Amy L MacNeill

Colorado State University | CSU · Department of Microbiology, Immunology & Pathology

The Nix-TB clinical trial evaluated a new 6 month regimen containing three oral drugs; bedaquiline (B), pretomanid (Pa), and linezolid (L) (BPaL regimen) for the treatment of tuberculosis (TB). This regimen achieved remarkable results as almost 90% of the multidrug-resistant or extensively drug-resistant TB participants were cured but many patients...

The Nix-TB clinical trial evaluated a new 6-month regimen containing three-oral- drugs; bedaquiline (B), pretomanid (Pa) and linezolid (L) (BPaL regimen) for treatment of tuberculosis (TB). This regimen achieved remarkable results as almost 90% of the multidrug resistant (MDR) or extensively drug resistant (XDR) TB participants were cured but many...

The Nix-TB clinical trial evaluated a new 6-month regimen containing three-oral-drugs; bedaquiline (B), pretomanid (Pa) and linezolid (L) (BPaL regimen) for treatment of tuberculosis (TB). This regimen achieved remarkable results as almost 90% of the multidrug resistant (MDR) or extensively drug resistant (XDR) TB participants were cured but many p...

The Nix-TB clinical trial evaluated a new 6-month regimen containing three-oral- drugs; bedaquiline (B), pretomanid (Pa) and linezolid (L) (BPaL regimen) for treatment of tuberculosis (TB). This regimen achieved remarkable results as almost 90% of the multidrug resistant (MDR) or extensively drug resistant (XDR) TB participants were cured but many...

The Nix-TB clinical trial evaluated a new 6-month regimen containing three-oral- drugs; bedaquiline (B), pretomanid (Pa) and linezolid (L) (BPaL regimen) for treatment of tuberculosis (TB). This regimen achieved remarkable results as almost 90% of the multidrug resistant (MDR) or extensively drug resistant (XDR) TB participants were cured but many...

Human rhabdomyosarcomas are rarely cured by surgical resection alone. This is also true for high-grade soft tissue sarcomas in dogs. Dogs with spontaneous sarcoma are good models for clinical responses to new cancer therapies. Strategic combinations of immunotherapy and oncolytic virotherapy (OV) could improve treatment responses in canine and huma...

Human rhabdomyosarcomas are rarely cured by surgical resection alone. This is also true for high grade soft tissue sarcomas in dogs. Dogs with spontaneous sarcoma are good models for clinical responses to new cancer therapies. Strategic combinations of immunotherapy and oncolytic virotherapy (OV) could improve treatment responses in canine and huma...

This review provides a brief history of the impacts that a human-specific Orthopoxvirus (OPXV), Variola virus, had on mankind, recalls how critical vaccination was for the eradication of this disease, and discusses the consequences of discontinuing vaccination against OPXV. One of these consequences is the emergence of zoonotic OPXV diseases, inclu...

In collaboration with the American College of Veterinary Pathologists.

There are over 2250 known species of mammals classified within the phylogenetic order Rodentia. Individual rodent species have adapted to several vastly different environments, eat varied diets, and have species‐specific behavioral traits. This chapter reviews hematologic findings in a small handful of rodent species that are commonly seen in veter...

The poxvirus, myxoma virus (MYXV) has shown efficacy as an oncolytic virus (OV) in some cancer models. However, MYXV replication within murine cancer models and spontaneous canine sarcomas is short-lived. In mice, successful treatment of tumors requires frequent injections with MYXV. We hypothesize that treatment of cancer with a recombinant MYXV t...

Purpose: Rhabdomyosarcomas (RMS) are difficult tumors to treat with conventional therapies. Publications indicate that oncolytic virotherapy (OV) could benefit cancer patients with tumors that are refractory to conventional treatments. It is believed that the efficacy of OV can be enhanced when used in combination with other treatments. This study...

Replicating oncolytic viruses (OVs) are appealing, new, FDA‐approved, therapeutic options for humans with head and neck cancers and melanomas. These treatments are not yet available for veterinary patients, but recent clinical trials have shown several OVs to be safe in dogs and cats. Specific viruses being used to treat sarcomas in dogs include mo...

Background: A definitive diagnosis of immune-mediated hemolytic anemia (IMHA) can be difficult to make. However, it is critical to differentiate IMHA from other causes of anemia due to the impact on prognosis and outcome for IMHA patients. Recently published American College of Veterinary Internal Medicine recommendations for the diagnosis of IMHA...

