44 results on '"Herron AJ"'
Search Results
2. Villin-1 and Gelsolin Regulate Changes in Actin Dynamics That Affect Cell Survival Signaling Pathways and Intestinal Inflammation.
- Author
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Roy S, Esmaeilniakooshkghazi A, Patnaik S, Wang Y, George SP, Ahrorov A, Hou JK, Herron AJ, Sesaki H, and Khurana S
- Subjects
- Actin Cytoskeleton pathology, Alarmins metabolism, Animals, Cell Death, Cell Survival, Crohn Disease genetics, Crohn Disease pathology, Disease Models, Animal, Epithelial Cells pathology, Eukaryotic Initiation Factor-2 metabolism, GTP-Binding Proteins genetics, GTP-Binding Proteins metabolism, Gelsolin deficiency, Gelsolin genetics, HT29 Cells, HeLa Cells, Humans, Ileum pathology, Intestinal Mucosa pathology, Mice, Knockout, Microfilament Proteins genetics, Mitochondria metabolism, Mitochondria pathology, Phosphorylation, RNA Interference, Time Factors, Transfection, Actin Cytoskeleton metabolism, Crohn Disease metabolism, Epithelial Cells metabolism, Gelsolin metabolism, Ileum metabolism, Intestinal Mucosa metabolism, Microfilament Proteins metabolism, Signal Transduction, Stress, Physiological
- Abstract
Background & Aims: Cell stress signaling pathways result in phosphorylation of the eukaryotic translation initiation factor 2 subunit alpha (EIF2S1 or EIF2A), which affects regulation of protein translation. Translation reprogramming mitigates stress by activating pathways that result in autophagy and cell death, to eliminate damaged cells. Actin is modified during stress and EIF2A is dephosphorylated to restore homeostasis. It is not clear how actin affects EIF2A signaling. We studied the actin-binding proteins villin 1 (VIL1) and gelsolin (GSN) in intestinal epithelial cells (IECs) to determine whether they respond to cell stress response and affect signaling pathways., Methods: We performed studies with mice with disruptions in Vil1 and Gsn (double-knockout mice). Wild-type (WT) mice either were or were not (controls) exposed to cell stressors such as tumor necrosis factor and adherent-invasive Escherichia coli. Distal ileum tissues were collected from mice; IECs and enteroids were cultured and analyzed by histology, immunoblots, phalloidin staining, immunohistochemistry, electron microscopy, and flow cytometry. HT-29 cells were incubated with cell stressors such as DTT, IFN, and adherent-invasive E coli or control agents; cells were analyzed by immunoblots and quantitative polymerase chain reaction. Green fluorescent protein and green fluorescent protein tagged mutant EIF2A were expressed from a lentiviral vector. The mouse immunity-related GTPase (IRGM1) was overexpressed in embryonic fibroblasts from dynamin1 like (DNM1L) protein-knockout mice or their WT littermates. IRGM1 was overexpressed in embryonic fibroblasts from receptor interacting serine/threonine kinase 1-knockout mice or their WT littermates. Human IRGM was overexpressed in human epithelial cell lines incubated with the DNM1L-specific inhibitor Mdivi-1. Mitochondria were analyzed by semi-quantitative confocal imaging. We performed immunohistochemical analyses of distal ileum tissues from 6-8 patients with Crohn's disease (CD) and 6-8 individuals without CD (controls)., Results: In IECs exposed to cell stressors, EIF2A signaling reduced expression of VIL1 and GSN. However, VIL1 and GSN were required for dephosphorylation of EIF2A and recovery from cell stress. In mouse and human IECs, prolonged, unresolved stress was accompanied by continued down-regulation of VIL1 and GSN, resulting in constitutive phosphorylation of EIF2A and overexpression of IRGM1 (or IRGM), which regulates autophagy. Overexpression of IRGM1 (or IRGM) induced cell death by necroptosis, accompanied by release of damage-associated molecular patterns (DAMPs). In double-knockout mice, constitutive phosphorylation of EIF2A and over-expression of IRGM1 resulted in spontaneous ileitis that resembled human CD in symptoms and histology. Distal ileum tissues from patients with CD had lower levels of VIL1 and GSN, increased phosphorylation of EIF2A, increased levels of IRGM and necroptosis, and increased release of nuclear DAMPs compared with controls., Conclusions: In studies of intestinal epithelial tissues from patients with CD and embryonic fibroblasts from mice, along with enteroids and human IEC lines, we found that induction of cell stress alters the cytoskeleton in IECs via changes in the actin-binding proteins VIL1 and GSN. Acute changes in actin dynamics increase IEC survival, whereas long-term changes in actin dynamics lead to IEC death and intestinal inflammation. IRGM regulates necroptosis and release of DAMPs to induce gastrointestinal inflammation, linking IRGM activity with CD., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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3. Helminth community structure in two species of arctic-breeding waterfowl.
- Author
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Amundson CL, Traub NJ, Smith-Herron AJ, and Flint PL
- Abstract
Climate change is occurring rapidly at high latitudes, and subsequent changes in parasite communities may have implications for hosts including wildlife and humans. Waterfowl, in particular, harbor numerous parasites and may facilitate parasite movement across broad geographic areas due to migratory movements. However, little is known about helminth community structure of waterfowl at northern latitudes. We investigated the helminth communities of two avian herbivores that breed at high latitudes, Pacific black brant ( Branta bernicla nigricans ), and greater white-fronted geese ( Anser albifrons ), to examine effects of species, geographic area, age, and sex on helminth species richness, aggregation, prevalence, and intensity. We collected 83 and 58 black brant and white-fronted geese, respectively, from Arctic and Subarctic Alaska July-August 2014. We identified 10 known helminth species ( Amidostomum anseris , Amidostomum spatulatum , Drepanidotaenia lanceolata , Epomidiostomum crami , Heterakis dispar , Notocotylus attenuatus , Tetrameres striata , Trichostrongylus tenuis , Tschertkovilepis setigera , and Wardoides nyrocae ) and 1 previously undescribed trematode. All geese sampled were infected with at least one helminth species. All helminth species identified were present in both age classes and species, providing evidence of transmission at high latitudes and suggesting broad host susceptibility. Also, all but one helminth species were present at both sites, suggesting conditions are suitable for transmission across a large latitudinal/environmental gradient. Our study provides important baseline information on avian parasites that can be used to evaluate the effects of a changing climate on host-parasite distributions.
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- 2016
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4. Mutant p53 Promotes Epithelial Ovarian Cancer by Regulating Tumor Differentiation, Metastasis, and Responsiveness to Steroid Hormones.
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Ren YA, Mullany LK, Liu Z, Herron AJ, Wong KK, and Richards JS
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- Animals, Carcinoma, Ovarian Epithelial, Disease Progression, Heterozygote, Mice, Neoplasms, Glandular and Epithelial genetics, Ovarian Neoplasms genetics, Cell Differentiation genetics, Estradiol physiology, Genes, p53, Neoplasm Metastasis genetics, Neoplasms, Glandular and Epithelial pathology, Ovarian Neoplasms pathology
- Abstract
Mutations in the tumor protein p53 (TP53) are the most frequently occurring genetic events in high-grade ovarian cancers, especially the prevalence of the Trp53(R172H)-mutant allele. In this study, we investigated the impact of the Trp53(R172H)-mutant allele on epithelial ovarian cancer (EOC) in vivo We used the Pten/Kras(G12D)-mutant mouse strain that develops serous EOC with 100% penetrance to introduce the mutant Trp53(R172H) allele (homolog for human Trp53(R172H)). We demonstrate that the Trp53(R172H) mutation promoted EOC but had differential effects on disease features and progression depending on the presence or absence of the wild-type (WT) TP53 allele. Heterozygous WT/Trp53(R172H) alleles facilitated invasion into the ovarian stroma, accelerated intraperitoneal metastasis, and reduced TP53 transactivation activity but retained responsiveness to nutlin-3a, an activator of WT TP53. Moreover, high levels of estrogen receptor α in these tumors enhanced the growth of both primary and metastatic tumors in response to estradiol. Ovarian tumors homozygous for Trp53(R172H) mutation were undifferentiated and highly metastatic, exhibited minimal TP53 transactivation activity, and expressed genes with potential regulatory functions in EOC development. Notably, heterozygous WT/Trp53(R172H) mice also presented mucinous cystadenocarcinomas at 12 weeks of age, recapitulating human mucinous ovarian tumors, which also exhibit heterozygous TP53 mutations (∼50%-60%) and KRAS mutations. Therefore, we present the first mouse model of mucinous tumor formation from ovarian cells and supporting evidence that mutant TP53 is a key regulator of EOC progression, differentiation, and responsiveness to steroid hormones. Cancer Res; 76(8); 2206-18. ©2016 AACR., (©2016 American Association for Cancer Research.)
