36 results on '"Anthony TL"'
Search Results
2. Utilizing Novel Field and Data Exploration Methods to Explore Hot Moments in High-Frequency Soil Nitrous Oxide Emissions Data: Opportunities and Challenges
- Author
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O’Connell, CS, O’Connell, CS, Anthony, TL, Mayes, MA, Pérez, T, Sihi, D, Silver, WL, O’Connell, CS, O’Connell, CS, Anthony, TL, Mayes, MA, Pérez, T, Sihi, D, and Silver, WL
- Abstract
Soil nitrous oxide (N2O) emissions are an important driver of climate change and are a major mechanism of labile nitrogen (N) loss from terrestrial ecosystems. Evidence increasingly suggests that locations on the landscape that experience biogeochemical fluxes disproportionate to the surrounding matrix (hot spots) and time periods that show disproportionately high fluxes relative to the background (hot moments) strongly influence landscape-scale soil N2O emissions. However, substantial uncertainties remain regarding how to measure and model where and when these extreme soil N2O fluxes occur. High-frequency datasets of soil N2O fluxes are newly possible due to advancements in field-ready instrumentation that uses cavity ring-down spectroscopy (CRDS). Here, we outline the opportunities and challenges that are provided by the deployment of this field-based instrumentation and the collection of high-frequency soil N2O flux datasets. While there are substantial challenges associated with automated CRDS systems, there are also opportunities to utilize these near-continuous data to constrain our understanding of dynamics of the terrestrial N cycle across space and time. Finally, we propose future research directions exploring the influence of hot moments of N2O emissions on the N cycle, particularly considering the gaps surrounding how global change forces are likely to alter N dynamics in the future.
- Published
- 2022
3. Effect of bariatric surgery on diabetic nephropathy in obese type 2 diabetes patients in a retrospective 2-year study: A local pilot
- Author
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Serena Km Low, Sum Chee Fang, Anton Ks Cheng, Anthony Tl Chao, Lim Su Chi, and Benjamin Cc Lam
- Subjects
Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Bariatric Surgery ,030209 endocrinology & metabolism ,Pilot Projects ,Type 2 diabetes ,Diabetic nephropathy ,03 medical and health sciences ,0302 clinical medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Albuminuria ,Humans ,Insulin ,Diabetic Nephropathies ,030212 general & internal medicine ,Obesity ,Aged ,Retrospective Studies ,Glycated Hemoglobin ,business.industry ,Type 2 Diabetes Mellitus ,Middle Aged ,medicine.disease ,humanities ,Surgery ,Diabetes Mellitus, Type 2 ,Female ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Clinical record - Abstract
To determine the effects of bariatric surgery on albuminuria in obese patients with type 2 diabetes mellitus.Retrospective analyses of clinical records of obese patients with type 2 diabetes mellitus who had either micro- or macroalbuminuria and had undergone various bariatric surgery were retrieved from a local hospital database. Their clinical data from follow-up appointments including albuminuria were analysed.Of the 46 subjects with type 2 diabetes mellitus, 15 subjects had diabetic nephropathy and had pre- and post-bariatric surgery urine albumin-to-creatinine ratio or urine protein-to-creatinine ratio data available for analysis; 13 out of the 15 subjects (86.7%) showed improvement of urine albumin-to-creatinine ratio or urine protein-to-creatinine ratio after surgery; 2 showed equivocal results; 9 of 13 subjects (69.2%) showed remission of diabetic nephropathy; 7 of these 9 patients had microalbuminuria before surgery, 2 had macroalbuminuria before surgery. There were significant improvements to glycosylated haemoglobin, fasting plasma glucose, blood pressure and body weight post surgery. The usage of insulin and oral medications dropped significantly post surgery for all subjects.This study shows that bariatric surgery significantly improves diabetic nephropathy in obese type 2 diabetes mellitus subjects. The results suggest that in our local type 2 diabetes mellitus patients, it is possible not only to improve metabolic parameters, but also to reverse what may be considered established microvascular complications by means of bariatric surgery.
- Published
- 2017
4. Effect of bariatric surgery on diabetic nephropathy in obese type 2 diabetes patients in a retrospective 2-year study: A local pilot
- Author
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Chao, Anthony TL, primary, Chee Fang, Sum, additional, Lam, Benjamin CC, additional, Cheng, Anton KS, additional, Low, Serena KM, additional, and Su Chi, Lim, additional
- Published
- 2017
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5. Effect of bariatric surgery on diabetic nephropathy in obese type 2 diabetes patients in a local retrospective 2 year study
- Author
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Benjamin Lam, Anton Ks Cheng, Chee Fang Sum, Su Chi Lim, Serena Low, and Anthony Tl Chao
- Subjects
0301 basic medicine ,medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,02 engineering and technology ,General Medicine ,Type 2 diabetes ,medicine.disease ,Surgery ,Diabetic nephropathy ,03 medical and health sciences ,030104 developmental biology ,Endocrinology ,Diabetes mellitus ,0202 electrical engineering, electronic engineering, information engineering ,Internal Medicine ,Medicine ,020201 artificial intelligence & image processing ,business - Published
- 2016
6. Play interaction with infants and toddlers who are deafblind: setting the stage.
- Author
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Greeley J and Anthony TL
- Published
- 1995
7. Carbon-sink potential of continuous alfalfa agriculture lowered by short-term nitrous oxide emission events.
- Author
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Anthony TL, Szutu DJ, Verfaillie JG, Baldocchi DD, and Silver WL
- Abstract
Alfalfa is the most widely grown forage crop worldwide and is thought to be a significant carbon sink due to high productivity, extensive root systems, and nitrogen-fixation. However, these conditions may increase nitrous oxide (N
2 O) emissions thus lowering the climate change mitigation potential. We used a suite of long-term automated instrumentation and satellite imagery to quantify patterns and drivers of greenhouse gas fluxes in a continuous alfalfa agroecosystem in California. We show that this continuous alfalfa system was a large N2 O source (624 ± 28 mg N2 O m2 y-1 ), offsetting the ecosystem carbon (carbon dioxide (CO2 ) and methane (CH4 )) sink by up to 14% annually. Short-term N2 O emissions events (i.e., hot moments) accounted for ≤1% of measurements but up to 57% of annual emissions. Seasonal and daily trends in rainfall and irrigation were the primary drivers of hot moments of N2 O emissions. Significant coherence between satellite-derived photosynthetic activity and N2 O fluxes suggested plant activity was an important driver of background emissions. Combined data show annual N2 O emissions can significantly lower the carbon-sink potential of continuous alfalfa agriculture., (© 2023. The Author(s).)- Published
- 2023
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8. Restoring wetlands on intensive agricultural lands modifies nitrogen cycling microbial communities and reduces N 2 O production potential.
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Kasak K, Espenberg M, Anthony TL, Tringe SG, Valach AC, Hemes KS, Silver WL, Mander Ü, Kill K, McNicol G, Szutu D, Verfaillie J, and Baldocchi DD
- Subjects
- Denitrification, Nitrogen, Nitrogen Cycle, Nitrous Oxide analysis, Soil, Soil Microbiology, Microbiota, Wetlands
- Abstract
The concentration of nitrous oxide (N
2 O), an ozone-depleting greenhouse gas, is rapidly increasing in the atmosphere. Most atmospheric N2 O originates in terrestrial ecosystems, of which the majority can be attributed to microbial cycling of nitrogen in agricultural soils. Here, we demonstrate how the abundance of nitrogen cycling genes vary across intensively managed agricultural fields and adjacent restored wetlands in the Sacramento-San Joaquin Delta in California, USA. We found that the abundances of nirS and nirK genes were highest at the intensively managed organic-rich cornfield and significantly outnumber any other gene abundances, suggesting very high N2 O production potential. The quantity of nitrogen transforming genes, particularly those responsible for denitrification, nitrification and DNRA, were highest in the agricultural sites, whereas nitrogen fixation and ANAMMOX was strongly associated with the wetland sites. Although the abundance of nosZ genes was also high at the agricultural sites, the ratio of nosZ genes to nir genes was significantly higher in wetland sites indicating that these sites could act as a sink of N2 O. These findings suggest that wetland restoration could be a promising natural climate solution not only for carbon sequestration but also for reduced N2 O emissions., (Copyright © 2021 Elsevier Ltd. All rights reserved.)- Published
- 2021
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9. Hot moments drive extreme nitrous oxide and methane emissions from agricultural peatlands.
