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Sample records for thrombocytopenic purpura targeting

  1. Idiopathic thrombocytopenic purpura (ITP)

    MedlinePLUS

    Immune thrombocytopenic purpura; ITP; Immune thrombocytopenia ... ITP occurs when certain immune system cells produce antibodies against platelets. Platelets help your blood clot by clumping together to plug small holes in damaged ...

  2. Genotype and Phenotype Correlation in Hereditary Thrombotic Thrombocytopenic Purpura (Upshaw-Schulman Syndrome)

    ClinicalTrials.gov

    2015-09-01

    Thrombotic Thrombocytopenic Purpura; Congenital Thrombotic Thrombocytopenic Purpura; Familial Thrombotic Thrombocytopenic Purpura; Thrombotic Thrombocytopenic Purpura, Congenital; Upshaw-Schulman Syndrome

  3. Drug-induced thrombocytopenic purpura

    PubMed Central

    Sathiasekar, Anisha Cynthia; Deepthi, D. Angeline; Sathia Sekar, G. Suresh

    2015-01-01

    Drug-induced thrombocytopenic purpura is a skin condition result from a low platelet count due to drug-induced anti-platelet antibodies caused by drugs. Drug-induced thrombocytopenic purpura should be suspected when a patient, child or adult, has sudden, severe thrombocytopenia. Drug-induced thrombocytopenic purpura is even more strongly suspected when a patient has repeated episodes of sudden, severe thrombocytopenia PMID:26538982

  4. Thrombotic thrombocytopenic purpura in southeastern New England.

    PubMed

    Crowley, J P; Zaroulis, C G; O'Shea, P A; Clark, D D

    1983-05-01

    Eight patients with thrombotic thrombocytopenic purpura (TTP) originating within a 25-mile radius had their conditions diagnosed in a three-year period at a community teaching hospital in southeastern New England. In the preceding ten years, only one case of TTP had occurred in the same hospital. A niece-uncle relationship was present in two patients, and lymphocyte typing showed that they both shared an HLA haplotype. In the remaining patients, no social, familial, or environmental connection was established. Three patients died, all of whom were female. Six patients received exchange plasmapheresis with excellent responses in five. Autopsies in the three fatal cases showed widespread organ involvement with TTP but did not disclose evidence of any common underlying disease. This unusual occurrence should alert physicians to the possibility of localized outbreaks of TTP and the necessity of considering this diagnosis in all patients with unexplained thrombocytopenia. PMID:6383244

  5. [Pregnancy and labor in idiopathic thrombocytopenic purpura].

    PubMed

    Tampakoudis, P; Billi, H; Tantanassis, T; Kalachanis, I; Garipidou, B; Sinakos, Z; Mantalenakis, S

    1995-10-01

    Clinical data from eight pregnant women with idiopathic thrombocytopenic purpura (ITP) were retrospectively analyses. The mean age of the women was 28.2 years. Five women underwent splenectomy during childhood. The lowest maternal platelet count observed ranged from 8000 to 88000/mm3. Genital bleeding occurred in only one case. Treatment was based on administration of corticosteroids with or without human-pooled immunoglobulins. Caesarian section was performed in all cases. Six newborns were healthy and had a successful subsequent course. Two infants died, one in utero because of abruptio placentae and the other one 1 month post partum because of a cerebral haematoma. After a mean follow-up of eighteen months, thrombocytopenia is still present in two women, despite the continuous treatment. In conclusion, ITP rather rarely coincides with pregnancy. Treatment is usually successful for the mother but the risk for the fetus remains considerably high. PMID:8543133

  6. [Splenic embolization therapy of idiopathic thrombocytopenic purpura].

    PubMed

    Ji, S Q; Huang, Z Y; Qu, G L

    1991-11-01

    21 patients with chronic idiopathic thrombocytopenic purpura (ITP) and 3 patients with Evan's syndrome underwent partial splenic embolization (PSE). 22 patients underwent PSE once, while 2 patients were treated twice, thus a total of 26 procedures were carried out. Follow-up 3 months after embolization was available in all the 24 patients for their response to embolization therapy. 16 patients (67%) achieved complete remission (platelets greater than 100 x 10(9)/L) and 4 (17%) partial remission (platelets greater than 84 x 10(9)/L) after splenic embolization. A total efficacy rate of 83% was observed. This response to embolization after transcatheter vessel occlusion 3 months after is similar to the reported results of splenectomy. Not only may the morbidity and mortality associated with surgical splenectomy be avoided, but also the noninfarcted spleen may continue to provide immunologic functions. The most important experience in this series, however, was the emphasis on partial (60-70%) rather than total splenic arterial embolization. The sequestration site of platelets was associated with the outcome of splenic embolization. More splenic sequestration sites were found in responders, to the therapy. PMID:1815871

  7. Pulmonary Endarterectomy in a Patient with Immune Thrombocytopenic Purpura

    PubMed Central

    Y?ld?zeli, Bedrettin; Yanarta?, Mehmed; Keskin, Sibel; Atagündüz, I??k; Alt?nay, Ece

    2015-01-01

    Immune thrombocytopenic purpura (ITP) patients are at high risk for bleeding complications regarding surgeries involving cardiopulmonary bypass. We report an ITP patient with chronic thromboembolic pulmonary hypertension who underwent uncomplicated pulmonary endarterectomy with receiving postoperative intravenous immunoglobulin (IVIG) therapy. The positive outcome of this case may suggest that pulmonary endarterectomy surgery is performed safely for ITP patients. PMID:26090264

  8. Genetics Home Reference: Thrombotic thrombocytopenic purpura

    MedlinePLUS

    ... purpura also results from a reduction in ADAMTS13 enzyme activity; however, people with the acquired form do not ... activity of the enzyme. A lack of ADAMTS13 enzyme activity disrupts the usual balance between bleeding and clotting. ...

  9. Immune Thrombocytopenic Purpura Presenting as Unprovoked Gingival Hemorrhage: a Case Report

    PubMed Central

    Bal, Mehmet V; Koyuncuoglu, Cenker Z; Saygun, I??l

    2014-01-01

    Immune thrombocytopenic purpura is an autoimmune disease characterized by auto-antibody induced platelet destruction and reduced platelet production, leading to low blood platelet count. In this case report, the clinical diagnose of a patient with immune thrombocytopenic purpura and spontaneous gingival hemorrhage by a dentist is presented. The patient did not have any systemic disease that would cause any spontaneous hemorrhage. The patient was referred to a hematologist urgently and her thrombocyte number was found to be 2000/?L. Other test results were in normal range and immune thrombocytopenic purpura diagnose was verified. Then hematological treatment was performed and patient’s health improved without further problems. Hematologic diseases like immune thrombocytopenic purpura, in some cases may appear firstly in the oral cavity and dentists must be conscious of unexplained gingival hemorrhage. In addition, the dental treatment of immune thrombocytopenic purpura patients must be planned with a hematologist. PMID:25317211

  10. Mechanisms of action of therapeutics in idiopathic thrombocytopenic purpura.

    PubMed

    Cines, Douglas B; McKenzie, Steven E; Siegel, Don L

    2003-12-01

    Idiopathic thrombocytopenic purpura (ITP) is a common immune disorder caused by platelet-reactive autoantibodies. Antibody-coated platelets are cleared more rapidly from the circulation, often in the spleen, than they can be replaced by compensatory stimulation of platelet production in the bone marrow. In some patients, platelet production is depressed as well. ITP in adults does not generally remit spontaneously, and most patients require treatment to prevent bleeding at one time or another. Therapy with corticosteroids, danazol, intravenous immune globulin, anti-D antibody, and several other agents inhibits clearance of the antibody-coated platelets but is rarely curative. Most patients will sustain a hemostatic response after splenectomy, although relapses may occur at any time. Patients may be more responsive to these same modalities after splenectomy, but treatment with an immunosuppressant that inhibits T- and B-cell function and cooperation, including azathioprine, cyclophosphamide, cyclosporine, mycophenolate mofetil, or anti-CD20, may be required. Antiviral therapy is useful in patients with HIV or hepatitis C infection, but no consensus has been reached as to the efficacy of antibiotics to eradicate Helicobacter pylori. Promising results have been seen in several patients treated with a modified thrombopoietin. It may be possible to design therapeutics that exploit the apparent restricted immunoglobulin gene usage by antiplatelet antibodies, perhaps in the form of engineered anti-idiotypic antibodies or other compounds that specifically target autoantibody-producing B cells. Rationale therapy awaits a more thorough understanding of autoantibody production. PMID:14668641

  11. A Case of Immune Thrombocytopenic Purpura After Rabies Vaccination.

    PubMed

    Fulbright, Joy M; Williams, Sarah E; Pahud, Barbara A

    2015-10-01

    We describe a case of immune thrombocytopenic purpura (ITP) occurring 15 days after the first dose of a 4-dose rabies vaccination series. ITP is thought to be an immune-mediated process triggered by an infection or toxin. There is little evidence in the literature beyond case reports of an association of ITP with vaccines other than with the measles, mumps, and rubella vaccine. This is the third reported case of ITP associated with rabies vaccination. Because of the rare occurrence of this adverse event relative to the severity of rabies infection, the benefits of rabies vaccination, when indicated, outweigh the low and possible risk of ITP. PMID:26165405

  12. Intrahepatic splenosis after splenectomy performed for idiopathic thrombocytopenic purpura

    PubMed Central

    Tokta?, Osman; Yavuz, Alpaslan; ?liklerden, Ümit; Y?lmaz, Deniz; Bayram, ?rfan

    2015-01-01

    The term splenosis describes autotransplantation or implantation of ectopic splenic tissue within the abdominal cavity or in any other unusual body compartment. In addition to the diagnostic dilemma it causes, splenosis may also lead to persistence or recurrence of hematologic dysfunctions by its preserved immune activity especially in cases of splenectomy due to hematologic indications. Herein, we present a 40-year-old female who had splenectomy for idiopatic thrombocytopenic purpura, and was identified to have splenic tissue within left lobe of the liver during further assessment of ongoing thrombocytopenia.

  13. A report of disseminated adenocarcinoma presenting as thrombotic thrombocytopenic purpura

    PubMed Central

    Alonso, Joaquín Valle; Fonseca, Javier; Lopera, Elisa Lopera; Aguayo, Miguel Ángel; Montes, Yelda Hernandez; Llamas, Jose Carlos

    2011-01-01

    Thrombotic microangiopathies (TMAs) represent a heterogeneous group of diseases characterized by a microangiopathic hemolytic anemia, peripheral thrombocytopenia, and organ failure of variable severity. TMAs encompass thrombotic thrombocytopenic purpura (TTP), typically characterized by fever, central nervous system manifestations and hemolytic uremic syndrome (HUS), in which renal failure is the prominent abnormality. In patients with cancer TMAs may be related to various antineoplastic drugs or to the malignant disease itself. The reported series of patients with TMAs directly related to cancer are usually heterogeneous, retrospective, and encompass patients with hematologic malignancies with solid tumors or receiving chemotherapy, each of which may have distinct presentations and pathophysiological mechanisms. Patients with disseminated malignancy who present with microangiopathic hemolytic anemia and thrombocytopenia may be misdiagnosed as thrombotic thrombocytopenic purpura (TTP) Only a few cases of TTP secondary to metastatic adenocarcinoma are known in the literature. We present a case of a 34-year-old man with TTP syndrome secondary to metastatic small-bowel adenocarcinoma. Patients with disseminated malignancy had a longer duration of symptoms, more frequent presence of respiratory symptoms, higher lactate dehydrogenase levels, and more often failed to respond to plasma exchange treatment. A search for systemic malignancy, including a bone marrow biopsy, is appropriate when patients with TTP have atypical clinical features or fail to respond to plasma exchange. PMID:22184535

  14. A report of disseminated adenocarcinoma presenting as thrombotic thrombocytopenic purpura.

    PubMed

    Alonso, Joaquín Valle; Fonseca, Javier; Lopera, Elisa Lopera; Aguayo, Miguel Ángel; Montes, Yelda Hernandez; Llamas, Jose Carlos

    2011-08-31

    Thrombotic microangiopathies (TMAs) represent a heterogeneous group of diseases characterized by a microangiopathic hemolytic anemia, peripheral thrombocytopenia, and organ failure of variable severity. TMAs encompass thrombotic thrombocytopenic purpura (TTP), typically characterized by fever, central nervous system manifestations and hemolytic uremic syndrome (HUS), in which renal failure is the prominent abnormality. In patients with cancer TMAs may be related to various antineoplastic drugs or to the malignant disease itself. The reported series of patients with TMAs directly related to cancer are usually heterogeneous, retrospective, and encompass patients with hematologic malignancies with solid tumors or receiving chemotherapy, each of which may have distinct presentations and pathophysiological mechanisms. Patients with disseminated malignancy who present with microangiopathic hemolytic anemia and thrombocytopenia may be misdiagnosed as thrombotic thrombocytopenic purpura (TTP) Only a few cases of TTP secondary to metastatic adenocarcinoma are known in the literature. We present a case of a 34-year-old man with TTP syndrome secondary to metastatic small-bowel adenocarcinoma. Patients with disseminated malignancy had a longer duration of symptoms, more frequent presence of respiratory symptoms, higher lactate dehydrogenase levels, and more often failed to respond to plasma exchange treatment. A search for systemic malignancy, including a bone marrow biopsy, is appropriate when patients with TTP have atypical clinical features or fail to respond to plasma exchange. PMID:22184535