- Published
- 2016
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5. Comparison of Cesium-137 and X-ray Irradiators by Using Bone Marrow Transplant Reconstitution in C57BL/6J Mice.
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Gibson BW, Boles NC, Souroullas GP, Herron AJ, Fraley JK, Schwiebert RS, Sharp JJ, and Goodell MA
- Subjects
- Animals, Lethal Dose 50, Male, Mice, Mice, Inbred C57BL, Bone Marrow Transplantation, Cesium Radioisotopes administration & dosage, Transplantation Conditioning, X-Rays
- Abstract
Mice are used extensively in transplantation studies involving bone marrow ablation. Due to the increasing security issues and expenses involved with γ irradiators, self-contained X-ray irradiators have been increasing in popularity. We hypothesized that bone marrow ablation by irradiation of mice with a (137)Cs irradiator would be comparable to that from an X-ray source irradiator. A lethal-dose curve was obtained by irradiating C57BL/6J mice with 500, 700, 900, and 1100 cGy from either source. These data were used to determine the lethal radiation exposure range for a noncompetitive bone marrow engraftment curve for each source. At 90 d after reconstitution, the bone marrow engraftment curves revealed significant differences between the 2 sources in the establishment of B cell, myeloid, and T cell lineages. Murine B cell reconstitution after exposure to a (137)Cs source was greater than that after X-ray exposure at each dose level, whereas the converse was true for myeloid cell reconstitution. At the 1050- and 1100-cGy doses, mice irradiated by using the X-ray source demonstrated higher levels of T cell reconstitution but decreased survival compared with mice irradiated with the (137)Cs source. We concluded that although both sources ablated endogenous bone marrow sufficiently to enable stem cell engraftment, there are distinct physiologic responses that should be considered when choosing the optimal source for use in a study and that irradiation from the (137)Cs source was associated with lower overall morbidity due to opportunistic infection.
- Published
- 2015
6. Gregarines infecting Ischnura spp. in Texas, U.S.A., including description of Septemlaterospora rasberryi n. gen. n. sp. (Apicomplexa: Actinocephalidae: Acanthosporinae) and revision of Steganorhynchus dunwoodyi (Apicomplexa: Actinocephalidae: Menosporinae).
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Cook TJ and Smith-Herron AJ
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- Animals, Apicomplexa growth & development, Apicomplexa ultrastructure, Texas, Apicomplexa classification, Odonata parasitology
- Abstract
Septemlaterospora rasberryi n. gen. n. sp. (Apicomplexa: Eugregarinida: Actinocephalidae: Acanthosporinae) is described from adults of Ischnura ramburii (Odonata: Zygoptera: Coenagrionidae). Septemlaterospora n. gen is distinguished by the form of the oocysts: terminally truncated heptagonal bipyramids bearing 7 equatorial spines, 1 at each equatorial vertex, 7 terminal spines obliquely inserted at each pole, 1 at each vertex created by polar truncation; 21 spines total. The holdfast is compound, comprising a terminal epimerite and intercalating diamerite; epimerite is a thick disk or linearly crateriform sucker; diamerite is short (less than half of the total holdfast length) and very broadly obdeltoid. Association occurs immediately before syzygy and is cephalolateral and biassociative. Gametocysts are spherical with a conspicuous hyaline coat. Lacking conspicuous sporoducts, they dehisce by simple rupture. Steganorhynchus dunwoodyi is redescribed utilizing a new complete taxonomic data set, consisting of a larger set of metric characters and based on uniformly prepared, permanent specimens. New host and geographic records are reported for Calyxocephalus karyopera, Domadracunculus janovyi, Nubenocephalus secundus, and Steganorhynchus dunwoodyi, and the type host of D. janovyi is amended.
- Published
- 2014
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7. Assessment of riboflavin as a tracer substance: comparison of a qualitative to a quantitative method of riboflavin measurement.
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Herron AJ, Mariani JJ, Pavlicova M, Parrinello CM, Bold KW, Levin FR, Nunes EV, Sullivan MA, Raby WN, and Bisaga A
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- Adolescent, Adult, Dose-Response Relationship, Drug, Female, Fluorescence, Humans, Male, Middle Aged, Riboflavin administration & dosage, Riboflavin urine, Single-Blind Method, Medication Adherence, Riboflavin pharmacokinetics
- Abstract
Background: Noncompliance with medications may have major impacts on outcomes measured in research, potentially distorting the validity of controlled clinical trials. Riboflavin is frequently used in trials as a marker of adherence. It can be combined with study medication and is excreted in urine where it fluoresces under UV light. This study compares qualitative visual inspection of fluorescence to quantitative fluorometric analysis of riboflavin concentration in its ability to detect the presence of riboflavin in urine., Methods: Twenty-four volunteers received 0mg, 25mg, and 50mg doses of riboflavin under single-blind conditions, with 20 also receiving a 100mg dose. Five serial urine samples were collected over the following 36h. Quantitative measurement of riboflavin by fluorometric analysis and qualitative assessment of each sample using visual inspection were performed., Results: The overall false positive rate for qualitative assessment was 53%. For quantitative assessment, a riboflavin concentration of 900ng/mL was established to classify positive samples. More than 80% of samples were positive 2-24h following ingestion of 25mg and 50mg, and less than 80% were positive at 36h. At least 95% of observations for the 100mg dose were above 900ng/mL at all timepoints., Conclusions: Quantitative fluorometric assessment is superior to qualitative visual inspection alone in determining medication adherence. The combination of 25-50mg of daily riboflavin and a cut-off level of 900ng/mL allows for the acceptable sensitivity of missing detection of non-compliant participants while preserving a high level of power to detect all cases of medication compliance., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2013
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8. Effects of route of inoculation and viral genetic variation on antibody responses to polyomavirus SV40 in Syrian golden hamsters.
- Author
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Swain JL, Sroller V, Wong C, Zhang S, Halvorson SJ, Herron AJ, Kozinetz CA, and Butel JS
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- Animals, Antibodies, Neutralizing immunology, Antigens, Viral, Tumor administration & dosage, Cricetinae, Drug Administration Routes, Mesocricetus, Statistics, Nonparametric, Viral Nonstructural Proteins administration & dosage, Antibodies, Viral immunology, Antigens, Viral, Tumor immunology, Genetic Variation, Simian virus 40 genetics, Simian virus 40 immunology, Viral Nonstructural Proteins immunology
- Abstract
Genetic variants of polyomavirus SV40 are powerful agents with which to define viral effects on cells and carcinogenesis pathways. We hypothesized that differences in biologic variation among viral strains affect the process of viral infection and are reflected in antibody responses to the viral nonstructural large T-antigen (TAg) protein but not in neutralizing antibody responses against the inoculated viral particles. We analyzed the production of TAg antibody and neutralizing antibody in Syrian golden hamsters that were inoculated with SV40 viral strains by intracardiac, intravenous, or intraperitoneal routes and remained tumor free. Compared with the intraperitoneal route, intravascular (that is, intravenous, intracardiac) inoculation resulted in increased frequency of responsiveness to TAg but not in higher TAg antibody titers. The intravascular route was superior both for eliciting neutralizing antibody responses and for higher titers of those responses. Viruses with complex regulatory regions induced TAg antibody more often than did viruses with simple regulatory regions after intraperitoneal but not intravascular injections, with no differences in antibody titers. This viral genetic variation had no effect on neutralizing antibody production after intraperitoneal or intravascular inoculations or on neutralizing antibody titers achieved. These findings confirm that SV40 variants differ in their biologic properties. Route of inoculation combined with viral genetic variation significantly influence the development of serum antibodies to SV40 TAg in tumor-free hamsters. Route of inoculation-but not viral genetic variation-is an important factor in production of neutralizing antibody to SV40.