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Anthony TL and Silver WL
- Subjects
- Agriculture, Carbon Dioxide analysis, Ecosystem, Methane analysis, Soil, Greenhouse Gases, Nitrous Oxide analysis
- Abstract
Agricultural peatlands are estimated to emit approximately one third of global greenhouse gas (GHG) emissions from croplands, but the temporal dynamics and controls of these emissions are poorly understood, particularly for nitrous oxide (N
2 O). We used cavity ring-down spectroscopy and automated chambers in a drained agricultural peatland to measure over 70,000 individual N2 O, methane (CH4 ), and carbon dioxide (CO2 ) fluxes over 3 years. Our results showed that N2 O fluxes were high, contributing 26% (annual range: 16%-35%) of annual CO2 e emissions. Total N2 O fluxes averaged 26 ± 0.5 kg N2 O-N ha-1 y-1 and exhibited significant inter- and intra-annual variability with a maximum annual flux of 42 ± 1.8 kg N2 O-N ha-1 y-1 . Hot moments of N2 O and CH4 emissions represented 1.1 ± 0.2 and 1.3 ± 0.2% of measurements, respectively, but contributed to 45 ± 1% of mean annual N2 O fluxes and to 140 ± 9% of mean annual CH4 fluxes. Soil moisture, soil temperature, and bulk soil oxygen (O2 ) concentrations were strongly correlated with soil N2 O and CH4 emissions; soil nitrate ( NO 3 - ) concentrations were also significantly correlated with soil N2 O emissions. These results suggest that IPCC benchmarks underestimate N2 O emissions from these high emitting agricultural peatlands by up to 70%. Scaling to regional agricultural peatlands with similar management suggests these ecosystems could emit up to 1.86 Tg CO2 e y-1 (range: 1.58-2.21 Tg CO2 e y-1 ). Data suggest that these agricultural peatlands are large sources of GHGs, and that short-term hot moments of N2 O and CH4 are a significant fraction of total greenhouse budgets., (© 2021 John Wiley & Sons Ltd.)- Published
- 2021
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10. Productive wetlands restored for carbon sequestration quickly become net CO2 sinks with site-level factors driving uptake variability.
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Valach AC, Kasak K, Hemes KS, Anthony TL, Dronova I, Taddeo S, Silver WL, Szutu D, Verfaillie J, and Baldocchi DD
- Subjects
- California, Floods, Seasons, Carbon Dioxide metabolism, Carbon Sequestration, Climate Change, Ecosystem, Wetlands
- Abstract
Inundated wetlands can potentially sequester substantial amounts of soil carbon (C) over the long-term because of slow decomposition and high primary productivity, particularly in climates with long growing seasons. Restoring such wetlands may provide one of several effective negative emission technologies to remove atmospheric CO2 and mitigate climate change. However, there remains considerable uncertainty whether these heterogeneous ecotones are consistent net C sinks and to what degree restoration and management methods affect C sequestration. Since wetland C dynamics are largely driven by climate, it is difficult to draw comparisons across regions. With many restored wetlands having different functional outcomes, we need to better understand the importance of site-specific conditions and how they change over time. We report on 21 site-years of C fluxes using eddy covariance measurements from five restored fresh to brackish wetlands in a Mediterranean climate. The wetlands ranged from 3 to 23 years after restoration and showed that several factors related to restoration methods and site conditions altered the magnitude of C sequestration by affecting vegetation cover and structure. Vegetation established within two years of re-flooding but followed different trajectories depending on design aspects, such as bathymetry-determined water levels, planting methods, and soil nutrients. A minimum of 55% vegetation cover was needed to become a net C sink, which most wetlands achieved once vegetation was established. Established wetlands had a high C sequestration efficiency (i.e. the ratio of net to gross ecosystem productivity) comparable to upland ecosystems but varied between years undergoing boom-bust growth cycles and C uptake strength was susceptible to disturbance events. We highlight the large C sequestration potential of productive inundated marshes, aided by restoration design and management targeted to maximise vegetation extent and minimise disturbance. These findings have important implications for wetland restoration, policy, and management practitioners., Competing Interests: The authors declare no competing interest.
- Published
- 2021
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11. Mineralogical associations with soil carbon in managed wetland soils.
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Anthony TL and Silver WL
- Subjects
- Agriculture, Carbon, Minerals, Soil, Wetlands
- Abstract
Carbon (C)-rich wetland soils are often drained for agriculture due to their capacity to support high net primary productivity. Increased drainage is expected this century to meet the agricultural demands of a growing population. Wetland drainage can result in large soil C losses and the concentration of residual soil minerals such as iron (Fe) and aluminum (Al). In upland soils, reactive Fe and Al minerals can contribute to soil C accumulation through sorption to poorly crystalline minerals and coprecipitation of organo-metal complexes, as well as C loss via anaerobic respiration by Fe-reducing bacteria. The role of these minerals in soil C dynamics is often overlooked in managed wetland soils and may be particularly important in both drained and reflooded systems with elevated mineral concentrations. Reflooding drained soils have been proposed as a means to sequester C for climate change mitigation, yet little is known about how reactive Fe and Al minerals affect C cycling in restored wetlands. We explored the interactions among soil C and reactive Fe and Al minerals in drained and reflooded wetland soils. In reflooded soils, soil C was negatively associated with reactive Fe and reduced Fe(II), a proxy for anaerobic conditions (reactive Fe: R
2 = .54-.79; Fe(II): R2 = .59-.89). In drained soils, organo-Al complexes were positively associated with soil C and Fe(II) (Al R2 = .91; Fe(II): R2 = .54-.60). Soil moisture, organo-Al, and reactive Fe explained most of the variation observed in soil C concentrations across all sites (p < .01). Reactive Fe was negatively correlated to soil C concentrations across sites, suggesting these Fe pools may drive additional C losses in drained soils and limit C sequestration with reflooding. In contrast, reactive organo-Al in drained soils facilitates C storage via aggregation and/or formation of anaerobic (micro)sites that protect residual soil C from oxidation and may at least partially offset C losses., (© 2020 John Wiley & Sons Ltd.)- Published
- 2020
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12. Soil properties and sediment accretion modulate methane fluxes from restored wetlands.
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Chamberlain SD, Anthony TL, Silver WL, Eichelmann E, Hemes KS, Oikawa PY, Sturtevant C, Szutu DJ, Verfaillie JG, and Baldocchi DD
- Subjects
- California, Carbon analysis, Conservation of Natural Resources, Carbon Dioxide analysis, Geologic Sediments analysis, Methane analysis, Soil chemistry, Wetlands
- Abstract
Wetlands are the largest source of methane (CH
4 ) globally, yet our understanding of how process-level controls scale to ecosystem fluxes remains limited. It is particularly uncertain how variable soil properties influence ecosystem CH4 emissions on annual time scales. We measured ecosystem carbon dioxide (CO2 ) and CH4 fluxes by eddy covariance from two wetlands recently restored on peat and alluvium soils within the Sacramento-San Joaquin Delta of California. Annual CH4 fluxes from the alluvium wetland were significantly lower than the peat site for multiple years following restoration, but these differences were not explained by variation in dominant climate drivers or productivity across wetlands. Soil iron (Fe) concentrations were significantly higher in alluvium soils, and alluvium CH4 fluxes were decoupled from plant processes compared with the peat site, as expected when Fe reduction inhibits CH4 production in the rhizosphere. Soil carbon content and CO2 uptake rates did not vary across wetlands and, thus, could also be ruled out as drivers of initial CH4 flux differences. Differences in wetland CH4 fluxes across soil types were transient; alluvium wetland fluxes were similar to peat wetland fluxes 3 years after restoration. Changing alluvium CH4 emissions with time could not be explained by an empirical model based on dominant CH4 flux biophysical drivers, suggesting that other factors, not measured by our eddy covariance towers, were responsible for these changes. Recently accreted alluvium soils were less acidic and contained more reduced Fe compared with the pre-restoration parent soils, suggesting that CH4 emissions increased as conditions became more favorable to methanogenesis within wetland sediments. This study suggests that alluvium soil properties, likely Fe content, are capable of inhibiting ecosystem-scale wetland CH4 flux, but these effects appear to be transient without continued input of alluvium to wetland sediments., (© 2018 John Wiley & Sons Ltd.)- Published
- 2018
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13. The role of multiorgan procurement for abdominal transplant in general surgery resident education.
