Patogénesis de la babesiosis bovina ocasionada por la babesia bigemina y alteraciones macro y microscópicas

Fifteen calves were inoculated with Babesia bigemine to study macroscopic and microscopic lesions In this one month experiment the calves were euthanatized and dissected every other day. The macroscopic findings inciuded yellowish icterus discoioration of the aponeurotic and subcutaneous tissue, petechial hemorrhages on serous surfaces, excess of penicardial, pleural and peritoneal fluid, which color turned from ambar to yellow reddish. These alterations were observed in the calves dissected at days, 6, 10, 12 and 14 P1. An increase in size of the parotid, mandibular, suprapharingeal, preescapular, mediastinic, splenic, mesentenic, prefemoral and renal lymph nodes was seen in the calves at days 4, 10, 12, 16, 18, 20, 22 and 24 P1. The spleen was three times its normal size in the calf dissected at day 12 P1. Microscopically vascular congestion and leukocyte margination were observed in all the tissues studied. Macrophages with hemosiderin, erythrophagocitosis, hyalin degeneration in arteries, lymphoid and reticular atrophy and hyperplasia were observed in the lymph nodes since day 6 P1, to day 30 PT. Similar lesions were present in the spleen, hemal lymph nodes and tonsiis. Portal lymphoid infiltration, severe leukocyte margination in hepatic veins and portal arteries were observed at days 24, 26, 28 and 30 P1. Kupffer cell hyperplasia was observed since day 6 PT and persisted during the experiment. Leukocyte margination in the central nervous system was evident since day 12 P1 until day 30 P1. Vascular congestion, edema and perivascular and peribronchiolar hemorrhages in the pulmonary tissue were observed from day 6 Pb to day 26 P1. Leukocyte margination, endothelial hyperplasia and perivascuiar and periglomerular lymphoid infiltration were observed in the kidneys since day 8 P1 until day 30 P1. Macroscopic and microscopic alterations in calves which suffered Babesiosis were described.Se inocularon 15 terneros con Babesia bigemina, para estudiar las alteraciones macro y microscópicas. Este experimento tuvo una duración de un mes. Los terneros fueron sacrificados cada tercer día. Los hallazgos macroscópicos consistieron en coloración amarilla de fascias y aponeurosis, hemorragias petequiales en serosas, exceso de líquido pericardíaco, pleural y peritoneal, cuya coloración varió desde ámbar hasta rojo amarillo, en los terneros sacrificados en los días 5, 10, 12 y 14 de post-inoculación. Los terneros sacrificados durante los días 4, 10, 12, 16, 18, 20, 22 y 24 presentaron aumento de tamaño de los ganglios linfáticos parotídeo, mandibular, suprafaríngeo, preescapular, mediastínico. esplénico, mesentérico, prefemoral y renal. El bazo se encontró aumentado hasta 3 veces su tamaño normal, lo cual ocurrió en el ternero sacrificado durante el día 12 post-inoculación. Microscópicamente se halló congestión vascular y marginación leucocitaria en todos los órganos. En los ganglios linfáticos se encontró hemosiderosis, eritrofagocitosis, degeneración hialina en arteriolas, atrofía e hiperplasia linfoide y reticular. Esto se observó desde el día 6 hasta el final del experimento, variando en intensidad de acuerdo con el tiempo y el parámetro estudiado. Cambios similares se presentaron en el bazo, ganglios hemolinfáticos y tonsilas. En el hígado se encontró infiltración linfocitaria periportal y marginación leucocitaria muy marcada en venas hepáticas terminales y arterias portales. Todo esto fue observado durante los días 2, 26, 28 y 30. La hiperplasia de las células de Kupffer se hizo evidente desde el día 6 de inoculación y permaneció notoria durante todo el estudio. La marginación leucocitaria en vasos del sistema nervioso se hizo notoria a partir del día 12 y persistió durante todo el experimento, pero variando en intensidad. La congestión y el edema pulmonar estuvieron presentes desde el día 6 hasta el 26 post-inoculación. La congestión, el edema y las hemorragias perivasculares y peribronquiales estuvieron presentes desde el día 6 hasta el 26 post-inoculación. En el riñón la marginación leucocitaria, hiperplasia endotelial e infiltración linfocitaria perivascuIar y periglomerular fueron evidentes desde el día 8 hasta el final del experimento. En este trabajo se demostraron alteraciones anatómicas e histológicas de terneros que padecieron la babesiosis.Ganado de doble propósito-Ganaderia doble proposit

Alteraciones hematológicas y clínicas en la babesiosis bovina ocasionada por la Babesia bigemina.