- Published
- 2012
9. Swine as models in biomedical research and toxicology testing.
- Author
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Swindle MM, Makin A, Herron AJ, Clubb FJ Jr, and Frazier KS
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- Animal Use Alternatives, Animals, Biomedical Research, Drug-Related Side Effects and Adverse Reactions, Female, Humans, Male, Swine, Toxicity Tests, Models, Animal, Sus scrofa anatomy & histology, Sus scrofa physiology, Swine, Miniature anatomy & histology, Swine, Miniature physiology
- Abstract
Swine are considered to be one of the major animal species used in translational research, surgical models, and procedural training and are increasingly being used as an alternative to the dog or monkey as the choice of nonrodent species in preclinical toxicologic testing of pharmaceuticals. There are unique advantages to the use of swine in this setting given that they share with humans similar anatomic and physiologic characteristics involving the cardiovascular, urinary, integumentary, and digestive systems. However, the investigator needs to be familiar with important anatomic, histopathologic, and clinicopathologic features of the laboratory pig and minipig in order to put background lesions or xenobiotically induced toxicologic changes in their proper perspective and also needs to consider specific anatomic differences when using the pig as a surgical model. Ethical considerations, as well as the existence of significant amounts of background data, from a regulatory perspective, provide further support for the use of this species in experimental or pharmaceutical research studies. It is likely that pigs and minipigs will become an increasingly important animal model for research and pharmaceutical development applications.
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- 2012
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10. Suprapubic bladder catheterization of male spinal-cord-injured Sprague-Dawley rats.
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Robinson MA, Herron AJ, Goodwin BS, and Grill RJ
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- Animals, Blood Urea Nitrogen, Creatinine blood, Male, Proteinuria pathology, Proteinuria veterinary, Rats, Spinal Cord Injuries complications, Urinary Bladder, Neurogenic etiology, Urinary Bladder, Neurogenic therapy, Urinary Catheterization adverse effects, Urinary Catheterization methods, Laboratory Animal Science methods, Rats, Sprague-Dawley, Spinal Cord Injuries veterinary, Urinary Bladder, Neurogenic veterinary, Urinary Catheterization veterinary
- Abstract
The rat spinal-cord-injury (SCI) model is widely used to study the pathologic mechanisms that contribute to sensory and motor dysfunction in humans. This model is thought to mimic many of the negative outcomes experienced by humans after spinal contusion injury. We theorized that manual bladder expression contributed to the kidney and bladder lesions reported in previous studies using the rat SCI model. In the present study, rats were surgically implanted with bladder catheters after spinal contusion injury to provide continuous drainage of urine. After 72 h, the rats were euthanized and their kidneys and bladders examined histologically. BUN, serum creatinine, and urine protein were compared at 0 and 72 h after surgery. Kidney and bladder lesions were similar in SCI rats with and without implanted bladder catheters. BUN at 72 h was higher than baseline values in both groups, whereas serum creatinine was higher at 72 h compared with baseline values only in the catheterized rats. These findings indicate that suprapubic bladder catheterization does not reduce hydronephrosis in SCI rats and that the standard of care for bladder evacuation should continue to be manual expression of urine.
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- 2012
11. Disrupting circadian homeostasis of sympathetic signaling promotes tumor development in mice.
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Lee S, Donehower LA, Herron AJ, Moore DD, and Fu L
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- Animals, Mice, Neoplasms, Experimental genetics, Neoplasms, Experimental physiopathology, Sympathetic Nervous System metabolism, Circadian Rhythm genetics, Homeostasis, Neoplasms, Experimental pathology, Signal Transduction
- Abstract
Background: Cell proliferation in all rapidly renewing mammalian tissues follows a circadian rhythm that is often disrupted in advanced-stage tumors. Epidemiologic studies have revealed a clear link between disruption of circadian rhythms and cancer development in humans. Mice lacking the circadian genes Period1 and 2 (Per) or Cryptochrome1 and 2 (Cry) are deficient in cell cycle regulation and Per2 mutant mice are cancer-prone. However, it remains unclear how circadian rhythm in cell proliferation is generated in vivo and why disruption of circadian rhythm may lead to tumorigenesis., Methodology/principal Findings: Mice lacking Per1 and 2, Cry1 and 2, or one copy of Bmal1, all show increased spontaneous and radiation-induced tumor development. The neoplastic growth of Per-mutant somatic cells is not controlled cell-autonomously but is dependent upon extracellular mitogenic signals. Among the circadian output pathways, the rhythmic sympathetic signaling plays a key role in the central-peripheral timing mechanism that simultaneously activates the cell cycle clock via AP1-controlled Myc induction and p53 via peripheral clock-controlled ATM activation. Jet-lag promptly desynchronizes the central clock-SNS-peripheral clock axis, abolishes the peripheral clock-dependent ATM activation, and activates myc oncogenic potential, leading to tumor development in the same organ systems in wild-type and circadian gene-mutant mice., Conclusions/significance: Tumor suppression in vivo is a clock-controlled physiological function. The central circadian clock paces extracellular mitogenic signals that drive peripheral clock-controlled expression of key cell cycle and tumor suppressor genes to generate a circadian rhythm in cell proliferation. Frequent disruption of circadian rhythm is an important tumor promoting factor.
- Published
- 2010
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12. MMP13, Birc2 (cIAP1), and Birc3 (cIAP2), amplified on chromosome 9, collaborate with p53 deficiency in mouse osteosarcoma progression.
- Author
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Ma O, Cai WW, Zender L, Dayaram T, Shen J, Herron AJ, Lowe SW, Man TK, Lau CC, and Donehower LA
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- Adaptor Proteins, Signal Transducing biosynthesis, Adaptor Proteins, Signal Transducing deficiency, Adaptor Proteins, Signal Transducing genetics, Animals, Baculoviral IAP Repeat-Containing 3 Protein, Bone Neoplasms enzymology, Cell Cycle Proteins, Cell Transformation, Neoplastic genetics, Comparative Genomic Hybridization, Gene Amplification, Genomic Instability, Humans, Inhibitor of Apoptosis Proteins deficiency, Matrix Metalloproteinase 13 biosynthesis, Mice, Mice, Inbred C57BL, Osteosarcoma enzymology, Phosphoproteins biosynthesis, Phosphoproteins deficiency, Phosphoproteins genetics, RNA, Neoplasm biosynthesis, RNA, Neoplasm genetics, Tumor Cells, Cultured, Tumor Suppressor Protein p53 genetics, Ubiquitin-Protein Ligases, YAP-Signaling Proteins, Bone Neoplasms genetics, Inhibitor of Apoptosis Proteins genetics, Matrix Metalloproteinase 13 genetics, Osteosarcoma genetics, Tumor Suppressor Protein p53 deficiency
- Abstract
Osteosarcoma is the primary malignant cancer of bone and particularly affects adolescents and young adults, causing debilitation and sometimes death. As a model for human osteosarcoma, we have been studying p53(+/-) mice, which develop osteosarcoma at high frequency. To discover genes that cooperate with p53 deficiency in osteosarcoma formation, we have integrated array comparative genomic hybridization, microarray expression analyses in mouse and human osteosarcomas, and functional assays. In this study, we found seven frequent regions of copy number gain and loss in the mouse p53(+/-) osteosarcomas but have focused on a recurrent amplification event on mouse chromosome 9A1. This amplicon is syntenic with a similar chromosome 11q22 amplicon identified in several human tumor types. Three genes on this amplicon, the matrix metalloproteinase gene MMP13 and the antiapoptotic genes Birc2 (cIAP1) and Birc3 (cIAP2), show elevated expression in mouse and human osteosarcomas. We developed a functional assay using clonal osteosarcoma cell lines transduced with lentiviral short hairpin RNA vectors to show that down-regulation of MMP13, Birc2, or Birc3 resulted in reduced tumor growth when transplanted into immunodeficient recipient mice. These experiments revealed that high MMP13 expression enhances osteosarcoma cell survival and that Birc2 and Birc3 also enhance cell survival but only in osteosarcoma cells with the chromosome 9A1 amplicon. We conclude that the antiapoptotic genes Birc2 and Birc3 are potential oncogenic drivers in the chromosome 9A1 amplicon.
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- 2009
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13. Scaffold Attachment Factor B1 (SAFB1) heterozygosity does not influence Wnt-1 or DMBA-induced tumorigenesis.
