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1.
Animals (Basel) ; 13(4)2023 Feb 16.
Article in English | MEDLINE | ID: mdl-36830474

ABSTRACT

Annual monitoring of leatherback sea turtle (Dermochelys coriacea) nesting grounds in Grenada, West Indies has identified relatively low hatch rates compared to worldwide trends. This study investigated the impact of selected environmental variables on leatherback sea turtle embryonic development and hatching success rates on Levera Beach in Grenada between 2015-2019. The mean number of nests per year and eggs per nest were 667.6 ± 361.6 and 80.7 ± 23.0 sd, respectively. Within excavated nests, 35.6% ± 22.0 sd of eggs successfully developed embryos and 30.6% ± 22.6 sd of eggs successfully hatched. The number of eggs per nest, along with embryo and hatching success rates, differed by nesting year. Embryo development success rate was associated with nest location, and both embryo development and hatching success rates were positively associated with nest depth and negatively associated with the percentage of eggs exhibiting microbial growth and with the presence of inspissated yolk. There was no embryo development or hatchling success association with month of the nesting season, distance from the high-water mark, distance from vegetation, nor maternal carapace length. The mean nest temperature was 31.7 °C ± 1.64 sd and mean temperatures during the middle third of egg incubation suggest clutches are highly skewed towards a preponderance of female hatchlings. Histopathologic findings in hatchling mortalities included severe, acute, multifocal, heterophilic bronchopneumonia with intralesional bacteria in 4/50 (8%) hatchlings. Data from this study guide conservation strategies by identifying risk factors and further avenues of research needed to support reproductive success of leatherback sea turtles in Grenada and the greater Caribbean region.

2.
Brachytherapy ; 22(2): 195-198, 2023.
Article in English | MEDLINE | ID: mdl-36424254

ABSTRACT

PURPOSE: The current standard of care for muscle-invasive bladder cancer is neoadjuvant chemotherapy followed by radical cystectomy with lymph node dissection. Although this treatment provides therapeutic benefit, it is associated with notable morbidity. Bladder sparing techniques, such as concurrent chemo-radiation, are less invasive and prioritize organ preservation in individuals with invasive bladder cancer and offer comparable disease control. High-dose-rate brachytherapy is an emerging paradigm in the management of muscle-invasive bladder cancer. During high-dose-rate brachytherapy, radioactive sources are introduced to the area of the primary tumor through specialized catheters. The specific placement of brachytherapy catheters results in heightened effectiveness of the radiation treatment with less radiation damage to surrounding structures. For bladder-sparing therapies such as brachytherapy to rival radical cystectomy, these techniques need to be refined further by radiation oncologists. PROCEDURE: One such modality for developing and practicing these techniques is the use of cadaveric models in innovation-focused clinical training facilities, which provide a simulated sterile surgical environment without the concern for extending intraoperative time. FINDINGS AND CONCLUSIONS: The objective of this technical note is to demonstrate how clinical training facilities such as the Houston Methodist Institute for Technology, Innovation & Education are ideal for the development, testing, and training of novel brachytherapy techniques using cadaveric models. By utilizing a network of similarly innovative training centers, research and development of brachytherapy techniques can be expedited, and novel bladder-sparing treatment methods can be implemented as the standard of care for bladder cancer.


Subject(s)
Brachytherapy , Robotic Surgical Procedures , Urinary Bladder Neoplasms , Humans , Brachytherapy/methods , Feasibility Studies , Urinary Bladder Neoplasms/radiotherapy , Cystectomy/methods , Combined Modality Therapy , Cadaver , Neoplasm Invasiveness
3.
Cell Host Microbe ; 30(6): 836-847.e6, 2022 06 08.
Article in English | MEDLINE | ID: mdl-35568027

ABSTRACT

Changes in the microbiota composition are associated with many human diseases, but factors that govern strain abundance remain poorly defined. We show that a commensal Escherichia coli strain and a pathogenic Salmonella enterica serovar Typhimurium isolate both utilize nitrate for intestinal growth, but each accesses this resource in a distinct biogeographical niche. Commensal E. coli utilizes epithelial-derived nitrate, whereas nitrate in the niche occupied by S. Typhimurium is derived from phagocytic infiltrates. Surprisingly, avirulent S. Typhimurium was shown to be unable to utilize epithelial-derived nitrate because its chemotaxis receptors McpB and McpC exclude the pathogen from the niche occupied by E. coli. In contrast, E. coli invades the niche constructed by S. Typhimurium virulence factors and confers colonization resistance by competing for nitrate. Thus, nutrient niches are not defined solely by critical resources, but they can be further subdivided biogeographically within the host into distinct microhabitats, thereby generating new niche opportunities for distinct bacterial species.


