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21.
DR Toomey WSD Wilcock SC Solomon WC Hammond JA Orcutt 《Science (New York, N.Y.)》1998,280(5367):1224-1227
Relative travel time delays of teleseismic P and S waves, recorded during the Mantle Electromagnetic and Tomography (MELT) Experiment, have been inverted tomographically for upper-mantle structure beneath the southern East Pacific Rise. A broad zone of low seismic velocities extends beneath the rise to depths of about 200 kilometers and is centered to the west of the spreading center. The magnitudes of the P and S wave anomalies require the presence of retained mantle melt; the melt fraction near the rise exceeds the fraction 300 kilometers off axis by as little as 1%. Seismic anisotropy, induced by mantle flow, is evident in the P wave delays at near-vertical incidence and is consistent with a half-width of mantle upwelling of about 100 km. 相似文献
22.
K. Hosoya L. K. Lord A. Lara‐Garcia W. C. Kisseberth C. A. London C. G. Couto 《Veterinary and comparative oncology》2009,7(4):244-255
The purpose of this study was to evaluate prevalence of serum alanine transaminase (ALT) elevation in dogs receiving lomustine (CCNU) and to analyse the pattern of occurrence and potential risk factors. Serum ALT activity in 109 dogs during single‐agent CCNU chemotherapy was retrospectively analysed. The median initial dose, dose‐intensity and cumulative dose of CCNU were 64 mg m?2, 21 mg m?2 week?1 and 171 mg m?2, respectively. The overall prevalence of major ALT elevation [> 5‐fold upper reference limit (URL)] was 29% (32/109) and developed most commonly after one to three doses of CCNU. These ALT elevations occurred without preceding mild ALT elevation in 53% (17/32) of the cases. Three dogs (2.8%) developed clinical hepatopathy. For severe ALT elevation (>10‐fold URL), age ≤5‐year‐old was associated with higher risk. The findings of this study showed that elevation of ALT is common during CCNU chemotherapy in dogs and severe elevation can develop on a sudden onset. 相似文献
23.
Non‐immunosuppressive FTY720‐derivative OSU‐2S mediates reactive oxygen species‐mediated cytotoxicity in canine B‐cell lymphoma 
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下载免费PDF全文 R. Mani R. Yan X. Mo C.‐S. Chen M. A. Phelps R. Klisovic J. C. Byrd W. C. Kisseberth C. A. London N. Muthusamy 《Veterinary and comparative oncology》2017,15(3):1115-1118
OSU‐2S is a FTY720 (Fingolimod) derivative that lacks immunosuppressive properties but exhibits strong anti‐tumour activity in several haematological and solid tumour models. We have recently shown OSU‐2S to mediate potent cytotoxicity in human mantle cell lymphoma cell lines and primary cells. We report here the pre‐clinical activity of OSU‐2S in spontaneous B‐cell lymphoma of dogs which shares many characteristics of human lymphoma. OSU‐2S mediated apoptosis in canine B‐cell lines and primary B‐cell lymphoma cells obtained from spontaneous lymphoma bearing dogs. OSU‐2S induced reactive oxygen species (ROS) in canine lymphoma cells and inhibition of ROS partially rescued OSU‐2S‐mediated cell death. These studies provide a rational basis for the use of spontaneous lymphoma in pet dogs as a preclinical large animal model for the development of OSU‐2S as small molecule for treating people and dogs with lymphoma. 相似文献
24.
The purpose of this study was to determine the cardiovascular, analgesic, and sedative effects of IV medetomidine (M, 20 µg kg?1), medetomidine–hydromorphone (MH, 20 µg kg?1 ? 0.1 mg kg?1), and medetomidine–butorphanol (MB, 20 µg kg?1 ? 0.2 mg kg?1) in dogs. Using a randomized cross‐over design and allowing 1 week between treatments, six healthy, mixed‐breed dogs (five males and one female) weighing 20 ± 3 kg, were induced to anesthesia by face‐mask administration of 2.9% ET sevoflurane to facilitate instrumentation prior to administration of the treatment combinations. Dogs were intubated and instrumented to enable measurement of heart rate (HR), systolic arterial pressure (SAP), mean arterial pressure (MAP), diastolic arterial pressure (DAP), mean pulmonary arterial pressure (PAP), pulmonary arterial occlusion pressure (PAOP), central venous pressure (CVP), pulmonary arterial temperature (TEMP), and cardiac output via thermodilution using 5 mL of 5% dextrose, and recording the average of the three replicate measurements. Cardiac index (CI) and systemic (SVR) and pulmonary vascular resistances were calculated. After instrumentation was completed, administration of sevoflurane was discontinued, and the dogs were allowed to recover for 30 minutes prior to administration of the treatment drugs. After collection of the baseline samples for blood gas analysis and recording the baseline cardiovascular variables, the test agents were administered IV over 10 seconds and the CV variables recorded at 5, 10, 15, 30, 45, and 60 minutes post‐injection. In addition, arterial blood was sampled for blood gas analysis at 15 and 45 minutes following injection. Intensity and duration of analgesia (assessed by toe‐pinch response using a hemostat) and level of sedation were evaluated at the above time points and at 75 and 90 minutes post‐injection. Data were analyzed using anova for repeated measures with posthoc differences between means identified using Bonferroni's method (p < 0.05). Administration of M, MH, or MB was associated with increases in SAP, MAP, DAP, PAP, PAOP, CVP, SVR, and TEMP and with decreases in HR and CI. No differences in CV variables between treatment groups were identified at any time. PaO2 increased over time in all groups and was significantly higher when MH was compared with M. At 45 minutes, PaO2 tended to decrease over time and was significantly lower when MH and MB were compared with M at 15 minutes. Analgesia scores for MH and MB were significantly higher compared with M through 45 minutes, while analgesia scores for MH were significantly higher compared with M through 90 minutes. Sedation scores were higher for MH and MB compared with M throughout 90 minutes. Durations of lateral recumbency were 108 ± 10.8, 172 ± 15.5, and 145 ± 9.9 minutes for M, MH, and MB, respectively. We conclude that MH and MB are associated with improved analgesia and sedation and have similar CV effects when compared with M. 相似文献
25.
