No description available.

The development of different organs and tissues along the gastrointestinal tract, including the pancreas, depends on signalling between the endoderm and the adjacent mesenchyme. The Nkx gene Bapx1 is involved in spatial control of organ-positioning in the spleno-pancreatic region, and deficiency in this gene results in unacceptable proximity of the splenic mesenchyme to the pancreas. This permits agitating signals from the splenic mesenchyme to induce an in vivo (and in vitro) transformation of pancreatic epithelium to a cystic structure with gut like features. Also, wild type splenic mesenchyme is competent to induce a similar transformation. These findings illustrate the importance for strict control of organ positioning during spleno-pancreatic development. Several growth factors and receptors involved in pancreatic development are activated by protease processing. Some of these growth factors have been implicated as substrates for members of the A Disintegrin And Metalloprotease (ADAM) family. The ADAMs 9, 10, and 17 are expressed during pancreatic development and in the adult pancreas, suggesting a possible role for these ADAMs in pancreatic development and function. Animal model systems are widely used to investigate gene function during development and disease. However, spatial, molecular, and quantitative phenotype screening in animals is a time consuming effort. Optical Projection Tomography is a 3-dimensional imaging technique that, in combination with improvements in sample preparation and computer processing, can be used to visualize and quantify characteristics of intact adult mouse organs such as the total β-cell content in the pancreas.

African trypanosomes are protozoan blood parasites that infect both humans and livestock. BALB/c mice are highly susceptible to experimental infections by Trypanosoma congolense while C57BL/6 mice are relatively resistant, as measured by degree and pattern of parasitemia and survival time. Rapid death observed in highly susceptible BALB/c mice is due to a systemic inflammatory response syndrome (SIRS). A small subset of pathogenic, MHC class II-restricted CD4+ T cells, activated during the course of T. congolense infections, mediates early mortality in infected highly susceptible BALB/c mice via excessive synthesis of the cytokine IFN-gamma. Since these pathogenic T cells are matrixadherent, they could be distinguished from conventional Th1 cells. There is a possibility that this subpopulation of T cells has unique surface markers.<p> The complement system is highly activated in African trypanosomiasis, leading to persistent hypocomplementemia. Amplification of the alternative pathway of complement is faster in BALB/c mice than in C57BL/6 mice and the degradation of complement component C3b to complement component C3d, during the amplification of the alternative pathway of complement, proceeds faster in BALB/c than in C57BL/6 mice (Ogunremi et al., 1993). T. congolense-infected BALB/c mice have more immune complexes containing trypanosomal variant surface glycoprotein (VSG) than C57BL/6 mice in their plasma (Pan & Tabel, unpublished). T. congolense-infected BALB/c mice might have more VSG-C3d immune complexes than infected C57BL/6 mice. The receptor for complement component C3d is the cell surface molecule CR2, also referred to as CD21. It is known that CR2 is widely expressed on B lymphocytes and follicular dendritic cells. There is also some evidence that CR2 is expressed on a subpopulation of activated T cells. Binding of VSG-C3d immune complexes to the complement receptor CR2 might costimulate the CR2+ T cells to produce IFN-ã. I hypothesize that IFN-ã-producing T cells in T. congolense-infected BALB/c mice are CR2+ and that the CR2+ T cells increase in numbers in experimental murine T. congolense infections.<p> Kinetic studies were carried out by staining spleen cells of T. congolense-infected BALB/c mice for the presence of CR2 on T cells (CD3+ cells). Total numbers of spleen cells showed a 5-fold increase with progressive T. congolense infections. The total numbers of T cells in the spleen showed a 7-fold increase at day 8 post infection. The total numbers of CR2+ T cells in the spleen showed a 3 to 7-fold increase with progressive infection. Parallel studies on B lymphocytes (CD19+ cells) showed that absolute numbers of B cells in the spleen had a 5 to 6-fold increase with progressive infection. Absolute numbers of CR2+ B cells in the spleen showed a 4-fold increase at day 7 post infection. The total numbers of CR2+ cells in the spleen showed an increase while the mean numbers of CR2 molecules per cell showed a reduction with progressive infection.<p> These results show that CR2+ T cells in the spleen increase in numbers with progressive T. congolense infections in BALB/c mice. I suggest that CD4+CR2+ T cells might play a role in the pathogenesis of T. congolense infections.

