44 results on '"Koch GE"'
Search Results
2. Topochemical distribution of lignin and hydroxycinnamic acids in sugar-cane cell walls and its correlation with the enzymatic hydrolysis of polysaccharides
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Koch Gerald, Carvalho Walter, Milagres Adriane MF, Siqueira Germano, and Ferraz André
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Fuel ,TP315-360 ,Biotechnology ,TP248.13-248.65 - Abstract
Abstract Background Lignin and hemicelluloses are the major components limiting enzyme infiltration into cell walls. Determination of the topochemical distribution of lignin and aromatics in sugar cane might provide important data on the recalcitrance of specific cells. We used cellular ultraviolet (UV) microspectrophotometry (UMSP) to topochemically detect lignin and hydroxycinnamic acids in individual fiber, vessel and parenchyma cell walls of untreated and chlorite-treated sugar cane. Internodes, presenting typical vascular bundles and sucrose-storing parenchyma cells, were divided into rind and pith fractions. Results Vascular bundles were more abundant in the rind, whereas parenchyma cells predominated in the pith region. UV measurements of untreated fiber cell walls gave absorbance spectra typical of grass lignin, with a band at 278 nm and a pronounced shoulder at 315 nm, assigned to the presence of hydroxycinnamic acids linked to lignin and/or to arabino-methylglucurono-xylans. The cell walls of vessels had the highest level of lignification, followed by those of fibers and parenchyma. Pith parenchyma cell walls were characterized by very low absorbance values at 278 nm; however, a distinct peak at 315 nm indicated that pith parenchyma cells are not extensively lignified, but contain significant amounts of hydroxycinnamic acids. Cellular UV image profiles scanned with an absorbance intensity maximum of 278 nm identified the pattern of lignin distribution in the individual cell walls, with the highest concentration occurring in the middle lamella and cell corners. Chlorite treatment caused a rapid removal of hydroxycinnamic acids from parenchyma cell walls, whereas the thicker fiber cell walls were delignified only after a long treatment duration (4 hours). Untreated pith samples were promptly hydrolyzed by cellulases, reaching 63% of cellulose conversion after 72 hours of hydrolysis, whereas untreated rind samples achieved only 20% hydrolyzation. Conclusion The low recalcitrance of pith cells correlated with the low UV-absorbance values seen in parenchyma cells. Chlorite treatment of pith cells did not enhance cellulose conversion. By contrast, application of the same treatment to rind cells led to significant removal of hydroxycinnamic acids and lignin, resulting in marked enhancement of cellulose conversion by cellulases.
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- 2011
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3. Accounting for risk in valuing forest carbon offsets
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Koch George W, Hungate Bruce A, and Hurteau Matthew D
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Environmental sciences ,GE1-350 - Abstract
Abstract Background Forests can sequester carbon dioxide, thereby reducing atmospheric concentrations and slowing global warming. In the U.S., forest carbon stocks have increased as a result of regrowth following land abandonment and in-growth due to fire suppression, and they currently sequester approximately 10% of annual US emissions. This ecosystem service is recognized in greenhouse gas protocols and cap-and-trade mechanisms, yet forest carbon is valued equally regardless of forest type, an approach that fails to account for risk of carbon loss from disturbance. Results Here we show that incorporating wildfire risk reduces the value of forest carbon depending on the location and condition of the forest. There is a general trend of decreasing risk-scaled forest carbon value moving from the northern toward the southern continental U.S. Conclusion Because disturbance is a major ecological factor influencing long-term carbon storage and is often sensitive to human management, carbon trading mechanisms should account for the reduction in value associated with disturbance risk.
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- 2009
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4. The electronic artificial urinary sphincter: ongoing innovation of a classic device-a narrative review.
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Koch GE and Kaufman MR
- Abstract
Background and Objective: While the modern artificial urinary sphincter (AUS) has benefited from incremental innovation, which has improved both device efficacy and complication rates, the foundational technology in use in Boston Scientific's AMS800 can be traced back to the fundamental hydraulic tenets of the AS721. Research and development in adaptive technology and electronic integration stand to further improve AUS outcomes., Methods: The Medline online retrieval system was queried using the MeSH terms "artificial urinary sphincter", "electronic", "complications", "history", and "development" in various combinations. Publications were reviewed if applicable, and their reference lists were used to collect additional articles as needed. Final article inclusion was based on senior author discretion., Key Content and Findings: The AMS800 AUS is the gold standard for male stress incontinence implants. A 2015 consensus conference set out the goals for sphincter device development in the coming decades. A future ideal sphincter would adjust cuff pressure dynamically as well as function with minimal manipulation, or even via electronic control. Multiple new devices are in various states of development. During the next decade, artificial urinary sphincter technology is likely to include multiple Food and Drug Administration (FDA)-approved devices with varying features aimed at satisfying the 2015 consensus conference goal for an "ideal" AUS., Conclusions: The future of stress incontinence therapy lies in both continued innovation for the AUS, as well as advances in regenerative medicine. Electronic and adaptive developments in AUS technology will increase device safety, efficacy, and longevity while improving the user and caregiver experience. For some, regenerative medicine may even make AUS technology obsolete., Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-22-858/coif). The series “50 Years Anniversary of the Modern Artificial Urinary Sphincter” was commissioned by the editorial office without any funding or sponsorship. M.R.K. receives honoraria from Boston Scientific to teach at resident and fellow educational course, but that did not support this review article in any way. The authors have no other conflicts of interest to declare., (2024 Translational Andrology and Urology. All rights reserved.)
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- 2024
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5. Skin-Sparing Debridement in Fournier's Gangrene.
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Koch GE, Amighi A, Skokan AJ, and Hagedorn JC
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- 2024
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6. Editorial Comment on "Early Post-Operative Events After Urethroplasty in Obese Patients: A Multi-Institutional Retrospective Series".
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Weiss T and Koch GE
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- Humans, Male, Urethral Stricture surgery, Retrospective Studies, Urologic Surgical Procedures, Male methods, Time Factors, Obesity complications, Obesity surgery, Postoperative Complications etiology, Urethra surgery
- Abstract
Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest.
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- 2024
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7. Implementation and Interim Analysis of a Standardized Renal Trauma Imaging and Urinary Extravasation Management Protocol.
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Chisholm L, Koch GE, Huang JJ, Bhalla RG, Ayangbesan A, Walton WJ, Dennis BM, Guillamondegui O, and Johnsen NV
- Abstract
Introduction: The AUA recommends delayed-phase imaging (DPI) in renal injuries to evaluate the collecting system. A renal trauma imaging protocol for early conservative management of urinary extravasation (UE) was implemented to improve guideline adherence. We aimed to determine if increased adherence led to changes in outcomes., Methods: Patients with American Association for the Surgery of Trauma III to V renal injury presenting from January 2018 to September 2022 were identified from an institutional trauma registry. Patients were included if a contrasted CT scan of the abdomen was obtained on admission. Frequency of DPI and patient outcomes were compared before and after protocol implementation., Results: Of 223 included patients, 131 (58.7%) were pre protocol and 92 (41.3%) were post protocol. Following protocol implementation, the rate of DPI on admission nearly doubled from 32.8% to 58.7% ( P < .001). The rate of follow-up cross-sectional imaging increased from 18.3% to 58.7% ( P < .001). Although there were no significant differences in rates of immediate or delayed interventions following protocol implementation, the postprotocol immediate intervention rate did decrease to 0%. Readmissions due to symptomatic UE were unchanged after protocol implementation (0.0% vs 0.0%)., Conclusions: Implementation of a multidisciplinary renal trauma early imaging and management protocol improved AUA guideline adherence. With protocol adherence, there was also an elimination of immediate interventions for UE. Despite decreases in early intervention, there was no significant increase in interval interventions or UE-related readmissions. More research is needed to determine the role for routine follow-up imaging in conservative management of high-grade renal trauma.