Subject(s)
Gastrointestinal Microbiome , Salmonella typhimurium , Escherichia coli , Humans , Nitrates , Nutrients
4.
Infect Immun ; 90(4): e0007022, 2022 04 21.
Article in English | MEDLINE | ID: mdl-35311578

ABSTRACT

Persistent infections generally involve a complex balance between protective immunity and immunopathology. We used a murine model to investigate the role of inflammatory monocytes in immunity and host defense against persistent salmonellosis. Mice exhibit increased susceptibility to persistent infection when inflammatory monocytes cannot be recruited into tissues or when they are depleted at specific stages of persistent infection. Inflammatory monocytes contribute to the pathology of persistent salmonellosis and cluster with other cells in pathogen-containing granulomas. Depletion of inflammatory monocytes during the chronic phase of persistent salmonellosis causes regression of already established granulomas with resultant pathogen growth and spread in tissues. Thus, inflammatory monocytes promote granuloma-mediated control of persistent salmonellosis and may be key to uncovering new therapies for granulomatous diseases.


Subject(s)
Monocytes , Salmonella Infections , Animals , Granuloma , Mice , Receptors, CCR2
5.
Sci Adv ; 7(27)2021 06.
Article in English | MEDLINE | ID: mdl-34193410

ABSTRACT

Malaria parasite infection weakens colonization resistance against Salmonella enterica serovar (S.) Typhimurium. S. Typhimurium is a member of the Enterobacterales, a taxon that increases in abundance when the colonic microbiota is disrupted or when the colonic mucosa is inflamed. However, here, we show that infection of mice with Plasmodium yoelii enhances S. Typhimurium colonization by weakening host control in the upper GI tract. P. yoelii-infected mice had elevated gastric pH. Stimulation of gastric acid secretion during P. yoelii infection restored stomach acidity and colonization resistance, demonstrating that parasite-induced hypochlorhydria increases gastric survival of S. Typhimurium. Furthermore, blockade of P. yoelii-induced TNF-α signaling was sufficient to prevent elevation of gastric pH and enhance S. Typhimurium colonization during concurrent infection. Collectively, these data suggest that abundance in the fecal microbiota of facultative anaerobes, such as S. Typhimurium, can be increased by suppressing antibacterial defenses in the upper GI tract, such as gastric acid.


Subject(s)
Gastrointestinal Microbiome , Malaria , Animals , Feces/microbiology , Intestine, Small , Mice , Salmonella typhimurium/physiology
6.
Vet World ; 14(1): 222-229, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33642807