  15. Treatment of Congenital Thrombotic Thrombocytopenic Purpura With Eculizumab.

    PubMed

    Pecoraro, Carmine; Ferretti, Alfonso Vincenzo Salvatore; Rurali, Erica; Galbusera, Miriam; Noris, Marina; Remuzzi, Giuseppe

    2015-12-01

    A 12-year-old boy was hospitalized for hemolytic anemia, thrombocytopenia, acute kidney injury, and generalized seizures. The childhood onset, severely decreased kidney function, absence of prodromal diarrhea, negative test results for Shiga-like toxin-producing Escherichia coli, elevated plasma levels of the terminal complement complex sC5b-9, and ex vivo testing in endothelial cells showing serum-induced complement activation were all consistent with a diagnosis of complement-mediated atypical hemolytic uremic syndrome. Before plasma ADAMTS13 (von Willebrand factor protease) activity results were available, the patient was treated with the anti-C5 monoclonal antibody eculizumab, and treatment was followed by prompt disease remission. However, results of ADAMT13 activity level tests and gene screening revealed a severe deficiency associated with 2 heterozygous mutations in the ADAMTS13 gene, fully consistent with a diagnosis of congenital thrombotic thrombocytopenic purpura. Screening for atypical hemolytic uremic syndrome-associated genes failed to show a mutation and an assay for plasma anti-factor H antibodies gave negative results both before and after eculizumab treatment initiation. The patient's clinical evolution suggests that complement activation plays a role in the pathogenesis of thrombotic thrombocytopenic purpura and provides unexpected new insights into the treatment of this life-threatening disease. PMID:26409664

  16. Dengue Virus Infection Triggering Thrombotic Thrombocytopenic Purpura in Pregnancy.

    PubMed

    Deepanjali, Surendran; Naik, Raghuramulu R; Mailankody, Sharada; Kalaimani, Sivamani; Kadhiravan, Tamilarasu

    2015-11-01

    We report a case of thrombotic thrombocytopenic purpura (TTP) that immediately followed symptomatic dengue virus infection in a pregnant lady. The patient developed dengue fever at 16 weeks of gestation, resulting in spontaneous abortion. Subsequently, fever reappeared with persistent thrombocytopenia and jaundice. Investigations revealed microangiopathic hemolysis; there was no evidence of disseminated intravascular coagulation. The TTP episode resolved after six cycles of therapeutic plasma exchange with fresh-frozen plasma. An ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif 13 repeats) activity assay, done during convalescence, showed normal activity. The patient had an uneventful second pregnancy and has remained free of TTP recurrence for more than 2 years now. We review the pathophysiological basis of TTP in dengue infection, and suggest that jaundice with disproportionate elevation of serum aspartate aminotransferase level in a patient with dengue should arouse the suspicion of TTP. PMID:26283741

  17. Initial management of adults with idiopathic (immune) thrombocytopenic purpura.

    PubMed

    George, J N

    2002-03-01

    Since idiopathic (immune) thrombocytopenic purpura (ITP) in adults is usually a chronic condition with few spontaneous remissions, the goal of treatment is not cure, but to maintain a hemostatically safe platelet level. The indication for treatment should be based not merely on platelet counts, but also clinical indices of bleeding. Although most patients show good initial response to prednisone, the side effects of steroids limit this treatment. Currently, long-term management usually involves splenectomy. Since splenectomy has surgical risks and may also predispose the patient to sepsis, a clinical trial using anti-D (WinRho-SDR) has been performed to determine whether this treatment can safely delay or avoid the need for surgery. The use of WinRho may also reveal the occurrence of spontaneous remissions, a previously unrecognized subgroup of adults with chronic ITP. PMID:11913992

  18. Immune Thrombocytopenic Purpura Secondary to Cytomegalovirus Infection: A Case Report

    PubMed Central

    Flores-Chang, Bessy S.; Arias-Morales, Carlos E.; Wadskier, Francis G.; Gupta, Sorab; Stoicea, Nicoleta

    2015-01-01

    Immune thrombocytopenic purpura (ITP) is defined as an acquired thrombocytopenia with antibodies detected against platelet surface antigens, and it is the most common form of thrombocytopenia in otherwise asymptomatic adults. ITP secondary to an underlying condition is a diagnosis of exclusion that is essential to establish for treatment efficacy. Secondary thrombocytopenia caused by cytomegalovirus (CMV) is common; however, case reports associated with diagnosis in immunocompetent adults are rare, and to the best of our knowledge only 20 publications have been associated with this diagnosis. Our report is based on a clinical presentation of a 37-year-old female complaining of petechiae, heavy menses, shortness of breath, and a platelet count of 1?×?109/L. Treatment with IVIG and steroids failed to improve platelet count. Subsequently, an infectious laboratory workup was performed, detecting CMV infection, and treatment with antiviral agents was initiated, causing platelet count to increase as viral load decreased. PMID:26579523

  19. Mechanisms of microvascular thrombosis in thrombotic thrombocytopenic purpura

    PubMed Central

    Tsai, Han-Mou

    2011-01-01

    Recent studies have demonstrated that thrombotic thrombocytopenic purpura (TTP), a serious thrombotic disorder affecting the arterioles and capillaries of multiple organs, is caused by a profound deficiency in the von Willebrand factor cleaving metalloprotease, ADAMTS13. ADAMTS13, a 190-kD plasma protease originating primarily in hepatic stellate cells, prevents microvascular thrombosis by cleaving von Willebrand factor when the substrate is conformationally unfolded by high levels of shear stress in the circulation. Deficiency of ADAMTS13, due to genetic mutations or inhibitory autoantibodies, leads to accumulation of superactive forms of vWF, resulting in vWF-platelet aggregation and microvascular thrombosis. Analysis of ADAMTS13 has led to the recognition of subclinical TTP and atypical TTP presenting with thrombocytopenia or acute focal neurological deficits without concurrent microangiopathic hemolysis. Infusion of plasma replenishes the missing ADAMTS13 and ameliorates the complications of hereditary TTP. The patients are at risk of both acute and chronic renal failure if they receive inadequate plasma therapy. The more frequent, autoimmune type of TTP requires plasma exchange therapy and perhaps immunomodulatory measures. Current studies focus on the factors affecting the phenotypic severity of TTP and newer approaches to improving the therapies for the patients. PMID:19180123

  20. Platelet antibody in idiopathic thrombocytopenic purpura and other thrombocytopenias

    SciTech Connect

    Sugiura, K.; Steiner, M.; Baldini, M.G.

    1980-10-01

    Platelet-associated immunoglobulin was measured by the use of fluorescent anti-1gG antibody. The method is simple, rapid, and sensitive and provides a precise quantitive assay of bound (direct) and free (indirect) 1gG with platelet specificity. We have evaluated this test in 30 normal volunteers and in 50 patients with immune and nonimmune, treated and untreated thrombocytopenias. All patients with immune thrombocytopenias (acute and chronic idiopathic thrombocytopenic purpura and systemic lupus erythematosus) having platelet counts < 100,000/..mu..l had elevated levels of platelet-bound 1gG and 86% had also positive results in the indirect assay. All patients with nonimmunological thrombocytopenias showed normal results in the direct and indirect assay of platelet-associated immunoglobulin. In patients studied repeatedly during the course of their illness, an inverse relation was found between platelet count and level of platelet-bound 1gG. Patients with systemic lupus erythematosus presented clear exceptions to this rule. Investigations of the absorbability of platelet autoantibodies and alloantibodies showed that this assay can readily differentiate between these two antibody species and can also identify specificities of alloantibodies.

  1. A role for tissue plasminogen activator in thrombotic thrombocytopenic purpura.

    PubMed

    Hoirisch-Clapauch, Silvia; Nardi, Antonio Egidio

    2014-12-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterized by generalized microvascular occlusion. TTP has been related to severe deficiency of ADAMTS13, an enzyme that cleaves von Willebrand factor multimers into less adhesive molecules. However, ADAMTS13 deficiency correlates poorly with severity of thrombocytopenia or microangiopathic hemolysis, with the frequency of neurologic complications or the response to plasma exchange. Also, some patients with severe hereditary ADAMTS13 deficiency consistently relapse every few weeks, whereas others remain asymptomatic into their forties. Taken together, these findings suggest that an additional element is missing in the pathophysiology of TTP. We postulate that both low ADAMTS13 activity and low tissue-plasminogen activator activity are required to trigger TTP attacks. Tissue-plasminogen activator end product, plasmin, extensively degrades von Willebrand factor, breaking-down the bonds between platelets and the blood vessel wall, so that low tissue-plasminogen activator activity prevents a mechanism similar to that of ADAMTS13. The hypothesis that low tissue-plasminogen activator activity plays an important role in TTP pathogenesis is further substantiated by TTP comorbidity. Problems prevalent in patients with TTP attacks or with long-term TTP remission, including increased body mass index, major depression, cognitive abnormalities, hypertension, and premature death, are somehow associated with low tissue-plasminogen activator activity. PMID:25459148

  2. Platelet antibody in prolonged remission of childhood idiopathic thrombocytopenic purpura

    SciTech Connect

    Ware, R.; Kinney, T.R.; Rosse, W.

    1985-11-01

    Evaluations were performed in 20 patients with childhood idiopathic thrombocytopenic purpura (ITP) who remained in remission longer than 12 months. The mean duration of follow-up from diagnosis was 39 months (range 17 to 87 months). Eleven patients (four girls) in group 1 had an acute course of ITP, defined as platelet count greater than 150 X 10(9)/L within 6 months of diagnosis. Nine patients (five girls) in group 2 had a chronic course, defined as platelet count less than 150 X 10(9)/L for greater than or equal to 1 year or requiring splenectomy in an attempt to control hemorrhagic symptoms. Platelet count and serum (indirect) platelet-associated IgG (PAIgG) levels were normal in all 20 patients at follow-up. Both direct and indirect PAIgG levels were measured using a SVI-monoclonal anti-IgG antiglobulin assay. All had normal direct PAIgG levels, except for one patient in group 1 who had a borderline elevated value of 1209 molecules per platelet. These data suggest that the prevalence of elevated platelet antibodies is low during sustained remission without medication in patients with a history of childhood ITP. These data may be relevant for pregnant women with a history of childhood ITP, with regard to the risk of delivering an infant with thrombocytopenia secondary to transplacental passage of maternal platelet antibody.

  3. Lupus-associated thrombotic thrombocytopenic purpura-like microangiopathy

    PubMed Central

    Blum, Daniel; Blake, Geoffrey

    2015-01-01

    Recently reported cases of lupus complicated by a thrombotic thrombocytopenic purpura (TTP)-like syndrome suggest a survival benefit to early treatment with plasma exchange. The following is a report of the eighth such case in the last ten years. A 44-year-old lady known for lupus presented with the nephrotic syndrome and a renal biopsy was consistent with class 4G lupus nephritis. She was given high-dose steroids and cytotoxic therapy, but her induction therapy was complicated by the classic pentad of TTP. She was subsequently treated with another course of high-dose steroids, a different cytotoxic agent, and plasma exchange, with clinical resolution shortly thereafter. Similar to seven recently reported cases of microangiopathy in lupus, this lady’s TTP-like syndrome improved dramatically after initiation of plasma exchange, despite not having a severely deficient ADAMTS13. This has implications on both current clinical practice and on the pathogenesis of TTP-like syndromes in lupus. PMID:26558190

  4. Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura.

    PubMed

    Ruggenenti, P; Noris, M; Remuzzi, G

    2001-09-01

    The term thrombotic microangiopathy (TMA) defines a lesion of vessel wall thickening (mainly arterioles or capillaries), intraluminal platelet thrombosis, and partial or complete obstruction of the vessel lumina. Depending on whether renal or brain lesions prevail, two pathologically indistinguishable but somehow clinically different entities have been described: the hemolytic uremic syndrome (HUS) and the thrombotic thrombocytopenic purpura (TTP). Injury to the endothelial cell is the central and likely inciting factor in the sequence of events leading to TMA. Loss of physiological thromboresistance, leukocyte adhesion to damaged endothelium, complement consumption, abnormal von Willebrand factor release and fragmentation, and increased vascular shear stress may then sustain and amplify the microangiopathic process. Intrinsic abnormalities of the complement system and of the von Willebrand factor pathway may account for a genetic predisposition to the disease that may play a paramount role in particular in familial and recurrent forms. Outcome is usually good in childhood, Shiga toxin-associated HUS, whereas renal and neurological sequelae are more frequently reported in adult, atypical, and familial forms of HUS and in TTP. Plasma infusion or exchange is the only treatment of proven efficacy. Bilateral nephrectomy and splenectomy may serve as rescue therapies in very selected cases of plasma resistant HUS or recurrent TTP, respectively. PMID:11532079

  5. Nonsteroidal Anti-inflammatory Drug Induced Thrombotic Thrombocytopenic Purpura.

    PubMed

    Oregel, Karlos Z; Ramdial, Jeremy; Glück, Stefan

    2013-01-01

    A 21-year-old male presented to the emergency department after a 5-day history of recurrent vomiting and decreased urine output. History revealed ingestion of ibuprofen. During the diagnostic workup, the following was identified: white blood cell count 13.4 (×10(3)/mcL), hemoglobin 11.9 (×10(6)/mcL) with an MCV of 73 fL, hematocrit 34% and platelets were 31,000/mcL, sodium of 130 mmol/L, potassium of 5.1 mmol/L, chloride of 83 mmol/L, bicarbonate of 21 mmol/L, blood urea nitrogen of 184 mg/dL and creatinine of 19.1 mg/dL. He was later diagnosed with thrombotic thrombocytopenic purpura (TTP) based on the fact that he presented with most components of the TTP pentad (except for fever), which included altered mental status, acute kidney injury, thrombocytopenia, and evidence of red cell fragmentation and his ADAMTS13 level was found to be less than 10% prior to therapy. The patient then received plasma exchange, oral corticosteroids, and hemodialysis, which led to a full recovery of platelet count and renal function. PMID:25512716

