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Harvey F Lodish - One of the best experts on this subject based on the ideXlab platform.
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Histone deacetylase 2 is required for chromatin condensation and subsequent Enucleation of cultured mouse fetal erythroblasts
Haematologica, 2010Co-Authors: Victor Yeh, Maki Murata-hori, Tzutzuy Ramirez, Harvey F LodishAbstract:Background During the final stages of differentiation of mammalian erythroid cells, the chromatin is condensed and enucleated. We previously reported that Rac GTPases and their downstream target, mammalian homolog of Drosophila diaphanous 2 (mDia2), are required for Enucleation of in vitro cultured mouse fetal liver erythroblasts. However, it is not clear how chromatin condensation is achieved and whether it is required for Enucleation. Design and Methods Mouse fetal liver erythroblasts were purified from embryonic day 14.5 pregnant mice and cultured in erythropoietin-containing medium. Enucleation was determined by flow-cytometry based analysis after treatment with histone deacetylase inhibitors or infection with lentiviral short harirpin RNA. Results We showed that histone deacetylases play critical roles in chromatin condensation and Enucleation in cultured mouse fetal liver erythroblasts. Enzymatic inhibition of histone deacetylases by trichostatin A or valproic acid prior to the start of Enucleation blocked chromatin condensation, contractile actin ring formation and Enucleation. We further demonstrated that histone deacetylases 1, 2, 3 and 5 are highly expressed in mouse fetal erythroblasts. Short hairpin RNA down-regulation of histone deacetylase 2, but not of the other histone deacetylases, phenotypically mimicked the effect of trichostatin A or valproic acid treatment, causing significant inhibition of chromatin condensation and Enucleation. Importantly, knock-down of histone deacetylase 2 did not affect erythroblast proliferation, differentiation, or apoptosis. Conclusions These results identify histone deacetylase 2 as an important regulator, mediating chromatin condensation and Enucleation in the final stages of mammalian erythropoiesis.
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Histone Deacetylases Are Essential for Chromatin Condensation and Enucleation in Mammalian Erythroblasts
Blood, 2008Co-Authors: Francisco J. Sánchez-rivera, Harvey F LodishAbstract:In the last steps of differentiation mammalian erythroid cells undergo chromatin condensation and Enucleation; the latter process does not occur in other vertebrates. Enucleation was critical for the evolution of mammals, as it permits an enhanced hemoglobin concentration – and thus oxygen- carrying capacity – in mammalian red blood cells. We previously reported that Rac GTPases and their downstream forming target mDia2 are required for mouse fetal erythroblast Enucleation. We also found that the nucleus undergoes a gradual ~10- fold decrease in volume during erythropoiesis. Since histone deacetylases (HDACs) play important roles in chromatin condensation, we hypothesized that HDACs are involved in mammalian erythroblast Enucleation. To test this hypothesis, we purified E13.5 mouse fetal TER119 negative erythroblasts and cultured them in fibronectin-coated plates. Cells were then treated with Trichostatin A (TSA), a pan-HDAC inhibitor, at different times during erythropoiesis. TSA completely blocked Enucleation and kinetic studies showed this inhibitory effect occurred earlier than the step catalyzed by the Rac-mDia2 pathway. This indicates that chromatin condensation is required for the final extrusion of the nucleus. We further investigated the activity ofHDAC6 specifically, since HDAC6 is known to interact with mDia2. We found that mDia2is acetylated in vitro and in vivo and that HDAC6 interacts with and deacetylates mDia2. Treatment of purified TER119 negative mouse fetal erythroblasts with a specific HDAC6inhibitor partially blocked Enucleation. We conclude that histone deacetylase activities are essential for mammalian erythroblasts to undergo Enucleation and that HDACs act both on chromatin condensation and mDia2 deacetylation to promote Enucleation.