African trypanosomes are protozoan blood parasites that infect both humans and livestock. BALB/c mice are highly susceptible to experimental infections by Trypanosoma congolense while C57BL/6 mice are relatively resistant, as measured by degree and pattern of parasitemia and survival time. Rapid death observed in highly susceptible BALB/c mice is due to a systemic inflammatory response syndrome (SIRS). A small subset of pathogenic, MHC class II-restricted CD4+ T cells, activated during the course of T. congolense infections, mediates early mortality in infected highly susceptible BALB/c mice via excessive synthesis of the cytokine IFN-gamma. Since these pathogenic T cells are matrixadherent, they could be distinguished from conventional Th1 cells. There is a possibility that this subpopulation of T cells has unique surface markers.<p> The complement system is highly activated in African trypanosomiasis, leading to persistent hypocomplementemia. Amplification of the alternative pathway of complement is faster in BALB/c mice than in C57BL/6 mice and the degradation of complement component C3b to complement component C3d, during the amplification of the alternative pathway of complement, proceeds faster in BALB/c than in C57BL/6 mice (Ogunremi et al., 1993). T. congolense-infected BALB/c mice have more immune complexes containing trypanosomal variant surface glycoprotein (VSG) than C57BL/6 mice in their plasma (Pan & Tabel, unpublished). T. congolense-infected BALB/c mice might have more VSG-C3d immune complexes than infected C57BL/6 mice. The receptor for complement component C3d is the cell surface molecule CR2, also referred to as CD21. It is known that CR2 is widely expressed on B lymphocytes and follicular dendritic cells. There is also some evidence that CR2 is expressed on a subpopulation of activated T cells. Binding of VSG-C3d immune complexes to the complement receptor CR2 might costimulate the CR2+ T cells to produce IFN-ã. I hypothesize that IFN-ã-producing T cells in T. congolense-infected BALB/c mice are CR2+ and that the CR2+ T cells increase in numbers in experimental murine T. congolense infections.<p> Kinetic studies were carried out by staining spleen cells of T. congolense-infected BALB/c mice for the presence of CR2 on T cells (CD3+ cells). Total numbers of spleen cells showed a 5-fold increase with progressive T. congolense infections. The total numbers of T cells in the spleen showed a 7-fold increase at day 8 post infection. The total numbers of CR2+ T cells in the spleen showed a 3 to 7-fold increase with progressive infection. Parallel studies on B lymphocytes (CD19+ cells) showed that absolute numbers of B cells in the spleen had a 5 to 6-fold increase with progressive infection. Absolute numbers of CR2+ B cells in the spleen showed a 4-fold increase at day 7 post infection. The total numbers of CR2+ cells in the spleen showed an increase while the mean numbers of CR2 molecules per cell showed a reduction with progressive infection.<p> These results show that CR2+ T cells in the spleen increase in numbers with progressive T. congolense infections in BALB/c mice. I suggest that CD4+CR2+ T cells might play a role in the pathogenesis of T. congolense infections.

Thesis--Helsinki. / Includes bibliographical references.

Thesis (M.S.)--University of Delaware, 2009. / Principal faculty advisor: Calvin L. Keeler, Jr., Dept. of Animal & Food Sciences. Includes bibliographical references.