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Bayer J, Moulton CA, Monden K, Goldstein RM, McKenna GJ, Testa G, Ruiz RM, Anthony TL, Onaca N, Klintmalm GB, and Kim PTW
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- Adult, Educational Measurement methods, Female, Humans, Male, Prospective Studies, Abdomen surgery, Clinical Competence, Education, Medical, Graduate methods, General Surgery education, Internship and Residency, Organ Transplantation education, Tissue and Organ Procurement methods
- Abstract
Background: To assess the impact of participation of multiorgan procurement (MP) by general surgery (GS) residents on surgical knowledge and skills, a prospective cohort study of GS residents during transplant surgery rotation was performed., Methods: Before and after participation in MPs, assessment of knowledge was performed by written pre and post tests and surgical skills by modified Objective Structured Assessment of Technical Skill (OSATS) score. Thirty-nine residents performed 84 MPs., Results: Significant improvement was noted in the written test scores (63.3% vs 76.7%; P < 0.001). Better surgical score was associated with female gender (15.4 vs 13.3, P = <0.01), prior MP experience (16.2 vs 13.7, P = 0.03), and senior level resident (15.1 vs 13.0, P = 0.03). Supraceliac aortic dissection (P = 0.0017) and instrument handling (P = 0.041) improved with more MP operations., Conclusions: Participation in MP improves residents' knowledge of abdominal anatomy and surgical technique., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2018
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14. Eversion Bile Duct Anastomosis: A Safe Alternative for Bile Duct Size Discrepancy in Deceased Donor Liver Transplantation.
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Leal-Leyte P, McKenna GJ, Ruiz RM, Anthony TL, Saracino G, Testa G, Klintmalm GB, and T W Kim P
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- Adolescent, Adult, Aged, Anastomosis, Surgical adverse effects, Anastomosis, Surgical methods, Bile Ducts anatomy & histology, Bile Ducts pathology, Case-Control Studies, Child, Constriction, Pathologic epidemiology, Constriction, Pathologic etiology, Constriction, Pathologic surgery, Endoscopy, Digestive System methods, Female, Humans, Incidence, Liver Transplantation adverse effects, Male, Middle Aged, Organ Size, Postoperative Complications etiology, Postoperative Complications surgery, Risk Factors, Stents, Treatment Outcome, Young Adult, Bile Ducts surgery, Endoscopy, Digestive System instrumentation, Liver Transplantation methods, Postoperative Complications epidemiology
- Abstract
Bile duct size discrepancy in liver transplantation may increase the risk of biliary complications (BCs). The aim of this study was to evaluate the safety and outcomes of the eversion bile duct anastomosis technique in deceased donor liver transplantation (DDLT) with duct-to-duct anastomosis. A total of 210 patients who received a DDLT with duct-to-duct anastomosis from 2012 to 2017 were divided into 2 groups: those who had eversion bile duct anastomosis (n = 70) and those who had standard bile duct anastomosis (n = 140). BC rates were compared between the 2 groups. There was no difference in the cumulative incidence of biliary strictures (P = 0.20) and leaks (P = 0.17) between the 2 groups. The BC rate in the eversion group was 14.3% and 11.4% in the standard anastomosis group. All the BCs in the eversion group were managed with endoscopic stenting. A severe size mismatch (≥3:1 ratio) was associated with a significantly higher incidence of biliary strictures (44.4%) compared with a 2:1 ratio (8.2%; P = 0.002). In conclusion, the use of the eversion technique is a safe alternative for bile duct discrepancy in DDLT. However, severe bile duct size mismatch may be a risk factor for biliary strictures with such a technique., (© 2018 The Authors. Liver Transplantation published by Wiley Periodicals, Inc. on behalf of American Association for the Study of Liver Diseases.)
- Published
- 2018
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15. What is the impact of age on reoperation rates for femoral neck fractures treated with internal fixation and hemiarthroplasty? A comparison of hip fracture outcomes in the very elderly population.
- Author
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Griffin J, Anthony TL, Murphy DK, Brennan KL, and Brennan ML
- Abstract
Methods: A retrospective comparative study was performed at a level 1 trauma center at which electronic medical records and digital radiographs were reviewed for 949 femoral neck fractures. For the primary outcome of reoperation based on age, Kaplan-Meier models were built and analysis applied., Results: A total of 334 fractures were nondisplaced treated with closed reduction and percutaneous pinning (CRPP), and 615 were displaced managed with hemiarthroplasty (HA). Overall, 98 patients (10.33%) required reoperation. Increasing reoperation rates for CRPP was seen with each subsequent age group. The opposite was seen with HA in which increasing age groups showed lower reoperation rates.
- Published
- 2016
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16. Early Identification of Infants and Toddlers With Deafblindness.
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Anthony TL
- Subjects
- Child, Preschool, Deaf-Blind Disorders complications, Deaf-Blind Disorders psychology, Early Intervention, Educational, Humans, Infant, Deaf-Blind Disorders diagnosis
- Abstract
Data from the 2014 National Center on Deaf-Blindness Count show that fewer than 100 infants and toddlers are currently identified with deaf-blindness across the United States and that identification rates for this population vary greatly from state to state. The author presents a key rationale for timely and accurate identification of early-onset deafblindness and of the challenges involved in current early identification practices. Health and educational providers play a vital role in efforts to understand the impact of deafblindness on early development, high-risk conditions, and diagnoses associated with pediatric deafblindness, as well as the warning signs of early-onset hearing and vision loss. Subsequent to diagnosis, medical treatments may be available to restore or augment sensory functioning. Therefore, early detection and identification of deafblindness should serve as a catalyst for prompt referral to appropriate early intervention services for both child and family.
- Published
- 2016
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17. Inferior vena cava reconstruction for leiomyosarcoma of Zone I-III requiring complete hepatectomy and bilateral nephrectomy with autotransplantation.
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Fernandez HT, Kim PT, Anthony TL, Hamman BL, Goldstein RM, and Testa G
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- Female, Humans, Leiomyosarcoma pathology, Leiomyosarcoma therapy, Middle Aged, Prognosis, Tomography, X-Ray Computed, Transplantation, Autologous, Treatment Outcome, Vascular Neoplasms pathology, Vascular Neoplasms therapy, Vena Cava, Inferior pathology, Hepatectomy, Kidney Transplantation, Leiomyosarcoma surgery, Liver Transplantation, Nephrectomy, Plastic Surgery Procedures, Vascular Neoplasms surgery, Vena Cava, Inferior surgery
- Abstract
The inferior vena cava (IVC) is the most common site of leiomyosarcomas arising from a vascular origin. Leiomyosarcomas of the IVC are categorized by anatomical location. Zone I refers to the infrarenal portion of the IVC, Zone II from the hepatic veins to the renal veins, and Zone III from the right atrium to the hepatic veins. This is a rare presentation of a Zone I-III leiomyosarcoma. Fifty-two-years-old female with a medical history significant only for HTN was admitted to the hospital with bilateral lower extremity edema and dyspnea. Two-dimensional echo demonstrated a right atrial thrombus, extending into the IVC. On subsequent CT and MRI, a 15 cm mass was noted that began in the right atrium and extended into the IVC, with continuation below the renal veins to above the level of the confluence of the common iliac veins. The patient underwent a complete resection of the mass, replacement of the IVC with Dacron graft, total hepatectomy and bilateral nephrectomy, with liver and kidney autotransplantation. Pathology was consistent with a high grade spindle cell sarcoma of vena cava origin. Patient was readmitted approximately 4 weeks postoperatively to begin adjuvant chemotherapy. This case represents a zone I-III IVC leiomyosarcoma treated with surgical R0 resection. This included a hepatectomy, bilateral nephrectomy, and hepatic and left renal autotransplantation. These complex tumors should be treated with surgical resection, and require a multidisciplinary approach., (© 2015 Wiley Periodicals, Inc.)
- Published
- 2015
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18. Ratio of hepatic arterial flow to recipient body weight predicts biliary complications after deceased donor liver transplantation.