Se inocularon 15 terneros con Babesia bigemina para estudiar alteraciones en la temperatura corporal, hematología, médula ósea, hematocrito y hemoglobina. Este experimento tuvo una duración de un mes, los terneros fueron sacrificados cada tercer día. En la temperatura determinada tanto en la mañana como en la tarde, se observó ascenso notable en la fase aguda y luego se encontró descenso en la etapa crónica de la enfermedad. El hematocrito tuvo descenso marcado durante la fase aguda de la enfermedad, luego subió progresivamente hacia el final del estudio: alteraciones similares se hallaron en la hemoglobina. Los hemoparásitos aparecieron en la corriente sanguínea al cuarto día de inoculación y persistieron aunque en bajo porcentaje durante todo el experimento. En los días iniciales del experimento se observó un descenso marcado en el recuento leucocitario total, después de la fase aguda se observó un aumento en este tipo de células. Inicialmente se presentó un descenso en las células eritroides de la médula ósea, especialmente en rubricitos y metarrubricitos, después de la fase aguda se presentó ascenso en todas las células de la línea eritroide. Las células de la línea mieloide presentaron ascenso ligero, en este ascenso también se incluyó linfocitos y plasmocitos, hacia el final se observó descenso paulatino de este tipo de célulaGanado de leche-Ganadería lech

Host-Brucella interactions and the Brucella genome as tools for subunit antigen discovery and immunization against brucellosis

Vaccination is the most important approach to counteract infectious diseases. Thus, the development of new and improved vaccines for existing, emerging, and re-emerging diseases is an area of great interest to the scientific community and general public. Traditional approaches to subunit antigen discovery and vaccine development lack consideration for the critical aspects of public safety and activation of relevant protective host immunity. The availability of genomic sequences for pathogenic Brucella spp. and their hosts have led to development of systems-wide analytical tools that have provided a better understanding of host and pathogen physiology while also beginning to unravel the intricacies at the host-pathogen interface. Advances in pathogen biology, host immunology, and host-agent interactions have the potential to serve as a platform for the design and implementation of better-targeted antigen discovery approaches. With emphasis on Brucella spp., we probe the biological aspects of host and pathogen that merit consideration in the targeted design of subunit antigen discovery and vaccine development

Systems Biology Analysis of Brucella Infected Peyers Patch Reveals Rapid Invasion with Modest Transient Perturbations of the Host Transcriptome

Brucella melitensis causes the most severe and acute symptoms of all Brucella species in human beings and infects hosts primarily through the oral route. The epithelium covering domed villi of jejunal-ileal Peyer’s patches is an important site of entry for several pathogens, including Brucella. Here, we use the calf ligated ileal loop model to study temporal in vivo Brucella-infected host molecular and morphological responses. Our results document Brucella bacteremia occurring within 30 min after intraluminal inoculation of the ileum without histopathologic traces of lesions. Based on a system biology Dynamic Bayesian Network modeling approach (DBN) of microarray data, a very early transient perturbation of the host enteric transcriptome was associated with the initial host response to Brucella contact that is rapidly averted allowing invasion and dissemination. A detailed analysis revealed active expression of Syndecan 2, Integrin alpha L and Integrin beta 2 genes, which may favor initial Brucella adhesion. Also, two intestinal barrier-related pathways (Tight Junction and Trefoil Factors Initiated Mucosal Healing) were significantly repressed in the early stage of infection, suggesting subversion of mucosal epithelial barrier function to facilitate Brucella transepithelial migration. Simultaneously, the strong activation of the innate immune response pathways would suggest that the host mounts an appropriate protective immune response; however, the expression of the two key genes that encode innate immunity anti-Brucella cytokines such as TNF-a and IL12p40 were not significantly changed throughout the study. Furthermore, the defective expression of Toll-Like Receptor Signaling pathways may partially explain the lack of proinflammatory cytokine production and consequently the absence of morphologically detectable inflammation at the site of infection. Cumulatively, our results indicate that the in vivo pathogenesis of the early infectious process of Brucella is primarily accomplished by compromising the mucosal immune barrier and subverting critical immune response mechanisms.The open access fee for this work was funded through the Texas A&M University Open Access to Knowledge (OAK) Fund

Systems Biology Analysis of Gene Expression during In Vivo Mycobacterium avium paratuberculosis Enteric Colonization Reveals Role for Immune Tolerance