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Enucleation of cultured mouse fetal erythroblasts requires Rac GTPases and mDia2
Nature cell biology, 2008Co-Authors: Senthil Raja Jayapal, Harvey F LodishAbstract:Mammalian erythroid cells undergo Enucleation, an asymmetric cell division involving extrusion of a pycnotic nucleus enveloped by the plasma membrane. The mechanisms that power and regulate the Enucleation process have remained obscure. Here, we show that deregulation of Rac GTPase during a late stage of erythropoiesis completely blocks Enucleation of cultured mouse fetal erythroblasts without affecting their proliferation or differentiation. Formation of the contractile actin ring (CAR) on the plasma membrane of enucleating erythroblasts was disrupted by inhibition of Rac GTPases. Furthermore, we demonstrate that mDia2, a downstream effector of Rho GTPases and a formin protein required for nucleation of unbranched actin filaments, is also required for Enucleation of mouse fetal erythroblasts. We show that Rac1 and Rac2 bind to mDia2 in a GTP-dependent manner and that downregulation of mDia2, but not mDia1, by small interfering RNA (siRNA) during the late stages of erythropoiesis blocked both CAR formation and erythroblast Enucleation. Additionally, overexpression of a constitutively active mutant of mDia2 rescued the Enucleation defects induced by the inhibition of Rac GTPases. These results reveal important roles for Rac GTPases and their effector mDia2 in Enucleation of mammalian erythroblasts.
Mostafa M Elhilali - One of the best experts on this subject based on the ideXlab platform.
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greenlight laser xps photoselective vapo Enucleation versus holmium laser Enucleation of the prostate for the treatment of symptomatic benign prostatic hyperplasia a randomized controlled study
The Journal of Urology, 2015Co-Authors: Ahmed M Elshal, Adel Nabeeh, Serge Carrier, Mohamed A Elkoushy, Ahmed R Elnahas, Ahmed M. Shoma, Mostafa M ElhilaliAbstract:Purpose: After the advent of the GreenLight XPS™ (180 W) 532 nm laser, photoselective vapo-Enucleation of the prostate could compete with holmium laser Enucleation of the prostate as a size independent procedure. We assessed whether photoselective vapo-Enucleation of the prostate-XPS is not less effective than holmium laser Enucleation of prostate for improvement of lower urinary tract symptoms secondary to benign prostatic hyperplasia.Materials and Methods: A randomized controlled noninferiority trial comparing holmium laser Enucleation of the prostate to photoselective vapo-Enucleation of the prostate-XPS 180 W was conducted. I-PSS, flow rate, residual urine, prostate specific antigen and prostate volume changes as well as perioperative and late adverse events were compared. Noninferiority of I-PSS at 1 year was evaluated using a 1-sided test at 5% level of significance. The statistical significance of other comparators was assessed at the (2-sided) 5% level.Results: Overall 50 and 53 patients were incl...
Mohamed A Elkoushy - One of the best experts on this subject based on the ideXlab platform.
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greenlight laser xps photoselective vapo Enucleation versus holmium laser Enucleation of the prostate for the treatment of symptomatic benign prostatic hyperplasia a randomized controlled study
The Journal of Urology, 2015Co-Authors: Ahmed M Elshal, Adel Nabeeh, Serge Carrier, Mohamed A Elkoushy, Ahmed R Elnahas, Ahmed M. Shoma, Mostafa M ElhilaliAbstract:Purpose: After the advent of the GreenLight XPS™ (180 W) 532 nm laser, photoselective vapo-Enucleation of the prostate could compete with holmium laser Enucleation of the prostate as a size independent procedure. We assessed whether photoselective vapo-Enucleation of the prostate-XPS is not less effective than holmium laser Enucleation of prostate for improvement of lower urinary tract symptoms secondary to benign prostatic hyperplasia.Materials and Methods: A randomized controlled noninferiority trial comparing holmium laser Enucleation of the prostate to photoselective vapo-Enucleation of the prostate-XPS 180 W was conducted. I-PSS, flow rate, residual urine, prostate specific antigen and prostate volume changes as well as perioperative and late adverse events were compared. Noninferiority of I-PSS at 1 year was evaluated using a 1-sided test at 5% level of significance. The statistical significance of other comparators was assessed at the (2-sided) 5% level.Results: Overall 50 and 53 patients were incl...
James E Lingeman - One of the best experts on this subject based on the ideXlab platform.