Pancreatic pseudocysts are a complication of acute or chronic pancreatitis or result from blunt trauma to the pancreas. It is a localized fluid collection around the pancreas surrounded by a wall of fibrous tissue or inflammation. We present a case of a 56-years old male who presented with abdominal pain and sepsis due to spontaneous rupture of the hemorrhagic pancreatic cyst into the peritoneal cavity and spleen. 56-years old male with medical history of gastroesophageal reflux disease presented with epigastric and left upper quadrant intermittent abdominal pain. Patient denied fever, chills, nausea, and vomiting, family history of pancreatic cancer, anticoagulation use, gallstones, alcohol intake and prior history of pancreatitis. On admission, vitals were B.P 137/82, Pulse 102, RR 16, O2 saturation 92% on room air. Physical exam was significant for left upper quadrant and epigastric tenderness. Labs were lipase 230, amylase 112, lactate 0.7, wbc 7.0, hemoglobin of 15.2 and triglyceride levels were 189mg/dl. Computed tomography (CT) abdomen showed acute pancreatitis and a 4.5 x 4.4 x 2.8 cm cystic lesion between the tail of the pancreas and splenic hilum. Ultrasound of the abdomen showed normal gallbladder with no evidence of biliary ductal dilatation. Magnetic resonance cholangiopancreatography (MRCP) abdomen showed 4.3 cm walled off, possibly hemorrhagic fluid collection, between the spleen and the pancreas. Patient had normal CA-19 level. Patient was evaluated by general surgery who recommended conservative management with repeat CT in 6 weeks with possible pancreatectomy and removal of mass if not resolved. Patient was readmitted 3 days after discharge with worsening abdominal pain and sepsis. Physical exam was significant for epigastric and left upper quadrant tenderness without guarding or rebound. Labs showed lactate 3.4, wbc 11.3, hgb 12.1 and lipase 600. Repeat CT scan showed rupture of the hemorrhagic pancreatic cyst with possible extravasation and enlarged spleen with perisplenic and subcapsular blood represent splenic infarcts. Repeat MRCP confirmed CT findings. Patient was planned for splenectomy and distal pancreatectomy. Most pancreatic pseudocysts resolve spontaneously [1]. Bleeding, infection, rupture, pseudoaneurysm, splenic and biliary complications and portal hypertension are some of the complications if left untreated. Hemorrhage into the pancreatic pseudocyst is a rare complication with a reported incidence of 10-30% with a high mortality rate (40%). Bleeding most commonly involves splenic artery (30–50%), followed by the gastroduodenal artery (17%) and pancreaticoduodenal arteries (11%) [2]. Diagnosis is made by ultrasound, CT scan, MRI or ERCP. Treatment involves either percutaneous drainage, or endoscopic or surgical approach. Spontaneous rupture into the peritoneal cavity is a rare life threatening complication requiring immediate surgical intervention. This case highlights the early recognition of complications of ruptured pancreatic pseudocyst to prevent fatal consequences. References: 1: Lerch MM, Stier A, Wahnschaffe U, Mayerle J: Pancreatic Pseudocysts: Observation, Endoscopic Drainage, or Resection. Deutsches Ärzteblatt International 2009, 106:614-621.10.3238/arztebl.2009.0614. 2: Novacic K1, Vidjak V, Suknaic S, Skopljanac A: Embolization of a large pancreatic pseudoaneurysm converted from pseudocyst (hemorrhagic pseudocyst). JOP 2008, 9:317-21. joplink.net/prev/200805/13.html

Adult female guinea pigs received subcutaneous implants of diethylstilbestrol-cholestrol pellets which produced splenomegaly and increased numbers of splenic Kurloff cells. Latex spheres subsequently injected intravenously were not phagocytized by Kurloff cells within the lungs and spleen as examined with the electron microscope. This is considered as evidence that Kurloff cells are probably not phagocytic. The origin of these cells is discussed.

Currently, the intensive chemotherapy remains the first line treatment for B cell acute lymphoblastic leukemia (B-ALL). Although these regimens have significantly improved patient outcomes, their use is associated with debilitating morbidities and fatal relapses, highlighting the great need in new agents that target essential survival signals in leukemia. Thus, the overall goal of my project was to gain insights into the signaling abnormalities that regulate aberrant proliferation and survival of B-ALL cells in an effort to identify novel targets in this malignancy. This study demonstrated that pre-B cell receptor (pre-BCR)-independent spleen tyrosine kinase (SYK) activity was required for the survival and proliferation of a p53-/-PrkdcSCID/SCID mouse model of B-ALL. I extended this discovery to human disease, demonstrating that SYK was activated in primary B-ALL, independent of the pre-BCR expression. The small molecule SYK inhibitor fostamatinib (fosta) significantly attenuated proliferation of 79 primary diagnostic B-ALL samples at clinically achievable concentrations. Importantly, fosta treatment reduced dissemination of engrafting B-ALL cells into the spleen, liver, kidney and central nervous system (CNS) in a NOD.Prkdcscid/scidIl2rgtm1Wjl/SzJ xenotransplant model of B-ALL. Analysis of signaling abnormalities using a high-throughput phospho-flow cytometry platform demonstrated that pediatric and adult B-ALL samples exhibit variable basal activation of BCR, iii PI3K/AKT/mTOR, MAPK and JAK/STAT pathways. Importantly, we identified that fosta-mediated inhibition of SYK, PLC2, CRKL and EIF4E phosphorylation in B-ALL was predictive of its anti-leukemic activity, and was distinct from the cellular actions of other small molecule inhibitors of key nodal signaling pathways. Examination of molecular mechanism of fosta action by gene expression profiling revealed transcriptional effects of fosta treatment that included, most notably, potent inhibition of pathways involved in lymphocyte activation and inflammation. In conclusion, this study demonstrates that SYK signaling is crucial for B-ALL survival and provides detailed characterization of cellular and molecular mechanisms of fosta action in B-ALL. These data argue in favor of testing small molecule SYK inhibitors in pediatric and adult B-ALL.