Kisseberth WC Vail DM Yaissle J Jeglum KA Couto CG Ward H Khanna C Obradovich JE 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2008,22(1):83-88
BACKGROUND: The dosage of carboplatin in cats has been reported anecdotally and experimentally in non-tumor-bearing cats, but the dosage for carboplatin treatment in tumor-bearing cats has yet to be defined in a prospective clinical trial. PURPOSE: To determine the maximally tolerated dose (MTD) and dose-limiting toxicosis (DLT) of carboplatin in tumor-bearing cats. CATS: Fifty-nine cats with measurable solid tumors. METHODS: The starting dose of carboplatin was 160 mg/m(2) of body surface area IV. Doses were increased by 20 mg/m(2) in cohorts of 3-14 cats until the MTD was reached. RESULTS: The 59 cats entered into this multi-institutional phase I study received 1 or more doses of carboplatin at various dosages and were evaluated for toxicity, response to treatment, or both. The MTD was 240 mg/m(2) and neutropenia was the DLT. For the 1st cycle of treatment in 44 cats evaluated for neutropenia, 6 episodes of grade 3 or greater neutropenia occurred on days 7 (n=1), 14 (n=4), and 21 (n=1). There was no evidence of drug-induced nephrotoxicosis or pulmonary edema. Preliminary evidence of antitumor activity was observed in 7 of 59 (11.9%; 95% CI, 5.6-22.8%) cats evaluated for response to treatment. There was 1 complete response (cutaneous hemangiosarcoma) and 6 partial responses (4 injection site sarcomas, 1 oral squamous cell carcinoma, 1 lymphoma). Responses were of short duration (median, 42 days; range, 7-168 days). CONCLUSIONS AND CLINICAL IMPORTANCE: The dose of carboplatin recommended to treat tumor-bearing cats is 240 mg/m(2) IV every 3-4 weeks. 相似文献
26.
Fosmire SP Thomas R Jubala CM Wojcieszyn JW Valli VE Getzy DM Smith TL Gardner LA Ritt MG Bell JS Freeman KP Greenfield BE Lana SE Kisseberth WC Helfand SC Cutter GR Breen M Modiano JF 《Veterinary pathology》2007,44(4):467-478
The significance of p16/Rb tumor suppressor pathway inactivation in T-cell non-Hodgkin's lymphoma (NHL) remains incompletely understood. We used naturally occurring canine NHL to test the hypothesis that p16 inactivation has specific pathologic correlates. Forty-eight samples (22 T-cell NHL and 26 B-cell NHL) were included. As applicable, metaphase- or array-based comparative genomic hybridization, Southern blotting, promoter methylation, and Rb phosphorylation were used to determine the presence, expression, and activity of p16. Fisher's exact test was used to test for significance. Deletion of p16 (or loss of dog chromosome 11) was restricted to high-grade T-cell NHL (lymphoblastic T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified). These were characterized by a concomitant increase of tumor cells with Rb phosphorylation at canonical CDK4 sites. Rb phosphorylation also was seen in high-grade B-cell NHL (diffuse large B-cell lymphoma and Burkitt-type lymphoma), but in those cases, it appeared to be associated with c-Myc overexpression. The data show that p16 deletion or inactivation occurs almost exclusively in high-grade T-cell NHL; however, alternative pathways can generate functional phenotypes of Rb deficiency in low-grade T-cell NHL and in high-grade B-cell NHL. Both morphologic classification according to World Health Organization criteria and assessment of Rb phosphorylation are prognostically valuable parameters for canine NHL. 相似文献
27.
