrated by Western blotting. Immunoreactivity to bacterial hsp60 by ELISA was significantly elevated in the sera of patients with normal-pressure glaucoma. Furthermore, patients with either normal-pressure or primary open-angle glaucoma had increased serum immunoreactivity to human hsp60. CONCLUSIONS: Anti-Ro/SS-A positivity by ELISA in 10 patients with normal-pressure glaucoma was associated with a high level of serum immunoreactivity to bacterial hsp60, which may indicate that their glaucomatous optic neuropathy involves an as yet unidentified autoimmune mechanism. The identification of autoantibodies that react with human hsp60 in patients with normal-pressure and primary open-angle glaucoma may signify a common finding associated with the glaucomatous optic neuropathy process in some patients and appears to be unrelated to intraocular pressure levels.

Adult↗

Late removal of releasable sutures after trabeculectomy or combined trabeculectomy with cataract extraction supplemented with antifibrotics.

PURPOSE: Releasable scleral flap sutures have been effectively used in trabeculectomy. The suggested time for suture removal is within the first two postoperative weeks. The authors wished to determine whether the use of intraoperative antifibrotics alters the time of suture removal and the results of surgery. METHODS: The charts of 324 patients (388 eyes) undergoing trabeculectomy and 141 patients (174 eyes) undergoing combined trabeculectomy with cataract extraction with a minimum follow-up of 12 months were retrospectively reviewed. All eyes received intraoperative antifibrotics; mitomycin C in 534 eyes and 5-fluorouracil in 29 eyes. Two releasable scleral flap sutures were used in all of the eyes. RESULTS: The removal time of at least one of the two releasable sutures was later than 21 days postoperatively in 89 eyes of 83 patients with trabeculectomy (22.9%) and in 58 eyes of 55 patients with combined surgery (33.3%). The suture removal was deferred in 39 eyes because of an early complication such as hypotony (intraocular pressure (IOP) < or = 5 mm Hg), bleb leak, or shallow or flat anterior chamber. There was no complication in the other 108 eyes, but suture removal was delayed until the IOP was more than 10 mm Hg. Immediate IOP reduction was (mean +/- standard deviation) 6.3 +/- 2.8 mm Hg when suture removal was performed beyond 3 weeks. There was a decreased response as the postoperative time until suture removal increases (r = -0.57). No serious complication associated with late suture removal was noted during the follow-up period (mean +/- standard deviation, 19.8 +/- 10.1 months). CONCLUSION: Intraoperative pharmacologic modulation of wound healing in trabeculectomy and combined trabeculectomy with cataract extraction extends the period that releasable suture removal is clinically effective. However the response decreases with a longer interval to releasable suture removal.

Aged↗

Autoantibodies to small heat shock proteins in glaucoma.

PURPOSE: To identify the low-molecular-weight retinal proteins that are the targets of serum autoantibodies in patients with glaucoma and to study the ability of these antibodies to induce retinal apoptosis. METHODS: Serum immunoreactivity against retinal proteins was examined in age-matched groups of 60 patients with normal-pressure glaucoma, 36 patients with high-pressure glaucoma, and a control group of 20 healthy subjects, by means of western blot analysis and enzyme-linked immunosorbent assay. The specificity of the immunoreactivity to small heat shock proteins, including alpha-crystallins and hsp27, was tested by immunoprecipitation of these proteins in retinal fractions. The direct effects of antibodies specific to small heat shock proteins were then studied in isolated intact human retina (ex vivo) and cultured rat retinal cells (in vitro) by immunocytochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) technique in conjunction with fluorescence microscopy and confocal imaging. RESULTS: Serum immunoreactivity against retinal proteins with low molecular weight in patients with glaucoma was to small heat shock proteins, including alpha-crystallins and hsp27. In addition, patients with normal pressure glaucoma had a higher titer of autoantibodies to small heat shock proteins than did age-matched patients with high-pressure glaucoma or control subjects. It was observed that when antibodies against small heat shock proteins were applied directly to retina tissue or cells, they could trigger cell death through an apoptotic mechanism. CONCLUSIONS: These findings suggest that increased titers of circulating antibodies against retinal small heat shock proteins may have pathogenic significance in some patients with glaucomatous optic neuropathy.

Aged↗

Parapapillary chorioretinal atrophy in patients with ocular hypertension. I. An evaluation as a predictive factor for the development of glaucomatous damage.