O hemangiossarcoma é uma neoplasia maligna de origem endotelial vascular de ocorrência comum em cães. Nessa espécie, o órgão primário mais acometido é o baço. O hemangiossarcoma de partes moles em cães é caracterizado por ter um comportamento biológico muito agressivo e metástases, principalmente para o pulmão e fígado, são frequentes e ocorrem de maneira rápida no início do curso da doença. O óbito ocorre na maioria dos casos devido a hemorragia interna aguda secundária à ruptura do tumor e/ou devido ao processo metastástico. A cirurgia continua a ser o principal método de tratamento para quase todos os cães com hemangiossarcoma, mas a quimioterapia adjuvante é indicada em razão do alto índice metastático e do prognóstico ruim associado com o procedimento cirúrgico sozinho. Um estudo retrospectivo foi realizado para determinar o tempo de sobrevida e potenciais fatores de risco em cães diagnosticados com hemangiossarcoma visceral. Prontuários de 42 cães foram revisados. Dados como idade e peso no momento do diagnóstico, raça, sexo, localização do tumor, estágio clínico da doença, tipo de tratamento, e tempo mediano de sobrevida foram analisados. Vinte e três cães foram tratados apenas com cirurgia, enquanto que 19 cães foram tratados com cirurgia e quimioterapia adjuvante. Houve diferença estatística na sobrevida dos cães tratados com cirurgia e Doxorrubicina (274 dias) em comparação com cães tratados apenas com cirurgia (66 dias). Cães com hemangiossarcoma esplênico tiveram um tempo mediano de sobrevida mais longo do que os cães com hemangiossarcoma localizados em outros sítios primários e com metástase (274 versus 117 versus 38 dias, respectivamente, p = 0,013). O tempo mediano global de sobrevida para esses 42 cães foi de 237 dias, e a taxa de sobrevida de um ano foi estimada em 26,32%. Conclui-se que a localização primária do hemangiossarcoma teve associação com o prognóstico e que o uso da Doxorrubicina após o tratamento cirúrgico aumentou a sobrevida dos cães diagnosticados com essa doença. Neste estudo, o estadiamento clínico dos cães não influenciou o prognóstico / Hemangiosarcoma is a very common canine neoplasm of vascular endothelial origin. In the dog, the most frequent primary site for hemangiosarcoma is the spleen. Typically, canine hemangiosarcoma has a very aggressive biologic behavior with metastases, especially to lung and liver, occurring early in the course of the disease. In the majority of cases, death is related to acute hemoabdomen secondary to tumor rupture and/or metastases. Surgery remains the main method of treatment for most dogs with this type o cancer, but adjuvant chemotherapy is highly recommended due to the high risk of metastasis and the poor outcome associated with surgery alone. A retrospective study was performed to determine survival times and potential risk factors in dogs diagnosed with visceral hemangiosarcoma. Medical records of 42 dogs were reviewed. Age and baseline weight at the time of diagnosis, breed, sex, tumor location, clinical stage of the disease, treatment type and median survival time were evaluated. Twenty-three dogs were treated with surgery alone, while 19 dogs were treated with surgery and adjuvant chemotherapy. There was significant difference in survival between dogs treated with surgery alone (66 days) and with surgery followed by Doxorubicin (274 days). Dogs with splenic hemangiosarcoma had a longer median survival time than dogs with hemangiosarcoma of other sites, and with metastasis (274 versus 117 versus 38 days, respectively, p = 0,013). The overall median survival time for these 42 dogs was 237 days, and the one-year survival rate was estimated to be 26.32%. In conclusion, primary tumor location was associated with prognosis and the addition of doxorubicin after surgery did improve survival. In this study, clinical stage had no association with prognosis