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Kim PT, Saracino G, Jennings L, Ramsay M, McKenna GJ, Testa G, Anthony TL, Onaca N, Ruiz RM, Goldstein RM, Levy MF, and Klintmalm GB
- Subjects
- Adult, Blood Flow Velocity, Cholestasis etiology, Female, Hepatic Artery physiopathology, Humans, Male, Middle Aged, Regional Blood Flow, Retrospective Studies, Risk Assessment, Risk Factors, Texas, Treatment Outcome, Young Adult, Anastomotic Leak etiology, Biliary Tract Diseases etiology, Body Weight, Hepatic Artery surgery, Liver Transplantation adverse effects, Liver Transplantation methods, Transplant Recipients
- Abstract
Objectives: Adequate hepatic arterial (HA) flow to the bile duct is essential in liver transplantation. This study was conducted to determine if the ratio of directly measured HA flow to weight is related to the occurrence of biliary complications after deceased donor liver transplantation., Methods: A retrospective review of 2684 liver transplants carried out over a 25-year period was performed using data sourced from a prospectively maintained database. Rates of biliary complications (biliary leaks, anastomotic and non-anastomotic strictures) were compared between two groups of patients with HA flow by body weight of, respectively, <5 ml/min/kg (n = 884) and ≥5 ml/min/kg (n = 1800)., Results: Patients with a lower ratio of HA flow to weight had higher body weight (92 kg versus 76 kg; P < 0.001) and lower HA flow (350 ml/min versus 550 ml/min; P < 0.001). A lower ratio of HA flow to weight was associated with higher rates of biliary complications at 2 months, 6 months and 12 months (19.8%, 28.2% and 31.9% versus 14.8%, 22.4% and 25.8%, respectively; P < 0.001)., Conclusions: A ratio of HA flow to weight of < 5 ml/min/kg is associated with higher rates of biliary complications. This ratio may be a useful parameter for application in the prevention and early detection of biliary complications., (© 2014 International Hepato-Pancreato-Biliary Association.)
- Published
- 2014
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19. Posttransplant lymphoproliferative disorder presenting as a small bowel obstruction in a patient with pancreas transplantation alone.
- Author
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Kruel CR, Ruiz RM, Shiller SM, Anthony TL, Goldstein RM, Kim PT, Levy MF, McKenna GJ, Onaca N, Testa G, and Klintmalm GB
- Abstract
Posttransplant lymphoproliferative disorder (PTLD) is a well-known complication associated with the transplant recipient. We chronicle a case of PTLD in a failed graft presenting as a small bowel obstruction in a pancreas-only transplant patient. While typical symptoms may be elusive in the complex immunosuppressed patient, graft pain along with persistent graft pancreatitis and a positive Epstein-Barr viremia should raise suspicion for an underlying PTLD.
- Published
- 2014
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20. Antibody-mediated rejection in ABO compatible husband to wife living donor liver transplant and review of the literature.
- Author
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Kheradmand T, Anthony TL, Harland RC, Testa G, Hart J, Renz J, Te HS, and Marino SR
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- Adult, B-Lymphocytes immunology, B-Lymphocytes pathology, Complement C4b, Female, Graft Rejection pathology, Graft Rejection therapy, Histocompatibility Testing, Humans, Immunoglobulins, Intravenous therapeutic use, Liver Cirrhosis immunology, Liver Cirrhosis pathology, Liver Cirrhosis surgery, Male, Peptide Fragments blood, Plasmapheresis, Spouses, T-Lymphocytes immunology, T-Lymphocytes pathology, Transaminases blood, Transplantation, Homologous, ABO Blood-Group System immunology, Autoantibodies blood, Graft Rejection immunology, HLA Antigens immunology, Isoantibodies blood, Liver Transplantation, Living Donors
- Abstract
Role of donor specific antibodies (DSAs) in liver allograft function has not been fully defined. We report an ABO compatible orthotopic liver transplant case with DSAs to donor HLA, where the patient developed immediate antibody-mediated rejection (AMR).The patient, a 43-year-old female with cirrhosis, underwent ABO-compatible living-donor liver transplant from her husband. On post-operative day (POD)1, serum transaminases were sharply elevated. Retrospective testing of pre-transplant serum demonstrated presence of strong class I and class II anti-HLA antibodies and positive T- and B-cell flow-cytometric crossmatches (FCXM). Transaminase levels improved with plasmapheresis and thymoglobulin. On POD7, her liver enzymes became elevated again and allograft biopsy stained positive for C4d. Patient was treated with intravenous immunoglobulin and rituximab and recovered over time. Pre-transplant sera of patient were retrospectively tested by C1q assay to determine the cytotoxic function of DSAs; DSAs were positive for C1q binding. Our results suggest that pre-liver transplant antibody testing may be helpful in identifying patients at risk for development of AMR., (Copyright © 2014 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
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21. Kinetics of 5-HT2B receptor signaling: profound agonist-dependent effects on signaling onset and duration.
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Unett DJ, Gatlin J, Anthony TL, Buzard DJ, Chang S, Chen C, Chen X, Dang HT, Frazer J, Le MK, Sadeque AJ, Xing C, and Gaidarov I
- Subjects
- Adrenergic alpha-Antagonists pharmacology, Amphetamines pharmacokinetics, Arrestins metabolism, Calcium metabolism, Dose-Response Relationship, Drug, Ergot Alkaloids pharmacology, Extracellular Signal-Regulated MAP Kinases metabolism, HEK293 Cells, Humans, Phenoxybenzamine pharmacology, Phosphorylation, Radioligand Assay, beta-Arrestins, Receptor, Serotonin, 5-HT2B drug effects, Serotonin Receptor Agonists pharmacology, Signal Transduction drug effects
- Abstract
The kinetics of drug-receptor interactions can profoundly influence in vivo and in vitro pharmacology. In vitro, the potencies of slowly associating agonists may be underestimated in assays capturing transient signaling events. When divergent receptor-mediated signaling pathways are evaluated using combinations of equilibrium and transient assays, potency differences driven by kinetics may be erroneously interpreted as biased signaling. In vivo, drugs with slow dissociation rates may display prolonged physiologic effects inconsistent with their pharmacokinetic profiles. We evaluated a panel of 5-hydroxytryptamine2B (5-HT2B) receptor agonists in kinetic radioligand binding assays and in transient, calcium flux assays, and inositol phosphate accumulation assays; two functional readouts emanating from Gαq-mediated activation of phospholipase C. In binding studies, ergot derivatives demonstrated slow receptor association and dissociation rates, resulting in significantly reduced potency in calcium assays relative to inositol phosphate accumulation assays. Ergot potencies for activation of extracellular signal-regulated kinases 1 and 2 were also highly time-dependent. A number of ergots produced wash-resistant 5-HT2B signaling that persisted for many hours without appreciable loss of potency, which was not explained simply by slow receptor-dissociation kinetics. Mechanistic studies indicated that persistent signaling originated from internalized or sequestered receptors. This study provides a mechanistic basis for the long durations of action in vivo and wash-resistant effects in ex vivo tissue models often observed for ergots. The 5-HT2B agonist activity of a number of ergot-derived therapeutics has been implicated in development of cardiac valvulopathy in man. The novel, sustained nature of ergot signaling reported here may represent an additional mechanism contributing to the valvulopathic potential of these compounds.
- Published
- 2013
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22. Latanoprost's effects on TIMP-1 and TIMP-2 expression in human ciliary muscle cells.