- Author
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Kaipparettu BA, Dobrzycka KM, Britton O, Lee AV, Herron AJ, Li Y, Lewis MT, Medina D, and Oesterreich S
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- 9,10-Dimethyl-1,2-benzanthracene, Animals, Carcinogens, DNA-Binding Proteins metabolism, Female, Insulin-Like Growth Factor I metabolism, Male, Mice, Mice, Knockout, Neoplasms, Experimental chemically induced, Neoplasms, Experimental genetics, Neoplasms, Experimental pathology, RNA-Binding Proteins metabolism, Wnt1 Protein metabolism, DNA-Binding Proteins genetics, Heterozygote, RNA-Binding Proteins genetics, Wnt1 Protein genetics
- Abstract
Background: Scaffold Attachment Factor B1 (SAFB1) is a multifunctional protein which has been implicated in breast cancer previously. We recently generated SAFB1 knockout mice (SAFB1-/-), but pleiotropic phenotypes including high lethality, dwarfism associated with low IGF-I levels, and infertility and subfertility in male and female mice, respectively, do not allow for straightforward tumorigenesis studies in these mice. Therefore, we asked whether SAFB1 heterozygosity would influence tumor development and progression in MMTV-Wnt-1 oncomice or DMBA induced tumorigenicity, in a manner consistent with haploinsufficiency of the remaining allele., Methods: We crossed female SAFB1+/- (C57B6/129) mice with male MMTV-Wnt-1 (C57B6/SJL) mice to obtain SAFB1+/+/Wnt-1, SAFB1+/-/Wnt-1, and SAFB1+/- mice. For the chemical induced tumorigenesis study we treated 8 weeks old SAFB1+/- and SAFB+/+ BALB/c mice with 1 mg DMBA once per week for 6 weeks. Animals were monitored for tumor incidence and tumor growth. Tumors were characterized by performing H&E, and by staining for markers of proliferation and apoptosis., Results: We did not detect significant differences in tumor incidence and growth between SAFB1+/+/Wnt-1 and SAFB1+/-/Wnt-1 mice, and between DMBA-treated SAFB1+/+ and SAFB1+/-mice. Histological evaluation of tumors showed that SAFB1 heterozygosity did not lead to changes in proliferation or apoptosis. There were, however, significant differences in the distribution of tumor histologies with an increase in papillary and cribriform tumors, and a decrease in squamous tumors in the SAFB1+/-/Wnt-1 compared to the SAFB1+/+/Wnt-1 tumors. Of note, DMBA treatment resulted in shortened survival of SAFB1+/- mice compared to their wildtype littermates, however this trend did not reach statistical significance., Conclusion: Our data show that SAFB1 heterozygosity does not influence Wnt-1 or DMBA-induced mammary tumorigenesis.
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- 2009
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14. SV40 lymphomagenesis in Syrian golden hamsters.
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McNees AL, Vilchez RA, Heard TC, Sroller V, Wong C, Herron AJ, Hamilton MJ, Davis WC, and Butel JS
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- Animals, Antibodies, Viral immunology, Antibody Formation, Antigens, Viral genetics, Cells, Cultured, Cricetinae, DNA, Viral genetics, Haplorhini, Lymph Nodes immunology, Lymphoma immunology, Lymphoma pathology, Mesocricetus, Regulatory Sequences, Nucleic Acid, Simian virus 40 genetics, Tumor Virus Infections immunology, Tumor Virus Infections pathology, Lymphoma virology, Simian virus 40 pathogenicity, Tumor Virus Infections virology
- Abstract
Simian virus 40 (SV40) isolates differ in oncogenic potential in Syrian golden hamsters following intraperitoneal inoculation. Here we describe the effect of intravenous exposure on tumor induction by SV40. Strains SVCPC (simple regulatory region) and VA45-54(2E) (complex regulatory region) were highly oncogenic following intravenous inoculation, producing a spectrum of tumor types. Three lymphoma cell lines were established; all expressed SV40 T-antigen, were immortalized for growth in culture, and were tumorigenic following transplantation in vivo. New monoclonal antibodies directed against hamster lymphocyte surface antigens are described. The cell lines expressed MHC class II and macrophage markers and were highly phagocytic, indicating a histiocytic origin. Many hamsters that remained tumor-free developed SV40 T-antigen antibodies, suggesting that viral replication occurred. This study shows that route of exposure influences the pathogenesis of SV40-mediated carcinogenesis, that SV40 strain VA45-54(2E) is lymphomagenic in hamsters, that hamster lymphoid cells of histiocytic origin can be transformed in vivo and established in culture, and that reagents to hamster leukocyte differentiation molecules are now available.
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- 2009
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15. Activation of MAPK pathways links LMNA mutations to cardiomyopathy in Emery-Dreifuss muscular dystrophy.
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Muchir A, Pavlidis P, Decostre V, Herron AJ, Arimura T, Bonne G, and Worman HJ
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- Amino Acid Substitution genetics, Animals, COS Cells, Cardiomyopathies enzymology, Cells, Cultured, Chlorocebus aethiops, Enzyme Activation genetics, Gene Expression Profiling, Male, Mice, Mice, Transgenic, Cardiomyopathies genetics, Lamin Type A genetics, MAP Kinase Signaling System genetics, Mitogen-Activated Protein Kinases metabolism, Muscular Dystrophy, Emery-Dreifuss enzymology, Muscular Dystrophy, Emery-Dreifuss genetics
- Abstract
Mutations in LMNA, which encodes nuclear Lamins A and C cause diseases affecting various organs, including the heart. We have determined the effects of an Lmna H222P mutation on signaling pathways involved in the development of cardiomyopathy in a knockin mouse model of autosomal dominant Emery-Dreifuss muscular dystrophy. Analysis of genome-wide expression profiles in hearts using Affymetrix GeneChips showed statistically significant differences in expression of genes in the MAPK pathways at the incipience of the development of clinical disease. Using real-time PCR, we showed that activation of MAPK pathways preceded clinical signs or detectable molecular markers of cardiomyopathy. In heart tissue and isolated cardiomyocytes, there was activation of MAPK cascades and downstream targets, implicated previously in the pathogenesis of cardiomyopathy. Expression of H222P Lamin A in cultured cells activated MAPKs and downstream target genes. Activation of MAPK signaling by mutant A-type lamins could be a cornerstone in the development of heart disease in autosomal dominant Emery-Dreifuss muscular dystrophy.
- Published
- 2007
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16. Pathology and nuclear abnormalities in hearts of transgenic mice expressing M371K lamin A encoded by an LMNA mutation causing Emery-Dreifuss muscular dystrophy.
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Wang Y, Herron AJ, and Worman HJ
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- Animals, Cell Nucleus ultrastructure, Cells, Cultured, Embryo Loss, Female, Genes, Lethal, Humans, Male, Mice, Mice, Transgenic, Muscular Dystrophy, Emery-Dreifuss pathology, Mutant Proteins physiology, Myocardium metabolism, Myocardium ultrastructure, Organ Specificity, Transgenes, Heart Defects, Congenital genetics, Heart Defects, Congenital pathology, Lamin Type A genetics, Muscular Dystrophy, Emery-Dreifuss genetics, Point Mutation physiology
- Abstract
Mutations in LMNA, which encodes nuclear lamins A and C, cause a broad range of diseases, including autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD) and related disorders with a predominant cardiomyopathy. Homozygous Lmna model "knock-in" and null mice develop cardiomyopathy, whereas heterozygous mice do not. Overexpression of lamin A mutants that cause cardiomyopathy in cultured cells induces morphological abnormalities in the nuclear envelope and lamina; however, effects on tissue and organ pathology have not been determined. We used the heart-selective alpha-myosin heavy chain promoter to drive expression in transgenic mice of human wild-type and M371K lamin A, which causes EDMD. Mice expressing M371K lamin A were born at approximately 0.07 of the expected frequency and those born typically died at 2-7 weeks of age. Histological analysis showed increased eosinophilia and fragmentation of cardiomyofibrils, nuclear pyknosis and edema without fibrosis or significant inflammation, indicative of acute or subacute injury. Mice expressing human wild-type lamin A were born at only slightly less than the expected frequency and had normal life spans. Confocal immunofluorescence microscopy demonstrated abnormal nuclear envelopes with intranuclear foci of lamins in cardiac cells expressing M371K lamin A. Electron microscopy revealed extensively convoluted nuclear envelopes, intranuclear inclusions and chromatin clumps in cardiomyocyte nuclei. These results demonstrate that expression of a lamin A mutant that induces alterations in nuclear morphology can cause tissue and organ damage in mice with a normal complement of wild-type lamins.
- Published
- 2006
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17. Simmondsin for weight loss in rats.