  6. Lupus-associated thrombotic thrombocytopenic purpura-like microangiopathy.

    PubMed

    Blum, Daniel; Blake, Geoffrey

    2015-11-01

    Recently reported cases of lupus complicated by a thrombotic thrombocytopenic purpura (TTP)-like syndrome suggest a survival benefit to early treatment with plasma exchange. The following is a report of the eighth such case in the last ten years. A 44-year-old lady known for lupus presented with the nephrotic syndrome and a renal biopsy was consistent with class 4G lupus nephritis. She was given high-dose steroids and cytotoxic therapy, but her induction therapy was complicated by the classic pentad of TTP. She was subsequently treated with another course of high-dose steroids, a different cytotoxic agent, and plasma exchange, with clinical resolution shortly thereafter. Similar to seven recently reported cases of microangiopathy in lupus, this lady's TTP-like syndrome improved dramatically after initiation of plasma exchange, despite not having a severely deficient ADAMTS13. This has implications on both current clinical practice and on the pathogenesis of TTP-like syndromes in lupus. PMID:26558190

  7. Treatment options for chronic idiopathic (immune) thrombocytopenic purpura.

    PubMed

    George, J N

    2000-01-01

    The goal of treatment for idiopathic (immune) thrombocytopenic purpura (ITP) is to prevent serious bleeding. Traditionally, corticosteroids have been used as first-line therapy followed by splenectomy. Experience with splenectomy over 60 years shows that approximately two thirds of patients achieve normal platelet counts during the initial observation, but that thrombocytopenia often recurs with longer follow-up. We know that long-term use of corticosteroids can lead to significant morbidities; there is no consensus regarding the appropriate timing or indications for splenectomy. To address the Issue of appropriate use of splenectomy, we designed a multicenter clinical trial that will randomize patients to either standard care, involving prednisone followed by splenectomy, or to a novel regimen of limited prednisone treatment followed by WinRho SDF (Nabi, Boca Raton, FL) (anti-D) therapy to maintain the platelet count in a safe range for 1 year. Anti-D can be administered easily in an outpatient setting with few side effects and can provide predictable, transient increases in platelet count. The hypothesis is that prolonged maintenance therapy with a nontoxic regimen may increase the percentage of patients who will experience a spontaneous remission from thrombocytopenia, thereby avoiding an invasive and permanent surgical procedure, splenectomy, and its potentially life-threatening sequelae. PMID:10676922

  8. Management of Chronic Subdural Haematoma in a Case of Idiopathic Thrombocytopenic Purpura

    PubMed Central

    Patnaik, Ashis; Mishra, Sudhansu S.; Senapati, Satya B.; Pattajoshi, Acharya S.

    2012-01-01

    Intracranial hemorrhage is a rare devastating complication of idiopathic thrombocytopenic purpura (ITP), mostly presenting as intraparenchymal or subarachnoid haemorrhage. Isolated chronic subdural haematoma (SDH) is still very rare and the optimal management is unsettled. Spontaneous resolution of chronic SDH in patients with idiopathic thrombocytopenic purpura is possible. We report a case of spontaneous chronic SDH in a patient with ITP with hemiparesis where the haematoma significantly decreased in size with complete resolution of hemiparesis as a result of platelet transfusions and continuing therapy with steroids. Surgical treatment of subdural haematoma with consequent bleeding complications can be avoided in this scenario. PMID:23741595

  9. Rapid encephalopathy associated with anti-D immune globulin treatment for idiopathic thrombocytopenic purpura.

    PubMed

    Golla, Sunitha; Horkan, Clare; Dogaru, Grigore; Teske, Thomas E; Christopher, Kenneth

    2008-01-01

    Rho (D) immune globulin intravenous (IV RhIG, WinRho SDF) has been shown to be a safe treatment for idiopathic thrombocytopenic purpura. Common side effects of IV RhIG include mild hemolysis, febrile reaction and headache. Significant hemolysis with renal impairment is infrequently noted. A single case of irreversible encephalopathy following IV RhIG has been reported. We report a second case of encephalopathy following an infusion of IV RhIG for treatment of idiopathic thrombocytopenic purpura. PMID:18957844

  10. Depression and cognitive impairment following recovery from thrombotic thrombocytopenic purpura.

    PubMed

    Han, Bowie; Page, Evaren E; Stewart, Lauren M; Deford, Cassandra C; Scott, James G; Schwartz, Lauren H; Perdue, Jedidiah J; Terrell, Deirdra R; Vesely, Sara K; George, James N

    2015-08-01

    After recovery from an acute episode of acquired thrombotic thrombocytopenic purpura (TTP), patients often describe problems with memory, concentration, and endurance. We have previously reported the occurrence of depression and cognitive impairment in these patients. In this study, we describe the frequency, severity, and clinical course of depression and cognitive impairment. Fifty-two (85%) out of 61 eligible Oklahoma Registry patients who had recovered from TTP, documented by ADAMTS13 activity <10%, have had at least one (median, four) evaluation for depression over 11 years using the Beck Depression Inventory-II; 31 (59%) patients screened positive for depression at least once; in 15 (29%), the results suggested severe depression at least once. Nine of these 15 patients had a psychiatric interview, the definitive diagnostic evaluation; the diagnosis of major depressive disorder was established in eight (89%) patients. In 2014, cognitive ability was evaluated in 33 patients by the Montreal Cognitive Assessment and the Repeatable Battery for Assessment of Neuropsychological Status (RBANS). Both tests detected significant cognitive impairment in the patients as a group. Fifteen out of the 33 patients had been evaluated by extensive cognitive tests in 2006. The 2014 RBANS results were significantly worse than the 2006 results for the overall score and two out of the five RBANS domains (immediate and delayed memory). Neither depression nor cognitive impairment was significantly associated with the occurrence of relapses or ADAMTS13 activity <10% during remission. These observations emphasize the importance of screening evaluations for depression and cognitive impairment after recovery from acquired TTP. PMID:25975932

  11. Helicobacter pylori eradication in patients with chronic immune thrombocytopenic purpura

    PubMed Central

    Noonavath, Ravinder Naik; Lakshmi, Chandrasekharan Padma; Dutta, Tarun Kumar; Kate, Vikram

    2014-01-01

    AIM: To assess the effect of Helicobacter pylori (H. pylori) eradication on platelet counts in patients with chronic immune thrombocytopenic purpura (cITP). METHODS: A total of 36 cITP patients were included in the study. The diagnosis of H. pylori was done by rapid urease test and Giemsa staining of the gastric biopsy specimen. All H. pylori positive patients received standard triple therapy for 14 d and were subjected for repeat endoscopy at 6 wk. Patients who continued to be positive for H. pylori on second endoscopy received second line salvage therapy. All the patients were assessed for platelet response at 6 wk, 3rd and 6th months. RESULTS: Of the 36 patients, 17 were positive for H. pylori infection and eradication was achieved in 16 patients. The mean baseline platelet count in the eradicated patients was 88615.38 ± 30117.93/mm3 and platelet count after eradication at 6 wk, 3 mo and 6 mo was 143230.77 ± 52437.51/mm3 (P = 0.003), 152562.50 ± 52892.3/mm3 (P = 0.0001), 150187.50 ± 41796.68/mm3 (P = 0.0001) respectively and in the negative patients, the mean baseline count was 71000.00 ± 33216.46/mm3 and at 6 wk, 3rd and 6th month follow up was 137631.58 ± 74364.13/mm3 (P = 0.001), 125578.95 ± 71472.1/mm3 (P = 0.005), 77210.53 ± 56892.28/mm3 (P = 0.684) respectively. CONCLUSION: Eradication of H. pylori leads to increase in platelet counts in patients with cITP and can be recommended as a complementary treatment with conventional therapy. PMID:24944483

  12. Risk Factors for Autoimmune Diseases Development After Thrombotic Thrombocytopenic Purpura.

    PubMed

    Roriz, Mélanie; Landais, Mickael; Desprez, Jonathan; Barbet, Christelle; Azoulay, Elie; Galicier, Lionel; Wynckel, Alain; Baudel, Jean-Luc; Provôt, François; Pène, Frédéric; Mira, Jean-Paul; Presne, Claire; Poullin, Pascale; Delmas, Yahsou; Kanouni, Tarik; Seguin, Amélie; Mousson, Christiane; Servais, Aude; Bordessoule, Dominique; Perez, Pierre; Chauveau, Dominique; Veyradier, Agnès; Halimi, Jean-Michel; Hamidou, Mohamed; Coppo, Paul

    2015-10-01

    Autoimmune thrombotic thrombocytopenic purpura (TTP) can be associated with other autoimmune disorders, but their prevalence following autoimmune TTP remains unknown. To assess the prevalence of autoimmune disorders associated with TTP and to determine risk factors for and the time course of the development of an autoimmune disorder after a TTP episode, we performed a cross sectional study. Two-hundred sixty-one cases of autoimmune TTP were included in the French Reference Center registry between October, 2000 and May, 2009. Clinical and laboratory data available at time of TTP diagnosis were recovered. Each center was contacted to collect the more recent data and diagnosis criteria for autoimmunity. Fifty-six patients presented an autoimmune disorder in association with TTP, 9 years before TTP (median; min: 2 yr, max: 32 yr) (26 cases), at the time of TTP diagnosis (17 cases) or during follow-up (17 cases), up to 12 years after TTP diagnosis (mean, 22 mo). The most frequent autoimmune disorder reported was systemic lupus erythematosus (SLE) (26 cases) and Sjögren syndrome (8 cases). The presence of additional autoimmune disorders had no impact on outcomes of an acute TTP or the occurrence of relapse. Two factors evaluated at TTP diagnosis were significantly associated with the development of an autoimmune disorder during follow-up: the presence of antidouble stranded (ds)DNA antibodies (hazard ratio (HR): 4.98; 95% confidence interval (CI) [1.64-15.14]) and anti-SSA antibodies (HR: 9.98; 95% CI [3.59-27.76]). A follow-up across many years is necessary after an acute TTP, especially when anti-SSA or anti-dsDNA antibodies are present on TTP diagnosis, to detect autoimmune disorders early before immunologic events spread to prevent disabling complications. PMID:26496263

  13. Risk Factors for Autoimmune Diseases Development After Thrombotic Thrombocytopenic Purpura

    PubMed Central

    Roriz, Mélanie; Landais, Mickael; Desprez, Jonathan; Barbet, Christelle; Azoulay, Elie; Galicier, Lionel; Wynckel, Alain; Baudel, Jean-Luc; Provôt, François; Pène, Frédéric; Mira, Jean-Paul; Presne, Claire; Poullin, Pascale; Delmas, Yahsou; Kanouni, Tarik; Seguin, Amélie; Mousson, Christiane; Servais, Aude; Bordessoule, Dominique; Perez, Pierre; Chauveau, Dominique; Veyradier, Agnès; Halimi, Jean-Michel; Hamidou, Mohamed; Coppo, Paul

    2015-01-01

    Abstract Autoimmune thrombotic thrombocytopenic purpura (TTP) can be associated with other autoimmune disorders, but their prevalence following autoimmune TTP remains unknown. To assess the prevalence of autoimmune disorders associated with TTP and to determine risk factors for and the time course of the development of an autoimmune disorder after a TTP episode, we performed a cross sectional study. Two-hundred sixty-one cases of autoimmune TTP were included in the French Reference Center registry between October, 2000 and May, 2009. Clinical and laboratory data available at time of TTP diagnosis were recovered. Each center was contacted to collect the more recent data and diagnosis criteria for autoimmunity. Fifty-six patients presented an autoimmune disorder in association with TTP, 9 years before TTP (median; min: 2 yr, max: 32 yr) (26 cases), at the time of TTP diagnosis (17 cases) or during follow-up (17 cases), up to 12 years after TTP diagnosis (mean, 22 mo). The most frequent autoimmune disorder reported was systemic lupus erythematosus (SLE) (26 cases) and Sjögren syndrome (8 cases). The presence of additional autoimmune disorders had no impact on outcomes of an acute TTP or the occurrence of relapse. Two factors evaluated at TTP diagnosis were significantly associated with the development of an autoimmune disorder during follow-up: the presence of antidouble stranded (ds)DNA antibodies (hazard ratio (HR): 4.98; 95% confidence interval (CI) [1.64–15.14]) and anti-SSA antibodies (HR: 9.98; 95% CI [3.59–27.76]). A follow-up across many years is necessary after an acute TTP, especially when anti-SSA or anti-dsDNA antibodies are present on TTP diagnosis, to detect autoimmune disorders early before immunologic events spread to prevent disabling complications. PMID:26496263

  14. Complement and cytokine response in acute Thrombotic Thrombocytopenic Purpura

    PubMed Central

    Westwood, John-Paul; Langley, Kathryn; Heelas, Edward; Machin, Samuel J; Scully, Marie