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a survey of morcellator preference and cost comparison of the lumenis versacut and wolf piranha morcellators
Urology, 2018Co-Authors: Marcelino E Rivera, Kevin Heinsimer, Nadya York, James E Lingeman, Amy Elizabeth KrambeckAbstract:OBJECTIVE: To evaluate operating room (OR) costs associated with the 2 available morcellators in the United States in a matched cohort and to determine benign prostatic hyperplasia surgeon's morcellator preference. MATERIALS AND METHODS: Patients from 2013, the last year our institution exclusively used the VersaCut device, were matched 1:1 with the most recent patient cohort, utilizing the Wolf Piranha morcellator. Cost of morcellation including the expense of OR time and disposable instrument costs were calculated. A survey to the Endourological Society e-mail listserv was sent to determine morcellator preference. RESULTS: We identified 142 patients who underwent holmium laser Enucleation of the prostate in 2013. When compared with the VersaCut group, morcellation efficiency (4.4 vs 7.0 g/min, P <.01) and expense of OR time ($1420.80 vs $992.21, P <.005) both favored the Piranha morcellator system even when the costs of disposable instruments were factored into the analysis ($1338.81 vs $1637.50, P <.05). A total of 126 urologists responded to the survey. Of these, 56 (44.5%) perform transurethral prostate Enucleations, which included 48 (86%) holmium. More endourologists use the VersaCut (n = 33, 59%) than the Piranha (n = 24, 43%) morcellator. Qualities that impacted the preference of morcellator included the preferred device is safer, faster, easier to use, reusable, and less expensive. CONCLUSION: We identified a significant improved efficiency and improved cost savings utilizing the Piranha morcellator even when controlling for disposable costs. Of the endourologists who responded to the survey, less than half perform transurethral Enucleation. Morcellator preference is largely based on safety, efficiency, and ease of use, whereas cost and reusablility were of lesser importance.
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outcomes of holmium laser Enucleation of the prostate in the re treatment setting
Author, 2017Co-Authors: Tracy Marien, Nadya York, Amy E Krambeck, Mustafa Kadihasanoglu, Teerayut Tangpaitoon, Andrew T Blackburne, Haidar Abdulmuhsin, Michael S Borofsky, Mitchell R Humphreys, James E LingemanAbstract:Purpose: Holmium laser Enucleation of the prostate can also be applied in the re-treatment setting when other benign prostatic hyperplasia therapies fail. We compared outcomes in men who underwent holmium laser Enucleation of the prostate in the primary vs the re-treatment setting.Materials and Methods: We retrospectively reviewed the records of 2,242 patients who underwent holmium laser Enucleation of the prostate at a total of 4 academic hospitals between 2003 and 2015. Patient demographics, and operative and perioperative outcomes were compared between re-treatment and primary holmium laser Enucleation of the prostate.Results: Of the 360 of 2,242 men (16%) who underwent re-treatment holmium laser Enucleation of the prostate the procedure was done for residual urinary symptoms in 71%. The most common primary procedure was transurethral resection of the prostate in 42% of cases. Mean time between prior benign prostatic hyperplasia surgery and re-treatment was 68 months (range 1 to 444). There were no sig...
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predictors of Enucleation and morcellation time during holmium laser Enucleation of the prostate
Author, 2015Co-Authors: Francesca M Monn, Marawan El M Tayeb, Naeem Bhojani, Matthew J Mellon, James C Sloan, Ronald S Boris, James E LingemanAbstract:Objective To examine predictors of Enucleation and morcellation times within a large cohort of men undergoing holmium laser Enucleation of the prostate (HoLEP) for benign prostatic hypertrophy. Materials and Methods Preoperative, perioperative, and postoperative clinical characteristics were available from men treated with HoLEP between 1998 and 2013 at Indiana University Health Methodist Hospital. Stepwise linear regression was performed to determine clinical variables which are associated with Enucleation and morcellation times. Results We identified 960 patients who underwent HoLEP. Average (range) Enucleation time was 65.7 (11-245) minutes and morcellation time was 19.7 (3-260) minutes. History of anticoagulation was associated with a small decrease in Enucleation time (P = .013) whereas increasing HoLEP specimen weight was associated with increasing Enucleation time (P <.001). History of intermittent catheterization, urinary tract infections (UTI), presence of dense prostatic tissue (colloquially referred to as “beach balls”), and increasing specimen weight were associated with increasing morcellation time (P <.05 each). Having HoLEP performed by a less experienced urologist was associated with longer Enucleation and morcellation times. Conclusion Prostate volume is significantly associated with increased Enucleation and morcellation times during HoLEP. Additionally, history of UTI and clean intermittent catheterization (CIC) is associated with modest increases in Enucleation and morcellation times. Dense enucleated prostate tissue significantly impacts the ability to morcellate effectively. Increasing surgeon experience can significantly improve both Enucleation and morcellation efficiency.