ABSTRACT

BACKGROUND AND AIM: Salmonella enterica causes enteric disease in mammals and may potentially be transmitted from marine turtles that shed the pathogen in the environment. Marine turtle-associated human salmonellosis is a potential public health concern in Grenada, as the island supports populations of leatherback turtles (Dermochelys coriacea), hawksbill turtles (Eretmochelys imbricata), and green turtles (Chelonia mydas) that interface with veterinarians and conservation workers, the local population, and the thousands of visitors that frequent the island yearly. To date, the prevalence of S. enterica has only been examined in a small subset of marine turtles in the Caribbean and no studies have been conducted in Grenada. The aim of this study was to quantify the prevalence of S. enterica in leatherback, hawksbill and green turtles in Grenada, characterize phenotypes and DNA profiles, and explore the potential risk to human health in the region. MATERIALS AND METHODS: A total of 102 cloacal swabs were obtained from nesting leatherback turtles and foraging hawksbill and green turtles. Samples were cultured on enrichment and selective media and isolates were phenotypically characterized using serotyping, pulsed-phase gel electrophoresis, and antibiotic susceptibility. Enrichment broths were additionally screened by polymerase chain reaction (PCR) using S. enterica-specific primers. RESULTS: S. enterica was cultured from 15/57 (26.3%) leatherback turtles, 0/28 hawksbill, and 0/17 green turtles. This included S. enterica serovars Montevideo, S. I:4,5,12:i:-, Salmonella Typhimurium, Salmonella Newport, S. I:6,7:-:-, and S. I:4,5,12:-:-. Five/15 leatherback turtles carried multiple serovars. Eight pulsotype groups were identified with multiple clustering; however, there was no clear association between pulsotype group and serotype profile. Five/71 isolates showed resistance to streptomycin or ampicillin. Twenty-one/57 leatherback turtles, 14/28 hawksbill turtles, and 8/17 green turtles tested positive for S. enterica by quantitative PCR. CONCLUSION: Nesting leatherback turtles actively shed S. enterica and poses a risk for zoonosis; however, the presence of viable pathogen in green and hawksbill species is unclear. These findings help elucidate the role of marine turtles as potential sources of zoonotic S. enterica and provide baseline data for one health research in Grenada and the wider Caribbean region.

7.
J Parasitol ; 107(2): 267-274, 2021 03 01.
Article in English | MEDLINE | ID: mdl-33784742

ABSTRACT

The hawksbill turtle Eretmochelys imbricata is a critically endangered species with a worldwide distribution. Limited information is available about the naturally occurring intestinal parasites of this species and what impact these parasites may have on the health of the hawksbill turtle. Diaschistorchis pandus was identified postmortem in 5 hawksbill turtles from Grenada, West Indies, using morphologic characterization. Sanger sequencing was performed for conserved ribosomal regions (5.8S, ITS2, 28S) and the mitochondrial cytochrome c oxidase subunit 1 gene (COI). Phylogenetic analysis of the 28S rRNA gene sequence data shows D. pandus clustering with other trematodes in the family Pronocephalidae, corroborating morphological classification. No genetic sequences have been previously reported for this trematode species, which has limited the collection of objective epidemiological data about this parasite of marine turtles.


Subject(s)
Trematoda/classification , Trematode Infections/veterinary , Turtles/parasitology , Animals , Autopsy/veterinary , DNA, Helminth/chemistry , DNA, Helminth/genetics , Endangered Species , Grenada , Intestine, Small/parasitology , Intestine, Small/pathology , Male , Phylogeny , RNA, Ribosomal, 28S/genetics , Trematoda/anatomy & histology , Trematoda/genetics , Trematoda/isolation & purification , Trematode Infections/parasitology
8.
Cell Host Microbe ; 28(6): 789-797.e5, 2020 12 09.
Article in English | MEDLINE | ID: mdl-33301718

ABSTRACT

The colonic microbiota exhibits cross-sectional heterogeneity, but the mechanisms that govern its spatial organization remain incompletely understood. Here we used Citrobacter rodentium, a pathogen that colonizes the colonic surface, to identify microbial traits that license growth and survival in this spatial niche. Previous work showed that during colonic crypt hyperplasia, type III secretion system (T3SS)-mediated intimate epithelial attachment provides C. rodentium with oxygen for aerobic respiration. However, we find that prior to the development of colonic crypt hyperplasia, T3SS-mediated intimate attachment is not required for aerobic respiration but for hydrogen peroxide (H2O2) respiration using cytochrome c peroxidase (Ccp). The epithelial NADPH oxidase NOX1 is the primary source of luminal H2O2 early after C. rodentium infection and is required for Ccp-dependent growth. Our results suggest that NOX1-derived H2O2 is a resource that governs bacterial growth and survival in close proximity to the mucosal surface during gut homeostasis.