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- 2024
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8. Multidisciplinary management in Fournier's gangrene.
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Koch GE, Abbasi B, Agoubi L, Breyer BN, Clark N, Dick BP, Friedrich JB, Hampson LA, Hernandez A, Maine R, Osterberg EC, Teal L, Woodle CT, and Hagedorn JC
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- Humans, Male, Patient Care Team, Combined Modality Therapy, Anti-Bacterial Agents therapeutic use, Fournier Gangrene therapy, Fournier Gangrene diagnosis, Fournier Gangrene surgery, Debridement methods
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- 2024
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9. Unlocking Peer Review: Elevating Scholarly Writing and Research Competence in Urology Residency.
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Dwyer K and Koch GE
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- Humans, Biomedical Research education, Peer Review, Writing standards, Peer Review, Research, Education, Medical, Graduate methods, Curriculum, Urology education, Internship and Residency methods
- Abstract
Purpose of Review: It is incumbent upon training programs to set the foundation for evidence-based practices and to create opportunities for trainees to develop into academic leaders. As dedicated resident research time and funding have declined in recent years, residency programs and the field at large will need to create new ways to incorporate scholarly activity into residency curricula., Recent Findings: Literature across specialties demonstrates barriers to resident involvement including lack of time, cost, and absent scholarly mentorship. Peer review stands as a ready-made solution that can be formalized into a collaborative relationship with journals. A formal relationship between professional societies, academic journals, and residencies can facilitate the use of peer review as a teaching tool for residency programs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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10. George E. Koch, MD.
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Koch GE
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- 2024
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11. Context reinstatement requires a schema relevant virtual environment to benefit object recall.
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Koch GE and Coutanche MN
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How does our environment impact what we will later remember? Early work in real-world environments suggested that having matching encoding/retrieval contexts improves memory. However, some laboratory-based studies have not replicated this advantageous context-dependent memory effect. Using virtual reality methods, we find support for context-dependent memory effects and examine an influence of memory schema and dynamic environments. Participants (N = 240) remembered more objects when in the same virtual environment (context) as during encoding. This traded-off with falsely "recognizing" more similar lures. Experimentally manipulating the virtual objects and environments revealed that a congruent object/environment schema aids recall (but not recognition), though a dynamic background does not. These findings further our understanding of when and how context affects our memory through a naturalistic approach to studying such effects., (© 2024. The Psychonomic Society, Inc.)
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- 2024
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12. The urologist's role in bowel management of adult spina bifida: a narrative review.
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Sundell M, Koch GE, and Kaufman M
- Abstract
Background and Objective: Urologists are central to the coordinated care of patients with spina bifida (SB), and efforts to optimize bladder management and protection of the upper tracts are well established. However, the urologist's role in treating this population often extends to the management of bowel dysfunction which may be less defined. The methods available to the urologist for bowel management range from lifestyle modifications to medical and surgical therapy, with many patients requiring combinations of multiple strategies to combat conflicting symptoms of constipation and fecal incontinence (FI). This narrative review aims to compile a detailed algorithm of management options, for the practicing urologist to more confidently address this important facet of care., Methods: A detailed review was conducted using PubMed and Google Scholar databases to assess the contemporary literature surrounding neurogenic bowel dysfunction in adult SB. Articles published in English between 1990 and 2023 were considered., Key Content and Findings: This review presents and investigates a schema of increasingly definitive and invasive treatments for bowel dysfunction including lifestyle adaptations, pharmacological treatment, transanal irrigation (TAI), sacral neuromodulation (SNM), antegrade continence procedures, and bowel diversion. TAI and medical bowel care are beneficial in postponing or avoiding more invasive surgical interventions. Should conservative measures prove ineffective, surgical management provides the most definitive bowel control., Conclusions: Symptoms of constipation and FI that result from neurogenic bowel are best managed with an individualized approach guided by the general treatment algorithm presented in this review. Educated on the numerous appropriate options, patients will often trial methods before proceeding with more invasive treatments. Additional work is required to further evaluate management options specific to the SB populations, especially in more contemporary and largely experimental treatment modalities such as SNM., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-23-389/coif). G.E.K. received a research grant from the Society of Urologic Prosthetic Surgeons for research unrelated to this manuscript. The other authors have no conflicts of interest to declare., (2024 Translational Andrology and Urology. All rights reserved.)
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- 2024
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13. Qualitative Analysis of Patient Experiences Reaching Urethroplasty for Recurrent Urethral Stricture Disease.
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Ayangbesan A, Koch GE, Dagostino C, Proctor JM, Gambrah H, Bhalla RG, Bonnet K, Schlundt D, and Johnsen NV
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- Humans, Male, Quality of Life, Urethra surgery, Treatment Outcome, Urologic Surgical Procedures, Male methods, Patient Outcome Assessment, Retrospective Studies, Urethral Stricture etiology
- Abstract
Purpose: Despite the inferior outcomes, urethral stricture patients often undergo multiple endoscopic procedures prior to undergoing definitive urethroplasty. We sought to qualitatively evaluate the patient experience of obtaining urethroplasty to better understand the impact of this experience on quality of life., Materials and Methods: Patients treated with urethroplasty between September 2019 and July 2021 were identified and invited to participate in our study if they had undergone ≥ 2 endoscopic procedures prior to urethroplasty. Semistructured telephone interviews were conducted, coded, and analyzed using an iterative inductive-deductive approach., Results: Of the 105 urethroplasty patients during the study period, 50 (47.6%) had undergone ≥ 2 endoscopic procedures prior (IQR 3-5), of whom 20 participated in the study. Qualitative themes related to repeat endoscopic procedures included unmet treatment expectations, dissatisfaction with catheterization and repeat procedures, and negative impacts of recurrent stricture symptoms and treatments on quality of life. External factors associated with a delay to urethroplasty included financial constraints, surgeon access, and time off work., Conclusions: A trajectory of declining quality of life and unmet treatment expectations are the primary factors driving the decision to proceed with urethroplasty. However, external factors such as recovery costs and access to specialists play important roles in delaying surgery. These findings illustrate the need for improved community provider education and patient counseling to better inform expectations of both patients and providers with various treatment outcomes. Furthermore, these data highlight the need to improve access to specialized care for urethral stricture patients.
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- 2024
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14. The Role of Alumni Networks and Career Advising in Early Career Stability of Urologists: Results of a Multi-institutional Study.
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Cabo JJS, Koch GE, Tallman JE, Thavaseelan S, Oberle M, Terris M, Kronenberg DG, Buckley JC, Scarpato KR, and Chang SS
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- Humans, Urologists, Career Choice, Employment, Surveys and Questionnaires, Internship and Residency, Urology
- Abstract
Objective: To characterize training program and early career factors that impact decision-making and job retention following graduation in a diverse population of urologists., Materials and Methods: We performed a computer-based survey distributed to residency graduates from 25 urology training programs. Five focus institutions were identified with a goal >30% response rate. The survey included questions about training program specifics and post-training employment characteristics., Results: We obtained 180 responses from urology residency graduates of 25 programs. Overall, 72% (N = 129) remain in their initial post-training position at a median of 6years postgraduation (Interquartile Range (IQR) 3-10). On Cox-regression analysis stronger trainee-rated formal career advising was associated with lower risk of changing jobs (HR 0.77, 0.60-0.99, P = .048). Location/proximity to family was the most consistently cited as the top reason for selecting a job (41%). Sixty-three respondents (35%) joined practices employing graduates of the same residency program. Cox regression analysis showed that joining a practice with alumni of the same program was associated with lower risk of changing jobs from one's initial post-training position (HR 0.39, 95% CI 0.17-0.91, P = .03)., Conclusion: In this multi-institutional study of urologists, we observed a high rate of job retention out to a median of 6years following completion of training, with formal career advising and joining alumni in practice being associated with job retention. Collectively, our data highlights that training programs should emphasize advising programs and alumni networking in guiding their graduates in the job search process., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2023
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15. A Disease-Specific Antibiogram to Evaluate Empiric Coverage Patterns in Fournier's Gangrene.