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experience with more than 1 000 holmium laser prostate Enucleations for benign prostatic hyperplasia
The Journal of Urology, 2010Co-Authors: Amy E Krambeck, Shelly E Handa, James E LingemanAbstract:Purpose: Holmium laser prostate Enucleation is a contemporary treatment for benign prostatic hyperplasia. We report our experience with more than 1,000 procedures.Materials and Methods: From June 1998 to March 2009 we performed 1,065 holmium laser prostate Enucleations. After receiving institutional review board approval we retrospectively reviewed the database. Reported short-term, intermediate term and long-term results are 0 to 6, 6 to 12 and greater than 12 months, respectively.Results: Bladder stones were present in 50 patients (4.7%) and 87 of the 717 (12.1%) with laboratory studies available had renal insufficiency. Preoperative urinary retention was present in 411 cases (38.7%). Significant preoperative stress and urge incontinence was noted in 8 and 16 patients, respectively. Mean transrectal ultrasound prostate volume was 99.3 gm (range 9 to 391). Mean preoperative American Urological Association symptom score was 20.3 (range 1 to 35) and maximum urinary flow was 8.4 cc per second (range 1.1 to ...
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holmium laser Enucleation of prostate holep the methodist hospital experience with greater than 75 gram Enucleations
The Journal of Urology, 2003Co-Authors: Ramsay L Kuo, James E Lingeman, Samuel C Kim, Ryan F Paterson, Stephanie L Watkins, Garrick R Simmons, Ronald E SteeleAbstract:ABSTRACTPurpose: Holmium laser Enucleation of the prostate (HoLEP) effectively removes obstructive prostate tissue in minimally invasive fashion. We present our large Enucleation outcomes (greater than 75 gm retrieved). We examined post-procedural prostate specific antigen (PSA) and transrectal ultrasound (TRUS) volume changes to assess tissue removal completeness.Materials and Methods: We retrospectively reviewed HoLEPs performed from April 1, 1999 through September 30, 2002 to identify all Enucleations greater than 75 gm. Demographic, laboratory, operative and pathological data were obtained. Patients were surveyed to document longer term complications.Results: The cohort of 108 patients had a mean age and specimen weight of 71.5 years (range 53 to 90) and 120.6 gm (range 75.3 to 376), respectively. Average procedural time and hospital stay were 166.8 minutes (range 75 to 473) and 1.2 days (range 0 to 4), respectively. No deaths or episodes of transurethral resection syndrome occurred. Postoperative com...
Ahmed M Elshal - One of the best experts on this subject based on the ideXlab platform.
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greenlight laser xps photoselective vapo Enucleation versus holmium laser Enucleation of the prostate for the treatment of symptomatic benign prostatic hyperplasia a randomized controlled study
The Journal of Urology, 2015Co-Authors: Ahmed M Elshal, Adel Nabeeh, Serge Carrier, Mohamed A Elkoushy, Ahmed R Elnahas, Ahmed M. Shoma, Mostafa M ElhilaliAbstract:Purpose: After the advent of the GreenLight XPS™ (180 W) 532 nm laser, photoselective vapo-Enucleation of the prostate could compete with holmium laser Enucleation of the prostate as a size independent procedure. We assessed whether photoselective vapo-Enucleation of the prostate-XPS is not less effective than holmium laser Enucleation of prostate for improvement of lower urinary tract symptoms secondary to benign prostatic hyperplasia.Materials and Methods: A randomized controlled noninferiority trial comparing holmium laser Enucleation of the prostate to photoselective vapo-Enucleation of the prostate-XPS 180 W was conducted. I-PSS, flow rate, residual urine, prostate specific antigen and prostate volume changes as well as perioperative and late adverse events were compared. Noninferiority of I-PSS at 1 year was evaluated using a 1-sided test at 5% level of significance. The statistical significance of other comparators was assessed at the (2-sided) 5% level.Results: Overall 50 and 53 patients were incl...