    2014-01-01

    Complement dysregulation is key in the pathogenesis of atypical Haemolytic Uraemic Syndrome (aHUS), but no clear role for complement has been identified in Thrombotic Thrombocytopenic Purpura (TTP). We aimed to assess complement activation and cytokine response in acute antibody-mediated TTP. Complement C3a and C5a and cytokines (interleukin (IL)-2, IL-4, IL-6, IL-10, tumour necrosis factor, interferon-? and IL-17a) were measured in 20 acute TTP patients and 49 remission cases. Anti-ADAMTS13 immunoglobulin G (IgG) subtypes were measured in acute patients in order to study the association with complement activation. In acute TTP, median C3a and C5a were significantly elevated compared to remission, C3a 63·9 ng/ml vs. 38·2 ng/ml (P < 0·001) and C5a 16·4 ng/ml vs. 9·29 ng/ml (P < 0·001), respectively. Median IL-6 and IL-10 levels were significantly higher in the acute vs. remission groups, IL-6: 8 pg/ml vs. 2 pg/ml (P = 0·003), IL-10: 6 pg/ml vs. 2 pg/ml (P < 0·001). C3a levels correlated with both anti-ADAMTS13 IgG (rs = 0·604, P = 0·017) and IL-10 (rs = 0·692, P = 0·006). No anti-ADAMTS13 IgG subtype was associated with higher complement activation, but patients with the highest C3a levels had 3 or 4 IgG subtypes present. These results suggest complement anaphylatoxin levels are higher in acute TTP cases than in remission, and the complement response seen acutely may relate to anti-ADAMTS13 IgG antibody and IL-10 levels. PMID:24372446

  15. Treatment of immune thrombocytopenic purpura in children : current concepts.

    PubMed

    Shad, Aziza T; Gonzalez, Corina E; Sandler, S G

    2005-01-01

    Treatment of immune thrombocytopenic purpura (ITP), the most common bleeding disorder of childhood, is a controversial subject for most practitioners. Diagnosis and management of ITP has historically been based primarily on expert opinion rather than on evidence. Due to a paucity of carefully conducted clinical trials in children, the management of ITP varies widely, ranging from observation only, to aggressive management with intravenous immunoglobulin (IVIG), intravenous anti-D rhesus (Rh)0 immunoglobulin (IV RhIG), corticosteroids, and splenectomy. To address the controversies, the American Society of Hematology (ASH) and the British Society for Hematology (BSH) have developed ITP practice guidelines. These guidelines, based on expert opinion, differ in their recommendations for treatment. The ASH guidelines favor therapy based on a low platelet count, and the more current BSH guidelines recommend a more conservative 'wait and watch' approach. In addition to treating children with severe bleeding symptoms, there is a tendency (not evidence based) to treat early in order to prevent a life-threatening bleeding episode, including intracerebral hemorrhage. Corticosteroids are a highly effective therapy, inexpensive, and can usually increase the platelet count within hours to days. However, chronic or prolonged use is associated with toxicity. In the US, based on the knowledge of known toxicities of corticosteroids, as well as the efficacy of alternative treatments (IV RhIG, IVIG), many pediatricians prefer to treat with IVIG and IV RhIG, reserving corticosteroid treatment for serious bleeding or refractory disease. However, in the UK, for the most part, corticosteroids are used as first-line therapy in children with ITP. Splenectomy is rarely indicated in children except for those with life-threatening bleeding and chronic, severe ITP with impairment of quality of life. For children who develop chronic or refractory ITP, immunosuppressive drugs and/or chemotherapy agents may offer some promise. However, the long-term effects of these drugs in children are unknown and they should not be considered unless there is unequivocal evidence that the patient is refractory to IV RhIG, IVIG, and corticosteroids. To date, virtually all of the randomized clinical trials conducted in children with ITP have focused on platelet counts as the sole outcome measure. Only carefully designed, multicenter, randomized clinical trials comparing the effects of different treatment modalities in terms of bleeding, quality of life, adverse effects, and treatment-related costs will be able to address the controversies surrounding childhood ITP treatment and allow management of this condition to be based on scientific data rather than treatment philosophy. PMID:16220997

  16. Rapid irreversible encephalopathy associated with anti-D immune globulin treatment for idiopathic thrombocytopenic purpura.

    PubMed

    Christopher, Kenneth; Horkan, Clare; Barb, Ilie T; Arbelaez, Christian; Hodgdon, Travis A; Yodice, Paul C

    2004-11-01

    Intravenous Rho (D) immune globulin (IV RhIG, WinRho SDF) has been shown to be a safe treatment for idiopathic thrombocytopenic purpura (ITP). Common side effects of IV RhIG include mild hemolysis, febrile reaction, and headache. Significant hemolysis with renal impairment following IV RhIG has been reported. We report a case of irreversible encephalopathy 48 hr following an infusion of IV RhIG for treatment of ITP. PMID:15495245

  17. A review of immune thrombocytopenic purpura: focus on the novel thrombopoietin agonists

    PubMed Central

    Khan, Meaghan; Mikhael, Joseph

    2010-01-01

    Immune thrombocytopenic purpura (ITP) is an autoimmune disorder that is characterized by antibody-mediated platelet destruction and decreased platelet production. ITP and its treatments have been recognized to cause diminished quality of life in those afflicted with this illness on levels comparable to other chronic diseases. The disease can be self-limiting, but in adults it often is a chronic process requiring medical intervention to maintain appropriate platelet counts and to reduce bleeding events. Many patients go on to develop disease that is refractory to current interventions. Historically, the aim of treatment has been focused on reducing the amount of antibody-mediated destruction but newer therapies have centered on the decreased platelet production. Two new medications that target production of platelets have recently been USA, Food and Drug Administration (FDA) approved for the treatment of chronic relapsing ITP. Here, we provide an overview of ITP and a comprehensive review of the newest therapies aimed at the stimulation of platelet production. PMID:22282680

  18. Clopidogrel-Associated Thrombotic Thrombocytopenic Purpura following Endovascular Treatment of Spontaneous Carotid Artery Dissection

    PubMed Central

    Rubano, Jerry A.; Chen, Kwan; Sullivan, Brianne; Vosswinkel, James A.; Jawa, Randeep S.

    2015-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening multisystem disease secondary to platelet aggregation. We present a patient who developed profound thrombocytopenia and anemia 8 days following initiation of therapy with clopidogrel after stent placement for carotid artery dissection. She did not have a disintegrin and metalloproteinase with thrombospondin domain 13 (ADAMTS 13) deficiency. Management included steroids and therapeutic plasma exchange. Clopidogrel has rarely been associated with TTP. Unlike other causes of acquired TTP, the diagnosis of early clopidogrel-associated TTP is largely clinical given the infrequent reduction in ADAMTS 13 activity. PMID:26623244

  19. Intravenous anti-D immunoglobulin in the treatment of resistant immune thrombocytopenic purpura in pregnancy.

    PubMed

    Sieunarine, K; Shapiro, S; Al Obaidi, M J; Girling, J

    2007-04-01

    A 35-week pregnant 38-year-old woman presented with isolated thrombocytopenia (platelet count 4 x 10(9)/l). Investigations confirmed immune thrombocytopenic purpura, and she received treatment with prednisolone and intravenous immunoglobulins with no increment in the platelet count. At 37 and 38 weeks of the pregnancy, she received two doses of WinRho (anti-D immunoglobulin) at 50 microg/kg. Five days later, with a platelet count of 46 x 10(9)/l, she had an uncomplicated normal vaginal delivery. WinRho is a useful adjunct to other first-line treatment modalities for immune thrombocytopenia in pregnancy. PMID:17309547

  20. Immune Thrombocytopenic Purpura Associated with Hepatitis A Infection in a Five-year Old Boy: A Case Report

    PubMed Central

    Urganci, N; Kilicaslan, O; Kalyoncu, D; Yilmaz, S

    2014-01-01

    ABSTRACT Acute hepatitis A infection is usually a self-limiting disease and mostly asymptomatic in children younger than six years old. Extrahepatic autoimmune manifestations such as immune thrombocytopenic purpura (ITP) have been reported rarely in children with acute hepatitis A infection. We report herein a paediatric case with ITP which is due to hepatitis A virus infection. PMID:25781273

  1. The spleen and splenectomy in immune (idiopathic) thrombocytopenic purpura.

    PubMed

    Sandler, S G

    2000-01-01

    The benefits of surgical splenectomy in patients with immune (Idiopathic) thrombocytopenia purpura (ITP) probably reflect the combined effects of eliminating a source of antiplatelet antibody synthesis as well as the primary site of platelet destruction. The recent availability of intravenous Rho(D) Immune globulin (WinRho SDF; Nabi, Boca Raton, FL) presents an opportunity to extend the duration of nonsurgical (spleen-sparing) management of chronic ITP by inducing reversible Fc blockade. While new methods for laparoscopic splenectomy may offer improved surgical outcomes and reduced costs for ITP patients in the near-term, the long-term consequences of splenectomy remain to be determined. Partial splenectomy has been shown to be effective in the management of anemia in hereditary spherocytosis and elliptocytosis, while preserving vital splenic phagocytic and immune functions. The concept that cell destruction occurs in reticuloendothelial cells has been updated with recognition that the mononuclear phagocyte is neither a reticular nor an endothelial cell. Immune phagocytosis is now understood to be mediated by macrophage IgG Fc and complement receptors. A key factor for devising a strategy for selecting medical or surgical splenectomy, or postponing splenectomy, is an assessment of the relative importance of splenic immune versus phagocytic function in the pathogenesis of ITP. PMID:10676918

  2. Neglect-induced pseudo-thrombotic thrombocytopenic purpura due to vitamin B12 deficiency.

    PubMed

    Asano, Takeshi; Narazaki, Hidehiko; Kaizu, Kiyohiko; Matsukawa, Shouhei; Takema-Tochikubo, Yuki; Fujii, Shuichi; Saitoh, Nobuyuki; Mashiko, Kunihiko; Fujino, Osamu

    2015-10-01

    Although thrombotic thrombocytopenic purpura (TTP) is rare, early diagnosis and treatment are important for decreasing the mortality rate. Acquired vitamin B12 deficiency is frequently overlooked because of its rarity in developed countries, particularly in children and adolescents. The hematological changes in vitamin B12 deficiency present as megaloblastic anemia, increased lactate dehydrogenase, vasoconstriction, increased platelet aggregation, and abnormal activation of the coagulation followed by microangiopathy as well as neutropenia and thrombocytopenia. We report herein the case of a 15-year-old girl who had been neglected, which might have caused pseudo-TTP through malnutrition, particularly vitamin B12 deficiency. When we encounter cases of TTP in children, clinicians must be aware of the possibility of malnutrition, particularly with vitamin B12 deficiency, even in developed countries, and investigate the cause of malnutrition including neglect. PMID:26387768

  3. Ciprofloxacin-Induced Thrombotic Thrombocytopenic Purpura: A Case of Successful Treatment and Review of the Literature

    PubMed Central

    Hashmi, Hafiz Rizwan Talib; Diaz-Fuentes, Gilda; Jadhav, Preeti; Khaja, Misbahuddin

    2015-01-01

    A 49-year-old African American woman was admitted to our hospital with abdominal pain, nausea, vomiting, lethargy, and confusion. She was receiving ciprofloxacin for a urinary-tract infection prior to admission. Laboratory examination revealed anemia, thrombocytopenia, elevated lactate dehydrogenase, and serum creatinine. Peripheral smear showed numerous schistocytes, and the patient was diagnosed with thrombotic thrombocytopenic purpura (TTP). Ciprofloxacin was identified as the offending agent. The patient received treatment with steroids and plasmapheresis, which led to rapid clinical recovery. This is the first case to our knowledge of successfully treated ciprofloxacin-induced TTP; previously reported cases had fulminant outcomes. Quinolones are an important part of the antibiotic armamentarium, and this case can raise awareness of the association between quinolones and TTP. A high index of suspicion for detection and early and aggressive management are vitally important for a successful outcome. PMID:26587293

  4. What's new in the diagnosis and pathophysiology of thrombotic thrombocytopenic purpura.

    PubMed

    Sadler, J Evan

    2015-12-01

    Severe ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) deficiency causes thrombotic thrombocytopenic purpura (TTP), which is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and the absence of oliguric or anuric renal failure. However, some patients with this constellation of findings do not have ADAMTS13 deficiency, and some patients with ADAMTS13 deficiency have renal failure or relatively normal blood counts. Consequently, many investigators and clinicians have incorporated severe ADAMTS13 deficiency into the case definition of TTP. This change has facilitated the timely initiation of treatment for patients with atypical clinical features who otherwise would not be recognized as having TTP. Conversely, excluding severe ADAMTS13 deficiency focuses attention on the diagnosis and treatment of other causes of thrombotic microangiopathy that require different treatment. The rapid return of ADAMTS13 data is important to make the best use of this information. PMID:26637781

  5. Lower Extremity Wounds in Patients With Idiopathic Thrombocytopenic Purpura and Systemic Lupus Erythematosus.

    PubMed

    Akita, Sadanori

    2015-09-01

    Infections in lower extremities are sometimes concerned with systemic immunological disorders such as idiopathic thrombocytopenic purpura and systemic lupus erythematosus, which are treated with systemic steroids. Steroid therapy impairs the epithelial wound healing and with systemic condition, especially with systemic lupus erythematosus, the wound is susceptible for infection. Even a pyoderma gangrenosum sometimes occurs in a patient with idiopathic thrombocytopenic purpura with an incisional wound of hernia. The severe signs and symptoms are the deep skin and soft tissue infections, mainly caused by group A streptococcus, composed of necrotizing fasciitis and muscle necrosis. Medically suspected necrotizing fasciitis patients should be empirically and immediately administered with broad-spectrum antibiotics, which may cover the common suspected pathogens. In type I (polymicrobial) infection, the selection of antimicrobial should be based on medical history and Gram staining and culture. The coverage against anaerobes is important in type I infection. Metronidazole, clindamycin, or beta-lactams with beta-lactamase inhibitor or carbapenems are the treatment of choice against anaerobes, while early surgical debridement-wide enough and deep enough-is the core treatment of necrotizing fasciitis and results in significantly better mortality compared with those who underwent surgery after a few hours of delay. When necrotizing fasciitis is considered and the patient is brought to the operation room, aggressive and extensive surgical debridement is explored. Tissue involved should be completely removed until no further evidence of infection is seen. When further debridement is required, the patient must return to the operating room immediately. In this context, the temporal coverage using the artificial dermis after debridement is useful because there is no loss of the patient's own tissue and yet it is easier for "second-look" surgery or secondary reconstruction, and extensive enough debridement is always the mainstay of the therapy. PMID:26353824

  6. Successful treatment with rituximab of a patient with coincident acquired hemophilia A and thrombotic thrombocytopenic purpura.