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Anthony TL, Lindsey JD, and Weinreb RN
- Subjects
- Blotting, Western, Cells, Cultured, Ciliary Body cytology, Ciliary Body enzymology, Dose-Response Relationship, Drug, Enzyme Activation, Enzyme Inhibitors pharmacology, Humans, Latanoprost, Matrix Metalloproteinases metabolism, Muscle, Smooth cytology, Muscle, Smooth enzymology, Protein Kinase C antagonists & inhibitors, Protein Kinase C physiology, RNA, Messenger biosynthesis, Reverse Transcriptase Polymerase Chain Reaction, Tetradecanoylphorbol Acetate pharmacology, Tissue Inhibitor of Metalloproteinase-1 biosynthesis, Tissue Inhibitor of Metalloproteinase-2 biosynthesis, Antihypertensive Agents pharmacology, Ciliary Body drug effects, Muscle, Smooth drug effects, Prostaglandins F, Synthetic pharmacology, Tissue Inhibitor of Metalloproteinase-1 genetics, Tissue Inhibitor of Metalloproteinase-2 genetics
- Abstract
Purpose: To determine the effect of treatment with latanoprost on the tissue inhibitors of metalloproteinase (TIMP)-1 and -2 in cultured human ciliary muscle (HCM) cells., Methods: Confluent serum-starved HCM cells were exposed to increasing concentrations of latanoprost acid (LA, 1 nM to 10 micro M) for 6, 18, and 24 hours. TIMP-1 and -2 mRNA transcripts were evaluated by RT-PCR. Gelatin zymography was used to measure changes in the amount of matrix metalloproteinase (MMP) in the culture medium. To evaluate the potential role of PKC, HCM cells were treated with phorbol 12-myrisate 13-acetate (PMA) in the absence or presence of the PKC inhibitor bisindolylmaleimide I (Bis I) or the PKA inhibitor KT5720. Data were quantitated by densitometry and statistically analyzed with the Student-Newman-Keuls test., Results: TIMP-1 and -2 mRNA transcripts and proteins were detected in primary cultures of HCM cells. TIMP-1 mRNA levels were unchanged at 6 hours, but increased 45% +/- 17% and 54% +/- 13% in cultures exposed for 18 hours to 1 and 10 micro M LA, respectively (n = 3). In contrast, 6 hours of exposure to LA increased expression of TIMP-2 mRNA by up to 11.3% +/- 0.2% (n = 3). However, no significant induction of TIMP-2 mRNA was observed at either 18 or 24 hours (n = 3). TIMP-1 protein was significantly increased in cultures exposed to LA for 18 and 24 hours. In contrast, TIMP-2 protein expression was insignificantly different from control cultures at 6, 18, and 24 hours of treatment. HCM cells exposed to PMA for 24 hours produced similar increases in TIMP-1 mRNA levels, as seen with latanoprost (n = 5). However, no significant induction of TIMP-2 mRNA was observed. Zymographic analysis of the media from these cultures confirmed dose-dependent increases of MMP-1 at 6, 18, and 24 hours, whereas dose-dependent increases in MMP-2 were seen only after 24 hours' exposure to LA (n = 3). TIMP-1 protein levels were increased 27% +/- 9.3% and 15% +/- 11% in the media of cells exposed for 24 hours to 100 nM LA and 100 nM PMA, respectively (n = 5). The increases in TIMP-1 protein induced by LA were essentially eliminated by Bis I (n = 3) and unaffected by KT5720 (n = 3)., Conclusions: For the most part, TIMP-1, and not TIMP-2, contributes to regulation of MMP within the uveoscleral outflow pathway after exposure to latanoprost. Moreover, this induction appears to be meditated by activation of PKC.
- Published
- 2002
23. Intraocular distribution of 70-kDa dextran after subconjunctival injection in mice.
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Kim TW, Lindsey JD, Aihara M, Anthony TL, and Weinreb RN
- Subjects
- Animals, Conjunctiva metabolism, Injections, Mice, Microscopy, Fluorescence, Molecular Weight, Tissue Distribution, Dextrans pharmacokinetics, Eye metabolism, Fluorescent Dyes pharmacokinetics, Rhodamines pharmacokinetics
- Abstract
Purpose: To investigate the intraocular distribution kinetics of 70-kDa dextran after subconjunctival injection., Methods: The right eye of 15 mice received a single subconjunctival injection of a 1.5-microL solution of 0.25% 70-kDa tetramethylrhodamine-dextran (TMR-D). The distribution of fluorescent labeling in eye sections was examined by fluorescence microscopy at 0.25, 1, 4, 24, or 72 hours after the injection. The brightness and homogeneity of fluorescence in the sclera, choroid, and retina were scored near the injection site, on the side of the globe opposite the injection site, and adjacent to the optic nerve head. Fluorescence intensity within the sclera and choroid adjacent to the optic nerve was assessed quantitatively by imaging densitometry., Results: TMR-D readily diffused transsclerally and dispersed throughout a large portion of the sclera, uvea, and cornea. Shortly after the injection, homogenous fluorescence was observed in the sclera and choroid on the same meridian as that of the injection site. This fluorescence gradually decreased in intensity with distance from the injection site. At the opposite meridian, fluorescence in the choroid was more intense than in the adjacent sclera and could be traced up to the ciliary muscle. TMR-D was also observed in the retinal and optic nerve vessels. The intensity of scleral and choroidal fluorescence adjacent to the optic nerve reached a maxima at 1 hour, and then decreased slowly, with half-lives of approximately 16 and 100 hours, respectively. Visible fluorescence was maintained at least until 72 hours in the sclera, choroid, iris, and cornea. Specific fluorescent labeling was never found in the contralateral eyes., Conclusions: Macromolecular 70-kDa dextran can be readily delivered to the mouse retina and uveal tissues by subconjunctival injection through transscleral diffusion, local hematogenous spread, and possibly movement through the uveoscleral outflow pathway. Subconjunctival injection may be a useful approach for delivering macromolecules to the retina and uvea.
- Published
- 2002
24. Differential regulation of Ca(2+)-dependent Cl- currents by FP prostanoid receptor isoforms in Xenopus oocytes.
- Author
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Anthony TL, Fujino H, Pierce KL, Yool AJ, and Regan JW
- Subjects
- Animals, Dinoprost metabolism, Enzyme Inhibitors pharmacology, Phosphoric Monoester Hydrolases antagonists & inhibitors, Protein Isoforms metabolism, Xenopus laevis, Calcium metabolism, Chloride Channels physiology, Oocytes metabolism, Receptors, Prostaglandin metabolism
- Abstract
The FP(A) and FP(B) prostanoid receptor isoforms are G-protein-coupled receptors that are activated by prostaglandin F(2alpha) (PGF(2alpha)). Differences in their carboxyl termini prompted us to examine the intracellular calcium (Ca(2+)) signaling of these receptor isoforms using the Xenopus oocyte expression system. Protein expression was determined by immunofluorescence microscopy and whole cell binding with [3H]PGF(2alpha). Positive immunolabeling was observed on the outer membranes of oocytes expressing FLAG-tagged FP receptor isoforms, but not on control (water-injected) oocytes. Intracellular signaling was examined using a two-electrode voltage clamp. Specific whole-cell binding was also detected for both receptor isoforms. Bath application of 10 microM PGF(2alpha) to FP(A)-expressing oocytes produced a chloride (Cl-) current response similar to that of an injection of inositol 1,4,5-trisphosphate (InsP(3)) (5.76+/-0.6 microA, peak current; N=23) that returned to control levels within 25 min. In FP(B)-expressing oocytes the activation of the Cl- current was delayed or completely absent (1.38+/-0.2 microA, peak current; N=18). Control oocytes were not responsive to the application of PGF(2alpha) (0.87+/-0.1 microA, peak current; N=10). Activation of Cl- currents for both FP receptor isoforms was dependent upon intracellular Ca(2+) stores as a 30-min pretreatment with thapsigargin (1 microM; N=5) blocked the PGF(2alpha) induction of the Cl- current. These data indicate that the FP prostanoid receptor isoforms differ in their ability to activate Ca(2+)-dependent Cl- channels when expressed in Xenopus oocytes. The difference appears to be in the ability of the two FP prostanoid receptor isoforms to mobilize intracellular calcium.
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- 2002
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25. Expression of alpha(2)-adrenergic receptor subtypes in prenatal rat spinal cord.