Subject(s)
Citrobacter rodentium/growth & development , Citrobacter rodentium/metabolism , Cytochrome-c Peroxidase/physiology , Hydrogen Peroxide/metabolism , NADPH Oxidase 1/physiology , Anaerobiosis , Animals , Colon/microbiology , DNA, Bacterial , Feces/microbiology , Female , Germ-Free Life , Homeostasis , Host-Pathogen Interactions , Intestinal Mucosa/microbiology , Mice , Mice, Inbred C57BL , Mice, Knockout , RNA, Ribosomal, 16S , Specific Pathogen-Free Organisms , Type III Secretion Systems/physiology
9.
Rep Pract Oncol Radiother ; 25(6): 856-859, 2020.
Article in English | MEDLINE | ID: mdl-32982590

ABSTRACT

Jehovah's Witnesses are well-known in the medical community for their inability to accept blood products. Novel methods of treatment are often needed to avoid anemia and hematologic toxicity as inability to receive blood products may increase the risk of treatment related complications. We provide an overview of radiation treatment for Jehovah's Witness patients with an emphasis on bone marrow sparing strategies with intensity modulated radiation therapy (IMRT) to minimize hematologic toxicity.

10.
Cell Host Microbe ; 28(2): 273-284.e6, 2020 08 12.
Article in English | MEDLINE | ID: mdl-32668218

ABSTRACT

The clinical spectra of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) intersect to form a scantily defined overlap syndrome, termed pre-IBD. We show that increased Enterobacteriaceae and reduced Clostridia abundance distinguish the fecal microbiota of pre-IBD patients from IBS patients. A history of antibiotics in individuals consuming a high-fat diet was associated with the greatest risk for pre-IBD. Exposing mice to these risk factors resulted in conditions resembling pre-IBD and impaired mitochondrial bioenergetics in the colonic epithelium, which triggered dysbiosis. Restoring mitochondrial bioenergetics in the colonic epithelium with 5-amino salicylic acid, a PPAR-γ (peroxisome proliferator-activated receptor gamma) agonist that stimulates mitochondrial activity, ameliorated pre-IBD symptoms. As with patients, mice with pre-IBD exhibited notable expansions of Enterobacteriaceae that exacerbated low-grade mucosal inflammation, suggesting that remediating dysbiosis can alleviate inflammation. Thus, environmental risk factors cooperate to impair epithelial mitochondrial bioenergetics, thereby triggering microbiota disruptions that exacerbate inflammation and distinguish pre-IBD from IBS.


Subject(s)
Anti-Bacterial Agents/adverse effects , Diet, High-Fat/adverse effects , Dysbiosis/pathology , Energy Metabolism/physiology , Inflammatory Bowel Diseases/microbiology , Irritable Bowel Syndrome/microbiology , Animals , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Dysbiosis/chemically induced , Enterobacteriaceae/growth & development , Gastrointestinal Microbiome , Humans , Intestinal Mucosa/microbiology , Intestinal Mucosa/pathology , Leukocyte L1 Antigen Complex/metabolism , Mesalamine/therapeutic use , Mice , Mice, Inbred C57BL , Mitochondria/metabolism , PPAR gamma/agonists
11.
Contemp Clin Trials ; 91: 105977, 2020 04.
Article in English | MEDLINE | ID: mdl-32151753

ABSTRACT

A growing body of evidence demonstrates that home-based, multicomponent interventions can effectively reduce exposures to asthma triggers and decrease asthma symptoms. However, few of these studies have targeted adults. To address this and other research gaps, we designed and implemented a pragmatic randomized clinical trial, the Houston Home-based Integrated Intervention Targeting Better Asthma Control (HIITBAC) for African Americans, to assess the effectiveness of a home-based intervention to improve asthma control and quality of life in African-American adults-a population disproportionately affected by asthma. The primary goals were to help participants reduce allergens and irritants in their homes and better manage their disease through knowledge, improved medication use, and behavior change. HIITBAC had two groups: clinic-only and home-visit groups. Both groups received enhanced clinical care, but the home-visit group also received a detailed home assessment and four additional home visits spaced over roughly one year. We recruited 263 participants. Of these, 152 (57.8%) were recruited through electronic health record data, 51 (19.4%) through Emergency Medical Services data, and 60 (22.8%) through other efforts (e.g., emergency departments, community events, outreach). Seventy participants (26.6%) were lost to follow up, substantially more in the home-visit than in the clinic-only group. We describe the HIITBAC methodology and cohort, discuss lessons learned about recruitment and retention, and highlight adaptations we implemented to address these lessons.


