Genetic Control of Resistance to Trypanosoma brucei brucei Infection in Mice

Trypanosoma brucei are extracellular protozoa transmitted to mammalian host by the tsetse fly. They developed several mechanisms that subvert host's immune defenses. Therefore analysis of genes affecting host's resistance to infection can reveal critical aspects of host-parasite interactions. Trypanosoma brucei brucei infects many animal species including livestock, with particularly severe effects in horses and dogs. Mouse strains differ greatly in susceptibility to T. b. brucei. However, genes controlling susceptibility to this parasite have not been mapped. We analyzed the genetic control of survival after T. b. brucei infection using CcS/Dem recombinant congenic (RC) strains, each of which contains a different random set of 12.5% genes of their donor parental strain STS/A on the BALB/c genetic background. The RC strain CcS-11 is even more susceptible to parasites than BALB/c or STS/A. In F2 hybrids between BALB/c and CcS-11 we detected and mapped four loci, Tbbr1-4 (Trypanosoma brucei brucei response 1–4), that control survival after T. b. brucei infection. Tbbr1 (chromosome 3) and Tbbr2 (chromosome 12) have independent effects, Tbbr3 (chromosome 7) and Tbbr4 (chromosome 19) were detected by their mutual inter-genic interaction. Tbbr2 was precision mapped to a segment of 2.15 Mb that contains 26 genes

Gastric obstruction secondary to metastatic breast cancer: a case report and literature review

<p>Abstract</p> <p>Introduction</p> <p>Gastrointestinal tract soft tissues metastasis is a well-known occurrence with invasive lobular breast cancer subtypes. Gastric involvement is more common, with reports of both diffuse and localized involvements. Usually, a gastric localized involvement presents as wall thickening with an appearance similar to that of a gastrointestinal stromal tumour; rarely does a localized metastatic deposit grow aggressively to present as a large tumour causing obstructive symptoms. Our case highlights one such unusual presentation in a patient presenting with non-specific gastrointestinal symptoms. To the best of our knowledge, there have been no previous reports on a similar presentation occurring from a localized metastasis.</p> <p>Case presentation</p> <p>A 65-year-old Caucasian woman awaiting an outpatient oral gastroduodenoscopy for symptoms of intermittent vomiting, epigastric pains and weight loss of six weeks’ duration presented acutely with symptoms of haematemesis and abdominal distension. An initial contrast-enhanced computed tomography scan showed a grossly dilated stomach with a locally advanced stenosing tumour mass at the pylorus. Our patient had a history of left mastectomy and axillary clearance followed by adjuvant endocrine therapy for an oestrogen receptor- and progesterone receptor-positive, grade 2, invasive lobular breast cancer. The oral gastroduodenoscopy confirmed the computed tomography findings; biopsies of the pyloric mass on immunohistochemistry stains were strongly positive for pancytokeratin and gross cystic disease fluid proteins, consistent with an invasive lobular breast cancer metastasis. She received a palliative gastrojejunal bypass and her adjuvant endocrine treatment was switched over to exemestane.</p> <p>Conclusion</p> <p>Our case highlights the aggressive behaviour of a localized gastric metastasis that is unusual and unexpected. Gastrointestinal symptomatology can be non-specific and, at times, non-diagnostic on conventional mucosal biopsies. A high index of clinical suspicion in patients with a previous history of invasive lobular breast cancer can aid in an early diagnosis and treatment. A combined treatment approach with chemoendocrine therapies achieves remission and improves patient survival.</p

Immunology and immunopathology of African trypanosomiasis

Major modifications of immune system have been observed in African trypanosomiasis. These immune reactions do not lead to protection and are also involved in immunopathology disorders. The major surface component (variable surface glycoprotein,VSG) is associated with escape to immune reactions, cytokine network dysfunctions and autoantibody production. Most of our knowledge result from experimental trypanosomiasis. Innate resistance elements have been characterised. In infected mice, VSG preferentially stimulates a Th 1-cell subset. A response of <FONT FACE=Symbol>gd</FONT> and CD8 T cells to trypanosome antigens was observed in trypanotolerant cattle. An increase in CD5 B cells, responsible for most serum IgM and production of autoantibodies has been noted in infected cattle. Macrophages play important roles in trypanosomiasis, in synergy with antibodies (phagocytosis) and by secreting various molecules (radicals, cytokines, prostaglandins,...). Trypanosomes are highly sensitive to TNF-alpha, reactive oxygen and nitrogen intermediates. TNF-alpha is also involved in cachexia. IFN-gamma acts as a parasite growth factor. These various elements contribute to immunosuppression. Trypanosomes have learnt to use immune mechanisms to its own profit. Recent data show the importance of alternative macrophage activation, including arginase induction. L-ornithine produced by host arginase is essential to parasite growth. All these data reflect the deep insight into the immune system realised by trypanosomes and might suggest interference therapeutic approaches.<br>Modificações importantes no sistema imune são observadas na tripanosomíase Africana. Essas reações imunológicas não protegem e estão envolvidas em distúrbios imunopatológicos. O principal componente de superfície (glicoproteína variante de superfície, VSG) está associado à evasão das respostas imune, às disfunções da rede de citocinas e à produção de autoanticorpos. Muitos de nossos conhecimentos resultam da tripanosomíase experimental. Componentes da imunidade inata estão sendo caracterizados. Em camundongos infectados, a VSG estimula preferencialmente células Th1. Uma resposta de <FONT FACE=Symbol>gd</FONT> e células T CD8 aos antígenos do tripanossoma foi observada em gado tripanotolerante. Um aumento em células B CD5, responsável por IgM sérica e produção de autoanticorpos, foi observado no gado infectado. Os macrófagos desempenham importantes funções na tripanosomíase, em sinergismo com anticorpos (fagocitose) e pela secreção de várias moléculas (radicais, citocinas, prostaglandinas). Tripanossomas são altamente sensíveis ao TNF-alfa, espécies reativas de oxigênio e nitrogênio. O TNF-alfa também está envolvido em caquexia. O IFN-gama atua como um fator de crescimento do parasita. Esses vários componentes contribuem para a imunossupressão. Os tripanossomas usam os mecanismos imunes para seu próprio benefício. Dados recentes mostram a importância da ativação alternativa de macrófagos, incluindo a indução pela arginase. A L-ornitina produzida pela arginase do hospedeiro é essencial para o crescimento do parasita. Todos esses dados mostram o envolvimento no sistema imune realizado pelos tripanossomas e sugerem a interferência de métodos terapêuticos