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Boozer CN and Herron AJ
- Subjects
- Acetonitriles administration & dosage, Animals, Appetite Depressants administration & dosage, Body Composition drug effects, Body Weight drug effects, Cyclohexanes administration & dosage, Dose-Response Relationship, Drug, Erythrocytes drug effects, Glucosides administration & dosage, Kidney drug effects, Kidney pathology, Leukocytes drug effects, Liver drug effects, Liver pathology, Male, Obesity blood, Obesity pathology, Obesity physiopathology, Organ Size drug effects, Rats, Rats, Sprague-Dawley, Thinness blood, Thinness physiopathology, Acetonitriles therapeutic use, Appetite Depressants therapeutic use, Cyclohexanes therapeutic use, Eating drug effects, Glucosides therapeutic use, Obesity drug therapy, Weight Loss drug effects
- Abstract
Objective: To investigate the safety and efficacy for weight loss of simmondsin, a dietary supplement extracted from the seed of the jojoba plant (Simmondsia chinensis)., Animals: Sprague-Dawley male rats were fed various levels of simmondsin for 8 weeks (lean rats) or 16 weeks (high fat-induced obese rats)., Measurements: Food intake, body weight and composition, histopathology, hematology parameters., Results: Simmondsin produced a clear dose-response effect on food intake and body weight. No remarkable histopathologic changes were noted in the liver, kidney and spleen. One lean animal, in the 0.5% group, had approximately a 20% depression in red bone marrow cells. Significant effects on hematology parameters were seen almost exclusively in groups consuming simmondsin at the highest level (0.5%) and these effects appeared to be reversed by removing simmondsin from the diet., Conclusion: Simmondsin at both the 0.15% level and the 0.25% level significantly reduced food intake and body weight without apparent negative effects. At dose levels much higher than therapeutic levels, there seemed to be reversible effects on circulating red and white blood cells. Future studies should determine long-term effects of lower doses on blood cell parameters.
- Published
- 2006
- Full Text
- View/download PDF
18. Human mesenchymal stem cells as a gene delivery system to create cardiac pacemakers.
- Author
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Potapova I, Plotnikov A, Lu Z, Danilo P Jr, Valiunas V, Qu J, Doronin S, Zuckerman J, Shlapakova IN, Gao J, Pan Z, Herron AJ, Robinson RB, Brink PR, Rosen MR, and Cohen IS
- Subjects
- Acetylcholine pharmacology, Adrenergic beta-Agonists pharmacology, Animals, Cells, Cultured drug effects, Cells, Cultured physiology, Cells, Cultured transplantation, Cesium pharmacology, Cholinergic Agents pharmacology, Coculture Techniques, Dogs, Electroporation, Gap Junctions physiology, Gap Junctions ultrastructure, Heart Rate, Heart Ventricles cytology, Humans, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Ion Transport drug effects, Isoproterenol pharmacology, Mesenchymal Stem Cells drug effects, Mice, Myocytes, Cardiac drug effects, Patch-Clamp Techniques, Potassium Channels, Rats, Recombinant Fusion Proteins physiology, Transfection, Genetic Therapy, Ion Channels physiology, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells cytology, Muscle Proteins physiology, Myocytes, Cardiac physiology
- Abstract
We tested the ability of human mesenchymal stem cells (hMSCs) to deliver a biological pacemaker to the heart. hMSCs transfected with a cardiac pacemaker gene, mHCN2, by electroporation expressed high levels of Cs+-sensitive current (31.1+/-3.8 pA/pF at -150 mV) activating in the diastolic potential range with reversal potential of -37.5+/-1.0 mV, confirming the expressed current as I(f)-like. The expressed current responded to isoproterenol with an 11-mV positive shift in activation. Acetylcholine had no direct effect, but in the presence of isoproterenol, shifted activation 15 mV negative. Transfected hMSCs influenced beating rate in vitro when plated onto a localized region of a coverslip and overlaid with neonatal rat ventricular myocytes. The coculture beating rate was 93+/-16 bpm when hMSCs were transfected with control plasmid (expressing only EGFP) and 161+/-4 bpm when hMSCs were expressing both EGFP+mHCN2 (P<0.05). We next injected 10(6) hMSCs transfected with either control plasmid or mHCN2 gene construct subepicardially in the canine left ventricular wall in situ. During sinus arrest, all control (EGFP) hearts had spontaneous rhythms (45+/-1 bpm, 2 of right-sided origin and 2 of left). In the EGFP+mHCN2 group, 5 of 6 animals developed spontaneous rhythms of left-sided origin (rate=61+/-5 bpm; P<0.05). Moreover, immunostaining of the injected regions demonstrated the presence of hMSCs forming gap junctions with adjacent myocytes. These findings demonstrate that genetically modified hMSCs can express functional HCN2 channels in vitro and in vivo, mimicking overexpression of HCN2 genes in cardiac myocytes, and represent a novel delivery system for pacemaker genes into the heart or other electrical syncytia.
- Published
- 2004
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19. Social environment influences the progression of atherosclerosis in the watanabe heritable hyperlipidemic rabbit.
- Author
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McCabe PM, Gonzales JA, Zaias J, Szeto A, Kumar M, Herron AJ, and Schneiderman N
- Subjects
- Adrenal Glands pathology, Animals, Aortic Diseases blood, Aortic Diseases etiology, Aortic Diseases pathology, Arteriosclerosis blood, Arteriosclerosis pathology, Behavior, Animal, Body Weight, Corticosterone blood, Disease Progression, Hemodynamics, Hyperlipidemias genetics, Insulin blood, Lipids blood, Male, Organ Size, Rabbits, Social Environment, Testis pathology, Testosterone blood, Arteriosclerosis etiology
- Abstract
Background: Although there is evidence that emotionally stressful behavior can accelerate the progression of atherosclerosis, there is less data to support the notion that affiliative social behavior can slow disease progression. The present study examines the influence of social environment on the progression of atherosclerosis in the Watanabe Heritable Hyperlipidemic (WHHL) rabbit, a model that spontaneously develops lesions because of a genetic defect in lipoprotein clearance., Methods and Results: WHHL rabbits were assigned to 1 of 3 social or behavioral groups: an unstable group, in which unfamiliar rabbits were paired daily, with the pairing switched each week; a stable group, in which littermates were paired daily for the entire study; and an individually caged group. The stable group exhibited more affiliative social behavior and less agonistic behavior than the unstable group and significantly less aortic atherosclerosis than each of the other 2 groups. Although the unstable and individually caged groups had comparable aortic lesion areas, the severity of the disease progressed faster in the unstable group, as indexed by a larger area of calcification and increased fibrous cap thickness in complex lesions. The unstable group showed increased agonistic behavior and signs of chronic adrenocortical and gonadal activation, whereas the individually caged group was relatively sedentary, had low glucocorticoid levels, and was hyperinsulinemic compared with the other groups., Conclusions: The present study demonstrates that social environment can slow, as well as accelerate, the progression of atherosclerosis. It also emphasizes the importance of behavioral factors in atherogenesis, even in a model of disease with strong genetic determinants.
- Published
- 2002
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20. Unusual immunophenotype of a soft tissue sarcoma in a European polecat (Mustela putorius).
- Author
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Zaias J, Kornegay RW, Altman NH, and Herron AJ
- Subjects
- Abdominal Neoplasms immunology, Animals, Immunohistochemistry, Leiomyosarcoma immunology, Male, Muscle, Smooth, Phenotype, Soft Tissue Neoplasms immunology, Abdominal Neoplasms veterinary, Ferrets, Leiomyosarcoma veterinary, Soft Tissue Neoplasms veterinary
- Abstract
The most commonly reported tumors in ferrets are carcinomas, followed by round cell tumors. Soft tissue sarcomas are reported and characterized much less frequently. Because domesticated ferrets (Mustela putorius furo) are direct descendants of European polecats (Mustela putorius), the types and prevalence of tumors are expected to be similar in the two species. Presented here is a case report of unusual immunohistochemical staining characteristics of an abdominal wall leiomyosarcoma in a close relative of domestic ferrets, the European polecat. Sections of tissue were preserved in 10% buffered formalin, embedded in paraffin, and sectioned at 5 mm. Routine staining with hematoxylin and eosin and several immunohistochemical tests were performed to identify the tumor tissue of origin. Although the tumor did not stain with antibody to desmin, further staining for smooth muscle actin was consistent with a smooth muscle origin. To the authors' knowledge, this report is the first description of a leiomyosarcoma in the European polecat. This report emphasizes the importance of using additional secondary markers to accurately diagnose anaplastic tumors.