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Koch GE, Launer BM, Li AN, and Johnsen NV
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- Male, Humans, Anti-Bacterial Agents therapeutic use, Microbial Sensitivity Tests, Retrospective Studies, Fournier Gangrene drug therapy, Fournier Gangrene surgery, Bacteremia drug therapy
- Abstract
Objective: To analyze our local antibiogram and antibiotic resistance patterns given concern for multidrug-resistant and fungal organisms in contemporary series detailing causative organisms in Fournier's Gangrene (FG)., Methods: All patients from 2018 to 2022 were identified from the institutional FG registry. Microorganisms and sensitivities were collected from operative tissue cultures. The primary outcome of this study was the adequacy of our empiric. Secondary outcomes included the rate of bacteremia, the concordance of blood cultures and tissue cultures, and the rate of fungal tissue infections., Results: Escherichia coli and Streptococcus anginosus were most common, identified in 12 patients each (20.0%). Enterococcus faecalis (9, 15.0%), S agalactiae (8, 13.3%) and mixed cultures without a predominant organism (9, 15.0%) were also common. A fungal organism was identified in 9 (15.0%) patients. Patients who were started on Infectious Diseases Society of America guideline adherent antibiotic regimen were not significantly different in terms of bacteremia rate (P = .86), mortality (P = .25), length of stay (P = .27), or final antibiotic duration (P = .43) when compared to those on alternative regimens. Patients with a tissue culture positive for a fungal organism were not significantly different in terms of Fournier's Gangrene Severity Index (P = .25) or length of stay (P = .19)., Conclusion: Local disease-specific antibiograms can be a powerful tool to guide empiric antibiotic therapy in FG. Although fungal infections are responsible for a majority of the gaps in empiric antimicrobial coverage at our institution they were present in only 15% of patients and their effect on outcomes does not justify addition of empiric antifungal agents., Competing Interests: Declaration of Competing Interest None Declared., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
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16. Editorial Comment.
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Koch GE
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- 2023
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17. Leading Antimicrobial Stewardship From the Operating Room.
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Koch GE, Tallman JE, and Dmochowski RR
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- Humans, Operating Rooms, Anti-Bacterial Agents therapeutic use, Antimicrobial Stewardship
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- 2023
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18. Representations within the Intraparietal Sulcus Distinguish Numerical Tasks and Formats.
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Koch GE, Libertus ME, Fiez JA, and Coutanche MN
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- Adult, Humans, Temporal Lobe, Semantics, Occipital Lobe, Magnetic Resonance Imaging methods, Brain Mapping, Parietal Lobe diagnostic imaging, Brain
- Abstract
How does our brain understand the number five when it is written as an Arabic numeral, and when presented as five fingers held up? Four facets have been implicated in adult numerical processing: semantic, visual, manual, and phonological/verbal. Here, we ask how the brain represents each, using a combination of tasks and stimuli. We collected fMRI data from adult participants while they completed our novel "four number code" paradigm. In this paradigm, participants viewed one of two stimulus types to tap into the visual and manual number codes, respectively. Concurrently, they completed one of two tasks to tap into the semantic and phonological/verbal number codes, respectively. Classification analyses revealed that neural codes representing distinctions between the number comparison and phonological tasks were generalizable across format (e.g., Arabic numerals to hands) within intraparietal sulcus (IPS), angular gyrus, and precentral gyrus. Neural codes representing distinctions between formats were generalizable across tasks within visual areas such as fusiform gyrus and calcarine sulcus, as well as within IPS. Our results identify the neural facets of numerical processing within a single paradigm and suggest that IPS is sensitive to distinctions between semantic and phonological/verbal, as well as visual and manual, facets of number representations., (© 2022 Massachusetts Institute of Technology.)
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- 2023
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19. Prodromal Fournier's Gangrene: A Potential Opportunity for Early Intervention.
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Koch GE, Dropkin BM, and Kaufman MR
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- Male, Humans, Debridement, Severity of Illness Index, Fournier Gangrene diagnosis, Fournier Gangrene surgery
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- 2022
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20. Author Reply.
- Author
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Koch GE and Johnsen NV
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- 2022
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21. Expectant Management of Blunt Grade III Renal Injuries: Early Discharge Outcomes From a Level I Trauma Center.
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Koch GE, Bhalla RG, Ayangbesan A, Huang JJ, Walton WJ, Dennis BM, Guillamondegui OD, and Johnsen NV
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- Humans, Patient Discharge, Injury Severity Score, Watchful Waiting, Kidney surgery, Retrospective Studies, Trauma Centers, Wounds, Nonpenetrating diagnosis, Wounds, Nonpenetrating therapy, Wounds, Nonpenetrating complications
- Abstract
Objectives: To determine whether patients with American Association for the Surgery of Trauma (AAST) grade III blunt renal injuries discharged within 48 hours of admission have increased rates of readmission for renal-related complications compared to patients observed for over 48 hours., Methods: Renal trauma patients from 2005 through 2020 were identified from our institutional trauma registry. Patients with AAST III blunt renal injuries who survived beyond 48 hours of admission were included. Univariable analysis was used to identify variables associated with discharge within 48 hours. Reasons for readmission were compared between patients discharged before and after 48 hours of admission., Results: Of the 1751 renal trauma patients, 377 (21.5%) met inclusion criteria. Sixty-five of 377 (17.2%) AAST III injuries were discharged within 48 hours of admission. Forty (10.6%) patients required readmission, 3 in the early discharge group and 37 in the standard discharge group. No patient required readmission for renal-related complications., Conclusion: Patients with AAST grade III blunt renal injuries are not at increased risk for early renal-related complications if discharged within 48 hours of admission and should be considered for early discharge. The very low rate of renal-related complications for AAST III blunt renal injuries supports their categorization as "low-grade" renal trauma., (Copyright © 2022 Elsevier Inc. All rights reserved.)
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- 2022
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22. Male Stress Urinary Incontinence.
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Koch GE and Kaufman MR
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- Humans, Male, Prostatectomy adverse effects, Treatment Outcome, Suburethral Slings, Urinary Incontinence etiology, Urinary Incontinence, Stress etiology, Urinary Incontinence, Stress surgery, Urinary Sphincter, Artificial
- Abstract
Male stress urinary incontinence most commonly presents secondary to prostate treatment of prostate cancer or benign prostatic hyperplasia, although it can be seen following trauma or secondary to neurologic dysfunction. Patient selection is supremely important when choosing the appropriate nonoperative or surgical treatment. Although most patients prefer the passive mechanism of adjustable balloon devices or slings, the artificial urinary sphincter provides the most efficacious and durable results with regard to patient satisfaction and continence. Changes in prostate treatment modalities and anti-incontinence device development will offer more surgical options for patients in the future., (Copyright © 2022 Elsevier Inc. All rights reserved.)
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- 2022
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23. How a Large Academic Training Program Influences Early Career Decision-making and Employment Stability in Urology.