    PubMed

    Yamamoto, Kazuhiko; Sandou, Yasuhisa; Niiya, Masami; Osada, Yuuki; Ikeuchi, Kazuhiro; Yamamoto, Yoshikazu; Shiote, Yasuhiro; Makita, Masanori; Imajo, Kenji

    2015-11-01

    A 66-year-old man was admitted for oral hemorrhage, purpura, and APTT prolongation. Factor VIII (FVIII) activity was decreased, due to the presence of FVIII inhibitor. He was diagnosed with acquired hemophilia A (AHA) and treated with prednisolone. Eight months later, the FVIII inhibitor titer again increased. Upon readmission, thrombocytopenia and autoimmune hemolytic anemia were found. We suspected Evans syndrome accompanied by AHA, and we treated the patient with IVIG. However, his platelet count did not increase. Speech disturbance and delirium were observed from the 12th day of hospitalization. He was subsequently diagnosed with thrombotic thrombocytopenic purpura (TTP) because ADAMTS13 inhibitor was detected, causing a decrease in ADAMTS13 activity. We initiated plasma exchange (PE) and steroid-pulse therapy. After PE for 3 days, laboratory test results and psychiatric symptoms showed dramatic improvement. However, after a 2-day period without PE, the patient's platelet count decreased markedly. Therefore, we administered rituximab to eliminate these inhibitors. His platelet count recovered rapidly, and we were able to gradually wean the patient from PE. After two additional administrations of rituximab, neither inhibitor was detected. To date, the patient has remained in complete remission for approximately 3 years. PMID:26666718

  7. Hemorrhagic Stroke in an Adolescent Female with HIV-Associated Thrombotic Thrombocytopenic Purpura

    PubMed Central

    Rakhmanina, Natella; Wong, Edward CC; Davis, Jeremiah C; Ray, Patricio E

    2014-01-01

    HIV-1 infection can trigger acute episodes of Idiopathic Thrombocytoponic Purpura (ITP), and Thrombotic Thrombocytopenic Purpura (TTP), particularly in populations with advanced disease and poor adherence to antiretroviral therapy (ART). These diseases should be distinguished because they respond to different treatments. Previous studies done in adults with HIV-TTP have recommended the prompt initiation or re-initiation of ART in parallel with plasma exchange therapy to improve the clinical outcome of these patients. Here, we describe a case of HIV-TTP resulting in an acute hemorrhagic stroke in a 16 year old female with perinatally acquired HIV infection and non-adherence to ART, who presented with severe thrombocytopenia, microangiopathic hemolytic anemia, and a past medical history of HIV-ITP. Both differential diagnosis and treatments for HIV-ITP and HIV-TTP were considered simultaneously. A decrease in plasma ADAMTS13 activity (<5%) without detectable inhibitory antibodies confirmed the diagnosis of HIV-TTP. Re-initiation of ART and plasma exchange resulted in a marked decrease in the HIV-RNA viral load, recovery of the platelet count, and complete recovery was achieved with sustained virologic suppression. PMID:25429351

  8. Vitamin B12 Deficiency and Hemoglobin H Disease Early Misdiagnosed as Thrombotic Thrombocytopenic Purpura: A Series of Unfortunate Events

    PubMed Central

    Andreadis, Panagiotis; Theodoridou, Stamatia; Pasakiotou, Marily; Arapoglou, Stergios; Gigi, Eleni; Vetsiou, Evaggelia; Vlachaki, Efthymia

    2015-01-01

    We herein would like to report an interesting case of a patient who presented with anemia and thrombocytopenia combined with high serum Lactic Dehydrogenase where Thrombotic Thrombocytopenic Purpura was originally considered. As indicated a central venous catheter was inserted in his subclavian vein which led to mediastinal hematoma and finally intubation and Intensive Care Unit (ICU) hospitalization. After further examination patient was finally diagnosed with B12 deficiency in a setting of H hemoglobinopathy. There have been previous reports where pernicious anemia was originally diagnosed and treated as Thrombotic Thrombocytopenic Purpura but there has been none to our knowledge that was implicated with hemothorax and ICU hospitalization or correlated with thalassemia and we discuss the significance of accurate diagnosis in order to avoid adverse reactions and therapy implications. PMID:26609455

  9. Two novel heterozygote missense mutations of the ADAMTS13 gene in a child with recurrent thrombotic thrombocytopenic purpura

    PubMed Central

    Rossio, Raffaella; Ferrari, Barbara; Cairo, Andrea; Mancini, Ilaria; Pisapia, Giovanni; Palazzo, Giulia; Peyvandi, Flora

    2013-01-01

    Background Thrombotic thrombocytopenic purpura is a rare, life-threatening disease characterised by microangiopathic haemolytic anaemia, thrombocytopenia and symptoms related to organ ischaemia, mainly involving the brain and the kidney. It is associated with a deficiency of ADAMTS13, a plasma metalloprotease that cleaves von Willebrand factor. The congenital form (Upshaw-Schulman syndrome) is rare and is associated with mutations of the ADAMTS13 gene on chromosome 9q34. The clinical symptoms of congenital thrombotic thrombocytopenic purpura are variable, with some patients developing their first episode during the neonatal period or childhood and others becoming symptomatic in adulthood. Materials and methods We describe a case of thrombotic thrombocytopenic purpura, who presented to our attention with a relapsing form of the disease: the first episode occurred at the age of 13 months. Phenotype and genotype tests were performed in the patient and his family. Results The undetectable level of ADAMTS13 in the patient was caused by two novel heterozygote missense mutations on the ADAMTS13 gene: one mutation is c.788C > T (p.Ser263Phe) on exon 7 and the second is c.3251G > A (p.Cys1084Tyr) on exon 25 of the ADAMTS13 gene. All the relatives who have been investigated were found to carry one of these missense mutations in a heterozygous state. Discussion Although Upshaw-Schulman syndrome is a rare disease, it should be considered in all children with thrombocytopenia and jaundice in the neonatal period. In fact, once a child is confirmed to carry mutations of the ADAMTS13 gene causing early thrombotic thrombocytopenic purpura, prophylactic treatment should be started to avoid recurrence of symptoms. Genotype tests of relatives would also be important for those women in the family who could be carriers of ADAMTS13 mutations, particularly during pregnancy. PMID:23058857

  10. Triad of Idiopathic Thrombocytopenic Purpura, Preeclampsia, and HELLP Syndrome in a Parturient: A Rare Confrontation to the Anesthetist.

    PubMed

    Mehta, Tanu; Parikh, Geeta P; Shah, Veena R

    2014-01-01

    Idiopathic thrombocytopenic purpura (ITP) with HELLP represents a rare complication that requires combined care of obstetrician, anesthesiologist, hematologist, and neonatologist. At 37-week gestation a 35-year-old parturient (G2A1P0) a known case of chronic ITP presented with severe pregnancy induced hypertension (PIH), thrombocytopenia, and elevated liver enzymes. We describe successful anesthetic management of this patient who was taken for emergency caesarean section. PMID:25548684

  11. Triad of Idiopathic Thrombocytopenic Purpura, Preeclampsia, and HELLP Syndrome in a Parturient: A Rare Confrontation to the Anesthetist

    PubMed Central

    Mehta, Tanu; Parikh, Geeta P.; Shah, Veena R.

    2014-01-01

    Idiopathic thrombocytopenic purpura (ITP) with HELLP represents a rare complication that requires combined care of obstetrician, anesthesiologist, hematologist, and neonatologist. At 37-week gestation a 35-year-old parturient (G2A1P0) a known case of chronic ITP presented with severe pregnancy induced hypertension (PIH), thrombocytopenia, and elevated liver enzymes. We describe successful anesthetic management of this patient who was taken for emergency caesarean section. PMID:25548684

  12. Vaccine administration and the development of immune thrombocytopenic purpura in children.

    PubMed

    Cecinati, Valerio; Principi, Nicola; Brescia, Letizia; Giordano, Paola; Esposito, Susanna

    2013-05-01

    The most important reasons cited by the opponents of vaccines are concerns about vaccine safety. Unlike issues such as autism for which no indisputable documentation of direct relationship with vaccine use is available, immune thrombocytopenic purpura (ITP) is an adverse event that can really follow vaccine administration, and may limit vaccine use because little is known about which vaccines it may follow, its real incidence and severity, the risk of chronic disease, or the possibility of recurrences after new doses of the same vaccine. The main aim of this review is to clarify the real importance of thrombocytopenia as an adverse event and discuss how it may interfere with recommended vaccination schedules. The available data clearly indicate that ITP is very rare and the only vaccine for which there is a demonstrated cause-effect relationship is the measles, mumps and rubella (MMR) vaccine that can occur in 1 to 3 children every 100,000 vaccine doses. However, also in this case, the incidence of ITP is significantly lower than that observed during the natural diseases that the vaccine prevents. Consequently, ITP cannot be considered a problem limiting vaccine use except in the case of children suffering from chronic ITP who have to receive MMR vaccine. In these subjects, the risk-benefit ratio of the vaccine should be weighed against the risk of measles in the community. PMID:23324619

  13. Thrombotic thrombocytopenic purpura and other thrombotic microangiopathic hemolytic anemias: diagnosis and classification.

    PubMed

    Shenkman, Boris; Einav, Yulia

    2014-01-01

    Thrombotic microangiopathies (TMAs) include several diseases, most prominently are thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS). TMAs are characterized by profound thrombocytopenia, microangiopathic hemolytic anemia and organ ischemia. In most cases TTP results from deficiency of ADAMTS13, the von Willebrand factor-cleaving protease leading to increase of ultra-large von Willebrand factor (ULVWF) multimers. Congenital TTP is due to mutations in the gene of ADAMTS13 whereas acquired TTP is due to production of autoantibodies against ADAMTS13. In both cases severe deficiency of ADAMTS13 exists. However, the presence of ADAMTS13 activity does not rule out TTP. Diagnostic criteria of TTP are based on clinical features of neurologic and renal disfunction along with anemia and thrombocytopenia, low ADAMTS13 activity, and the presence of ULVWF. The standard treatment of TTP includes plasma exchange, protein A immunoabsobtion, immunosuppressive drugs, CD20 antibodies against B cells, and splenectomy. HUS is commonly caused by infection with Shiga-toxin produced by Escherichia coli. HUS is characterized by thrombocytopenia, anemia, renal impairment and diarrhea. Rarely, atypical HUS appears as a consequence of mutations related to the alternative pathway for the compliment system. Plasmapheresis in HUS is not efficient. Alternatively, plasma therapy and in some cases dialysis are used. TMA diseases may be associated with other infections, bone marrow transplantation, pregnancy, systemic vasculitis, and certain drugs. PMID:24418304

  14. Efficacy and response to intravenous anti-D immunoglobulin in chronic idiopathic thrombocytopenic purpura.

    PubMed

    Ramadan, K M A; El-Agnaf, M

    2005-08-01

    This review explored the effectiveness of anti-D in the management of chronic idiopathic thrombocytopenic purpura (ITP). Of 16 patients, 14 non-splenectomized and two splenectomized, with chronic ITP received anti-D immunoglobulin at a dose of 50-75 mcg/kg. A total number of 100 doses anti-D were given. Fourteen patients had previous treatment with steroids, which was discontinued either because of unresponsiveness or unacceptably high maintenance doses. Two patients had no previous treatments with any modality. Anti-D was given as a short i.v. infusion whenever platelet count dropped below 30 x 10(9)/l or patient was haemorrhagic or preoperatively. Response was defined as an absolute platelet count >30 x 10(9)/l or an increment by > or =20 x 10(9)/l. Response was obtained in 14 patients with a response rate of 87%. Fifteen patients were not on any other form of treatment at the time of anti-D therapy and one patient had a concurrent steroid therapy. The improvement in platelet count lasted for more than 8 weeks post-57% of anti-D infusions. We report two patients with previous splenectomy for ITP who responded to anti-D therapy. The side-effects profile was very mild with no patients required red cell transfusion. PMID:16048495

  15. Refractory Immune Thrombocytopenic Purpura and Cytomegalovirus Infection: A Call for a Change in the Current Guidelines

    PubMed Central

    Shimanovsky, Alexei; Patel, Devbala; Wasser, Jeffrey

    2016-01-01

    Immune thrombocytopenic purpura (ITP) is characterized by a decreased platelet count caused by excess destruction of platelets and inadequate platelet production. In many cases, the etiology is not known, but the viral illness is thought to play a role in the development of some cases of ITP. The current (2011) American Society of Hematology ITP guidelines recommend initial diagnostic studies to include testing for HIV and Hepatitis C. The guidelines suggest that initial treatment consist of observation, therapy with corticosteroids, IVIG or anti D. Most cases respond to the standard therapy such that the steroids may be tapered and the platelet counts remain at a hemostatically safe level. Some patients with ITP are dependent on long-term steroid maintenance, and the thrombocytopenia persists with the tapering of the steroids. Recent case reports demonstrate that ITP related to cytomegalovirus (CMV) can persist in spite of standard therapy and that antiviral therapy may be indicated. Herein we report a case of a 26-year-old female with persistent ITP that resolved after the delivery of a CMV-infected infant and placenta. Furthermore, we review the current literature on CMV-associated ITP and propose that the current ITP guidelines be amended to include assessment for CMV, even in the absence of signs and symptoms, as part of the work-up for severe and refractory ITP, especially prior to undergoing an invasive procedure such as splenectomy.