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Huang Y, Stamer WD, Anthony TL, Kumar DV, St John PA, and Regan JW
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- Animals, Antibody Specificity immunology, COS Cells, Female, Fetus, Neurites metabolism, Neurites ultrastructure, Neurons cytology, Pregnancy, Rats, Rats, Sprague-Dawley, Spinal Cord cytology, Spinal Cord metabolism, Stem Cells cytology, Stem Cells metabolism, Cell Differentiation genetics, Gene Expression Regulation, Developmental physiology, Neurons metabolism, RNA, Messenger metabolism, Receptors, Adrenergic, alpha-2 genetics, Receptors, Adrenergic, alpha-2 metabolism, Spinal Cord embryology
- Abstract
The results of molecular cloning have revealed three subtypes of the alpha(2)-adrenergic receptors (alpha(2) AR) that have been defined alpha(2)C10 (alpha(2A)), alpha(2)C2 (alpha(2B)) and alpha(2)C4 (alpha(2C)). The differential expression of alpha(2) AR subtypes is affected by developmental factors in rat submandibular gland, lung and brain. In the spinal cord of postnatal and adult rats, alpha(2A) and alpha(2C) AR subtypes are expressed and appear to mediate pain perception. However, the relative expression of alpha(2) AR subtypes in the prenatal spinal cord is unknown. In the present study subtype-specific antibodies and reverse transcription-polymerase chain reaction (RT-PCR) were used to determine the expression and localization of the alpha(2) AR subtypes in sections of embryonic day 14 rat spinal cords and primary cultures of cells isolated from these cords. Spinal cords were removed from day 14 embryos, and were sectioned or used for the preparation of cell cultures. After 9 days in culture, neurons were examined by immunofluorescence microscopy or used for preparation of total RNA. In both intact spinal cords and isolated cells, positive immunoreactivity was detected with antibodies against alpha(2A) and alpha(2B) subtypes, but not with antibodies against the alpha(2C) subtype. Using a dual-labeling approach, anti-alpha(2A) and anti-alpha(2B) immunoreactivity was present on the same population of neurons. RT-PCR results were consistent with immunofluorescence studies, and showed that mRNA encoding the alpha(2A) and alpha(2B) subtypes was present in total RNA prepared from primary cultures of rat spinal cord neurons. In contrast to spinal cords of postnatal or adult rats that express alpha(2A) and alpha(2C) AR subtypes on different neurons, prenatal spinal cords contain alpha(2A) and alpha(2B) AR subtypes, and these two subtypes appear to be co-expressed in the same cells.
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- 2002
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26. Detection of prostaglandin EP(1), EP(2), and FP receptor subtypes in human sclera.
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Anthony TL, Lindsey JD, Aihara M, and Weinreb RN
- Subjects
- Adult, Aged, Cells, Cultured, Fibroblasts metabolism, Humans, RNA, Messenger metabolism, Receptors, Prostaglandin genetics, Receptors, Prostaglandin E genetics, Receptors, Prostaglandin E, EP1 Subtype, Receptors, Prostaglandin E, EP2 Subtype, Sclera cytology, Receptors, Prostaglandin metabolism, Receptors, Prostaglandin E metabolism, Sclera metabolism
- Abstract
Purpose: To examine the expression of five prostaglandin (PG) receptors, EP(1), EP(2), EP(3), EP(4), and FP and their corresponding mRNA transcripts in human sclera and cultured human scleral fibroblasts (HSFs)., Methods: Primary cultures of HSFs were established from donor eyes. Also, sclera from human donor eyes was snap frozen and sectioned. Immunocytochemistry was performed on HSFs and tissue sections with subtype-specific antibodies to the EP(1), EP(2), EP(3), EP(4), and FP receptors. The presence of mRNA for the receptor subtypes was examined from total RNA obtained from human sclera and confirmed with restriction digest analysis., Results: Positive EP(1) and FP receptor immunoreactivity was observed in fibroblasts within the sections from human sclera. In primary cultures of HSFs, EP(1) and FP labeling was observed over the entire cell surface. EP(2) immunoreactivity within HSFs was mostly present in the juxtanuclear region. RT-PCR analysis of total RNA isolated from human sclera and HSFs confirmed the presence of EP(1), EP(2), and FP receptor subtypes. The identity of the polymerase chain reaction products was confirmed by restriction enzyme analysis. No mRNA or immunoreactivity above basal levels was detected for the EP(3) and EP(4) prostanoid receptor subtypes in tissue sections or primary cultures., Conclusions: The EP(1), EP(2), and FP receptor subtypes are present in HSFs, suggesting that these cells may respond to endogenous PGs and their structural analogues through interaction with these receptor subtypes.
- Published
- 2001
27. Guanethidine evokes vasodilatation in guinea pig mesenteric artery by acting on sensory nerves.
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Zheng ZL, Shimamura K, Anthony TL, and Kreulen DL
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- Animals, Capsaicin pharmacology, Female, Guinea Pigs, Male, Mesenteric Arteries physiology, Neurons, Afferent physiology, Nitric Oxide metabolism, Vasodilation physiology, Adrenergic Agents pharmacology, Guanethidine pharmacology, Mesenteric Arteries drug effects, Mesenteric Arteries innervation, Neurons, Afferent drug effects, Vasodilation drug effects
- Abstract
In precontracted, endothelium-free guinea pig mesenteric artery rings, in which adrenergic vasoconstrictor responses had been eliminated, guanethidine (1-30 microM) produced a vasodilatation of 69.3+/-4.4%. The vasodilatation was reduced 89% by capsaicin (10 microM) or 55% by tetrodotoxin (10 microM), indicating mediation of this effect by primary sensory nerves. The nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (100 microM, 30 min) but not its stereoisomer reduced the guanethidine vasodilatation by 70%. Blockade of monoamine uptake with ouabain (25 microM, 15 min) or cocaine (5 microM, 5 min) reduced the guanethidine-induced vasodilatation by 85 and 67%, respectively. These results suggest that guanethidine produced vasodilatation by being transported into capsaicin-sensitive primary sensory nerves where it functioned as a substrate for nitric oxide synthase to generate a vasodilatory substance.
- Published
- 2000
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28. Characterization of ep prostanoid receptor subtypes in primary cultures of bovine ciliary epithelial cells by immunofluorescent microscopy and functional studies.
- Author
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Anthony TL, Pierce KL, and Regan JW
- Subjects
- Animals, Cattle, Cells, Cultured, Ciliary Body drug effects, Colforsin pharmacology, Cyclic AMP biosynthesis, Dinoprostone pharmacology, Dose-Response Relationship, Drug, Fluorescent Antibody Technique, Indirect, Inositol Phosphates biosynthesis, Isoproterenol pharmacology, Microscopy, Fluorescence, Pigment Epithelium of Eye drug effects, RNA, Messenger biosynthesis, Receptors, Prostaglandin E classification, Receptors, Prostaglandin E genetics, Reverse Transcriptase Polymerase Chain Reaction, Ciliary Body metabolism, Pigment Epithelium of Eye metabolism, Receptors, Prostaglandin E metabolism
- Abstract
Purpose: To determine the expression and functional coupling of EP prostanoid receptor subtypes to second messenger pathways in bovine ciliary epithelium., Methods: Primary cultures of bovine ciliary epithelial (BCE) cells were established and maintained in culture up to four passages. EP receptor protein expression was examined by indirect immunofluorescence microscopy with subtype selective antibodies in both tissue sections and primary cultures of BCE cells. Messenger RNA expression was determined using reverse transcription and polymerase chain reaction. The effects of prostanoid agonists on total inositol phosphate accumulation and cAMP formation were used to assess functional activity., Results: Positive immunoreactivity was obtained in both frozen thin-sections and primary cultures of bovine ciliary process to the prostanoid EP(1 ), EP(2), EP(3) and EP(4) receptor subtypes. Reverse transcription followed by the polymerase chain reaction yielded products corresponding to each of the prostanoid EP subtypes which was confirmed by restriction enzyme analysis. PGE(2) dose-dependently stimulated the accumulation of total inositol phosphates in cultured cells with an EC( 50) value of 100 nM. PGE(2), forskolin and isoproterenol produced dose-dependent increases in cAMP formation with EC(50) values of 100, 300 and 200 nM, respectively. Isoproterenol-stimulated cAMP formation was attenuated by the EP(3) receptor agonist sulprostone in cultured BCE cells. The inhibition elicited by sulprostone was reversed in cells pretreated with pertussis toxin., Conclusions: This study demonstrates the presence of functional prostanoid EP receptor subtypes in the bovine ciliary epithelium. EP(1) and EP(4) receptor subtypes were found primarily in the NPE cells, whereas, EP(2) receptor subtype immunofluorescence was detected in the PE cells. EP(3) receptor subtype labeling was observed in both the NPE and the PE cells. PGE(2) produces opposing effects on adenylyl cyclase through EP(2)/EP(4) and EP(3) receptor activation. The predominant effect of PGE(2) is on the adenylyl cyclase stimulatory receptors (EP(2)/EP(4)).