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Cabo JJ, Tallman JE, Koch GE, Scarpato KR, and Chang SS
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- Career Choice, Curriculum, Employment, Fellowships and Scholarships, Humans, Surveys and Questionnaires, Internship and Residency, Urology education
- Abstract
Objective: To characterize training and practice factors that influence early career stability and satisfaction in urology residency and fellowship graduates., Methods: A computer-based survey was distributed to residency and fellowship graduates from a single, large US training program from 1992 to 2015. Queries encompassed training program specifics, post-training practice characteristics, and a validated burnout assessment., Results: Of 108 surveyed individuals there were 77 (71.3%) respondents. Fifty-one (67.1%) remained in their first position after residency. While 52 (67.5%) urologists reported that the program did not formally assist in finding their first post-residency position, no respondent reported difficulty securing a position. Proximity to family was a major factor in selecting a post-residency position in 40 (51.9%) of respondents. Twenty-nine (37.7%) participants joined practices with at least one other graduate of the same urology training program on staff and 24 remain in this position (82%)., Conclusion: Urology graduates from a large US training program did not have difficulty finding employment after training and most remain in their first post-training position. While proximity to family was a strong consideration for graduates, the perceived importance of first-position characteristics varied widely. 37.7% of our cohort took initial positions at a practice already employing a graduate from the same training program with >80% staying in this position. Surveying a broader range of programs may help future graduates and training programs better tailor their mentorship curricula and alumni networks to trainee goals., (Copyright © 2022 Elsevier Inc. All rights reserved.)
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- 2022
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24. The Impact of Delayed-Phase Imaging at Admission on the Management of Urinary Extravasation in High-Grade Renal Trauma.
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Koch GE, Huang JJ, Walton WJ, Dennis BM, Guillamondegui OD, and Johnsen NV
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- Adult, Diagnostic Imaging methods, Female, Humans, Injury Severity Score, Male, Middle Aged, Time Factors, Young Adult, Hospitalization, Kidney diagnostic imaging, Kidney injuries, Urine
- Abstract
Purpose: American Urological Association Urotrauma guidelines recommend delayed-phase imaging on presentation for all renal injuries, although data to support it are anecdotal. Forgoing delays risks unrecognized collecting system injuries. We hypothesized that renal trauma patients without admission delays have more complications from urinary extravasation., Materials and Methods: From 2005 through 2020, 1,751 renal trauma patients were identified from our institutional trauma registry. Included patients had an estimated American Association for the Surgery of Trauma renal injury grade of III-V and a perinephric fluid collection. Propensity scores for receipt of delayed-phase imaging were calculated based on Injury Severity Score, arrival condition, admission systolic blood pressure, sex and renal injury grade. Propensity score-adjusted logistic regression was used to compare clinical outcomes between those with and without admission delays., Results: Ninety (28.6%) of 315 included patients had delays on presentation. Patients without delays had higher Injury Severity Scores (29 vs 23, p=0.002), fewer isolated renal injuries (27.6% vs 38.9%, p=0.05) and lower grade renal injuries (56.9% vs 41.1% grade 3, p=0.03). After propensity score adjustment, patients with delays were more likely to undergo immediate interventions (OR 11.75, 95% CI 2.99-78.10) and interval stent placement for urinary extravasation (OR 6.86, 95% CI 1.56-47.64) without a difference in urological complications (OR 5.07, 95% CI 0.25-766.16)., Conclusions: Delayed-phase imaging was associated with an increased odds of undergoing immediate and asymptomatic interval urological interventions without a difference in the odds of a complication after high-grade renal trauma. Post-trauma urinary extravasation requires further research to determine which patients require imaging and intervention.
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- 2021
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25. The Diagnosis and Management of Life-threatening Urologic Infections.
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Koch GE and Johnsen NV
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- Humans, Severity of Illness Index, Urologic Diseases microbiology, Bacterial Infections diagnosis, Bacterial Infections therapy, Urologic Diseases diagnosis, Urologic Diseases therapy
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Genitourinary infections are commonly encountered and managed in inpatient, outpatient, and emergency settings. Fournier's gangrene, emphysematous pyelonephritis, and obstructive pyelonephritis represent the most serious urologic infections and have a high risk of mortality if not managed promptly. Due to the rarity of these infections, the evidence for specific treatment strategies is scattered. This review aims to provide comprehensive, evidence-based recommendations for the diagnosis and management of these life-threatening urologic infections., (Copyright © 2021 Elsevier Inc. All rights reserved.)
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- 2021
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26. Side Effects of Intravesical BCG and Chemotherapy for Bladder Cancer: What They Are and How to Manage Them.
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Koch GE, Smelser WW, and Chang SS
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- Adjuvants, Immunologic administration & dosage, Administration, Intravesical, BCG Vaccine administration & dosage, Drug-Related Side Effects and Adverse Reactions diagnosis, Drug-Related Side Effects and Adverse Reactions therapy, Humans, Adjuvants, Immunologic adverse effects, BCG Vaccine adverse effects, Urinary Bladder Neoplasms drug therapy
- Abstract
Intravesical therapy for nonmuscle invasive bladder cancer decreases recurrence and progression but carries a high risk of side effects, which limit patient adherence. Appropriate management of the toxicities from intravesical therapy requires consideration of the agent used, the side effects experienced, and the timing of those side effects. Management strategies for intravesical toxicities ideally improve patient tolerance without sacrificing oncologic outcomes. This review aims to provide a comprehensive overview of the available evidence regarding the side effects of intravesical therapies for nonmuscle invasive bladder cancer and to propose practical strategies for toxicity management., (Copyright © 2020. Published by Elsevier Inc.)
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- 2021
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27. High-Risk Nonmuscle Invasive Bladder Cancer: Selecting the Appropriate Patient for Timely Cystectomy.
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Koch GE, Luckenbaugh AN, and Chang SS
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- Disease Progression, Epigenesis, Genetic, Humans, Neoplasm Invasiveness, Patient Selection, Risk, Surgical Oncology standards, Treatment Outcome, United States, Urinary Bladder pathology, Urinary Bladder Neoplasms genetics, Cystectomy adverse effects, Cystectomy methods, Medical Oncology standards, Surgical Oncology methods, Urinary Bladder Neoplasms surgery, Urology standards
- Abstract
The heterogenous nature of high-risk nonmuscle invasive bladder cancer encompasses a wide range of tumor biologies with varying recurrence and progression risks. Radical cystectomy provides excellent oncologic outcomes but is often underutilized. Timing for these patients is critical, however, to its effectiveness. Certain unfavorable tumor characteristics predict worse outcomes and may help select the most appropriate patients for more aggressive initial therapy. This manuscript aims to outline factors that predict worse outcomes in high-risk nonmuscle invasive bladder cancer and proposes which patients may benefit most from a timely radical cystectomy., (Copyright © 2020. Published by Elsevier Inc.)
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- 2021
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28. Image memorability is predicted by discriminability and similarity in different stages of a convolutional neural network.
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Koch GE, Akpan E, and Coutanche MN
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- Female, Humans, Judgment, Male, Mental Recall physiology, Photic Stimulation, Prospective Studies, Psychomotor Performance physiology, Young Adult, Discrimination, Psychological physiology, Memory physiology, Neural Networks, Computer, Visual Perception physiology
- Abstract
The features of an image can be represented at multiple levels-from its low-level visual properties to high-level meaning. What drives some images to be memorable while others are forgettable? We address this question across two behavioral experiments. In the first, different layers of a convolutional neural network (CNN), which represent progressively higher levels of features, were used to select the images that would be shown to 100 participants through a form of prospective assignment. Here, the discriminability/similarity of an image with others, according to different CNN layers dictated the images presented to different groups, who made a simple indoor versus outdoor judgment for each scene. We found that participants remember more scene images that were selected based on their low-level discriminability or high-level similarity. A second experiment replicated these results in an independent sample of 50 participants, with a different order of postencoding tasks. Together, these experiments provide evidence that both discriminability and similarity, at different visual levels, predict image memorability., (© 2020 Koch et al.; Published by Cold Spring Harbor Laboratory Press.)
- Published
- 2020
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29. Influences on memory for naturalistic visual episodes: sleep, familiarity, and traits differentially affect forms of recall.