OBJECTIVE: To determine whether parapapillary chorioretinal atrophy is a risk factor for the development of glaucomatous optic disc or visual field damage. METHODS: The initial morphometric parameters of the optic disc and parapapillary atrophy were retrospectively investigated in 350 eyes of 175 patients with ocular hypertension. The prognostic value of parapapillary atrophy at the baseline examination and its relationship with known risk factors for the development of glaucomatous damage were analyzed by multivariate analysis. RESULTS: Visual field loss, optic disc damage, or both were detected in 98 eyes of 53 patients during the follow-up period of at least 10 years. By univariate analysis, the presence of parapapillary atrophy, as well as higher parapapillary atrophy area-disc area, zone beta area-disc area, and parapapillary atrophy length-disc circumference ratios, at the baseline examination was associated with the conversion to glaucoma. In addition, higher intraocular pressure, larger vertical cup-disc ratio, and smaller neural rim area-disc area ratio at the baseline examination were associated with subsequent glaucomatous optic nerve damage. In a multivariate regression model adjusted for other factors, intraocular pressure (relative risk, 1.19), neural rim area-disc area ratio (relative risk, 0.72), and zone beta area-disc area ratio (relative risk, 1.32) were found to be associated with the development of optic disc damage, visual field damage, or both. CONCLUSION: The presence and the size of parapapillary atrophy are related to the development of subsequent optic disc or visual field damage in patients with ocular hypertension.

Choroid↗

Parapapillary chorioretinal atrophy in patients with ocular hypertension. II. An evaluation of progressive changes.

OBJECTIVE: To determine whether parapapillary chorioretinal atrophy in patients with ocular hypertension remained stationary or progressed along with glaucomatous optic nerve damage. METHODS: The morphometric parameters and progression of parapapillary atrophy were retrospectively investigated, using serial photographs, in 350 eyes of 175 patients with ocular hypertension. The association of parapapillary atrophy progression with subsequent glaucomatous conversion and with other baseline patient- and eye-specific characteristics was analyzed. RESULTS: Progression in the area and extension of parapapillary atrophy before noticeable optic disc or visual field changes was observed in 48 (49.0%) of 98 eyes that converted to glaucoma, while parapapillary atrophy progression was noted in 25 (9.9%) of 252 ocular hypertensive eyes that did not develop glaucomatous damage (P<.001). The predictive sensitivity and specificity of this observation were 49% and 90%, respectively. In a logistic multiple regression model, the progression of parapapillary atrophy was associated with a family history of glaucoma (odds ratio, 2.7) and the initial size of zone beta (odds ratio, 1.64, for an increase of 0.10 of the zone beta area-disc area ratio). CONCLUSION: The progression of parapapillary chorioretinal atrophy may be an early glaucomatous finding in some patients with ocular hypertension.

Choroid↗

Plasma and aqueous humor endothelin levels in primary open-angle glaucoma.

PURPOSE: Endothelins (ET) have some effects on the regulation of aqueous humor dynamics. To investigate their possible role in glaucoma, we measured plasma and aqueous humor ET levels in patients with and without primary open-angle glaucoma. METHODS: Plasma and aqueous humor samples were obtained from 31 patients with primary open-angle glaucoma and 24 patients without glaucoma. Measurements were made by radioimmunoassay (RIA) for ETs with the following cross-reactivities: ET-1, ET-2, and big ET-1, 100%; and ET-3, 70%. RESULTS: The ages (mean +/- SD) of the patients with primary open-angle glaucoma (72.3 +/- 10 years) and normal subjects (72.8 +/- 8 years) were similar (p = 0.92). There was no significant difference between plasma ET levels of the two groups (p = 0.07). However, aqueous humor ET levels (mean +/- SD) were higher in the primary open-angle glaucoma group (44.26 +/- 2.6 pg ml-1) than in normal subjects (42.17 +/- 1.6 pg ml-1) (p = 0.001). The ratios of corresponding aqueous humor to plasma levels of ETs were approximately 10% higher in the primary open-angle glaucoma group (3.76) than in normal subjects (3.41) (p = 0.0002). CONCLUSIONS: The small increase in aqueous humor endothelin levels in patients with primary open-angle glaucoma versus controls of similar age may be relevant to the understanding of the various roles of ETs in aqueous humor dynamics in these patients.

Aged↗

Comparative results of combined procedures for glaucoma and cataract: I. Extracapsular cataract extraction versus phacoemulsification and foldable versus rigid intraocular lenses.