- Published
- 2000
29. Cloned human aquaporin-1 is a cyclic GMP-gated ion channel.
- Author
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Anthony TL, Brooks HL, Boassa D, Leonov S, Yanochko GM, Regan JW, and Yool AJ
- Subjects
- Amino Acid Sequence, Animals, Aquaporin 1, Aquaporins genetics, Blood Group Antigens, Cells, Cultured, Cloning, Molecular, Humans, Insecta, Ion Channel Gating, Molecular Sequence Data, Oocytes, Radioligand Assay, Rats, Sequence Homology, Amino Acid, Xenopus laevis, Aquaporins metabolism, Cyclic GMP metabolism, Ion Channels metabolism
- Abstract
Aquaporin-1 (AQP1) is a member of the membrane intrinsic protein (MIP) gene family and is known to provide pathways for water flux across cell membranes. We show here that cloned human AQP1 not only mediates water flux but also serves as a cGMP-gated ion channel. Two-electrode voltage-clamp analyses showed consistent activation of an ionic conductance in wild-type AQP1-expressing oocytes after the direct injection of cGMP (50 nl of 100 mM). Current activation was not observed in control (water-injected) oocytes or in AQP5-expressing oocytes with osmotic water permeabilities equivalent to those seen with AQP1. Patch-clamp recordings revealed large conductance channels (150 pS in K(+) saline) in excised patches from AQP1-expressing oocytes after the application of cGMP to the internal side. Amino acid sequence alignments between AQP1 and sensory cyclic-nucleotide-gated channels showed similarities between the cyclic-nucleotide-gated binding domain and the AQP1 carboxyl terminus that were not present in AQP5. Competitive radioligand-binding assays with [(3)H]cGMP demonstrated specific binding (K(D) = 0.2 microM) in AQP1-expressing Sf9 cells but not in controls. These results indicate that AQP1 channels have the capacity to participate in ionic signaling after the activation of cGMP second-messenger pathways.
- Published
- 2000
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30. Prostaglandin F2 alpha receptors in the human trabecular meshwork.
- Author
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Anthony TL, Pierce KL, Stamer WD, and Regan JW
- Subjects
- Animals, COS Cells, Calcium metabolism, Cells, Cultured, Chickens, DNA Primers chemistry, Dinoprost pharmacology, Dose-Response Relationship, Drug, Fluorescent Antibody Technique, Indirect, Humans, Hydrolysis, Inositol Phosphates metabolism, Microscopy, Confocal, Polymerase Chain Reaction, RNA, Messenger metabolism, Receptors, Prostaglandin genetics, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins metabolism, Trabecular Meshwork cytology, Trabecular Meshwork drug effects, Transcription, Genetic, Transfection, Receptors, Prostaglandin metabolism, Trabecular Meshwork metabolism
- Abstract
Purpose: Prostaglandin F2 alpha (PGF2 alpha) and analogs, such as latanoprost, are thought to lower intraocular pressure (IOP), primarily by increasing uveoscleral outflow. However, outflow through the trabecular meshwork may be increased as well. The authors hypothesize that any effect on the trabecular meshwork is mediated by prostanoid FP receptors (receptors for prostaglandin F2 alpha) in this tissue., Methods: To test this hypothesis, tissue sections of the human trabecular meshwork and cultures of human trabecular meshwork cells were examined for the presence of FP receptors using immunofluorescence microscopy with affinity-purified antibodies raised against a glutathione-S-transferase (GST)-FPA receptor fusion protein. The presence of the receptor was confirmed by using reverse transcription-polymerase chain reaction (RT-PCR), functional assays of PGF2 alpha-stimulated inositol phosphate hydrolysis, and intracellular calcium measurements., Results: Positive FPA receptor immunolabeling was observed in sections of the human trabecular meshwork and in cultured human trabecular meshwork cells. In both cases, specific labeling could be blocked by preincubation with a GST-FPA receptor fusion protein. Cross-blocking experiments with other receptor fusion proteins did not block specific labeling in cultured trabecular meshwork cells. PGF2 alpha caused a dose-dependent increase in total inositol phosphate accumulation and intracellular calcium release in human trabecular meshwork cells that was consistent with the presence of FP receptors. Using RT-PCR, message-encoding prostanoid FPA receptors were found in total RNA isolated from human trabecular meshwork cells., Conclusions: Prostanoid FPA receptors exist in human trabecular meshwork cells, as shown by the presence of mRNA, protein, and functional response to PGF2 alpha. This study indicates that functional FP receptors are present in the human trabecular meshwork and that they may be involved in mediating some of the IOP-lowering effects of PGF2 alpha in the eye.
- Published
- 1998
31. Nitric oxide is a sensory nerve neurotransmitter in the mesenteric artery of guinea pig.
- Author
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Zheng Z, Shimamura K, Anthony TL, Travagli RA, and Kreulen DL
- Subjects
- Animals, Endothelium, Vascular drug effects, Endothelium, Vascular enzymology, Endothelium, Vascular physiology, Guinea Pigs, Mesenteric Artery, Inferior drug effects, Mesenteric Artery, Inferior enzymology, Neurons, Afferent enzymology, Nitric Oxide Synthase metabolism, Vasodilation drug effects, Vasodilation physiology, Mesenteric Artery, Inferior physiology, Neurons, Afferent physiology, Neurotransmitter Agents physiology, Nitric Oxide physiology
- Abstract
Previous studies have shown that the guinea pig inferior mesenteric artery receives spinal sensory vasodilatory innervation, which can be activated by colon distention and electrical nerve stimulation. In the present study, we investigated the hypotheses that nitric oxide synthase (NOS) is present in guinea pig primary sensory neurons in the dorsal root ganglion (DRG) and in nerve fibers surrounding the mesenteric arteries, and that nitric oxide (NO) is a sensory neurotransmitter in the inferior mesenteric artery in vitro. Double-labeling immunohistochemistry showed that neuronal NOS-IR was found in 12% of cells of guinea pig thoracic and lumbar DRGs; in 95.1% of these cells it was colocalized with substance P (SP), and SP immunoreactivity (SP-IR) was present in 23% of cells of the same DRGs. Neuronal NOS-like immunoreactivity was localized in nerve fibers surrounding guinea pig mesenteric artery and 25% of them were double stained with SP-IR. Endothelium-denuded inferior mesenteric artery preparations in vitro were incubated with guanethidine (30 microns, 30 min) and pre-contracted with methoxamine (30 microns). The NO donors, sodium nitroprusside (1 micron) and L-nitrosocysteine (300 microns), produced 91.0 +/- 5.5 and 90.4 +/- 9.6% vasodilatation of total vasodilatation in the vessel segments, respectively, which was capsaicin- or tetrodotoxin-insensitive. Repetitive electrical field stimulation of the preparations produced a frequency-dependent vasodilatation which was reduced by pretreatment with capsaicin or by tetrodotoxin (10 microns). The NOS inhibitor N omega-nitro-L-arginine (L-NNA) (100 microns, 30 min) diminished the nerve-evoked vasodilatation from 41.8 +/- 8.4 to 21.4 +/- 9.7% at 2 Hz and from 50.8 +/- 5.6 to 19.0 +/- 7.3% at 15 Hz (P < 0.05), whereas NG-nitro-L-arginine methyl ester (L-NAME, 100 microns-1 mM) did not significantly inhibit the relaxation. The stereo isomer nitro-D-arginine (D-NNA, 100 microns, 30 min) was ineffective. These findings suggest that NO is a neurotransmitter released from primary sensory nerves which mediates vasodilation in vitro.
- Published
- 1997
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32. A physiologically-evoked M1-muscarinic depolarization in guinea-pig inferior mesenteric ganglion neurons.