- Published
- 2001
21. Radiofrequency ablation of rabbit kidney using liquid electrode: acute and chronic observations.
- Author
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Patel VR, Leveillee RJ, Hoey MF, Herron AJ, Zaias J, and Hulbert JC
- Subjects
- Animals, Kidney diagnostic imaging, Kidney pathology, Necrosis, Postoperative Complications, Postoperative Period, Rabbits, Radiography, Reproducibility of Results, Time Factors, Catheter Ablation instrumentation, Electrodes, Kidney surgery
- Abstract
Background and Purpose: The percentage of small renal tumors being diagnosed has increased at least five-fold in the last 20 years. The question of how best to treat these lesions remains unanswered. We studied the effectiveness of "wet" radiofrequency (RF) ablation of renal tissue., Materials and Methods: New Zealand white rabbits (N = 48) underwent a 1- or 2-minute ablation of renal parenchyma with a modified insulated spinal needle capable of infusing saline, measuring temperature and impedance, and delivering RF energy. Animals were followed and examined up to 54 days after surgery., Results: All animals survived for the planned period. Intravenous urograms showed no fistula or urinoma formation and confirmed continued function of the remaining parenchyma. The 1-minute treatments consistently ablated 20% to 25% (average 7 cm) of the tissue, whereas the 2-minute treatments ablated 34% to 36% (average 10 cm). Acutely, there was coagulative necrosis and infiltration of inflammatory cells. Chronically, there were well-demarcated lesions with complete effacement of the tubular epithelium and destruction of the glomeruli., Conclusion: Wet radiofrequency ablation with a liquid electrode can reproducibly create large lesions safely and quickly. The technique may soon become an alternative, minimally invasive therapy for small renal tumors.
- Published
- 2000
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22. Interstitial laser hyperthermia model development for minimally invasive therapy of breast carcinoma.
- Author
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Robinson DS, Parel JM, Denham DB, González-Cirre X, Manns F, Milne PJ, Schachner RD, Herron AJ, Comander J, and Hauptmann G
- Subjects
- Adipose Tissue pathology, Animals, Breast pathology, Female, Fiber Optic Technology instrumentation, Humans, Hyperthermia, Induced instrumentation, Laser Therapy, Mammary Glands, Animal pathology, Models, Structural, Pilot Projects, Swine, Breast Neoplasms therapy, Hyperthermia, Induced methods
- Abstract
Background: This investigation describes the preclinical development of a laser fiberoptic interstitial delivery system for the thermal destruction of small breast cancers. We propose adaptation of this technology to stereotactic mammographic instrumentation currently employed for diagnostic core biopsy to thermally ablate a site of disease with maximal treatment efficacy, minimal observable superficial change, reduced patient trauma, and lowered overall treatment costs., Study Design: Laser hyperthermia is a clinical modality that seeks to achieve tumor destruction through controlled tissue heating. The advantage of laser-induced hyperthermia over traditionally used heat sources such as ultrasound, microwave, or radiowave radiation lies in the ability to focus heat localization to the specific tumor tissue site. Neodymium:yttrium aluminum garnet (Nd:YAG) laser light transmitted through a fiberoptic cable to a diffusing quartz tip can induce such temperature increases leading to localized tissue destruction. Because breast cancer occurs with greatest frequency in the mature woman whose breast tissue has undergone glandular involution with fatty replacement, this study concentrates on determining the resultant laser energy heat distribution within fat and fibrofatty tissue. This investigation studied the time-temperature responses of ex vivo human breast and porcine fibrofatty tissue, which led to an in vivo subcutaneous porcine model for the practical demonstration of a laser hyperthermia treatment of small volumes of porcine mammary chain tissue., Results: Spatial recordings of the resultant temperature fields through time exhibited similar, reproducible thermal profiles in both ex vivo human breast and subcutaneous porcine fat. In vivo laser-produced temperature fields in porcine subcutaneous fat were comparable to those in the ex vivo analyses, and showed a histologically, sharply defined, and controllable volume of necrosis with no injury to adjacent tissues or to overlying skin., Conclusions: Interstitially placed, fiberoptically delivered Nd:YAG laser energy is capable of controlled tissue denaturation to a defined volume for the treatment of small breast cancers. It is hoped that this minimally invasive approach, with further investigation and refinement, may lead to the effective treatment of small, well-defined breast cancers that are commonly diagnosed through stereographic mammography and stereotactic core biopsy. The juxtaposition of such a localized treatment modality with these increasingly used diagnostic tools is of considerable promise.
- Published
- 1998
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23. Immunoblastic malignant lymphoma in dolphins: histologic, ultrastructural, and immunohistochemical features.
- Author
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Bossart GD, Ewing R, Herron AJ, Cray C, Mase B, Decker SJ, Alexander JW, and Altman NH
- Subjects
- Animals, Cell Nucleus pathology, Cell Nucleus ultrastructure, Chromatin pathology, Chromatin ultrastructure, Female, Lymph Nodes pathology, Microscopy, Electron, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology, Precursor Cell Lymphoblastic Leukemia-Lymphoma ultrastructure, Splenic Neoplasms pathology, Splenic Neoplasms ultrastructure, Dolphins, Precursor Cell Lymphoblastic Leukemia-Lymphoma veterinary, Splenic Neoplasms veterinary
- Published
- 1997
- Full Text
- View/download PDF
24. Mycobacterial infections of animals: pathology and pathogenesis.
- Author
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Hines ME 2nd, Kreeger JM, and Herron AJ
- Subjects
- Animals, Humans, Immunity, Innate genetics, Mycobacterium growth & development, Mycobacterium pathogenicity, Mycobacterium Infections genetics, Mycobacterium Infections immunology, Mycobacterium Infections microbiology, Mycobacterium Infections pathology, Mycobacterium avium, Opportunistic Infections veterinary, Tuberculosis microbiology, Tuberculosis pathology, Tuberculosis transmission, Tuberculosis veterinary, Mycobacterium Infections veterinary
- Published
- 1995
25. The histologic, ultrastructural, and immunohistochemical characteristics of a thyroid oncocytoma in a dog.
- Author
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Tang KN, Mansell JL, Herron AJ, and Sangster LT
- Subjects
- Adenoma, Oxyphilic metabolism, Adenoma, Oxyphilic pathology, Adenoma, Oxyphilic ultrastructure, Animals, Dog Diseases metabolism, Dogs, Female, Immunoenzyme Techniques, Microscopy, Electron, Thyroid Neoplasms metabolism, Thyroid Neoplasms pathology, Thyroid Neoplasms ultrastructure, Adenoma, Oxyphilic veterinary, Dog Diseases pathology, Thyroid Neoplasms veterinary
- Published
- 1994
- Full Text
- View/download PDF
26. Involvement of canine oral papillomavirus in generalized oral and cutaneous verrucosis in a Chinese Shar Pei dog.
- Author
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Sundberg JP, Smith EK, Herron AJ, Jenson AB, Burk RD, and Van Ranst M
- Subjects
- Adrenal Cortex Hormones adverse effects, Animals, Dog Diseases pathology, Dogs, Female, Mouth Diseases immunology, Mouth Diseases pathology, Papillomavirus Infections immunology, Papillomavirus Infections pathology, Skin Diseases immunology, Skin Diseases pathology, Tumor Virus Infections immunology, Tumor Virus Infections pathology, Warts immunology, Warts pathology, Dog Diseases immunology, Immunocompromised Host, Mouth Diseases veterinary, Papillomaviridae, Papillomavirus Infections veterinary, Skin Diseases veterinary, Tumor Virus Infections veterinary, Warts veterinary
- Abstract
Severe papillomatosis developed in the oral cavity and spread throughout the haired skin of the trunk and limbs of an 8-month-old female Chinese Shar Pei dog. The dog had received corticosteroids prior to referral, which was associated with the onset of demodecosis and papillomatosis. Papillomavirus structural antigens were detected in biopsies by immunohistochemistry using a panel of monoclonal and polyclonal antibodies. An 8.2-kilobase papillomavirus-specific DNA molecule was detected in the cutaneous lesions by high stringency Southern blot hybridization using a cloned canine oral papillomavirus DNA probe. Restriction enzyme analysis revealed that the virus in the cutaneous lesions was identical to the canine oral papillomavirus. Discontinuation of the steroids combined with the use of a mitocide, antibiotics, and an autogenous vaccine resolved the demodecosis and papillomatosis. This case report suggests that corticosteroid-induced immunosuppression can expand the tissue tropism of papillomaviruses.