Subject(s)
Asthma/ethnology , Asthma/therapy , Black or African American , House Calls/statistics & numerical data , Patient Education as Topic/organization & administration , Comorbidity , Emergency Service, Hospital/statistics & numerical data , Female , Humans , Longitudinal Studies , Male , Patient-Centered Care/organization & administration , Quality of Life , Research Design , Respiratory Function Tests , Self-Management , Severity of Illness Index
12.
PLoS Negl Trop Dis ; 14(1): e0007940, 2020 01.
Article in English | MEDLINE | ID: mdl-31961893

ABSTRACT

Bats can harbor zoonotic pathogens, but their status as reservoir hosts for Leptospira bacteria is unclear. During 2015-2017, kidneys from 47 of 173 bats captured in Grenada, West Indies, tested PCR-positive for Leptospira. Sequence analysis of the Leptospira rpoB gene from 31 of the positive samples showed 87-91% similarity to known Leptospira species. Pairwise and phylogenetic analysis of sequences indicate that bats from Grenada harbor as many as eight undescribed Leptospira genotypes that are most similar to known pathogenic Leptospira, including known zoonotic serovars. Warthin-Starry staining revealed leptospiral organisms colonizing the renal tubules in 70% of the PCR-positive bats examined. Mild inflammatory lesions in liver and kidney observed in some bats were not significantly correlated with renal Leptospira PCR-positivity. Our findings suggest that Grenada bats are asymptomatically infected with novel and diverse Leptospira genotypes phylogenetically related to known pathogenic strains, supporting the hypothesis that bats may be reservoirs for zoonotic Leptospira.


Subject(s)
Chiroptera/microbiology , Disease Reservoirs/microbiology , Leptospira/classification , Leptospirosis/veterinary , Animals , Disease Reservoirs/veterinary , Grenada , Kidney/microbiology , Kidney/pathology , Leptospira/genetics , Leptospira/isolation & purification , Leptospirosis/microbiology , Leptospirosis/pathology , Liver/microbiology , Liver/pathology , Phylogeny
13.
PLoS Pathog ; 15(7): e1007847, 2019 07.
Article in English | MEDLINE | ID: mdl-31306468

ABSTRACT

Salmonella exploit host-derived nitrate for growth in the lumen of the inflamed intestine. The generation of host-derived nitrate is dependent on Nos2, which encodes inducible nitric oxide synthase (iNOS), an enzyme that catalyzes nitric oxide (NO) production. However, the cellular sources of iNOS and, therefore, NO-derived nitrate used by Salmonella for growth in the lumen of the inflamed intestine remain unidentified. Here, we show that iNOS-producing inflammatory monocytes infiltrate ceca of mice infected with Salmonella. In addition, we show that inactivation of type-three secretion system (T3SS)-1 and T3SS-2 renders Salmonella unable to induce CC- chemokine receptor-2- and CC-chemokine ligand-2-dependent inflammatory monocyte recruitment. Furthermore, we show that the severity of the pathology of Salmonella- induced colitis as well as the nitrate-dependent growth of Salmonella in the lumen of the inflamed intestine are reduced in mice that lack Ccr2 and, therefore, inflammatory monocytes in the tissues. Thus, inflammatory monocytes provide a niche for Salmonella expansion in the lumen of the inflamed intestine.


Subject(s)
Intestinal Mucosa/metabolism , Intestinal Mucosa/microbiology , Monocytes/metabolism , Salmonella typhimurium/metabolism , Salmonella typhimurium/pathogenicity , Animals , Chemokine CCL2/deficiency , Chemokine CCL2/genetics , Chemokine CCL2/metabolism , Female , Host Microbial Interactions/genetics , Host Microbial Interactions/physiology , Humans , Inflammation/metabolism , Inflammation/microbiology , Inflammation/pathology , Intestinal Mucosa/pathology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Models, Biological , Monocytes/pathology , Nitric Oxide Synthase Type II/metabolism , Receptors, CCR2/deficiency , Receptors, CCR2/genetics , Receptors, CCR2/metabolism , Salmonella Infections, Animal/metabolism , Salmonella Infections, Animal/microbiology , Salmonella Infections, Animal/pathology , Salmonella typhimurium/genetics , Type III Secretion Systems/metabolism
14.
J Wildl Dis ; 55(4): 961-964, 2019 10.
Article in English | MEDLINE | ID: mdl-30896366

ABSTRACT

Snake fungal disease (ophidiomycosis) is an emerging infection of snakes caused by Ophidiomyces ophiodiicola. Little is known about mechanisms of this pathogen's transmission and its implications for conservation of wild snake populations. We report four cases with evidence of vertical transmission of O. ophiodiicola from dam to offspring.