- Author
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Anthony TL and Kreulen DL
- Subjects
- Action Potentials, Animals, Atropine pharmacology, Carbachol pharmacology, Female, Gastrointestinal Motility, Guinea Pigs, Hexamethonium, Hexamethonium Compounds pharmacology, Male, Pirenzepine analogs & derivatives, Pirenzepine pharmacology, Receptors, Muscarinic classification, Receptors, Muscarinic drug effects, Colon innervation, Ganglia, Sympathetic physiology, Mechanoreceptors physiology, Receptors, Muscarinic physiology, Stress, Mechanical
- Abstract
The possibility of physiologically-evoked muscarinic excitatory synaptic potentials was examined in the inferior mesenteric ganglion (IMG) with intracellular microelectrodes in vitro. Three types of depolarizing responses were evoked concurrently by colonic distension: (1) fast nicotinic excitatory postsynaptic potentials (EPSPs); (2) an 'intermediate' time course depolarization and (3) a long time course potential that persisted throughout the period of distension. After hexamethonium was superfused over the ganglia the long time course potential was observed in 91% of IMG neurons. Intermediate time course of depolarizations were observed in 100% of IMG neurons and correlated with each propulsive contraction of the distal colon. The intermediate depolarizations had an average amplitude of 1.8 +/- 0.1 mV (n = 175 individual events; 27 preparations) with an average duration of 11.9 +/- 0.8 sec (n = 28 individual events). The intermediate time course synaptic potentials were accompanied by an increase in input resistance of 15% (n = 6). Superfusion of atropine (1 microM; n = 6) on the IMG or the M1-selective antagonist pirenzepine (1 microM; n = 5) abolished the intermediate time course synaptic potentials during distension. Superfusion of the M2-selective antagonist AF-DX 116 (1 microM; n = 4) had no effect. In all preparations examined, distension-induced intermediate time course depolarizations were blocked by tetrodotoxin (TTX) (3 microM). Pressure ejection of carbachol (1 mM, 60-100 ms pulses) evoked depolarizations of similar amplitude (6.5 +/- 0.7 mV; n = 18) and duration to the intermediate depolarizations observed during propulsive contractions.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1994
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33. CCKA receptors mediate slow depolarizations in cultured mammalian sympathetic neurons.
- Author
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Knoper SR, Meehan AG, Purnyn S, Coggan JS, Anthony TL, and Kreulen DL
- Subjects
- Animals, Benzodiazepinones pharmacology, Cells, Cultured, Devazepide, Female, Ganglia, Sympathetic cytology, Ganglia, Sympathetic drug effects, Gastrins pharmacology, Guinea Pigs, Male, Membrane Potentials drug effects, Membrane Potentials physiology, Receptors, Cholecystokinin antagonists & inhibitors, Receptors, Cholecystokinin drug effects, Sincalide pharmacology, Tetragastrin pharmacology, Ganglia, Sympathetic physiology, Phenylurea Compounds, Receptors, Cholecystokinin physiology
- Abstract
The effect of cholecystokinin octapeptide (CCK-8) was examined in guinea-pig celiac ganglion (CG) neurons in primary culture using standard intracellular recording techniques. Sulfated CCK-8 (CCK-8S; 1 microM) evoked slow depolarizing responses in 94% of CG neurons tested. In contrast, membrane potential was not affected by nonsulfated CCK-8 (CCK-8NS; 1 microM), CCK tetrapeptide (CCK-4; 1 microM), or gastrin (1 microM). The selective CCKA receptor antagonist L 364,718 potently inhibited CCK-8S-induced slow depolarizations (IC50 2.9 pM). In contrast, the selective CCKB receptor antagonist L 365,260 was a weak inhibitor of CCK-8S-induced slow depolarizations (IC50 1.3 microM). The depolarizing responses to CCK-8S were associated with an average increase in cell input resistance of 61%. Single electrode voltage clamp experiments indicated that CCK-8S-induced depolarizations were associated with a slow inward shift in holding current. Thus, the present findings indicate that guinea-pig cultured CG neurons are endowed with excitatory CCKA receptors the activation of which elicits a decrease in membrane conductance, thereby resulting in slow depolarizations.
- Published
- 1993
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34. Comparison of neurotransmission with nerve trunk and transmural field stimulation in guinea-pig mesenteric artery.
- Author
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Keef KD, Hottenstein OD, Meehan AG, Anthony TL, and Kreulen DL
- Subjects
- Action Potentials drug effects, Adenosine Triphosphate analogs & derivatives, Adenosine Triphosphate pharmacology, Animals, Electric Stimulation, Guinea Pigs, In Vitro Techniques, Male, Membrane Potentials drug effects, Mesenteric Arteries innervation, Phentolamine pharmacology, Prazosin pharmacology, Sympathetic Nervous System physiology, Tetrodotoxin pharmacology, Muscle, Smooth, Vascular innervation, Synaptic Transmission physiology
- Abstract
1. Intracellular electrical and contractile responses to sympathetic nerve trunk stimulation (NTS) and transmural electrical field stimulation (TMS) were compared in the guinea-pig mesenteric artery in vitro. 2. Step increases in voltage with NTS gave rise to excitatory junctional potentials (EJPs) which reached a plateau amplitude of 5-10 mV, whereas with TMS larger amplitude EJPs and sometimes action potentials were obtained. 3. EJPs of equal amplitude (1-7 mV) elicited with TMS and NTS had the same rise time, duration and decay half-time. 4. Slow depolarization obtained with repetitive stimulation was significantly greater in amplitude with TMS than with NTS. 5. Equal amplitude EJPs were obtained throughout the preparation with NTS. With TMS, the amplitude of responses declined substantially with distance from the stimulating electrodes. 6. Tetrodotoxin (TTX) completely blocked EJPs, slow depolarization and contraction with NTS; however, with TMS a TTX-resistant component was observed. The TTX-resistant response to TMS was abolished in the presence of a low-Ca2+ superfusion solution but was not affected by endothelium removal. 7. Phentolamine or prazosin abolished slow depolarization but not EJPs with NTS or TMS. Prazosin abolished contraction with NTS and reduced but did not abolish contraction with TMS. 8. alpha, beta-Methylene ATP abolished EJPs with NTS, whereas with TMS only EJPs obtained with low stimulus intensities were abolished. alpha, beta-Methylene ATP did not block contraction with either NTS or TMS. 9. Combined TTX, prazosin and alpha, beta-methylene ATP abolished EJPs initiated with TMS at all but the highest stimulus intensities (12-20 V, 0.3 ms duration). 10. It is concluded that responses obtained with NTS can be reliably attributed to the release of transmitter by the conduction of action potentials in paravascular nerves, whereas activation by TMS is a more complex phenomenon dependent upon stimulus strength and probably involving multiple forms of activation.
- Published
- 1991
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35. Volume-sensitive synaptic input to neurons in guinea pig inferior mesenteric ganglion.
- Author
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Anthony TL and Kreulen DL
- Subjects
- Animals, Colon physiology, Evoked Potentials drug effects, Female, Guinea Pigs, Hexamethonium, Hexamethonium Compounds pharmacology, In Vitro Techniques, Male, Mechanoreceptors physiology, Membrane Potentials drug effects, Muscle Contraction drug effects, Muscle, Smooth innervation, Muscle, Smooth physiology, Neurons drug effects, Norepinephrine pharmacology, Synapses drug effects, Colon innervation, Ganglia, Sympathetic physiology, Neurons physiology, Synapses physiology
- Abstract
The relationship between changes in intracolonic volume related to propulsive contractions and synaptic potentials recorded intracellularly in neurons in the inferior mesenteric ganglion (IMG) was investigated in vitro. Distension of the colon induced propulsive contractions (frequency, 2-5/min), which reduced intracolonic volume by 88%. Each propulsive contraction was sustained for 10-12 s, after which time the colon refilled. The sustained propulsive contractions were associated with a decrease in the amplitude and frequency of fast cholinergic excitatory postsynaptic potentials (EPSPs) and partial repolarization of the slow EPSP. The pressure-volume relationships of the colonic segments had two limbs: at distension pressures less than 15 cmH2O ("volume limb") the intracolonic volume was proportional to the distension pressure; greater than 15 cmH2O ("pressure limb") the intracolonic volume did not increase further. The changes in synaptic input were related to these pressure-volume relationships. In the volume limb, the frequency and amplitude of fast EPSPs were proportional to intracolonic volume and maximized with volume. In the pressure limb, there was a slow depolarization of the membrane that increased with greater distension pressures. Under isovolumic conditions, the changes in intraluminal pressure associated with colonic contractions were not associated with changes in excitatory synaptic input to IMG neurons. These experiments demonstrate that colonic mechanoreceptors to IMG neurons are sensitive to both intracolonic volume and pressure.
- Published
- 1990
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36. Multiple effects of capsaicin on synaptic transmission in a mammalian sympathetic ganglion in vitro.
- Author
-
Anthony TL and Kreulen DL
- Subjects
- Animals, Evoked Potentials drug effects, Female, Ganglia, Sympathetic drug effects, Guinea Pigs, In Vitro Techniques, Male, Membrane Potentials drug effects, Synapses drug effects, Capsaicin pharmacology, Ganglia, Sympathetic physiology, Synapses physiology, Synaptic Transmission drug effects
- Published
- 1988
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