- Author
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Coutanche MN, Koch GE, and Paulus JP
- Subjects
- Adolescent, Adult, Female, Humans, Male, Visual Perception physiology, Young Adult, Individuality, Memory, Episodic, Memory, Short-Term physiology, Mental Recall physiology, Recognition, Psychology physiology, Sleep physiology
- Abstract
The memories we form are composed of information that we extract from multifaceted episodes. Static stimuli and paired associations have proven invaluable stimuli for understanding memory, but real-life events feature spatial and temporal dimensions that help form new retrieval paths. We ask how the ability to recall semantic, temporal, and spatial aspects (the "what, when, and where") of naturalistic episodes is affected by three influences-prior familiarity, postencoding sleep, and individual differences-by testing their influence on three forms of recall: cued recall, free recall, and the extent that recalled details are recombined for a novel prompt. Naturalistic videos of events with rare animals were presented to 115 participants, randomly assigned to receive a 12- or 24-h delay with sleep and/or wakefulness. Participants' immediate and delayed recall was tested and coded by its spatial, temporal, and semantic content. We find that prior familiarity with items featured in events improved cued recall, but not free recall, particularly for temporal and spatial details. In contrast, postencoding sleep, relative to wakefulness, improved free recall, but not cued recall, of all forms of content. Finally, individuals with higher trait scores in the Survey of Autobiographical Memory spontaneously incorporated more spatial details during free recall, and more event details (at a trend level) in a novel recombination recall task. These findings show that prior familiarity, postencoding sleep, and memory traits can each enhance a different form of recall. More broadly, this work highlights that recall is heterogeneous in response to different influences on memory., (© 2020 Coutanche et al.; Published by Cold Spring Harbor Laboratory Press.)
- Published
- 2020
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30. Neural Patterns are More Similar across Individuals during Successful Memory Encoding than during Failed Memory Encoding.
- Author
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Koch GE, Paulus JP, and Coutanche MN
- Subjects
- Adult, Brain physiology, Default Mode Network diagnostic imaging, Default Mode Network physiology, Female, Functional Neuroimaging, Gyrus Cinguli diagnostic imaging, Gyrus Cinguli physiology, Hippocampus diagnostic imaging, Hippocampus physiology, Humans, Individuality, Machine Learning, Magnetic Resonance Imaging, Male, Neural Pathways diagnostic imaging, Neural Pathways physiology, Primary Visual Cortex diagnostic imaging, Primary Visual Cortex physiology, Temporal Lobe diagnostic imaging, Temporal Lobe physiology, Young Adult, Brain diagnostic imaging, Memory physiology, Memory, Episodic
- Abstract
After experiencing the same episode, some people can recall certain details about it, whereas others cannot. We investigate how common (intersubject) neural patterns during memory encoding influence whether an episode will be subsequently remembered, and how divergence from a common organization is associated with encoding failure. Using functional magnetic resonance imaging with intersubject multivariate analyses, we measured brain activity as people viewed episodes within wildlife videos and then assessed their memory for these episodes. During encoding, greater neural similarity was observed between the people who later remembered an episode (compared with those who did not) within the regions of the declarative memory network (hippocampus, posterior medial cortex [PMC], and dorsal Default Mode Network [dDMN]). The intersubject similarity of the PMC and dDMN was episode-specific. Hippocampal encoding patterns were also more similar between subjects for memory success that was defined after one day, compared with immediately after retrieval. The neural encoding patterns were sufficiently robust and generalizable to train machine learning classifiers to predict future recall success in held-out subjects, and a subset of decodable regions formed a network of shared classifier predictions of subsequent memory success. This work suggests that common neural patterns reflect successful, rather than unsuccessful, encoding across individuals., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)
- Published
- 2020
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31. Semantic knowledge influences whether novel episodic associations are represented symmetrically or asymmetrically.
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Popov V, Zhang Q, Koch GE, Calloway RC, and Coutanche MN
- Subjects
- Adult, Humans, Psycholinguistics, Semantics, Young Adult, Association, Memory, Episodic, Mental Recall physiology, Psychomotor Performance physiology
- Abstract
We provide new evidence concerning two opposing views of episodic associations: The independent-association hypothesis posits that associations are unidirectional and separately modifiable links (A→B and A←B); in contrast, the associative-symmetry hypothesis proposes that a single, bidirectional association exists between A and B (A↔B). We used a novel method to demonstrate that whether or not episodic associations are symmetric depends on whether there is a preexisting semantic relationship between A and B. In two experiments, participants studied 30 semantically unrelated and 30 semantically related pairs intermixed in a single list and then performed a series of up to eight cued-recall test cycles. All pairs were tested in each cycle, and the testing direction (A-? or B-?) alternated between cycles. Unrelated pairs exhibited associative symmetry-that is, accuracy and response times improved gradually on each test-suggesting that testing in both directions strengthened the same association. In contrast, semantically related pairs exhibited a stair-like pattern, in which performance did not change from odd to even tests when the test direction changed; it only improved between tests in the same direction. We concluded that episodic associations can have either a single bidirectional representation or separate directional representations, depending on the semantic relatedness of their constituent items.
- Published
- 2019
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32. Creatures great and small: Real-world size of animals predicts visual cortex representations beyond taxonomic category.
- Author
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Coutanche MN and Koch GE
- Subjects
- Adult, Female, Humans, Image Interpretation, Computer-Assisted methods, Image Processing, Computer-Assisted methods, Magnetic Resonance Imaging, Male, Recognition, Psychology physiology, Temporal Lobe diagnostic imaging, Visual Cortex diagnostic imaging, Young Adult, Body Size, Brain Mapping methods, Machine Learning, Pattern Recognition, Visual physiology, Temporal Lobe physiology, Visual Cortex physiology
- Abstract
Human occipitotemporal cortex contains neural representations for a variety of perceptual and conceptual features. We report a study examining neural representations of real-world size along the visual ventral stream, while carefully accounting for taxonomic categories that typically co-vary with size. We recorded brain activity during a functional Magnetic Resonance Imaging (fMRI) scan from eighteen participants as they were presented with images of twelve animal species. The animals were selected to vary on a number of dimensions, including taxonomic group, real-world size and prior familiarity. We apply multivariate analysis methods, including representational similarity analysis (RSA) and machine learning classifiers, to probe the distributed patterns of neural activity evoked by these presentations. We find that the real-world size of visually presented animate items is represented in posterior, but not anterior, regions of the ventral stream. A significant linear relationship is present for real-world size representation along the ventral stream. These representations remain after controlling for factors such as taxonomic category, familiarity and models of visual similarity, and even after restricting examinations to within-taxonomic category comparisons, suggesting that size information is found for within, as well as between, taxonomic categories. These findings are consistent with real-world size having an influence on activity patterns in early regions of the visual system., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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33. Novel pericatheter retrograde urethrogram technique is a viable method for postoperative urethroplasty imaging.
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Sussman RD, Hill FC, Koch GE, Patel V, and Venkatesan K
- Subjects
- Adult, Aged, Aged, 80 and over, Catheters, Indwelling, Contrast Media administration & dosage, Extravasation of Diagnostic and Therapeutic Materials, Humans, Male, Middle Aged, Retrospective Studies, Urethral Stricture surgery, Urinary Catheters, Young Adult, Plastic Surgery Procedures, Urethra diagnostic imaging, Urethra surgery, Urography methods, Wound Healing
- Abstract
Purpose: The purpose of this study is to describe our technique for pericatheter retrograde urethrogram (pcRUG) and to evaluate the utility of a pcRUG to detect a clinically significant leak after urethral reconstruction., Methods: We retrospectively reviewed our prospective IRB-approved database of patients undergoing urethral reconstruction. pcRUG was performed at 3-4 weeks after surgery, in standardized fashion. Patients were placed in oblique position, and with the penis stretched, diluted contrast was instilled via an angiocatheter alongside the indwelling urethral catheter under dynamic fluoroscopy. The image was then evaluated for the presence of any contrast extravasation. Patient with and without extravasation seen on initial pcRUG were compared., Results: From September 2012 through February 2017, 144 pericatheter retrograde urethrograms were performed on 130 patients. 115 patients (88.5%) had no extravasation on pcRUG. Fifteen patients (11.5%) demonstrated extravasation, with 13 of those patients (10%) undergoing a repeat pcRUG. Patients with extravasation seen on initial pcRUG were more likely to have strictures that were panurethral (36 vs. 9%, p = 0.029) and ≥10 cm (43 vs. 11%, p = 0.016). One patient (0.8%) presented with urinary leak and scrotal abscess after a urethra was assessed as sufficiently healed at the initial pcRUG and the catheter removed. There were otherwise no infectious or procedural complications related to pericatheter retrograde urethrogram., Conclusions: Our pericatheter retrograde urethrogram technique is a safe and reproducible technique to effectively assess urethral healing after urethroplasty and determine timing of catheter removal. The pcRUG is minimally invasive and is comparable in accuracy and sensitivity to voiding cystourethrography and retrograde urethrography that have traditionally been used to assess healing after urethroplasty.