Survival and persistence of Mycobacterium avium subsp. paratuberculosis (MAP) in the intestinal mucosa is associated with host immune tolerance. However, the initial events during MAP interaction with its host that lead to pathogen survival, granulomatous inflammation, and clinical disease progression are poorly defined. We hypothesize that immune tolerance is initiated upon initial contact of MAP with the intestinal Peyer's patch. To test our hypothesis, ligated ileal loops in neonatal calves were infected with MAP. Intestinal tissue RNAs were collected (0.5, 1, 2, 4, 8 and 12 hrs post-infection), processed, and hybridized to bovine gene expression microarrays. By comparing the gene transcription responses of calves infected with the MAP, informative complex patterns of expression were clearly visible. To interpret these complex data, changes in the gene expression were further analyzed by dynamic Bayesian analysis, and genes were grouped into the specific pathways and gene ontology categories to create a holistic model. This model revealed three different phases of responses: i) early (30 min and 1 hr post-infection), ii) intermediate (2, 4 and 8 hrs post-infection), and iii) late (12 hrs post-infection). We describe here the data that include expression profiles for perturbed pathways, as well as, mechanistic genes (genes predicted to have regulatory influence) that are associated with immune tolerance. In the Early Phase of MAP infection, multiple pathways were initiated in response to MAP invasion via receptor mediated endocytosis and changes in intestinal permeability. During the Intermediate Phase, perturbed pathways involved the inflammatory responses, cytokine-cytokine receptor interaction, and cell-cell signaling. During the Late Phase of infection, gene responses associated with immune tolerance were initiated at the level of T-cell signaling. Our study provides evidence that MAP infection resulted in differentially regulated genes, perturbed pathways and specifically modified mechanistic genes contributing to the colonization of Peyer's patch

昭和20年代, 教室の日常と研究余話(第922回千葉医学会例会・第13回千葉精神科集談会)

<p>Unique MAA Arcs and Mechanistic Genes in Tight Junction Pathway.</p

Role of SPI-1 Secreted Effectors in Acute Bovine Response to Salmonella enterica Serovar Typhimurium: A Systems Biology Analysis Approach

Salmonella enterica Serovar Typhimurium (S. Typhimurium) causes enterocolitis with diarrhea and polymorphonuclear cell (PMN) influx into the intestinal mucosa in humans and calves. The Salmonella Type III Secretion System (T3SS) encoded at Pathogenicity Island I translocates Salmonella effector proteins SipA, SopA, SopB, SopD, and SopE2 into epithelial cells and is required for induction of diarrhea. These effector proteins act together to induce intestinal fluid secretion and transcription of C-X-C chemokines, recruiting PMNs to the infection site. While individual molecular interactions of the effectors with cultured host cells have been characterized, their combined role in intestinal fluid secretion and inflammation is less understood. We hypothesized that comparison of the bovine intestinal mucosal response to wild type Salmonella and a SipA, SopABDE2 effector mutant relative to uninfected bovine ileum would reveal heretofore unidentified diarrhea-associated host cellular pathways. To determine the coordinated effects of these virulence factors, a bovine ligated ileal loop model was used to measure responses to wild type S. Typhimurium (WT) and a ΔsipA, sopABDE2 mutant (MUT) across 12 hours of infection using a bovine microarray. Data were analyzed using standard microarray analysis and a dynamic Bayesian network modeling approach (DBN). Both analytical methods confirmed increased expression of immune response genes to Salmonella infection and novel gene expression. Gene expression changes mapped to 219 molecular interaction pathways and 1620 gene ontology groups. Bayesian network modeling identified effects of infection on several interrelated signaling pathways including MAPK, Phosphatidylinositol, mTOR, Calcium, Toll-like Receptor, CCR3, Wnt, TGF-β, and Regulation of Actin Cytoskeleton and Apoptosis that were used to model of host-pathogen interactions. Comparison of WT and MUT demonstrated significantly different patterns of host response at early time points of infection (15 minutes, 30 minutes and one hour) within phosphatidylinositol, CCR3, Wnt, and TGF-β signaling pathways and the regulation of actin cytoskeleton pathway

Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus.

BACKGROUND & AIMS: Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations. METHODS: We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls. RESULTS: We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9)). CONCLUSIONS: We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

Controlled release vaccines and methods of treating Brucella diseases and disorders

Methods and compositions for the treatment of Brucella induced diseases and disorders are disclosed herein. In preferred embodiments, the invention relates to vaccines. In additional embodiments, the invention relates to formulations capable of releasing said vaccines at a controlled rate of release in vivo. In further embodiments, the invention relates to modified strains of the bacteria Brucella melitensis and Brucella abortus. In still further embodiments, the invention relates to compositions that do not induce clinical symptoms or splenomegaly in a subject receiving said compositions.U