Subject(s)
Dermatomycoses/veterinary , Infectious Disease Transmission, Vertical/veterinary , Onygenales/isolation & purification , Snakes/microbiology , Animals , Animals, Wild , Dermatomycoses/microbiology , Dermatomycoses/transmission , Ovoviviparity
15.
Acta Oncol ; 58(4): 491-498, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30676131

ABSTRACT

BACKGROUND: Up-front stereotactic radiosurgery (SRS) has been historically thought of as inadequate for brain metastases (BM) from newly diagnosed small cell lung cancer (SCLC). This study evaluates national practice patterns and clinical outcomes for BM from SCLC. MATERIAL AND METHODS: The National Cancer Database was queried (2004-2013) for patients with newly diagnosed metastatic SCLC receiving intracranial radiotherapy. Patients were grouped into three categories: upfront SRS, whole-brain radiotherapy (WBRT) alone, or WBRT with boost (SRS or fractionated radiotherapy). Statistics included temporal trend assessment by annual percent change (APC), logistic regression, exploratory Kaplan-Meier overall survival (OS) analysis without and with propensity matching, and Cox proportional hazards modeling. RESULTS: A total of 14,722 patients met selection criteria, of whom 487 (3.3%), 13,657 (92.8%), and 578 (3.9%) received upfront SRS, WBRT and WBRT with boost, respectively. Utilization of SRS showed a slight increasing trend from 2004 to 2013 (2.7-4.3%). In addition to socioeconomic factors, other variables associated with SRS use included diagnosis after 2010, treatment at academic centers, and residing in higher-educated regions. SRS was less often delivered to patients with node-positive disease (p < .05). On exploratory analysis, SRS cohort was observed to have a higher overall survival (OS) than WBRT-based groups (p < .001), namely in patients without extracranial metastases. CONCLUSIONS: Utilization of up-front SRS for SCLC BM has been increasing over time but is driven by socioeconomic disparities. Although there are likely numerous biases associated with the OS findings herein, further research is needed to validate this finding as well as the role of SRS on patients with brain metastases due to SCLC.


Subject(s)
Brain Neoplasms/mortality , Lung Neoplasms/mortality , Practice Patterns, Physicians' , Radiosurgery/mortality , Small Cell Lung Carcinoma/mortality , Aged , Brain Neoplasms/secondary , Brain Neoplasms/surgery , Female , Follow-Up Studies , Humans , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Male , Middle Aged , Retrospective Studies , Small Cell Lung Carcinoma/pathology , Small Cell Lung Carcinoma/surgery , Survival Rate , Treatment Outcome
16.
J Wildl Dis ; 54(1): 101-111, 2018 01.
Article in English | MEDLINE | ID: mdl-28982020