BACKGROUND AND OBJECTIVES: The refinements of small-incision cataract surgery by phacoemulsification with foldable intraocular lens (IOL) implantation have recently permitted new options for combined trabeculectomy with cataract extraction. The objectives of this study were to compare the long-term intraocular pressure (IOP) control and visual outcome between trabeculectomies combined with extracapsular cataract extraction (ECCE) versus those with phacoemulsification, and to analyze these same factors for foldable versus rigid IOLs. PATIENTS AND METHODS: The authors retrospectively reviewed the charts of 311 patients (397 eyes) who underwent combined trabeculectomy with cataract extraction and posterior chamber IOL implantation. In all of the surgeries, releasable scleral flap sutures were used. The mean follow-up was 22.9 +/- 15.1 months, with a minimum follow-up of 12 months. RESULTS: Trabeculectomy combined with phacoemulsification had a lower postoperative complication rate and was more effective than trabeculectomy combined with ECCE in reducing IOP to less than 20 mm Hg with or without medication (95% vs 82%) and in improving vision to levels of 20/40 or better (71% vs 52%) (P < .001). Regarding IOLs, foldable silicone lenses were found to be an effective alternative to polymethylmethacrylate lenses in combined surgeries in terms of a controlled IOP of less than 20 mm Hg (97% vs 97%) and visual recovery to 20/40 or better (78% vs 63%). CONCLUSION: The combination of trabeculectomy with releasable scleral flap sutures and small incision cataract surgery with foldable IOL implantation has improved postoperative IOP control and visual rehabilitation.

Aged↗

Comparative results of combined procedures for glaucoma and cataract: II. Limbus-based versus fornix-based conjunctival flaps.

BACKGROUND AND OBJECTIVE: One of the variables to be considered in a combined procedure for glaucoma and cataract is the type of conjunctival flap to be used. The objective of this study was to compare the effects of limbus-based and fornix-based conjunctival flaps on postoperative long-term intraocular pressure (IOP) control and visual acuity after combined trabeculectomy with phacoemulsification. PATIENTS AND METHODS: The authors retrospectively reviewed the charts of 189 patients (215 eyes) who underwent combined trabeculectomy with phacoemulsification, posterior chamber intraocular lens (IOL) implantation, and intraoperative mitomycin-C administration and who had a minimum follow-up of 12 months. The results of the limbus-based (151 eyes) versus fornix-based (64 eyes) conjunctival incisions used in these combined procedures were compared. RESULTS: In the limbus-based conjunctival flap group, 146 eyes (97%) achieved an IOP of less than 20 mm Hg, with or without medication; 62 eyes (97%) of the fornix-based conjunctival flap group (P > .05) achieved this result. A visual acuity of 20/40 or better was noted in 106 eyes (70%) in the limbus-based conjunctival flap group and in 45 eyes (70%) in the fornix-based conjunctival flap group (P > .05) at the last examination. Early wound leakage was observed more frequently in the fornix-based conjunctival flap group (8% vs 1%) (P = .014); however, it was not a serious clinical problem, as only 1 eye required surgical repair. Posterior capsular opacification was found more often in the limbus-based conjunctival flap group (25% vs 14%) (P = .072) and required more frequent laser capsulotomy (22% vs 9%) (P = 0.03). CONCLUSION: Limbus-based and fornix-based conjunctival flaps appear to be comparable with respect to postoperative IOP control and visual acuity after a combined trabeculectomy with phacoemulsification and posterior chamber IOL implantation in cases supplemented by intraoperative mitomycin-C.

Administration, Topical↗

Comparative optic disc analysis in normal pressure glaucoma, primary open-angle glaucoma, and ocular hypertension.

PURPOSE: The authors wished to determine whether characteristics of optic disc and parapapillary atrophy differ between eyes with ocular hypertension, primary open-angle glaucoma (POAG) and those with normal-pressure glaucoma, including a subset of patients with normal-pressure glaucoma with evidence of serum abnormalities of humoral autoimmunity. METHODS: Three hundred ninety-two eyes of 196 patients with ocular hypertension, 394 eyes of 197 patients with POAG, and 135 eyes of 68 patients with normal-pressure glaucoma were analyzed. Nerve fiber layer hemorrhage in the optic disc region, retinal arteriolar narrowing, and morphometric parameters of optic disc and parapapillary atrophy were investigated in these groups. Parapapillary atrophy was differentiated in two different zones (alpha and beta). RESULTS: Nerve fiber layer hemorrhage and arteriolar narrowing were found more frequently in patients with normal-pressure glaucoma than in patients with POAG (P = 0.014, P = 0.004) and ocular hypertension (P < 0.0001, P < 0.0001). Zone beta was detected more often in patients with normal-pressure glaucoma than in those with ocular hypertension (P < 0.001) and POAG (P = 0.013). Although patients with normal-pressure glaucoma had more advanced neural rim loss and larger parapapillary atrophy, there were similar correlations between neural rim area and the area and extension of parapapillary atrophy in patients with normal-pressure glaucoma and POAG. Parapapillary atrophy parameters also were similar in different stages of neural rim damage in patients with normal-pressure glaucoma and POAG (P > 0.05). Optic disc characteristics were not different (P > 0.05) between the subgroups of patients with normal-pressure glaucoma. CONCLUSION: The authors' findings support the idea that besides the enlargement of the area and extension of parapapillary atrophy that accompanies neural damage in glaucoma, the severity of the parapapillary atrophy also increases as assessed by the increase in zone beta in more damaged eyes. Furthermore, the final clinical appearance of optic nerve damage is similar among patients with POAG, normal-pressure glaucoma, and the subgroups of normal-pressure glaucoma, regardless of their possibly different mechanisms of neuropathy.