  16. Splenectomy for primary and recurrent immune thrombocytopenic purpura (ITP). Current criteria for patient selection and results.

    PubMed Central

    Akwari, O E; Itani, K M; Coleman, R E; Rosse, W F

    1987-01-01

    Of 565 patients with thrombocytopenia admitted to Duke University Hospital between 1975 and 1985, 100 had splenectomy. Ninety-eight patients had failed chronic immunosuppressive therapy and three patients had acute intracranial bleeding or total absence of platelets in the peripheral blood smear, and had urgent splenectomy. At primary splenectomy, accessory spleens were identified and resected in 18% of patients. There was no operative mortality. Fifty-eight patients had an excellent response to splenectomy and their steroids were tapered off within 3 weeks. Thirteen patients had a poor response to primary splenectomy of whom eight remitted spontaneously and five required accessory splenectomy resulting in complete remission in three patients. Twenty-nine patients were considered nonresponders, 25 of whom had radionuclide scanning for accessory spleens. Seven of these patients had accessory spleens identified but only four consented to accessory splenectomy. In three of the four patients, a complete remission was achieved. Neither platelet antibody titers nor measurements of platelet survival or turnover predicted platelet response to splenectomy. However, immune thrombocytopenic purpura (ITP) in older patients was significantly less likely to respond to splenectomy. These data support continuing use of splenectomy in selected patients with ITP and an aggressive search for accessory spleens in patients who relapse since they are easily localized at operation by hand-held isotope detector probe. Images Fig. 6. PMID:3662662

  17. Neonates born to mothers with immune thrombocytopenic purpura: a single-center experience of 20 years.

    PubMed

    Bayhan, Turan; Tavil, Betül; Korkmaz, Ay?e; Ünal, ?ule; Hanalio?lu, Damla; Yi?it, ?ule; Gümrük, Fatma; Çetin, Mualla; Yurdakök, Murat

    2016-01-01

    Neonates born to mothers with immune thrombocytopenic purpura (ITP) have an increased risk of having thrombocytopenia and bleeding. The aim of our study was to determine maternal and fetal factors that can predict bleeding risk in neonates born to mothers with ITP, and effective treatment strategies by retrospective analysis of our single-center data. We performed a retrospective data review of neonates that were recorded as 'neonates born to mothers with ITP' in the Neonatal ICU of Hacettepe University, Ihsan Dogramac? Children's Hospital, Ankara, Turkey. Medical records of 36 neonates born from 35 mothers were analyzed. Among the 36 neonates born to mothers with ITP, thrombocytopenia (platelet count of less than 150?×?10/l) was detected in 20 (56.0%) neonates on the first day of life. Twelve of the 20 neonates with thrombocytopenia (60.0%) required treatment to increase the platelet counts. Clinical findings related to thrombocytopenia occurred in three (15.0%) neonates, but none of them presented with severe bleeding. There was no statistically significant association between neonatal lowest platelet count and maternal lowest platelet count, maternal platelet count at the time of delivery, and duration of thrombocytopenia, respectively. Neonates born to mothers with ITP have an increased tendency to develop thrombocytopenia, but severe bleeding is very rare in these neonates. Clinicians should pay special attention to follow these neonates. According to our results, both intravenous immunoglobulin and methyl prednisolone were found to be in equivalent efficacy for the treatment of neonatal thrombocytopenia due to maternal ITP. PMID:26258676

  18. Adult idiopathic thrombocytopenic purpura (ITP)--a prospective tracking of its natural history.

    PubMed

    Kueh, Y K

    1995-08-01

    Thirty-seven Asian patients (30 women, 7 men) with chronic idiopathic thrombocytopenic purpura (ITP) followed prospectively for 4 to 15 years showed a highly variable clinical course. The women as a group had a much lower initial platelet count than the men (28 x 10(9)/l versus 54 x 10(9)/l). All the women but only 2 men required treatment for symptomatic thrombocytopenia. Six women developed secondary autoimmune disorders (4 systemic lupus erythematosus and 2 Evan's syndrome) after 14 to 33 months of clinical follow up. Although their responses to corticosteroid therapy were suboptimal when initiated for ITP, these 6 patients uniformly demonstrated a complete platelet response when corticosteroid treatment was re-introduced following the evolution of secondary autoimmune disorders. Four of the 5 untreated men were over 55 years of age. Their mild to moderate thrombocytopenia was discovered incidentally and they remained symptom-free after a follow up of at least 5 years. The overall response rates of this cohort of Asian patients to corticosteroid therapy and splenectomy are compared with those reported from the West. Three deaths are recorded in this study, one from intracranial haemorrhage and 2 gram negative septicaemia in steroid-dependent postsplenectomy patients. The variable behaviour of this cohort of ITP patients emphasises the need for individualised management. Asymptomatic thrombocytopenia can be observed without treatment. Two fatalities from gram negative septicaemia in asplenic, steroid-dependent patients caution against the hasty recommendation of splenectomy for refractory ITP. PMID:8919147

  19. Immunologic effects of anti-D (WinRho-SD) in children with immune thrombocytopenic purpura.

    PubMed

    Zimmerman, S A; Malinoski, F J; Ware, R E

    1998-02-01

    Intravenous immunoglobulin (IVIG) is an effective treatment for immune thrombocytopenic purpura (ITP) that induces transient blockade of the reticuloendothelial system (RES) with additional effects including alteration of T lymphocyte subsets and suppression of in vitro T lymphocyte proliferation. As anti-D also is an effective treatment for ITP, we investigated its in vitro and in vivo immunologic effects. The in vitro effects of various agents used in ITP therapy were compared using T lymphocyte proliferation assays. Anti-D caused significantly less inhibition than IVIG or dexamethasone, but non-specific protein was as suppressive as IVIG. Six children with chronic ITP were studied following anti-D administration. Patients received a single dose of anti-D (WinRho-SD, 50 microg/kg i.v. over 5 min) and were studied on day 0, day 7, and 1 month later. Anti-D did not affect T lymphocyte subsets including the T cell receptor variable beta repertoire, in vitro T lymphocyte proliferation to mitogens, recall antigens, or interleukin-2, in vitro IgG synthesis induced by pokeweed mitogen, or T lymphocyte cytokine mRNA levels. We conclude that anti-D has no demonstrable in vitro or in vivo effects on lymphocyte enumeration or function, and therefore likely is effective in the treatment of ITP primarily through RES blockade. PMID:9462545

  20. Defective circulating CD25 regulatory T cells in patients with chronic immune thrombocytopenic purpura

    PubMed Central

    Yu, Jin; Heck, Susanne; Patel, Vivek; Levan, Jared; Yu, Yu; Bussel, James B.

    2008-01-01

    Immune thrombocytopenic purpura (ITP) is characterized by the presence of antiplatelet autoantibodies as a result of loss of tolerance. CD4+CD25+ regulatory T cells (Tregs) are important for maintenance of peripheral tolerance. Decreased levels of peripheral Tregs in patients with ITP have been reported. To test whether inefficient production or reduced immunosuppressive activity of Tregs contributes to loss of tolerance in patients with chronic ITP, we investigated the frequency and function of their circulating CD4+CD25hi Tregs. We found a com-parable frequency of circulating CD4+CD25hiFoxp3+ Tregs in patients and controls (n = 16, P > .05). However, sorted CD4+CD25hi cells from patients with chronic ITP (n = 13) had a 2-fold reduction of in vitro immunosuppressive activity compared with controls (n = 10, P < .05). The impaired suppression was specific to Tregs as shown by cross-mixing experiments with T cells from controls. These data suggest that functional defects in Tregs contribute to breakdown of self-tolerance in patients with chronic ITP. PMID:18420827

  1. Late-Onset Immune Thrombocytopenic Purpura After Withdrawal of Interferon Treatment for Chronic Hepatitis C Infection

    PubMed Central

    Hsiao, Chien-Hao; Tseng, Kuo-Chih; Tseng, Chih-Wei; Tung, Chien-Hsueh

    2015-01-01

    Abstract Immune thrombocytopenic purpura (ITP) is a life-threatening complication following pegylated interferon alpha (PEG-IFN) plus ribavirin treatment, the standard treatment for hepatitis C virus (HCV) infection. We reported a rare case with late-onset ITP after withdrawal of PEG-IFN treatment. A 53-year-old male with hepatitis C developed massive gum bleeding and a severe, reversible, immune thrombocytopenia 2 weeks after cessation of PEG-IFN treatment for HCV due to anemia and depression. The platelet count decreased to 4000?cells/?L. The HCV viral load was undetectable at the end of PEG-IFN treatment and during follow-up for 5 months. Other potential autoimmune disorders were ruled out. Late-onset ITP associated with PEG-IFN treatment was diagnosed. The patient was treated successfully with steroid and azathioprine. Platelet count gradually increased to 117?×?103?cells/?L on the 18th day after admission. ITP is a rare complication in patients with hepatitis C or in patients who received PEG-IFN treatment. The particular case supported that it may occur even after withdrawal of PEG-IFN treatment. Physicians should be aware of this late-onset complication. PMID:26313770

  2. Two Types of Renovascular Lesions in Lupus Nephritis with Clinical Thrombotic Thrombocytopenic Purpura.

    PubMed

    Sekine, Akinari; Hasegawa, Eiko; Hiramatsu, Rikako; Mise, Koki; Sumida, Keiichi; Ueno, Toshiharu; Yamanouchi, Masayuki; Hayami, Noriko; Suwabe, Tatsuya; Hoshino, Junichi; Sawa, Naoki; Takaichi, Kenmei; Ohashi, Kenichi; Fujii, Takeshi; Ubara, Yoshifumi

    2015-01-01

    Renovascular lesions of lupus nephritis (LN) were classified into five categories by D'Agati in Heptinstall's Pathology of the Kidney, with thrombotic microangiopathy (TMA) and clinical thrombotic thrombocytopenic purpura (TTP) being combined. We encountered 2 cases with histological LN (class III and lass V), and they presented with clinical features of TTP, such as acute renal failure, microangiopathic hemolytic anemia, thrombocytopenia, fever, and central neurologic symptoms. Immunosuppressive therapy with plasmapheresis was performed in both patients. Case 1 progressed to end-stage renal failure requiring dialysis and died, while case 2 responded to treatment. In case 1, small renal arteries showed positive mural staining for IgG and C3, while intraluminal material was negative for IgG and C3 [although it was positive for phosphotungstic acid-hematoxylin (PTAH), indicating fibrin deposition]. In case 2, small renal arteries showed mural staining for IgG, C1q, and C3, with the intraluminal material also being positive for these immunoglobulins, but negative for PTAH. These cases suggest that immunosuppressive therapy with plasmapheresis can control LN when intravascular thrombosis is related to immune complexes associated with activation of the early complement components C1q and C3. In contrast, immunosuppressive therapy with plasmapheresis may not be effective when intravascular thrombosis is unrelated to these factors and involves fibrin deposition. Accordingly, in LN patients with clinical features of TTP, we report two types of renovascular lesions, in addition to typical vascular change of TMA with no immune deposits seen in nonlupus patients. PMID:26558253

  3. Two Types of Renovascular Lesions in Lupus Nephritis with Clinical Thrombotic Thrombocytopenic Purpura

    PubMed Central

    Sekine, Akinari; Hasegawa, Eiko; Hiramatsu, Rikako; Mise, Koki; Sumida, Keiichi; Ueno, Toshiharu; Yamanouchi, Masayuki; Hayami, Noriko; Suwabe, Tatsuya; Hoshino, Junichi; Sawa, Naoki; Takaichi, Kenmei; Ohashi, Kenichi; Fujii, Takeshi; Ubara, Yoshifumi

