783 research outputs found

    Tumor Spreading to the Contralateral Ovary in Bilateral Ovarian Carcinoma Is a Late Event in Clonal Evolution

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    Cancer of the ovary is bilateral in 25%. Cytogenetic analysis could determine whether the disease in bilateral cases is metastatic or two separately occurring primary tumors, but karyotypic information comparing the two cancerous ovaries is limited to a single report with 11 informative cases. We present a series of 32 bilateral ovarian carcinoma cases, analyzed by karyotyping and high-resolution CGH. Our karyotypic findings showed that spreading to the contralateral ovary had occurred in bilateral ovarian cancer cases and that it was a late event in the clonal evolution of the tumors. This was confirmed by the large number of similar changes detected by HR-CGH in the different lesions from the same patient. The chromosomal bands most frequently involved in structural rearrangements were 19p13 (n = 12) and 19q13 (n = 11). The chromosomal bands most frequently gained by both tumorous ovaries were 5p14 (70%), 8q23-24 (65%), 1q23-24 (57%), and 12p12 (48%), whereas the most frequently lost bands were 17p11 (78%), 17p13 (74%), 17p12 (70%), 22q13 (61%), 8p21 and 19q13 (52%), and 8p22-23 (48%). This is the first time that 5p14 is seen gained at such a high frequency in cancer of the ovary; possibly oncogene(s) involved in bilateral ovarian carcinogenesis or tumor progression may reside in this band

    Retinal blood flow in patients with primary open angle glaucoma and optic disc hemorrhage

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    Purpose:To investigate total retinal blood flow (TRBF) and retinal blood flow (RBF) in the superior (S) and the inferior (I) retinal hemifields in patients with primary open angle glaucoma (POAG) both with and without disc hemorrhage (DH). Methods:RBF measurements were obtained from 10 POAG with DH (mean age 71.7, SD=7.39; 9 females)and 10 age matched POAG without DH (mean age 70, SD = 5.27; 6 females) using Doppler SD-OCT (RTVue; Optovue Inc, Fremont, CA, USA) as well as bi-directional laser Doppler flowmetry with densitometry (CLBF-100, Canon, Tokyo, Japan). TRBF measurements were compared between groups, within group for SRBF and IRBF, and for inter-ocular asymmetry (ANOVA; p<0.05). Correlation between TRBF and age, and TRBF and Mean Deviation of Humphrey automated perimetry were also analyzed. Results:Venous TRBF in the POAG with DH group (n=10, 27.1 μl/min, SD 7) was significantly lower than in the age-matched POAG without DH group (n=10, 38.83 μl/min, SD 10.66, p=0.009). RBF was not significantly different between the superior and inferior hemifields for either POAG with DH (p=0.763) or POAG without DH (p=0.481). In the POAG with DH group, venous TRBF was significantly lower in the DH eye (n=8, 28.73 μl/min, SD 6.87) compared to the contralateral eye without DH (n=8, 38.44 μl/min, SD 7.11, p=0.015). There was no significant difference between IOP, MD, BP, HR and MOPP between the POAG with and without DH groups. Also, there was no significant relationship between age or MD index of automated static perimetry with venous TRBF for the POAG with, and without DH group. Conclusions:Venous TRBF was significantly lower in the POAG with DH group compared to both the POAG without DH group and the contralateral eye of the POAG with DH group. There was no within eye asymmetry when comparing SRBF and IRBF either with or without DH, or when comparing the hemifield with DH to that without

    The role of contextual constraints and chronic expectancies on behavior categorizations and dispositional inferences

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    The authors examined the roles of chronic expectancies and other contextual information in the dispositional inference process within the domain of ability judgments. Prior to viewing a videotaped performance under either cognitive load or no load, participants in Studies 1 and 2 were given additional information designed to constrain their categorizations of the performance. In Study 2, chronic future-event expectancies also were assessed. Analyses revealed that when under cognitive load, participants' ability inferences were assimilated to the constraint information (Studies 1 and 2) and to chronic expectancies (Study 2). Furthermore, Study 2 analyses revealed that these effects were mediated by participants' behavior categorizations. Evidence suggestive of a proceduralized form of correction for task difficulty (Studies 1 and 2) and an effortful, awareness-based correction for the constraint information and for chronic expectancies also was found. Results are examined in light of recent models of the dispositional inference process

    Phenotyping EMT and Met Cellular States in Lung Cancer Patient Liquid Biopsies at a Personalized Level Using Mass Cytometry