- Published
- 1994
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- View/download PDF
27. Analysis of DNA aneuploidy and c-myc oncoprotein content of canine plasma cell tumors using flow cytometry.
- Author
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Frazier KS, Hines ME 2nd, Hurvitz AI, Robinson PG, and Herron AJ
- Subjects
- Animals, Dog Diseases pathology, Dogs, Female, Flow Cytometry veterinary, Male, Plasmacytoma chemistry, Plasmacytoma genetics, Plasmacytoma pathology, Ploidies, Retrospective Studies, DNA, Neoplasm genetics, Dog Diseases genetics, Plasmacytoma veterinary, Proto-Oncogene Proteins c-myc analysis
- Abstract
To derive a method for determining malignant potential of plasma cell tumors, a retrospective analysis of the DNA ploidy and relative p62c-myc oncoprotein content using bivariate flow cytometry was performed on 23 formalin-fixed, paraffin-embedded tissues from 23 dogs. The samples included one tissue each from 17 males and six females 2 to 16 years of age (mean = 7.5 years). Twelve breeds were represented, including three Cocker Spaniels, three Golden Retrievers, and five of mixed breed. Ten of the samples were histologically classified as malignant-plasma cell tumors, and ten specimens were classified as benign. Three samples of plasmacytic inflammation, from two Cocker Spaniels and one Shih Tsu, were included as controls. The ploidy and relative c-myc content data obtained were compared with the histologic grade. A significant difference in ploidy was found between benign and malignant tumors (P < or = 0.05). Five of nine malignant plasma cell tumors were aneuploid; the remainder were diploid (4/9) or tetraploid (1/9). Only one of the benign plasmacytomas was aneuploid (1/10), whereas six were diploid (6/10), and three were tetraploid (3/10). All of the controls were diploid (3/32). When relative amounts of p62c-myc from malignant and benign tumors were compared by flow cytometry, a greater significant difference was established (P < or = 0.01) than bu using aneuploidy alone. Relative values of p62c-myc content ranged from 219 to 553 units in 8/10 malignant plasma cell tumors and from 86 to 392 units in 3/10 benign plasmacytomas.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1993
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- View/download PDF
28. Metastatic malignant melanoma in a mandarin duck (Aix galericulata).
- Author
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Reid HA, Herron AJ, Hines ME 2nd, Miller C, and Altman NH
- Subjects
- Animals, Ducks, Female, Lymphatic Metastasis, Lymphocytes pathology, Melanoma pathology, Skin Diseases pathology, Bird Diseases, Melanoma veterinary, Skin Diseases veterinary
- Abstract
A biopsy taken from a mass on the dorsal surface of the bill of an adult female mandarin duck (Aix galericulata) was diagnosed as a malignant melanoma by light microscopy. Two months later, the tumor had enlarged considerably; the duck developed severe dyspnea and was euthanatized. At necropsy, there were metastases to lymphoid tissues in the lower regions of the neck. To our knowledge, this is the first report of a malignant melanoma in a mandarin duck.
- Published
- 1993
29. Diagnosis of enteritis and enterotoxemia due to Clostridium difficile in captive ostriches (Struthio camelus).
- Author
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Frazier KS, Herron AJ, Hines ME 2nd, Gaskin JM, and Altman NH
- Subjects
- Animals, Animals, Domestic, Cecum microbiology, Cecum pathology, Enteritis diagnosis, Enteritis microbiology, Enteritis pathology, Enterotoxemia pathology, Bird Diseases, Clostridioides difficile, Enteritis veterinary, Enterotoxemia diagnosis
- Published
- 1993
- Full Text
- View/download PDF
30. Leptospirosis in a white-lipped tamarin (Saguinus labiatus).
- Author
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Reid HA, Herron AJ, Hines ME 2nd, Orchard EA, and Altman NH
- Subjects
- Animals, Female, Leptospirosis microbiology, Leptospirosis pathology, Monkey Diseases microbiology, Leptospirosis veterinary, Monkey Diseases pathology, Saguinus microbiology
- Published
- 1993
31. Immunohistochemical and morphologic features of an intradermal nevocellular nevus (benign intradermal junctional melanocytoma) in a rhesus monkey (Macaca mulatta).
- Author
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Frazier KS, Herron AJ, Hines ME 2nd, and Altman NH
- Subjects
- Animals, Female, Immunohistochemistry, Nevus, Pigmented chemistry, Nevus, Pigmented pathology, Skin Neoplasms chemistry, Skin Neoplasms pathology, Macaca mulatta, Monkey Diseases pathology, Nevus, Pigmented veterinary, Skin Neoplasms veterinary
- Published
- 1993
- Full Text
- View/download PDF
32. Metastasis of a myxoid leiomyosarcoma via the renal and hepatic portal circulation in a sarus crane (Grus antigone).
- Author
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Frazier KS, Herron AJ, Hines ME 2nd, Miller CL, Hensley GT, and Altman NH
- Subjects
- Actins analysis, Actins metabolism, Animals, Female, Immunohistochemistry, Kidney chemistry, Kidney Neoplasms secondary, Leiomyosarcoma pathology, Liver chemistry, Liver Neoplasms secondary, Myosins analysis, Myosins metabolism, Neoplasm Metastasis physiopathology, Portal Vein physiology, Renal Circulation physiology, Skin Neoplasms pathology, Vimentin analysis, Vimentin metabolism, Bird Diseases blood, Birds blood, Kidney blood supply, Leiomyosarcoma veterinary, Liver blood supply, Skin Neoplasms veterinary
- Abstract
A 12-year-old female sarus crane (Grus antigone) developed a recurrent proliferative lesion in the subcutaneous tissue of the tarsometatarsus, which failed to respond to medical and surgical therapy. The crane was killed and microscopic examination of the tissues taken at necropsy revealed a myxomatous, poorly-differentiated sarcoma with metastasis to the liver and kidney. Immunohistochemical staining for muscle actin, smooth muscle myosin and vimentin were positive, indicating that the primary and metastatic tumours were leiomyosarcomas. Location of the metastatic lesions in only the portal venous system of the liver and veins of the kidney indicated that the route of metastasis was the portal circulation via the ischiatic vein, caudal mesenteric vein and both the renal-portal shunt and hepatic portal vein. This is the first report of metastatic subcutaneous leiomyosarcoma in an avian species.
- Published
- 1993
- Full Text
- View/download PDF
33. Gastric extramedullary plasmacytoma in a dog.
- Author
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Brunnert SR, Dee LA, Herron AJ, and Altman NH
- Subjects
- Animals, Chemotherapy, Adjuvant, Diphenhydramine therapeutic use, Dog Diseases drug therapy, Dog Diseases pathology, Dogs, Doxorubicin therapeutic use, Female, Gastrectomy veterinary, Lymph Node Excision veterinary, Lymphatic Metastasis, Plasmacytoma drug therapy, Plasmacytoma pathology, Plasmacytoma surgery, Stomach Neoplasms drug therapy, Stomach Neoplasms pathology, Stomach Neoplasms surgery, Dog Diseases surgery, Plasmacytoma veterinary, Stomach Neoplasms veterinary
- Abstract
A 10-year-old mixed-breed dog was examined because of a 6-week history of daily vomiting and sporadic diarrhea. On gastroscopy, a crateriform mass was observed on the greater curvature of the stomach. Partial gastrectomy and lymphadenectomy of a large mesenteric lymph node was performed. Gastric plasmacytoma with lymph node metastasis was diagnosed by histologic and immunoperoxidase methods, and chemotherapy was initiated with doxorubicin hydrochloride and diphenhydramine hydrochloride. The dog remains clinically normal 30 months after initial diagnosis. Although gastric plasmacytomas are rare in dogs, long-term survival appears to be better with this disease than with other types of gastric neoplasia.
- Published
- 1992
34. Salivary gland oncocytes in African hedgehogs (Atelerix albiventris) mimicking cytomegalic inclusion disease.
- Author
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Brunnert SR, Hensley GT, Citino SB, Herron AJ, and Altman NH
- Subjects
- Animals, Cell Nucleus ultrastructure, Cell Transformation, Neoplastic pathology, Cytomegalovirus Infections diagnosis, Cytomegalovirus Infections pathology, Cytoplasmic Granules ultrastructure, Diagnosis, Differential, Female, Histocytochemistry methods, Lymphocytes pathology, Male, Microscopy, Electron, Salivary Gland Neoplasms diagnosis, Salivary Gland Neoplasms pathology, Salivary Glands pathology, Salivary Glands ultrastructure, Cytomegalovirus Infections veterinary, Hedgehogs, Salivary Gland Neoplasms veterinary
- Abstract
The salivary glands from three African hedgehogs contained multiple foci of cytomegalic cells, which occasionally had a mild to moderate infiltrate of lymphocytes at the periphery. The cytomegalic cells were 35 to 40 microns in diameter with abundant acidophilic granular to hyalin cytoplasm. The nuclei were enlarged with clumped marginalized chromatin and a large, (6 to 8 microns in diameter) central, brightly eosinophilic nucleolus that had the appearance of an inclusion body by light microscopy. Histochemically most of the cytomegalic cells contained cytoplasmic metachromatic granules with Feyrter's thionine inclusion stain. Scattered cells at the periphery of the cytomegalic foci contained periodic acid-Schiff-positive cytoplasmic granules. Ultrastructurally the cytomegalic cells contained numerous tightly-packed, often bizarre, enlarged mitochondria that completely filled the cytoplasm. The nucleus consisted of a dense central core of chromatin associated with the nucleolus and the remaining chromatin was clumped and marginalized. Nuclear and cytoplasmic virions consistent with cytomegalovirus were not present. Histochemical stains of the nucleus for heavy metals were negative. The ultrastructural and histochemical findings of the cytomegalic cells were consistent with oncocytes. Previous reports in the literature of similar cells in the salivary glands of insectivores appear to have been erroneously described as cytomegalovirus infections.