- Published
- 2017
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34. Excisional biopsy of an extravesicular hemangioma.
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Goldman C, Koch GE, Carvalho F, O'Neill EK, and Stamatakis L
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- 2017
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35. Variation across individuals and items determine learning outcomes from fast mapping.
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Coutanche MN and Koch GE
- Subjects
- Adolescent, Female, Humans, Male, Memory, Episodic, Photic Stimulation, Reaction Time, Vocabulary, Young Adult, Association Learning physiology, Brain Mapping, Individuality, Recognition, Psychology physiology, Semantics
- Abstract
An approach to learning words known as "fast mapping" has been linked to unique neurobiological and behavioral markers in adult humans, including rapid lexical integration. However, the mechanisms supporting fast mapping are still not known. In this study, we sought to help change this by examining factors that modulate learning outcomes. In 90 subjects, we systematically manipulated the typicality of the items used to support fast mapping (foils), and quantified learners' inclination to employ semantic, episodic, and spatial memory through the Survey of Autobiographical Memory (SAM). We asked how these factors affect lexical competition and recognition performance, and then asked how foil typicality and lexical competition are related in an independent dataset. We find that both the typicality of fast mapping foils, and individual differences in how different memory systems are employed, influence lexical competition effects after fast mapping, but not after other learning approaches. Specifically, learning a word through fast mapping with an atypical foil led to lexical competition, while a typical foil led to lexical facilitation. This effect was particularly evident in individuals with a strong tendency to employ semantic memory. We further replicated the relationship between continuous foil atypicality and lexical competition in an independent dataset. These findings suggest that semantic properties of the foils that support fast mapping can influence the degree and nature of subsequent lexical integration. Further, the effects of foils differ based on an individual's tendency to draw-on the semantic memory system., (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Published
- 2017
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36. Transobturator sling for post-prostatectomy incontinence: radiation's effect on efficacy/satisfaction.
- Author
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Wright HC, McGeagh K, Richter LA, Hwang JJ, Venkatesan K, Pysher A, Koch GE, Kowalczyk K, Bandi G, and Marchalik D
- Subjects
- Aged, Aged, 80 and over, Cohort Studies, Follow-Up Studies, Humans, Male, Middle Aged, Retrospective Studies, Time Factors, Treatment Outcome, Patient Satisfaction, Personal Satisfaction, Postoperative Complications surgery, Prostatectomy, Prostatic Neoplasms radiotherapy, Prostatic Neoplasms surgery, Suburethral Slings, Urinary Incontinence surgery
- Abstract
Introduction: We review our experience with the AdVance sling in patients with post- prostatectomy incontinence, comparing the role that adjuvant radiation therapy plays in sling success and patient satisfaction at short and long term follow ups., Materials and Methods: Men who underwent AdVance sling placement for post-prostatectomy incontinence from 2007 to present were identified using Current Procedural Terminology (CPT) codes. Manual chart review was performed. Level of incontinence was assessed using Expanded Prostate Cancer Index Composite (EPIC) and pads per day (PPD) use. Satisfaction was assessed by willingness to recommend the procedure to a friend. Outcomes in men who received radiation were compared to radiation-naïve men., Results: Fifty-two men underwent AdVance sling placement. Eighteen men received adjuvant radiation. Thirty-six men were available for short term (19.4 months) and 16 men for long term (61.5 months) follow up. Overall, significant improvement was seen in post-sling EPIC score (24.6, p < 0.001), EPIC incontinence score (39.1, p < .001), and pad use (3.2 PPD to 1.4 PPD, p < .001). Greater improvement in EPIC scores and PPD use was seen in radiation-free men. Irradiated men were less satisfied with the procedure at both short and long term follow up. Diminished efficacy and satisfaction occurred at extended follow up for both groups but was more pronounced with radiation., Conclusions: The majority of patients undergoing the AdVance sling procedure for post-prostatectomy urinary incontinence saw a significant reduction in pad use, and were overall satisfied in both radiated and non-radiated groups at short and long term follow up. However, improvements were greater in the non-radiated groups and diminished with time.
- Published
- 2017
37. Factors associated with recurrent stroke and recanalization in patients presenting with isolated symptomatic carotid occlusion.
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Damania D, Kung NT, Jain M, Jain AR, Liew JA, Mangla R, Koch GE, Sahin B, Miranpuri AS, Holmquist TM, Replogle RE, Benesch CG, Kelly AG, and Jahromi BS
- Subjects
- Aged, Aged, 80 and over, Arterial Occlusive Diseases complications, Arterial Occlusive Diseases drug therapy, Carotid Artery Diseases complications, Carotid Artery Diseases drug therapy, Female, Humans, Ischemic Attack, Transient etiology, Male, Middle Aged, Recurrence, Retrospective Studies, Risk Factors, Stroke etiology, Treatment Outcome, Anticoagulants therapeutic use, Arterial Occlusive Diseases therapy, Carotid Artery Diseases therapy, Endovascular Procedures statistics & numerical data, Ischemic Attack, Transient prevention & control, Stroke prevention & control
- Abstract
Background and Purpose: Patients with symptomatic internal carotid artery (ICA) occlusion constitute a small proportion of stroke/transient ischaemic attack patients who are at increased risk of early stroke recurrence and poor outcome. The optimal medical treatment for patients with symptomatic ICA occlusion who are ineligible for thrombolysis or thrombectomy is unknown., Methods: Consecutive patients presenting at a single center with newly diagnosed symptomatic ICA occlusion (not involving the circle of Willis) were retrospectively reviewed. Those treated with intravenous thrombolysis or intra-arterial thrombolysis/thrombectomy were excluded. Patients were divided into two groups based on whether they experienced recurrent in-hospital stroke., Results: The selected study population (n = 33) represented a small (20.4%) proportion of all newly symptomatic carotid occlusions, who nevertheless had an elevated risk of recurrent stroke during admission (24.2%). Of the variables examined (age, gender, admission National Institutes of Health Stroke Scale score, vascular risk factors, atrial fibrillation, prior stroke/transient ischaemic attack and anticoagulation within 48 h of presentation), only anticoagulation was significantly associated with a lower risk of in-hospital recurrent stroke. Anticoagulated patients showed a decreased incidence of stroke recurrence within the first week (6.7% vs. 38.9%, P = 0.032) and fewer strokes or deaths at 1 month (13.3% vs. 47.1%, P = 0.040). Hemorrhagic transformation was not observed in any patient. On follow-up imaging, ICA recanalization was significantly more frequent in anticoagulated patients (46.2% vs. 9.1%, P = 0.047)., Conclusion: Patients with newly diagnosed symptomatic ICA occlusion (not involving the circle of Willis) represent a small but high risk subgroup of patients with carotid occlusion. Early anticoagulation was associated with fewer recurrent strokes and increased ICA recanalization. Larger scale prospective studies may be justified., (© 2015 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)
- Published
- 2016
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38. 64-detector CT angiography within 24 hours after carotid endarterectomy and correlation with postoperative stroke.