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    Malignant pleural effusions (MPEs) can be utilized as liquid biopsy for phenotyping malignant cells and for precision immunotherapy, yet MPEs are inadequately studied at the single-cell proteomic level. Here we leverage mass cytometry to interrogate immune and epithelial cellular profiles of primary tumors and pleural effusions (PEs) from early and late-stage non-small cell lung cancer (NSCLC) patients, with the goal of assessing epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) states in patient specimens. By using the EMT-MET reference map PHENOSTAMP, we observe a variety of EMT states in cytokeratin positive (CK+) cells, and report for the first time MET-enriched CK+ cells in MPEs. We show that these states may be relevant to disease stage and therapy response. Furthermore, we found that the fraction of CD33+ myeloid cells in PEs was positively correlated to the fraction of CK+ cells. Longitudinal analysis of MPEs drawn 2 months apart from a patient undergoing therapy, revealed that CK+ cells acquired heterogeneous EMT features during treatment. We present this work as a feasibility study that justifies deeper characterization of EMT and MET states in malignant cells found in PEs as a promising clinical platform to better evaluate disease progression and treatment response at a personalized level

    Clinical Significance of Optic Disc Progression by Topographic Change Analysis Maps in Glaucoma: An 8-Year Follow-Up Study

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    Aim. To investigate the ability of Heidelberg Retina Tomograph (HRT3) Topographic Change Analysis (TCA) map to predict the subsequent development of clinical change, in patients with glaucoma. Materials. 61 eyes of 61 patients, which, from a retrospective review were defined as stable on optic nerve head (ONH) stereophotographs and visual field (VF), were enrolled in a prospective study. Eyes were classified as TCA-stable or TCA-progressed based on the TCA map. All patients underwent HRT3, VF, and ONH stereophotography at 9–12 months intervals. Clinical glaucoma progression was determined by masked assessment of ONH stereophotographs and VF Guided Progression Analysis. Results. The median (IQR) total HRT follow-up period was 8.1 (7.3, 9.1) years, which included a median retrospective and prospective follow-up time of 3.9 (3.1, 5.0) and 4.0 (3.5, 4.7) years, respectively. In the TCA-stable eyes, VF and/or photographic progression occurred in 5/13 (38.4%) eyes compared to 11/48 (22.9%) of the TCA-progressed eyes. There was no statistically significant association between TCA progression and clinically relevant (photographic and/or VF) progression (hazard ratio, 1.18; P=0.762). The observed median time to clinical progression from enrollment was significantly shorter in the TCA-progressed group compared to the TCA-stable group (P=0.04). Conclusion. Our results indicate that the commercially available TCA progression criteria do not adequately predict subsequent photographic and/or VF progression

    Evaluation of the retinal hemodynamics in patients with primary open angle glaucoma and differing nocturnal blood pressure profiles

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    Purpose: To evaluate the retinal hemodynamic response to normoxic hypercapnia among patients with primary open angle glaucoma (POAG) and differing nocturnal blood pressure (NBP) profiles, using Doppler spectral-domain optical coherence tomography (SD-OCT). Methods: Doppler SD-OCT retinal blood flow (RBF) measurement was acquired using the circum-papillary double circular scan protocol of the RTVue system (Optovue Inc., Freemont, CA). The sample consisted of 17 healthy controls (group mean age 62±7 years; group mean NBP dip 14±8%); 17 POAG with normal NBP dip (age 66±9 years; NBP dip 11±5%), termed “dippers”; and 16 POAG with high NBP dip (age 64±7 years; NBP dip 24±5%), “over-dippers”. The NBP dip magnitude was calculated by taking the difference between mean arterial pressure (MAP) during the day and night while awake and asleep, respectively. Automated gas blender (RespiractTM, Thornhill Research Inc., Toronto) was used to stably provoke normoxic hypercapnia (15% increase in the end-tidal carbon dioxide partial pressure relative to homeostatic baseline). Six Doppler SDOCT RBF scans were acquired, during baseline and also during normoxic hypercapnia. RBF parameters were calculated and ANOVA was used to compare values between groups (p<0.05). Results: Total RBF at baseline was significantly different between the groups with controls being the highest (37.1±4.4mL/min), and over-dippers the lowest (29.6±9.0mL/min). Venous area showed significant differences at baseline between the groups with the lowest value in the over-dipper group, and the highest in the control group (39.9±7.0(x10-3)mm, and 46.6±6.6x(10-3)mm, respectively). Velocity was not significantly different between groups (p=0.27) at baseline. Breathing normoxic hypercapnia provoked an increase in flow that was significantly lower in the over-dipper group (1.0±8.6mL/min) and highest in the controls (8.2±10.8mL/min). Change in velocity was significantly different (p=0.02) between the groups, being highest in the control group (2.4±3.3mm/s) and lowest in the over-dipper group (-0.6±3.1mm/s). Venous area change was not significantly different between groups. Conclusions: Patients with POAG who exhibited an exaggerated nocturnal reduction in MAP also demonstrated lower baseline RBF values and an impeded retinal vascular response to normoxic hypercapnia, indicating greater vascular dysregulation in this group
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