- Published
- 1991
- Full Text
- View/download PDF
35. Development of small-cell osteogenic sarcoma after ulnar ostectomy in a dog.
- Author
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Frazier K, Herron AJ, Dee J, Ghandur-Mnymneh L, and Altman NH
- Subjects
- Animals, Bone Neoplasms etiology, Dogs, Lung Neoplasms secondary, Lung Neoplasms veterinary, Male, Osteosarcoma etiology, Osteosarcoma secondary, Postoperative Complications veterinary, Ulna pathology, Bone Neoplasms veterinary, Dog Diseases etiology, Osteosarcoma veterinary, Ulna surgery
- Abstract
A 5-year-old male Saint Bernard was evaluated for vague forelimb lameness. Four and a half years earlier, the dog had undergone left ulnar ostectomy to correct a valgus deformity. Focal bone lysis was evident radiographically at the ostectomy site. Four months later, marked bony swelling was apparent and the dog was bearing partial weight. The dog was euthanatized, and at necropsy, a bone tumor with lung metastasis was found. Microscopically, features of the tumor were compatible with those of small-cell osteogenic sarcoma.
- Published
- 1991
36. IL-1 as a potent inducer of wound re-epithelization.
- Author
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Mertz PM, Sauder DL, Davis SC, Kilian PL, Herron AJ, and Eaglstein WH
- Subjects
- Animals, Epidermal Growth Factor physiology, Epithelial Cells, Epithelium physiology, Fibroblast Growth Factor 2 physiology, Interleukin-1 pharmacology, Skin injuries, Skin pathology, Swine, Interleukin-1 physiology, Wound Healing physiology
- Published
- 1991
37. Islet cell hyperplasia in an aged spider monkey (Ateles paniscus).
- Author
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Brunnert SR, Herron AJ, and Altman NH
- Subjects
- Animals, Female, Hyperplasia veterinary, Immunoenzyme Techniques, Immunohistochemistry, Islets of Langerhans ultrastructure, Microscopy, Electron, Aging pathology, Cebidae, Islets of Langerhans pathology, Monkey Diseases pathology
- Published
- 1990
- Full Text
- View/download PDF
38. Immunohistochemical and morphologic features of chordomas in ferrets (Mustela putorius furo).
- Author
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Herron AJ, Brunnert SR, Ching SV, Dillberger JE, and Altman NH
- Subjects
- Animals, Bone Neoplasms pathology, Chordoma pathology, Female, Immunohistochemistry, Male, Bone Neoplasms veterinary, Carnivora, Chordoma veterinary, Ferrets, Tail
- Published
- 1990
- Full Text
- View/download PDF
39. Leiomyosarcoma in a domestic ferret: morphologic and immunocytochemical diagnosis.
- Author
-
Brunnert SR, Herron AJ, and Altman NH
- Subjects
- Animals, Female, Fibrosarcoma diagnosis, Fibrosarcoma pathology, Fibrosarcoma veterinary, Immunohistochemistry, Leiomyosarcoma diagnosis, Leiomyosarcoma pathology, Rhabdomyosarcoma diagnosis, Rhabdomyosarcoma pathology, Rhabdomyosarcoma veterinary, Shoulder, Animals, Domestic, Carnivora, Ferrets, Leiomyosarcoma veterinary
- Published
- 1990
40. Subcutaneous leiomyosarcoma in a Peruvian squirrel monkey (Saimiri sciureus).
- Author
-
Brunnert SR, Herron AJ, and Altman NH
- Subjects
- Animals, Leiomyosarcoma pathology, Male, Skin Neoplasms pathology, Cebidae, Leiomyosarcoma veterinary, Monkey Diseases pathology, Saimiri, Skin Neoplasms veterinary
- Published
- 1990
- Full Text
- View/download PDF
41. Submission of diagnostic samples to a laboratory.
- Author
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Harrison LR and Herron AJ
- Subjects
- Animals, Animals, Domestic, Autopsy, Bacterial Infections veterinary, Birds, Infections diagnosis, Laboratories, Microbiological Techniques veterinary, Mycoses veterinary, Parasitic Diseases, Animal, Psittaciformes, Virus Diseases veterinary, Bird Diseases diagnosis, Clinical Laboratory Techniques veterinary, Infections veterinary, Specimen Handling veterinary
- Published
- 1984
- Full Text
- View/download PDF
42. Cloacal papillomas in psittacines.
- Author
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Sundberg JP, Junge RE, O'Banion MK, Basgall EJ, Harrison G, Herron AJ, and Shivaprasad HL
- Subjects
- Animals, Microscopy, Electron, Papilloma pathology, Papilloma ultrastructure, Species Specificity, Staining and Labeling, Birds, Cloaca pathology, Papilloma veterinary
- Abstract
Papilloma-like masses affecting the cloaca of 19 Amazons, 16 macaws, 3 parrots, 1 conure, and 1 parakeet were examined. Papillomatous lesions were characterized by proliferation of the lining epithelium on thin fibrovascular stalks. Carcinoma in situ was diagnosed in the cloaca of a macaw in addition to the other 16 macaws with papillomas. Papillomavirus group-specific antigens were not detected in any of the 41 lesions, using the peroxidase-antiperoxidase technique. The DNA extracts from 6 different frozen papillomas did not contain papillomavirus genomes detectable by Southern blot hybridization, using an African gray parrot cutaneous papillomavirus as a probe. Evidence of an infective agent was not found by electron microscopic examination of 8 of the papillomas. Inoculations of partially purified homogenates of a cloacal papilloma from a yellow-crowned Amazon did not induce lesion formation on cloacal mucosa of an adult yellow-crowned Amazon, green and yellow macaw, sulphur-crested cockatoo, or mollucan cockatoo.
- Published
- 1986
43. Extraskeletal osteogenic sarcoma in a guinea pig--.
- Author
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Cook RA, Burk RL, and Herron AJ
- Subjects
- Animals, Female, Guinea Pigs, Ossification, Heterotopic diagnosis, Osteosarcoma diagnosis, Ossification, Heterotopic veterinary, Osteosarcoma veterinary, Rodent Diseases diagnosis
- Published
- 1982
44. Myopathy in the nyala.
- Author
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Liu S, Dolensek EP, Herron AJ, Stover J, and Doherty JG
- Subjects
- Animals, Female, Male, Muscular Diseases blood, Muscular Diseases pathology, Myocardium pathology, Selenium blood, Vitamin E blood, Artiodactyla, Muscular Diseases veterinary
- Abstract
Between January 1973 and June 1981, a total of 21 nyalas (Tragelaphus angasi) died with clinical and/or pathologic evidence of myopathy. The main clinical signs were stiffness, inability to rise, and failure to suckle in newborn fawns. Death usually occurred without premonitory signs of disease. Gross lesions were characterized by white or pale patches of skeletal or cardiac muscle. Histologically, acute degeneration or necrosis and mineralization were commonly observed in skeletal muscle. Acute necrosis of the myocardium with or without arteriolar fibrinoid necrosis was usually found in juvenile animals. Interstitial fibrosis of the myocardium with arteriosclerosis was commonly observed in adults. The plasma alpha tocopherol values of 3 affected nyalas ranged from 0.03 to 0.08 mg/dl (mean, 0.05 mg/dl). Unaffected nyalas from the same herd had a range of 0.09 to 0.24 mg/dl (mean, 0.13 mg/dl), which is low enough to be considered clinically deficient. The blood selenium values of the affected nyalas and other nyalas from the same herd ranged from 0.30 to 0.33 ppm (mean, 0.32 ppm), and were considered normal.
- Published
- 1982
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