- Author
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Gallati CP, Jain M, Damania D, Kanthala AR, Jain AR, Koch GE, Kung NT, Wang HZ, Replogle RE, and Jahromi BS
- Subjects
- Aged, Carotid Stenosis pathology, Carotid Stenosis surgery, Cohort Studies, Female, Humans, Image Processing, Computer-Assisted, Intracranial Thrombosis etiology, Ischemic Attack, Transient etiology, Male, Middle Aged, Treatment Outcome, Cerebral Angiography methods, Endarterectomy, Carotid adverse effects, Postoperative Complications diagnosis, Stroke diagnosis, Stroke etiology, Tomography, X-Ray Computed methods
- Abstract
Object: Carotid endarterectomy (CEA) carries a small but not insignificant risk of stroke/transient ischemic attack (TIA), most frequently observed within 24 hours of surgery, which can lead to the need for urgent vascular imaging in the immediate postoperative period. However, distinguishing expected versus pathological postoperative changes may not be straightforward on imaging studies of the carotid artery early after CEA. The authors aimed to describe routine versus pathological anatomical findings on CTA performed within 24 hours of CEA, and to evaluate associations between these CTA findings and postoperative stroke/TIA., Methods: The authors reviewed 113 consecutive adult patients who underwent postoperative CTA within 24 hours of CEA at a single academic institution. Presence and location of arterial "flaps," luminal "step-off," intraluminal thrombus and hematoma were documented from postoperative CTA scans. Medical records were reviewed to determine the incidence of new postoperative neurological findings., Results: Postoperative CTA findings included common carotid artery (CCA) step-off (63.7%), one or more intraarterial flaps (27.4%), hematoma at the surgical site (15.9%), and new intraluminal thrombus (7.1%). Flaps were seen in the external carotid artery (ECA), internal carotid artery (ICA), and CCA in 18.6%, 9.7%, and 6.2% of patients, respectively. New postoperative neurological findings were present in 7.1% of patients undergoing CTA. Flaps (especially ICA/CCA) and/or intraluminal thrombi were more frequently seen in patients undergoing CTA for new postoperative stroke/TIA (85.7%) versus patients undergoing CTA for routine postoperative imaging (14.3%, p = 0.002)., Conclusions: CTA within 24 hours of CEA demonstrates characteristic anatomical findings. CCA step-offs and ECA flaps are relatively common and clinically insignificant, whereas ICA/CCA flaps and thrombi are less frequently seen and are associated with postoperative stroke/TIA.
- Published
- 2015
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39. Antibody-mediated blockade of the CXCR3 chemokine receptor results in diminished recruitment of T helper 1 cells into sites of inflammation.
- Author
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Xie JH, Nomura N, Lu M, Chen SL, Koch GE, Weng Y, Rosa R, Di Salvo J, Mudgett J, Peterson LB, Wicker LS, and DeMartino JA
- Subjects
- Adoptive Transfer, Animals, Antibodies pharmacology, Antigens immunology, Cells, Cultured, Freund's Adjuvant, Genes, T-Cell Receptor, Hypersensitivity, Delayed immunology, Ligands, Mice, Mice, Inbred C57BL, Mice, Transgenic, Peritoneum cytology, Peritoneum drug effects, Peritoneum immunology, Peritonitis chemically induced, Peritonitis immunology, Receptors, CXCR3, Receptors, Chemokine agonists, Receptors, Chemokine immunology, Th1 Cells transplantation, Th2 Cells immunology, Chemotaxis, Leukocyte, Inflammation immunology, Receptors, Chemokine antagonists & inhibitors, Th1 Cells immunology
- Abstract
Naïve T cells, when activated by specific antigen and cytokines, up-regulate adhesion molecules as well as chemokine receptors on their surface, which allows them to migrate to inflamed tissues. Human studies have shown that CXCR3 is one of the chemokine receptors that is induced during T cell activation. Moreover, CXCR3-positive T cells are enriched at inflammatory sites in patients with autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. In this study, we use a mouse model of inflammation to demonstrate that CXCR3 is required for activated T cell transmigration to inflamed tissue. Using an anti- mCXCR3 antibody, we have shown that in vitro-differentiated T helper (Th) 1 and Th2 cells up-regulated CXCR3 upon stimulation with specific antigen/major histocompatibility complex. However, only Th1 cells, when adoptively transferred to syngeneic recipients, are efficiently recruited to the peritoneum in an adjuvant-induced peritonitis model. Furthermore, the neutralizing anti-mCXCR3 antibody profoundly inhibits the recruitment of Th1 cells to the inflamed peritoneum. Real-time, quantitative reverse transcriptase-polymerase chain reaction analysis demonstrates that the CXCR3 ligands, interferon (IFN)-inducible protein 10 (CXCL10) and IFN-inducible T cell alpha chemoattractant (CXCL11), are among the many chemokines induced in the adjuvant-treated peritoneum. The anti-mCXCR3 antibody is also effective in inhibiting a delayed-type hypersensitivity response, which is largely mediated by enhanced trafficking of activated T cells to peripheral inflammatory sites. Collectively, our results suggest that CXCR3 has a critical role in T cell transmigration to sites of inflammation and thus, may serve as a molecular target for anti-inflammatory therapies.
- Published
- 2003
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40. The CXCR4 agonist ligand stromal derived factor-1 maintains high affinity for receptors in both Galpha(i)-coupled and uncoupled states.
- Author
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Di Salvo J, Koch GE, Johnson KE, Blake AD, Daugherty BL, DeMartino JA, Sirotina-Meisher A, Liu Y, Springer MS, Cascieri MA, and Sullivan KA
- Subjects
- Animals, Binding, Competitive drug effects, CHO Cells, Chemokine CXCL12, Chemokines, CXC pharmacology, Colforsin pharmacology, Cricetinae, Cyclic AMP metabolism, Dose-Response Relationship, Drug, Gene Expression, Guanosine 5'-O-(3-Thiotriphosphate) pharmacology, Humans, Jurkat Cells, Leukocytes, Mononuclear cytology, Leukocytes, Mononuclear drug effects, Leukocytes, Mononuclear metabolism, Pertussis Toxin, Receptors, CXCR4 agonists, Receptors, CXCR4 genetics, Signal Transduction drug effects, T-Lymphocytes cytology, T-Lymphocytes drug effects, T-Lymphocytes metabolism, Virulence Factors, Bordetella pharmacology, Chemokines, CXC metabolism, GTP-Binding Protein alpha Subunits, Gi-Go metabolism, Receptors, CXCR4 metabolism
- Abstract
The alpha chemokine receptor CXCR4 and its only characterized chemokine ligand, stromal cell-derived factor-1 (SDF-1), are postulated to be important in the development of the B-cell arm of the immune system. In addition, CXCR4 is a critical coreceptor in support of viral entry by T-cell line tropic strains (X4) of the Human Immunodeficiency Virus Type 1 (HIV-1), viral variants which predominate in some infected individuals in end stage disease. SDF-1 can block X4-tropic HIV-1 infection of CD4+ target cells in vitro, and allelic variants of the human gene encoding SDF-1 in vivo correlate with delayed disease progression. Therefore, CXCR4 may be an appropriate target for therapeutic intervention in acquired immunodeficiency syndrome (AIDS), and knowledge of the pharmacology of SDF-1 binding to its cognate receptor will be important in the interpretation of these experiments. We report here a Kd derived using a competition binding assay of 4.5 nM for CXCR4 endogenously expressed on peripheral blood monocytes and T-cells. This affinity is similar to that which SDF-1 exhibits when binding to endogenous CXCR4 on an established immortal Jurkat T-cell line as well as recombinant CXCR4 transfected into Chinese Hamster Ovary (CHO) cells. We also demonstrate that the determined affinity of SDF-1 for CXCR4 is reflective of its ability to induce a CXCR4-mediated signal transduction in these different cell types. Furthermore, using Bordetella pertussis toxin, we observe that high affinity binding of SDF-1 to CXCR4 is independent of the G-protein coupled state of the receptor, as uncoupling of G-protein did not lead to the appearance of measurable low affinity SDF-1 binding sites. Moreover, binding affinity and receptor number were unaffected by uncoupling for both recombinant and endogenously expressed CXCR4. Thus, SDF-1 is novel among agonist ligands of G protein-coupled receptors in that it appears to have equal affinity for both the G protein-coupled and uncoupled states of CXCR4.