ABSTRACT

: Streptococcus phocae is a pathogen of marine mammals, although its pathogenicity remains poorly understood. Recovery of this bacterium from asymptomatic carriers suggests that it is an opportunistic pathogen. We investigated the role of S. phocae in naturally occurring disease and its significance as a pathogen based on postmortem investigations. Between 2007 and 2012, 1,696 whole carcasses, tissue samples, or both were submitted from the northeastern Pacific and Arctic Canada for diagnostic testing. Streptococcus phocae was cultured from phocids ( n=66), otariids ( n=12), harbor porpoises ( Phocoena phocoena; n=5), and sea otters ( Enhydra lutris; n=2). Pathologic manifestations of S. phocae-associated disease included localized, as well as systemic, inflammatory lesions with common findings of suppurative bronchopneumonia ( n=17) and bacteremia ( n=27). Lung lesions were frequently culture-positive for S. phocae, suggesting commensal colonization of the oropharynx with subsequent opportunistic infection of the respiratory tract during tissue injury, coinfection, immunosuppression, or other debilitating conditions. The presence of a positive spleen culture, and interpretations at necropsy and histopathology, were used to determine the presence of S. phocae bacteremia. Less frequent lesions that were culture positive for S. phocae included abscesses ( n=9), meningitis ( n=7), and cellulitis ( n=1). The majority of cases with S. phocae lesions featured pre-existing conditions that presumably contributed to some degree of debilitation or immunosuppression, including emaciation ( n=29), liver mercury accumulation ( n=29), trauma ( n=22), severe pulmonary or cardiovascular nematodiasis ( n=9), concurrent bacterial or viral infections ( n=8), or sarcocystosis ( n=6). These findings suggest that S. phocae could be characterized as an opportunistic pathogen, associated with debilitating conditions in stranded and rehabilitating marine mammals. Wildlife investigators can use these results to draw more definitive conclusions regarding positive S. phocae cultures during postmortem studies in marine mammals.


Subject(s)
Otters/microbiology , Phocoena/microbiology , Seals, Earless/microbiology , Streptococcus/classification , Streptococcus/isolation & purification , Animals , Arctic Regions , Canada , Female , Male , Retrospective Studies
17.
Oncotarget ; 8(30): 48671-48687, 2017 Jul 25.
Article in English | MEDLINE | ID: mdl-28415769

ABSTRACT

Defects in resolving kinetochore-microtubule attachment mistakes during mitosis is linked to chromosome instability associated with carcinogenesis as well as resistance to cancer therapy. Here we report for the first time that tumor suppressor p53-binding protein 1 (53BP1) is phosphorylated at serine 1342 (S1342) by Aurora kinase B both in vitro and in human cells, which is required for optimal recruitment of 53BP1 at kinetochores. Furthermore, 53BP1 staining normally localized on the outer kinetochore, extended to the whole kinetochore when it is merotelically-attached, in concert with mitotic centromere-associated kinesin. Kinetochore-binding of pS1342-53BP1 is essential for efficient resolving of merotelic attachment, a spontaneous kinetochore-microtubule connection error that usually causes aneuploidy. Consistently, loss of 53BP1 results in significant increase in lagging chromosome events, micronuclei formation and aneuploidy, due to the unresolved merotely in both cancer and primary cells, which is prevented by ectopic wild type 53BP1 but not by the nonphophorylable S1342A mutant. We thus document a novel DNA damage-independent function of 53BP1 in maintaining faithful chromosome segregation during mitosis.


Subject(s)
Aurora Kinase B/metabolism , Kinetochores/metabolism , Microtubules/metabolism , Mitosis , Tumor Suppressor p53-Binding Protein 1/metabolism , Aneuploidy , Chromosome Segregation , Humans , Mutation
18.
J Am Anim Hosp Assoc ; 52(1): 36-41, 2016.
Article in English | MEDLINE | ID: mdl-26606201

ABSTRACT

Clinical features of feline hepatocellular carcinoma (HCA) have been poorly characterized. In this retrospective study, we describe the signalment, clinical features, clinicopathologic parameters, imaging characteristics, hepatic mass size and lobe distribution, concurrent disorders, and survival in 19 cats with HCA. HCA is a rare neoplasm in elderly cats often associated with weight loss, hyporexia, and increased hepatic transaminase activities. Concurrent disorders (e.g., hyperthyroidism, inflammatory bowel disease, cholangiohepatitis, copper-associated hepatopathy) often confounded interpretation of clinical and clinicopathologic findings; 42% of HCA were incidentally identified. Although an abdominal mass was palpated in only 21% of cats, many cats had masses identified on ultrasonographic imaging with 47% having lesions >4 cm. Tumors were nearly equally distributed between right and left liver lobes, and two cats had HCA in multiple liver lobes. Median survival of eight cats diagnosed antemortem was 1.7 (0.6 to 6.5) yr. Median survival of six cats undergoing HCA surgical resection was 2.4 (1.0 to 6.5) yr with two cats still alive at time of manuscript submission. Following surgical resection, one cat treated with carboplatin survived 4 yr. Two cats with HCA diagnosed antemortem without surgical resection survived for 0.6 and 1 yr.