    2015-01-01

    Renovascular lesions of lupus nephritis (LN) were classified into five categories by D'Agati in Heptinstall's Pathology of the Kidney, with thrombotic microangiopathy (TMA) and clinical thrombotic thrombocytopenic purpura (TTP) being combined. We encountered 2 cases with histological LN (class III and lass V), and they presented with clinical features of TTP, such as acute renal failure, microangiopathic hemolytic anemia, thrombocytopenia, fever, and central neurologic symptoms. Immunosuppressive therapy with plasmapheresis was performed in both patients. Case 1 progressed to end-stage renal failure requiring dialysis and died, while case 2 responded to treatment. In case 1, small renal arteries showed positive mural staining for IgG and C3, while intraluminal material was negative for IgG and C3 [although it was positive for phosphotungstic acid-hematoxylin (PTAH), indicating fibrin deposition]. In case 2, small renal arteries showed mural staining for IgG, C1q, and C3, with the intraluminal material also being positive for these immunoglobulins, but negative for PTAH. These cases suggest that immunosuppressive therapy with plasmapheresis can control LN when intravascular thrombosis is related to immune complexes associated with activation of the early complement components C1q and C3. In contrast, immunosuppressive therapy with plasmapheresis may not be effective when intravascular thrombosis is unrelated to these factors and involves fibrin deposition. Accordingly, in LN patients with clinical features of TTP, we report two types of renovascular lesions, in addition to typical vascular change of TMA with no immune deposits seen in nonlupus patients. PMID:26558253

  4. Intravenous anti-D treatment of immune thrombocytopenic purpura: experience in 272 patients.

    PubMed

    Scaradavou, A; Woo, B; Woloski, B M; Cunningham-Rundles, S; Ettinger, L J; Aledort, L M; Bussel, J B

    1997-04-15

    We report the results of intravenous anti-D (WinRho, WinRho SD) therapy in 261 non-splenectomized patients treated at the New York Hospital-Cornell Medical Center over the period from 1987 to 1994. Children (n = 124) and adult patients (n = 137) with classic immune thrombocytopenic purpura (ITP; n = 156) or human immunodeficiency virus (HIV) related thrombocytopenia (n = 105) and acute (n = 75) or chronic (n = 186) disease at the time of the initial anti-D treatment were studied. In addition, 11 previously splenectomized patients were treated as a separate group. Our objectives were to evaluate the following. (1) Efficacy of anti-D: The response after the initial infusion was analyzed according to clinical parameters, such as patient's age, HIV status, gender, disease duration, pretreatment platelet count, and hemoglobin value, as well as treatment-related factors, including the dose of anti-D, the solvent detergent treatment of the preparation, and the type of administration. (2) Use of anti-D as maintenance therapy: The duration of response after the initial infusion and the results of subsequent treatments were evaluated. (3) Safety/toxicity of anti-D: Postinfusion reactions and hemoglobin decrease after treatment were studied. Anti-D is a safe treatment providing a hemostatic platelet increase in greater than 70% of the Rh+ non-splenectomized patients. The group with the best results is HIV- children, but all patient groups respond and the effect lasts more than 21 days in 50% of the responders. Duration of response is not influenced by HIV status; furthermore, HIV+ patients show no adverse effects on hemoglobin decrease or HIV disease progression. Patients with chronic ITP after splenectomy have minimal or no response to intravenous anti-D. PMID:9108386

  5. Ribosomal and Immune Transcripts Associate with Relapse in Acquired ADAMTS13-Deficient Thrombotic Thrombocytopenic Purpura

    PubMed Central

    Edgar, Contessa E.; Terrell, Deirdra R.; Vesely, Sara K.; Wren, Jonathan D.; Dozmorov, Igor M.; Niewold, Timothy B.; Brown, Michael; Zhou, Fang; Frank, Mark Barton; Merrill, Joan T.; Kremer Hovinga, Johanna A.; Lämmle, Bernhard; James, Judith A.; George, James N.; Farris, A. Darise

    2015-01-01

    Approximately 40% of patients who survive acute episodes of thrombotic thrombocytopenic purpura (TTP) associated with severe acquired ADAMTS13 deficiency experience one or more relapses. Risk factors for relapse other than severe ADAMTS13 deficiency and ADAMTS13 autoantibodies are unknown. ADAMTS13 autoantibodies, TTP episodes following infection or type I interferon treatment and reported ensuing systemic lupus erythematosus in some patients suggest immune dysregulation. This cross-sectional study asked whether autoantibodies against RNA-binding proteins or peripheral blood gene expression profiles measured during remission are associated with history of prior relapse in acquired ADAMTS13-deficient TTP. Peripheral blood from 38 well-characterized patients with autoimmune ADAMTS13-deficient TTP in remission was examined for autoantibodies and global gene expression. A subset of TTP patients (9 patients, 24%) exhibited a peripheral blood gene signature composed of elevated ribosomal transcripts that associated with prior relapse. A non-overlapping subset of TTP patients (9 patients, 24%) displayed a peripheral blood type I interferon gene signature that associated with autoantibodies to RNA-binding proteins but not with history of relapse. Patients who had relapsed bimodally expressed higher HLA transcript levels independently of ribosomal transcripts. Presence of any one potential risk factor (ribosomal gene signature, elevated HLA-DRB1, elevated HLA-DRB5) associated with relapse (OR = 38.4; p = 0.0002) more closely than any factor alone or all factors together. Levels of immune transcripts typical of natural killer (NK) and T lymphocytes positively correlated with ribosomal gene expression and number of prior episodes but not with time since the most recent episode. Flow cytometry confirmed elevated expression of cell surface markers encoded by these transcripts on T and/or NK cell subsets of patients who had relapsed. These data associate elevated ribosomal and immune transcripts with relapse history in acquired, ADAMTS13-deficient TTP. PMID:25671313

  6. Eltrombopag enhances platelet adhesion by upregulating the expression of glycoprotein VI in patients with chronic immune thrombocytopenic purpura.

    PubMed

    Chiou, Tzeon-Jye; Chang, Yi-Fang; Wang, Ming-Chung; Kao, Chen-Wei; Lin, Hsuan-Yu; Chen, Tsai-Yun; Hsueh, Erh-Jung; Lan, Yii-Jenq; Sung, Yung-Chuan; Lin, Sheng-Feng; Bai, Li-Yuan; Chen, Caleb G

    2015-12-01

    Eltrombopag, a thrombopoietin receptor agonist, has been approved for the treatment of patients with immune thrombocytopenia because of its abilities to enhance platelet production and reduce hemorrhage. Both platelet count and platelet adhesion are crucial to stop bleeding. Although eltrombopag is known to improve platelet counts, its effects on platelet adhesion are not yet known. This study aimed to assess the efficacy of eltrombopag on platelet production and platelet adhesive affinity. To evaluate the efficacy of low-dose eltrombopag (25 mg) for patients with chronic refractory immune thrombocytopenic purpura (ITP) and to determine the ex vivo platelet adhesion ability before and after treatment with eltrombopag, we conducted an open-label, multicenter study in which 25 Taiwanese patients with chronic ITP were enrolled. During the 6-month evaluation, the starting and maximum doses of eltrombopag were 25 and 50 mg, respectively, to maintain the platelet count of ?50,000 per ?L. Flow-based adhesion assay was used to detect the percentage of platelets adhering to immobilized von Willebrand factor-collagen on microslides. Of the enrolled patients, 48% achieved a platelet count of ?50,000 per ?L. Interestingly, 83% of all responders required 25 mg of eltrombopag daily to achieve the target platelet count. In addition, the percentage of bleeding patients was significantly reduced in both responders and nonresponders by 50% from the baseline level throughout the treatment period. The ex vivo platelet adhesion capacity was elevated after the 6-month eltrombopag treatment in both responders and nonresponders. Furthermore, glycoprotein VI (GPVI) expression was significantly upregulated after treatment with eltrombopag. Low-to-intermediate dose of eltrombopag showed good efficacy to expedite platelet production and augment platelet adhesion. These 2 factors might explain the efficacy of eltrombopag in ameliorating hemorrhage in patients with ITP. PMID:26477577

  7. Unrecognized pattern of von Willebrand factor abnormalities in hemolytic uremic syndrome and thrombotic thrombocytopenic purpura.

    PubMed

    Galbusera, M; Benigni, A; Paris, S; Ruggenenti, P; Zoja, C; Rossi, C; Remuzzi, G

    1999-06-01

    Heterogeneous abnormalities in multimeric structure and fragmentation of endothelial-derived von Willebrand factor (vWF) have been reported in hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). This study was conducted to establish whether different patterns of vWF abnormalities were associated with different clinical syndromes. Plasmatic levels of vWF antigen (vWF:Ag), vWF release from endothelial cells (EC) exposed to patient sera, and vWF multimeric pattern were studied during episodes and again in remission in three groups of patients with severe forms of HUS and TTP paradigmatic of the most common clinical patterns of disease presentation: (1) plasma-responsive; (2) plasma-resistant; and (3) frequently relapsing. Plasma vWF:Ag and serum-induced vWF release from EC were increased in the acute phase of either plasma-responsive and plasma-resistant HUS and TTP, but normalized at remission only in plasma-responsive cases. Both indices were persistently normal in the relapsing forms. Enhanced vWF fragmentation as defined by disappearance of high molecular weight and increase in low molecular weight forms was a consistent finding of the acute phases, and always normalized in remission in all three groups. Unusually large vWF multimers were found exclusively in plasma of relapsing forms of HUS and TTP both during and between relapses. Enhanced levels of vWF:Ag and serum capability to induce vWF release in vitro are markers of disease activity and may reflect systemic endothelial injury and consequent activation. Their presence discriminates acute single-episode cases from relapsing forms and, when failing to normalize with plasma therapy, predicts plasma resistance. Enhanced low molecular weight multimers that closely paralleled disease activity suggest a permissive role of fragmented vWF in the formation of microvascular thrombi. Finally, finding of unusually large multimers exclusively in relapsing forms of HUS and TTP even between relapses, when no other clinical signs of disease activity could be detected, suggests that they cannot be the only factor in microvascular thrombosis. PMID:10361861

  8. Development and validation of a predictive model for death in acquired severe ADAMTS13 deficiency-associated idiopathic thrombotic thrombocytopenic purpura: the French TMA Reference Center experience

    PubMed Central

    Benhamou, Ygal; Assié, Cyrielle; Boelle, Pierre-Yves; Buffet, Marc; Grillberger, Rana; Malot, Sandrine; Wynckel, Alain; Presne, Claire; Choukroun, Gabriel; Poullin, Pascale; Provôt, François; Gruson, Didier; Hamidou, Mohamed; Bordessoule, Dominique; Pourrat, Jacques; Mira, Jean-Paul; Le Guern, Véronique; Pouteil-Noble, Claire; Daubin, Cédric; Vanhille, Philippe; Rondeau, Eric; Palcoux, Jean-Bernard; Mousson, Christiane; Vigneau, Cécile; Bonmarchand, Guy; Guidet, Bertrand; Galicier, Lionel; Azoulay, Elie; Rottensteiner, Hanspeter; Veyradier, Agnès; Coppo, Paul

    2012-01-01

    Background Acquired thrombotic thrombocytopenic purpura is still associated with a 10–20% death rate. It has still not been possible to clearly identify early prognostic factors of death. This study involved thrombotic thrombocytopenic purpura patients with acquired severe (<10% of normal activity) ADAMTS13 deficiency and aimed to identify prognostic factors associated with 30-day death. Design and Methods The study involved a prospective cohort of patients and was carried out between October 2000 and August 2010. A validation cohort of patients was set up from September 2010 to August 2011. Altogether, 281 (analysis cohort) and 66 (validation cohort) consecutive adult thrombotic thrombocytopenic purpura patients with acquired severe ADAMTS13 deficiency were enrolled. The study evaluated 30-day mortality after treatment initiation according to characteristics at inclusion. Results Non-survivors (11%) were older (P=10?6) and more frequently presented arterial hypertension (P=5.10?4) and ischemic heart disease (P=0.013). Prognosis was increasingly poor with age (P=0.004). On presentation, cerebral manifestations were more frequent in non-survivors (P=0.018) and serum creatinine level was higher (P=0.008). The most significant independent variables determining death were age, severe cerebral involvement and LDH level 10 N or over. A 3-level risk score for early death was defined and confirmed in the validation cohort using these variables, with higher values corresponding to increased risk of early death. Conclusions A risk score for early death was defined in patients with thrombotic thrombocytopenic purpura and validated on an independent cohort. This score should help to stratify early treatment and identify patients with a worse prognosis. PMID:22580997

  9. Refractory thrombotic thrombocytopenic purpura associated with oral contraceptives and factor V Leiden: a case report

    PubMed Central

    Tsirakis, George; Mantadakis, Elpis; Xylouri, Irini; Foudoulakis, Andreas; Vardaki, Eleftheria; Katsipi, Irene; Daphnis, Eugene; Samonis, George

    2009-01-01

    Introduction Thrombotic microangiopathies constitute a heterogeneous group of diseases characterised by microangiopathic haemolytic anaemia and thrombocytopaenia associated with platelet aggregation in the microcirculation responsible for ischaemic manifestations. Classically, thrombotic microangiopathies are described as encompassing two main syndromes: thrombotic thrombocytopaenic purpura and the haemolytic-uraemic syndrome Many cases of idiopathic thrombotic thrombocytopaenic purpura have, to date, been associated with severe ADAMTS13 metalloprotease deficiency while haemolytic uraemic syndrome usually occurs in the context of normal protease activity. Oestrogens and factor V Leiden have rarely been implicated in the pathogenesis of thrombotic microangiopathy. Case presentation We describe the case of a 17-year-old female with refractory thrombotic thrombocytopaenic purpura. The patient was receiving a new generation of oral contraceptives for dysmenorrhoea and had factor V Leiden. After undergoing prolonged and intense plasma exchange therapy for 40 days and high dose oral corticosteroids therapy for 90 days, our patient recovered fully. Conclusion Patients with refractory thrombotic thrombocytopaenic purpura should likely be evaluated for congenital thrombophilic disorders and for ingestion of drugs that have been associated with this rare form of thrombotic microangiopathy. Identification of these and as yet other unknown genetic and/or acquired risk factors may lead to more judicious treatment approaches. PMID:19829833