Immune‐mediated hemolytic anemia (IMHA) is an important cause of morbidity and mortality in dogs. IMHA also occurs in cats, although less commonly. IMHA is considered secondary when it can be attributed to an underlying disease, and as primary (idiopathic) if no cause is found. Eliminating diseases that cause IMHA may attenuate or stop immune‐media...

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Background Lymphoma is an important disease of pet guinea pigs, although validation of immunophenotyping techniques based on cytologic or hematologic samples has not been reported. Objective To describe an immunocytochemical method for immunophenotyping of lymphoma (as either T‐ or B‐cell) in guinea pigs, and to validate antibodies for this purpos...

Many oncolytic viruses that are efficacious in murine cancer models are ineffective in humans. The outcomes of oncolytic virus treatment in dogs with spontaneous tumors may better predict human cancer response and improve treatment options for dogs with cancer. The objectives of this study were to evaluate the safety of treatment with myxoma virus...

Background Cerebrospinal fluid (CSF) might be altered by iatrogenic blood contamination, precluding accurate diagnostic interpretation. Objectives Available formulas to correct for iatrogenic blood contamination are likely unreliable. Study objectives were to determine the effects of blood contamination on total nucleated cell counts (NCCs) and pr...

Bone marrow (BM) cytology and histopathology are complementary tools used to investigate hematological diseases. The purpose of this study was to determine if there are site-dependent differences in the diagnostic quality, myeloid to erythroid ratio (MER), and discordant findings in samples from different sites in the same dog. Eighteen apparently...

Vaginal and vulvar tumors are uncommon in dogs. Knowledge of canine primary clitoral neoplasia is restricted to a few case reports, and only carcinomas have been reported. Cytologic and histologic features reported in the literature seem to overlap with those of canine apocrine gland anal sac adenocarcinoma (AGASA). Clinical features also recall th...

Gamna–Gandy (GG) bodies are non-infectious, hyphal-like structures associated with siderotic nodules in lymphoid tissue; GG bodies are very rarely reported in veterinary cytologic samples. Cytologically, GG bodies can be misidentified as hyphae or plant material. Seven canine lymphoid tissue aspiration cases that contained GG bodies were investigat...

Diabetes mellitus is a common endocrinopathy of cats that is characterized by persistent fasting hyperglycemia. However, stress induces substantial hyperglycemia in cats that poses a challenge to the veterinarian who may wrongly interpret the high serum concentration of blood glucose as evidence of diabetes mellitus. Fructosamine is a glycated seru...

Cytology offers a rapid, relatively noninvasive means to identify lesions of all varieties including immune-mediated, degenerate, inflammatory, and neoplastic. One area that is particularly amenable to cytologic diagnosis is infectious disease. Organisms that can be seen and identified include fungal, bacterial, protozoal, parasitic, viral, and alg...

Clouded leopards in North American zoological institutions have a high frequency of pheochromocytomas and were identified in 32 of 70 (45%) animals necropsied. Archival sections of adrenal gland from 20 adult clouded leopards with unilateral or bilateral pheochromocytomas collected between 1984 and 2011 were examined by light microscopy and immunoh...

Cytopathic effects of incubating RMS cell cultures with MYXV-red (multiplicity of infection =0.1). Notes: Forty-eight hours after inoculation with MYXV-red, red fluorescence is observed within RMS cells. Magnification 1000×. Abbreviations: RMS, rhabdomyosarcoma; MYXV-red, myxoma virus with red fluorescent protein; RK13, rabbit kidney epithelial cel...

Agarose gel electrophoresis of PCR products from two of the three primer sets designed to detect MYXV DNA are shown. Notes: All tissue homogenates collected at euthanasia from PBS- and MYXV-red-treated mice were negative for MYXV DNA. However, MYXV DNA could be detected in tissue homogenates from MYXV-red*-treated mice that had an adverse reaction...

Veronica G Kinn, Valerie A Hilgenberg, Amy L MacNeill Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA Abstract: Rhabdomyosarcoma (RMS) is a devastating tumor of young people that is difficult to cure. To determine if oncolytic virus therap...

Study question: Does halofuginone (HF) inhibit the growth of human uterine leiomyoma cells in a mouse xenograft model? Summary answer: HF suppresses the growth of human uterine leiomyoma cells in a mouse xenograft model through inhibiting cell proliferation and inducing apoptosis. What is known already: Uterine leiomyomas are the most common b...

Virotherapy using oncolytic vaccinia virus (VACV) strains is one promising new strategy for canine cancer therapy. In this study we describe the establishment of an in vivo model of canine soft tissue sarcoma (CSTS) using the new isolated cell line STSA-1 and the analysis of the virus-mediated oncolytic and immunological effects of two different Li...