Liliana M. Marín M. Cristina Iazbik Sara Zaldivar‐Lopez Linda K. Lord Nicole Stingle Paulo Vilar Ana Lara‐Garcia Francisco Alvarez Kenji Hosoya Laura Nelson Antonio Pozzi Edward Cooper Mary A. McLoughlin Rebecca Ball William C. Kisseberth Cheryl A. London Robert Dudley Jonathan Dyce Melanie McMahon Phillip Lerche Richard Bednarski C. Guillermo Couto 《Journal of Veterinary Emergency and Critical Care》2012,22(3):332-340
28.
Kosarek CE Hu X Couto CG Kisseberth WC Green EM Au JL Wientjes MG 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2006,20(5):1172-1177
BACKGROUND: Low and nontoxic concentrations (10-50 microM) of suramin, which is a nonspecific inhibitor of multiple growth factors, including fibroblast growth factors, enhances the activities of cytotoxic chemotherapeutic agents, such as doxorubicin and paclitaxel, both in vitro and in vivo. Suramin has not been evaluated as a chemosensitizing agent in dogs with cancer. HYPOTHESIS: Nontoxic suramin can be used safely as a chemosensitizer in dogs. ANIMALS: Sixteen dogs of various breeds with measurable tumors were treated; 1 dog that had undergone amputation for osteosarcoma received adjuvant therapy. METHODS: The dogs received 53 courses of treatment with suramin in combination with doxorubicin. The suramin dosage was 6.75 mg/kg IV 3 h before standard doxorubicin administration every 2 weeks. The pharmacokinetics and clinical efficacy were determined. RESULTS: The pharmacokinetics of low-dose suramin followed a 2-compartment model with half-lives of 2 h and 6 days. The distribution volume was a 0.34 +/- 0.12 L/kg, and clearance was 1.86 +/- 0.76 mL/kg/h. During the time interval that doxorubicin was present at therapeutically active concentrations (ie, from the start of infusion to 24 hours), the plasma concentrations were maintained within 20% of the target range (8-60 microM) in 72% of the treatments. The toxicity of the suramin/doxorubicin combination was mild and comparable to the toxicity expected for doxorubicin monotherapy. Objective partial responses were observed in 2 out of 16 evaluable dogs (13%). All 5 dogs that previously received doxorubicin showed improved responses to the suramin/doxorubicin combination. CONCLUSIONS AND CLINICAL IMPORTANCE: A fixed, low-dose suramin regimen yields the desired target plasma concentrations in most dogs, and appears to enhance the activity of doxorubicin without enhancing toxicity. 相似文献
29.
Ito D Endicott MM Jubala CM Helm KM Burnett RC Husbands BD Borgatti A Henson MS Burgess KE Bell JS Kisseberth WC Valli VE Cutter GR Avery AC Hahn KA O'Brien TD Modiano JF 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2011,25(4):890-896
Background: Tumors have heterogeneous properties, which could be explained by the existence of hierarchically and biologically distinct tumor cells such as tumor‐initiating cells (TICs). This model is clinically important, as TICs are promising targets for cancer therapies. However, TICs in spontaneous B‐cell lymphoma have not been conclusively identified. Hypothesis/Objectives: Tumor cells with a progenitor phenotype exist in B‐cell lymphoma, reflecting a hierarchical organization. Animals: Twenty‐eight client‐owned dogs with previously untreated B‐cell lymphoma and 6 healthy dogs. Methods: This was a prospective study. Flow cytometry was used to identify lymphoid progenitor cells (LPCs) that coexpressed hematopoietic progenitor antigens CD34, CD117, and CD133, with lymphoid differentiation markers CD21 and/or CD22 in B‐cell lymphoma. The polymerase chain reaction for antigen receptor rearrangements was used to analyze clonality and relatedness of tumor populations. A xenograft model with NOD/SCID/IL‐2Rγ?/? mice was adapted to expand and serially transplant primary canine B‐cell lymphoma. Results: LPCs were expanded in lymph nodes from 28 dogs with B‐cell lymphoma compared with 6 healthy dogs (P= .0022). LPCs contained a clonal antigen receptor gene rearrangement identical to that of the bulk of tumor cells. Canine B‐cell lymphoma xenografts in recipient mice that maintained LPCs in the tumors were recurrently observed. Conclusions and Clinical Importance: These results suggest the presence of a hierarchy of tumor cells in B‐cell lymphoma as has been demonstrated in other cancers. These findings have the potential to impact not only the understanding of lymphoma pathogenesis but also the development of lymphoma therapies by providing novel targets for therapy. 相似文献
30.
W C Kisseberth W B Buck M E Mansfield R K Manuel 《American journal of veterinary research》1986,47(3):696-698
Cattle grazing preferences on fescue pastures treated with the herbicide glyphosate at a rate of 2.52 kg/ha by surface application were determined, and the time course of the effect was characterized. An initial grazing preference for treated pasture was observed for the first 5 to 7 days. Over the next 15 days, this preference was lost because of decreasing amounts of herbicide on the herbage and/or desiccation of the herbage. 相似文献