- Published
- 2000
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41. Characterization of a novel, non-peptidyl antagonist of the human glucagon receptor.
- Author
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Cascieri MA, Koch GE, Ber E, Sadowski SJ, Louizides D, de Laszlo SE, Hacker C, Hagmann WK, MacCoss M, Chicchi GG, and Vicario PP
- Subjects
- Adenylyl Cyclases metabolism, Animals, CHO Cells, Cations, Divalent pharmacology, Cricetinae, Enzyme Activation drug effects, Glucagon-Like Peptide-1 Receptor, Glucagon-Like Peptides, Hormone Antagonists chemistry, Hormone Antagonists pharmacology, Humans, Molecular Structure, Mutation, Protein Binding drug effects, Receptors, Glucagon genetics, Peptides metabolism, Pyridines pharmacology, Pyrroles pharmacology, Receptors, Glucagon antagonists & inhibitors, Receptors, Glucagon metabolism
- Abstract
We have identified a series of potent, orally bioavailable, non-peptidyl, triarylimidazole and triarylpyrrole glucagon receptor antagonists. 2-(4-Pyridyl)-5-(4-chlorophenyl)-3-(5-bromo-2-propyloxyphenyl)p yrr ole (L-168,049), a prototypical member of this series, inhibits binding of labeled glucagon to the human glucagon receptor with an IC50 = 3. 7 +/- 3.4 nM (n = 7) but does not inhibit binding of labeled glucagon-like peptide to the highly homologous human glucagon-like peptide receptor at concentrations up to 10 microM. The binding affinity of L-168,049 for the human glucagon receptor is decreased 24-fold by the inclusion of divalent cations (5 mM). L-168,049 increases the apparent EC50 for glucagon stimulation of adenylyl cyclase in Chinese hamster ovary cells expressing the human glucagon receptor and decreases the maximal glucagon stimulation observed, with a Kb (concentration of antagonist that shifts the agonist dose-response 2-fold) of 25 nM. These data suggest that L-168,049 is a noncompetitive antagonist of glucagon action. Inclusion of L-168, 049 increases the rate of dissociation of labeled glucagon from the receptor 4-fold, confirming that the compound is a noncompetitive glucagon antagonist. In addition, we have identified two putative transmembrane domain residues, phenylalanine 184 in transmembrane domain 2 and tyrosine 239 in transmembrane domain 3, for which substitution by alanine reduces the affinity of L-168,049 46- and 4. 5-fold, respectively. These mutations do not alter the binding of labeled glucagon, suggesting that the binding sites for glucagon and L-168,049 are distinct.
- Published
- 1999
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42. Potent, orally absorbed glucagon receptor antagonists.
- Author
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de Laszlo SE, Hacker C, Li B, Kim D, MacCoss M, Mantlo N, Pivnichny JV, Colwell L, Koch GE, Cascieri MA, and Hagmann WK
- Subjects
- Animals, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors chemistry, Humans, Mice, Pyridines chemical synthesis, Pyridines chemistry, Pyrroles chemical synthesis, Pyrroles chemistry, Structure-Activity Relationship, p38 Mitogen-Activated Protein Kinases, Calcium-Calmodulin-Dependent Protein Kinases antagonists & inhibitors, Enzyme Inhibitors pharmacology, Mitogen-Activated Protein Kinases, Pyridines pharmacology, Pyrroles pharmacology, Receptors, Glucagon antagonists & inhibitors
- Abstract
The SAR of 2-pyridyl-3,5-diaryl pyrroles, ligands of the human glucagon receptor and inhibitors of p38 kinase, were investigated. This effort resulted in the identification of 2-(4-pyridyl)-5-(4-chlorophenyl)-3-(5-bromo-2-propyloxyphenyl)pyrr ole 49 (L-168,049), a potent (Kb = 25 nM), selective antagonist of glucagon.
- Published
- 1999
- Full Text
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43. Quinoxapeptins: novel chromodepsipeptide inhibitors of HIV-1 and HIV-2 reverse transcriptase. I. The producing organism and biological activity.
- Author
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Lingham RB, Hsu AH, O'Brien JA, Sigmund JM, Sanchez M, Gagliardi MM, Heimbuch BK, Genilloud O, Martin I, Diez MT, Hirsch CF, Zink DL, Liesch JM, Koch GE, Gartner SE, Garrity GM, Tsou NN, and Salituro GM
- Subjects
- Actinomycetales classification, Actinomycetales metabolism, HIV Reverse Transcriptase, HIV-1 genetics, Humans, Hydroxyquinolines chemistry, Hydroxyquinolines pharmacology, In Vitro Techniques, Kinetics, Molecular Structure, Mutation, Nucleic Acid Synthesis Inhibitors, Peptides, Cyclic chemistry, Quinoxalines chemistry, RNA-Directed DNA Polymerase genetics, Reverse Transcriptase Inhibitors chemistry, HIV-1 enzymology, HIV-2 enzymology, Peptides, Cyclic metabolism, Peptides, Cyclic pharmacology, Quinoxalines metabolism, Quinoxalines pharmacology, RNA-Directed DNA Polymerase metabolism, Reverse Transcriptase Inhibitors metabolism, Reverse Transcriptase Inhibitors pharmacology
- Abstract
Quinoxapeptin A and B are novel chromodepsipeptides which were isolated from a nocardioform actinomycete with indeterminant morphology. Quinoxapeptins A and B are potent inhibitors of HIV-1 and HIV-2 reverse transcriptase and almost equally active against two single mutants forms as well as a double mutant form of HIV-1 reverse transcriptase. Quinoxapeptin A and B are specific inhibitors of HIV-1 and HIV-2 reverse transcriptase because they did not inhibit human DNA polymerase alpha, beta, gamma and delta. Quinoxapeptin A and B are structurally similar to luzopeptin A which was also active against HIV-1 and HIV-2 reverse transcriptase.
- Published
- 1996
- Full Text
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44. Actinoplanic acids A and B as novel inhibitors of farnesyl-protein transferase.
- Author
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Silverman KC, Cascales C, Genilloud O, Sigmund JM, Gartner SE, Koch GE, Gagliardi MM, Heimbuch BK, Nallin-Omstead M, and Sanchez M
- Subjects
- Enzyme Inhibitors pharmacology, Farnesyltranstransferase, Lactones pharmacology, Actinomycetales chemistry, Alkyl and Aryl Transferases, Enzyme Inhibitors isolation & purification, Lactones isolation & purification, Streptomyces chemistry, Transferases antagonists & inhibitors
- Abstract
Actinoplanic acids A and B are macrocyclic polycarboxylic acids that are potent reversible inhibitors of farnesyl-protein transferase. Actinoplanic acids A and B were isolated from Actinoplanes sp. MA 7066 while actinoplanic acid B was isolated from both MA 7066 and Streptomyces sp. MA 7099. Actinoplanic acids A and B are competitive with respect to farnesyl diphosphate and are selective inhibitors of farnesyl-protein transferase because they do not inhibit geranylgeranyl-protein transferase type 1 or squalene synthase. MA 7066 is believed to be a novel species of actinomycetes while MA 7099 is believed to be a novel strain of Streptomyces violaceusniger on the basis of morphological, biochemical and chemotaxonomic characteristics as well as its production of actinoplanic acids.
- Published
- 1995
- Full Text
- View/download PDF
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