Aged↗

Morphometrical analysis of retinal arterial macroaneurysms.

Twenty-one macroaneurysms and related vessels of 19 patients were evaluated morphometrically. Macroaneurysms were classified into two groups as hemorrhagic and exudative in terms of their major clinical sign. Average diameters of the macroaneurysms were arranged in a Gaussian distribution curve (mean and standard deviation: 281.60 +/- 57.28 micrometers). Regarding the distribution curve based on this data macroaneurysm can be defined as being greater than 109.76 micrometers. Macroaneurysms were most frequent on the superotemporal vessels (52.38%), followed by the inferotemporal (38.10%), inferonasal (4.76%) and superonasal vessels. Average diameter (r = +0.68, p = 0.0006) and area (r = +0.71, p = 0.0003) of the macroaneurysms were significantly correlated to the diameter of the relevant arterial segments. The distribution of the macroaneurysms in respect to arterial bifurcation (chi 2 = 18.762, p = 0.0003) and arteriovenous crossings (chi 2 = 8.286, p = 0.0405) were nonrandom with macroaneurysms clustering near this points. Hemorrhagic macroaneurysms were significantly closer to the optic disc (p < 0.01) and were located on relatively larger arterioles (p < 0.01). They were also more circular (p < 0.01) in shape and greater in area (p < 0.01) and diameter (p < 0.01) than the exudative ones. These findings suggest that the location of the macroaneurysm is closely related to its clinical appearance.

Adult↗

Morphometric analysis of exudative retinal arterial macroaneurysms: a geometrical approach to exudate curves.

We studied morphometrically the color transparencies and fluorescein angiograms of 5 patients with six exudative retinal arterial macroaneurysms. Our aim was to express the dependence of the exudate morphology upon the location of the macroaneurysm with an algebraic polynomial analysis. We derived the second-degree conical equations of the exudate curves and computed the location of their cardinal descriptive parameters. The relationship between the site of the macroaneurysms and the computed hypothetical parameters of their exudate curves revealed that the structural features of the exudates are dependent upon the distance of the macroaneurysm to the foveola, the gravitational force and the clearing capacity of the venous net. The point where the macroaneurysm develops approximately 3 mm from the center of the macula seems to be a 'crucial point'. Macroaneurysms located closer than this point may cause the exudates that occupy the fovea and create severe visual loss.

Aneurysm↗

The comparative analysis of optic disc damage in exfoliative glaucoma.

To compare the initial and follow-up discernible glaucomatous neuroretinal rim (NRR) and parapapillary chorioretinal changes in patients with primary open-angle glaucoma (POAG) and exfoliative glaucoma (EG), we analyzed 40 optic discs from 40 patients with POAG, 40 optic discs from 40 patients with EG and 20 optic discs from 20 normal subjects. The mean intraocular pressure was higher in the EG group when compared with POAG (p < 0.001). Although the mean disc areas in both groups were not significantly different, the mean initial NRR area to disc area ratio was significantly smaller in patients with EG (p < 0.001). At the initial diagnosis the most prominent NRR defects of the patients with POAG were at the inferotemporal and superotemporal sectors, followed by the temporal and nasal sectors. However, the NRR in the EG group was noticed to decrease diffusely without such a sectorial preference. There was no significant difference between the mean loss of the NRR to disc area ratio in both groups at the end of the follow-up period of 1 year (p > 0.05). The values of parapapillary chorioretinal atrophy areas in POAG and EG patients were not significantly different from each other, neither at the initial examination nor during the follow-up period (p > 0.05). Those results suggest that high intraocular pressure in eyes with EG may constitute a major risk for rapid and progressive glaucomatous optic disc damage.

Adult↗