Adenocarcinoma;apocrine gland;cytology;neuroendocrine;vulvar tumor

Over 6 million dogs are diagnosed with cancer in the USA each year. Treatment options for many of these patients are limited. It is important that the veterinary and scientific communities begin to explore novel treatment protocols for dogs with cancer. Oncolytic viral therapy is a promising treatment option that may prove to be relatively inexpens...

Oxidative stress inhibits albumin's ability to complex with cobalt. Feline serum-cobalt binding has not been described. The objective was to develop a cobalt binding test for use with feline serum, and correlate the results with other biochemical and cellular constituents in blood, and with clinical diseases of cats. A colorimetric test of cobalt b...

The objective of this study was to document Cytauxzoon felis infection in domestic cats from southern Illinois. Diagnosis of cytauxzoonosis was based upon clinical signs of illness and detection of prioplasms within erythrocytes on peripheral blood smears or schizonts in internal organs consistent with Cytauxzoon infection. Additionally, genomic DN...

Objective: To critically evaluate plasma fibrinogen concentration as a diagnostic indicator of inflammation in red-eared sliders (Trachemys scripta elegans). Design: Prospective induced-disease model and prospective cross-sectional study. Sample: Plasma samples from 12 purpose-bred red-eared sliders and 153 farm-raised red-eared sliders. Proc...

ABSTRACT A 7 yr old castrated male standard poodle weighing 25 kg was presented with a 5 day history of hematuria, dysuria, and the presence of a 2.5 cm, firm swelling within the prepuce. Abdominal radiographs revealed a soft-tissue mass on the distal prepuce and lysis of the cranial margin of the os penis. The patient was sedated and an ulcerated...

Myxoma virus, a rabbit poxvirus, can efficiently infect various types of mouse and human cancer cells. It is a strict rabbit-specific pathogen, and is thought to be safe as a therapeutic agent in all non-rabbit hosts tested including mice and humans. Interleukin-15 (IL15) is an immuno-modulatory cytokine with significant potential for stimulating a...

The process of vaccination introduced by Jenner generated immunity against smallpox and ultimately led to the eradication of the disease. Procedurally, in modern times, the virus is introduced into patients via a process called scarification, performed with a bifurcated needle containing a small amount of virus. What was unappreciated was that the...

Ranavirus is an emerging disease that infects fish, amphibians, and reptiles. Ranavirus induces an inflammatory response leading to death in many susceptible species. Red-eared sliders (RES; Trachemys scripta elegans) are vulnerable to ranavirus infection and are economically significant chelonians kept in the pet trade and utilized in research. Ea...

Vaginal exfoliative cytology is commonly used in biomedical and toxicological research to classify the stages of the rodent estrous cycle. However, mouse vaginal exfoliative cytology is commonly used as a stand-alone tool and has not been evaluated in reference to vaginal histology and serum sex hormone levels. In this study, the direct and Giemsa-...

Myxoma virus, a rabbit poxvirus, can efficiently infect various classes of mouse and human cancer cells. It is a strict rabbit-specific pathogen, safe to use in all non-rabbit hosts tested including mice and humans. Recombinant viruses were previously engineered to express tdTomatoRed fluorescent protein (vMyx-tdTr) and mouse interleukin-15 (vMyx-I...

The purpose of this paper by the Regulatory Affairs Committee (RAC) of the American Society for Veterinary Clinical Pathology (ASVCP) is to review the current regulatory guidances (eg, guidelines) and published recommendations for best practices in veterinary toxicologic clinical pathology, particularly in the pharmaceutical and biotechnology indus...

Myxoma virus (MYXV) has potential as an oncolytic virus, but is not fully effective as a single‐agent therapy. We hypothesized that intratumoral (IT) expression of interleukin‐15 (IL‐15) by MYXV would recruit cytotoxic effector cells and improve treatment efficacy. To test this, MYXV expressing a fluorescent protein (MYXV‐Tred) and MYXV‐Tred encodi...

Two recombinant myxoma viruses (MYXV expressing a fluorescent protein [MYXV-Tred] and MYXV-Tred encoding murine interleukin-15 [MYXV-IL15]) were evaluated for therapeutic effects in an aggressive B16F10 melanoma model in immunocompetent mice. It was hypothesized that continuous expression of IL-15 within a tumor would recruit cytotoxic effector cel...

Erythrophagia has been identified in multiple types of tumors in human medicine, but information in veterinary medicine is limited. In dogs and cats, erythrophagia has been reported to occur in mast cell and plasma cell tumors, lymphoma, megakaryocytic leukemia, and hemophagocytic histiocytic sarcoma. On the basis of clinical experience, we believe...