Subject(s)
Carcinoma, Hepatocellular/veterinary , Cat Diseases/pathology , Liver Neoplasms/veterinary , Animals , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Cat Diseases/mortality , Cats , Female , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Retrospective Studies
19.
Sci Rep ; 5: 14603, 2015 Oct 05.
Article in English | MEDLINE | ID: mdl-26434367

ABSTRACT

Childhood malaria is a risk factor for disseminated infections with non-typhoidal Salmonella (NTS) in sub-Saharan Africa. While hemolytic anemia and an altered cytokine environment have been implicated in increased susceptibility to NTS, it is not known whether malaria affects resistance to intestinal colonization with NTS. To address this question, we utilized a murine model of co-infection. Infection of mice with Plasmodium yoelii elicited infiltration of inflammatory macrophages and T cells into the intestinal mucosa and increased expression of inflammatory cytokines. These mucosal responses were also observed in germ-free mice, showing that they are independent of the resident microbiota. Remarkably, P. yoelii infection reduced colonization resistance of mice against S. enterica serotype Typhimurium. Further, 16S rRNA sequence analysis of the intestinal microbiota revealed marked changes in the community structure. Shifts in the microbiota increased susceptibility to intestinal colonization by S. Typhimurium, as demonstrated by microbiota reconstitution of germ-free mice. These results show that P. yoelii infection, via alterations to the microbial community in the intestine, decreases resistance to intestinal colonization with NTS. Further they raise the possibility that decreased colonization resistance may synergize with effects of malaria on systemic immunity to increase susceptibility to disseminated NTS infections.


Subject(s)
Gastrointestinal Microbiome/immunology , Malaria/microbiology , Plasmodium yoelii/physiology , Salmonella Infections/microbiology , Salmonella typhimurium/physiology , Animals , Cecum/immunology , Cecum/microbiology , Cecum/parasitology , Coinfection/immunology , Coinfection/microbiology , Coinfection/parasitology , Disease Susceptibility , Female , Intestinal Mucosa/immunology , Intestinal Mucosa/microbiology , Intestinal Mucosa/parasitology , Malaria/immunology , Mice, Inbred C57BL , Salmonella Infections/immunology , Salmonella Infections/parasitology
20.
J Avian Med Surg ; 28(2): 143-50, 2014 Jun.
Article in English | MEDLINE | ID: mdl-25115043

ABSTRACT

An adult male hyacinth macaw (Anodorhynchus hyacinthinus) that presented for acute onset nasal discharge and dyspnea had purulent discharge from the right naris and serosanguineous discharge from the left naris on physical examination. Results of a complete blood count revealed severe leukocytosis with a mature heterophilia. Computed tomography scans showed a large amount of soft-tissue attenuating material within the infraorbital sinus and associated diverticula. Aerobic culture results of the nasal discharge showed a mixed population of Staphylococcus intermedius and Pasteurella species, including Pasteurella pneumotropica; all isolated bacteria were susceptible to enrofloxacin. Clinical signs did not resolve over the course of 9 weeks of antibiotic treatment. The macaw died after cardiopulmonary arrest while hospitalized. At necropsy, a 2 x 2 x 3-cm firm, tan, friable, space-occupying mass surrounded by a thick exudate was present in the left preorbital diverticulum of the infraorbital sinus. The cranioventral one-third of the trachea contained a 4 x 0.5-cm white-yellow plaque. On histologic examination, the sinus mass was diagnosed as a nasal adenocarcinoma, and the tracheal plaque was caused by fungal infection, most likely with an Aspergillus species.


Subject(s)
Adenocarcinoma/veterinary , Bird Diseases/pathology , Nose Neoplasms/veterinary , Psittaciformes , Sinusitis/veterinary , Adenocarcinoma/diagnosis , Adenocarcinoma/pathology , Animals , Fatal Outcome , Male , Nose Neoplasms/diagnosis , Nose Neoplasms/pathology , Sinusitis/etiology , Sinusitis/pathology
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