To determine the oncolytic efficacy of an attenuated form of myxoma virus lacking the serp2 gene in canine tumor cells. Primary cells were isolated from tumors that were surgically removed from dogs and from connective tissue obtained from the cadaver of a dog. Cells of various established cell lines from tumors and nontumorous tissues were obtaine...

Virotherapy using oncolytic vaccinia virus (VACV) strains is one promising new strategy for canine cancer therapy. In this study we describe the establishment of an in vivo model of canine soft tissue sarcoma (CSTS) using the new isolated cell line STSA-1 and the analysis of the virus-mediated oncolytic and immunological effects of two different Li...

Short tandem repeat (STR) analysis of STSA-1 cells. The validation of the cell line was preformed as recently described [25].The STK kit (StockMarks for Dogs: Canine Genotyping Kit, Applied Biosystems, Foster City, CA) tested 10 different loci (A): PEZ 1, FHC 2054, FHC 2010; (B) PEZ 5, PEZ 20; PEZ 12; (C) PEZ 3, PEZ 6, PEZ 8, FHC 2079.The observed...

There is growing interest in utilizing replicating oncolytic viruses as cancer therapeutics agents. The effectiveness of myxoma virus-induced oncolysis was evaluated in two feline cancer cell cultures. Although myxoma virus is a rabbit-specific pathogen, protein expression driven by myxoma virus and production of infectious viral particles were det...

Vaccinia virus deleted for the innate immune evasion gene, E3L, has been shown to be highly attenuated and yet induces a protective immune response against challenge by homologous virus in a mouse model. In this manuscript the NYCBH vaccinia virus vaccine strain was compared to NYCBH vaccinia virus deleted for E3L (NYCBHΔE3L) in a rabbitpox virus (...

There is little scientific information available about the ability of ocular disease to cause a systemic inflammatory response. Horses are frequently affected with ocular disease and ensuring their systemic health prior to performing vision saving surgery under anaesthesia is essential for the successful treatment of ophthalmic disease. Ocular dise...

Adoptive transfer of tumor-specific T cells has shown some success for treating metastatic melanoma. We evaluated a novel strategy to improve adoptive therapy by administering both T cells and oncolytic myxoma virus to mice with syngeneic B16.SIY melanoma brain tumors. Adoptive transfer of activated CD8(+) 2C T cells that recognize SIY peptide doub...

Oncolytic viruses that selectively infect and lyse cancer cells have potential as therapeutic agents. Myxoma virus, a poxvirus that is known to be pathogenic only in rabbits, has not been reported to infect normal tissues in humans or mice. We observed that when recombinant virus was injected directly into the lateral ventricle of the mouse brain,...

A 4-year-old female spayed Bichon Frise dog that had been receiving cyclosporine A per os 3 times per week for 2 months to control allergic dermatitis developed lethargy, anorexia, fever, and multiple firm subcutaneous masses. Pyogranulomatous inflammation with branching nonseptate filamentous organisms approximately 2 mum in diameter, presumptivel...

An 8-year-old dog presented with several dermal excoriations. Lesion cytology revealed pyogranulomatous inflammation with branching, septate hyphae. A mold identified as Mycoleptodiscus indicus by morphology and sequencing was cultured from fine-needle aspirates. This is the first report of a Mycoleptodiscus species as an etiologic agent in a dog.

Intratracheal (i.t.) infection of mice with cowpox virus (CPXV), is lethal at a lower dose than intranasal (i.n.) inoculation. CPXV deleted for cytokine response modifier A (CPXVDeltacrmA) was attenuated compared to CPXV after i.t. inoculation. This attenuation could not be attributed to differences in virus replication, immunomodulators, or cells...

Myxoma virus (MYXV) is a poxvirus pathogenic only for European rabbits, but its permissiveness in human cancer cells gives it potential as an oncolytic virus. A recombinant MYXV expressing both the tdTomato red fluorescent protein and interleukin-15 (IL-15) (vMyx-IL-15-tdTr) was constructed. Cells infected with vMyx-IL-15-tdTr secreted bioactive IL...

Myxoma virus (MYX) prevents apoptosis in RK-13 cells and forms thick dermal lesions with 100% mortality in rabbits. MYX encodes the virulence factor SERP2, a serine proteinase inhibitor (serpin). SERP2 was mutated to evaluate SERP2 function during MYX infection. MYXDeltaSERP2::lacZ (deleted for SERP2) did not inhibit apoptosis in RK-13 cells; infec...