  10. Synergistic interactions between interferon-? and TRAIL modulate c-FLIP in endothelial cells, mediating their lineage-specific sensitivity to thrombotic thrombocytopenic purpura plasma–associated apoptosis

    PubMed Central

    Stefanescu, Radu; Bassett, Dustin; Modarresi, Rozbeh; Santiago, Francisco; Fakruddin, Mohamad

    2008-01-01

    Microvascular endothelial cell (MVEC) injury coupled to progression of platelet microthrombi facilitated by ADAMTS13 deficiency is characteristic of idiopathic and HIV-linked thrombotic thrombocytopenic purpura (TTP). Cytokines capable of inducing MVEC apoptosis in vitro are up-regulated in both TTP and HIV infection. However, the concentrations of these cytokines required to elicit EC apoptosis in vitro are 2- to 3-log–fold greater than present in patient plasmas. We report that clinically relevant levels of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) and interferon (IFN)–? act in synergy to induce apoptosis in dermal MVECs, but have no effect on large-vessel ECs or pulmonary MVECs. This reflects the tissue distribution of TTP lesions in vivo. Sensitivity to TTP plasma or TRAIL plus IFN-? is paralleled by enhanced ubiquitination of the caspase-8 regulator cellular FLICE-like inhibitory protein (c-FLIP), targeting it for proteasome degradation. c-FLIP silencing with anti-FLIP short interfering RNA (siRNA) in pulmonary MVECs rendered them susceptible to TTP plasma– and cytokine-mediated apoptosis, while up-regulation of c-FLIP by gene transfer partially protected dermal MVECs from such injury. TTP plasma–mediated apoptosis appears to involve cytokine-induced acceleration of c-FLIP degradation, sensitizing cells to TRAIL-mediated caspase-8 activation and cell death. Suppression of TRAIL or modulation of immunoproteasome activity may have therapeutic relevance in TTP. PMID:18339897

  11. The splenic autoimmune response to ADAMTS13 in thrombotic thrombocytopenic purpura contains recurrent antigen-binding CDR3 motifs.

    PubMed

    Schaller, Monica; Vogel, Monique; Kentouche, Karim; Lämmle, Bernhard; Kremer Hovinga, Johanna A

    2014-11-27

    Acquired thrombotic thrombocytopenic purpura (TTP) is the consequence of a severe ADAMTS13 deficiency resulting from autoantibodies inhibiting ADAMTS13 or accelerating its clearance. Despite the success of plasma exchange the risk of relapse is high. From 2 patients (A and B), splenectomized for recurrent episodes of acquired TTP, the splenic B-cell response against ADAMTS13 was characterized through generation of human monoclonal anti-ADAMTS13 autoantibodies (mAbs) by cloning an immunoglobulin G (IgG)4?- and IgG4?-Fab library using phage display technology and by Epstein-Barr virus transformation of switched memory B cells (CD19+/CD27+/IgG+). Sequence analysis of the anti-ADAMTS13 IgGs of both patients revealed that the VH gene use was limited in our patients to VH1-3 (55%), VH1-69 (17%), VH3-30 (7%), and VH4-28 (21%) and contained 8 unique and thus far not reported heavy-chain complementarity determining region 3 motifs, of which 4 were shared by the 2 patients. The discovery of several highly similar anti-ADAMTS13 autoantibodies in 2 unrelated TTP patients suggests that the autoimmune response is antigen driven, because the probability that such similar immunoglobulin rearrangements happen by chance is very low (< 10(-9)). PMID:25261198

  12. Comparison of single port and three port laparoscopic splenectomy in patients with immune thrombocytopenic purpura: Clinical comparative study

    PubMed Central

    Barbaros, Umut; Aksakal, Nihat; Tukenmez, Mustafa; Agcaoglu, Orhan; Bostan, Mustafa Sami; Kilic, Berkay; Kalayci, Murat; Dinccag, Ahmet; Seven, Ridvan; Mercan, Selcuk

    2015-01-01

    AIM: Single-port laparoscopic surgery (SILS) has become increasingly popular during the last decades. This prospective study was undertaken to evaluate the feasibility of single-port laparoscopic splenectomy compared with conventional multiport laparoscopic splenectomy. MATERIALS AND METHODS: Between February 2, 2009 and August 29, 2011, a total of 40 patients with the diagnosis of immune thrombocytopenic purpura were included to study. Patients were alienated into two groups according to the procedure type including SILS and conventional multiport splenectomy. RESULTS: There were 19 patients in group 1, and 21 in group 2. Operative time was significantly shorter in group 1 versus group 2 (112.4 ± 13.56 vs 71.2 ±18.1 minutes, respectively, P < 0.05). One patient in group 1 had converted to laparatomy due to preoperative bleeding. Postoperative pain analyses (VAS Score) revealed superiority of SILS in the early post-operative days (P < 0.05). CONCLUSIONS: SILS splenectomy is a safe and effective alternative to standard laparoscopic splenectomy. PMID:26195874

  13. Use of Recombinant Factor VIIa in a Pediatric Patient With Initial Presentation of Refractory Acute Immune Thrombocytopenic Purpura and Severe Bleeding

    PubMed Central

    Gurion, Reut; Siu, Anita; Weiss, Aaron R.; Masterson, Margaret

    2012-01-01

    Severe bleeding in acute immune thrombocytopenic purpura (ITP) is rare but can cause significant complications to the patient. Here we report the case of a pediatric patient with acute ITP and hematuria refractory to anti-D immune globulin, high dose intravenous immunoglobulin G, and high dose steroids. Her hematuria was successfully treated with recombinant factor VIIa (rFVIIa). While further investigation on the use of rFVIIa in ITP is warranted, this case report contributes to the pediatric literature for its use during the course of an initial presentation of ITP with hemorrhagic complications. PMID:23258971

  14. Kinetics and sites of destruction of /sup 111/In-oxine-labeled platelets in idiopathic thrombocytopenic purpura: a quantitative study

    SciTech Connect

    Heyns, A.D.; Loetter, M.G.; Badenhorst, P.N.; de Kock, F.; Pieters, H.; Herbst, C.; van Reenen, O.R.; Kotze, H.; Minnaar, P.C.

    1982-04-01

    Kinetics and quantification of the sites of destruction of /sup 111/In-oxine-labeled autologous platelets were investigated in eight patients with idiopathic thrombocytopenic purpura. The mean platelet count was 17 +/- 9 X 10(9)/liter; platelets were separated by differential centrifugation and labeled with 5.6 +/- 2.5 MBq /sup 111/In. Whole body and organ /sup 111/In-platelet distribution was quantitated with a scintillation camera and a computer-assisted imaging system acquisition matrix. Areas of interest were selected with the computer and organ /sup 111/In-radioactivity expressed as a percentage of whole body activity. Mean platelet survival was 49.5 +/- 29.6 hr and the survival curves were exponential. Equilibrium percentage organ /sup 111/In-radioactivity was (normal values in parentheses): spleen 33.7 +/- 8.8 (31.1 +/- 10.2); liver 16.1 +/- 9.5 (13.1 +/- 1.3); thorax 22.8 +/- 3.7 (28.2 +/- 5.6). Percentage organ /sup 111/In-activity at the time when labeled platelets had disappeared from the circulation was: spleen 44.5 +/- 16.4 (40 +/- 16); liver 16.0 +/- 11.5 (32.4 +/- 7.2); thorax 19.7 +/- 6.0 (17.7 +/- 10.3). Thorax activity corresponds to bone marrow radioactivity. Three patterns of platelet sequestration were evident. Three patients had mainly splenic sequestration, two mainly hepatic sequestration, and three diffuse reticuloendothelial system sequestration with a major component of platelets destroyed in the bone marrow. Splenectomy was performed in two patients. The pattern of /sup 111/In-platelet sequestration was not predictive of response of glucocorticoid therapy or indicative of the necessity for splenectomy. Quantitative /sup 111/In-labeled autologous platelet kinetic studies provide a new tool for the investigation of platelet disorders.U

  15. Solvent/detergent-treated plasma suppresses shear-induced platelet aggregation and prevents episodes of thrombotic thrombocytopenic purpura.

    PubMed

    Moake, J; Chintagumpala, M; Turner, N; McPherson, P; Nolasco, L; Steuber, C; Santiago-Borrero, P; Horowitz, M; Pehta, J

    1994-07-15

    Two children with congenital chronic relapsing thrombotic thrombocytopenic purpura (TTP) have episodes every 3 weeks. These relapses can be prevented by the infusion of normal fresh-frozen plasma (FFP) without concurrent plasmapheresis. We conducted a study to determine whether the exposure of normal plasma to agents that inactivate human immunodeficiency virus and other viruses destroys the component necessary for the effective treatment of this type of TTP that requires only plasma infusion to prevent or reverse relapses. Clinical responsiveness and von Willebrand factor (vWF)-mediated fluid shear stress-induced platelet aggregation were evaluated before and after the infusion of 10 mL/kg FFP or solvent [tri(n-butyl)phosphate]/detergent (Triton X-100)-treated plasma (S/D plasma). Platelet aggregation at shear stresses of 90 to 180 dyne/cm2 (similar to those in the partially occluded microcirculation) imposed for 30 seconds was excessive using the citrated platelet-rich plasma of both patients, and was associated with the presence of unusually large vWF forms in patient platelet-poor plasma. Infusion with either FFP or S/D plasma at 3-week intervals caused the platelet count to increase to (or above) normal within 1 week (on 12 of 12 occasions); the disappearance or diminution of unusually large vWF forms within 1 hour (on 6 of 10 occasions studied); and the reversal within 1 to 4 hours of excessive shear-induced platelet aggregation (on 8 of 9 occasions studied). We conclude that a component in normal plasma resistant to S/D treatment is responsible for preventing thrombocytopenia and TTP episodes, and for controlling excessive shear-induced aggregation in these patients. Our results suggest that excessive in vivo platelet aggregation in chronic relapsing TTP and excessive in vitro vWF-mediated shear-induced aggregation may be similar phenomena. PMID:8025277

  16. FATAL OUTCOME OF INFECTION BY DENGUE 4 IN A PATIENT WITH THROMBOCYTOPENIC PURPURA AS A COMORBID CONDITION IN BRAZIL

    PubMed Central

    Amâncio, Frederico Figueiredo; Pereira, Maira Alves; Iani, Felipe Campos de Melo; D'anunciação, Lorena; de Almeida, Jorge Luís Carvalho; Soares, Janer Aparecida Silveira; Ferraz, Marcela Lencine; Vale, Thiago Cardoso; Lambertucci, José Roberto; Carneiro, Mariângela

    2014-01-01

    Dengue is currently a major public-health problem. Dengue virus (DENV) is classified into four distinct serotypes, DENV 1-4. After 28 years of absence, DENV-4 was again detected in Brazil in 2010 in Roraima State, and one year later, the virus was identified in the northern Brazilian states of Amazonas and Pará, followed by Rio de Janeiro and São Paulo. In Minas Gerais, the first confirmed case of DENV-4 occurred in the municipality of Frutal in 2011 and has now been isolated from a growing number of patients. Although DENV-2 is associated with the highest risk of severe forms of the disease and death due to the infection, DENV-4 has also been associated with severe forms of the disease and an increasing risk of hemorrhagic manifestations. Herein, the first fatal case of confirmed DENV-4 in Brazil is reported. The patient was an 11-year-old girl from the municipality of Montes Claros in northern Minas Gerais State, Brazil. She had idiopathic thrombocytopenic purpura as a comorbid condition and presented with a fulminant course of infection, leading to death due to hemorrhagic complications. Diagnosis was confirmed by detection of Dengue-specific antibodies using IgM capture enzyme-linked immunosorbent assay and semi-nested RT-PCR. Primary care physicians and other health-care providers should bear in mind that DENV-4 can also result in severe forms of the disease and lead to hemorrhagic complications and death, mainly when dengue infection is associated with coexisting conditions. PMID:24879007

  17. Thrombotic Thrombocytopenic Purpura

    MedlinePLUS

    ... include infusions of fresh frozen plasma and plasma exchange, also called plasmapheresis (PLAZ-ma-feh-RE-sis). These treatments have greatly improved the outlook of the disorder. Rate This Content: NEXT >> Updated: March 21, 2014

  18. Thrombotic thrombocytopenic purpura following salvage chemotherapy with paclitaxel, ifosfamide and cisplatin in a patient with a refractory germ cell tumor: A case report and review of the literature

    PubMed Central

    ULAS, ARIFE; SILAY, KAMILE; AKINCI, SEMA; AKINCI, MUHAMMED BULENT; SENDUR, MEHMET ALI; DEDE, DIDEM SENER; POLAT, YUNUS HALIL; YALCIN, BULENT

    2015-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a rare form of thrombotic microangiopathy that is characterized by microvascular thrombosis, thrombocytopenia, hemolysis and end organ damage. An extensive variety of drugs, including certain chemotherapeutic agents, have been associated with TTP. However, paclitaxel, cisplatin and ifosfamide regimen (TIP)-induced TTP has not previously been described. The present study reports the case of a 43-year-old patient with a refractory testicular germ cell tumor who developed acute TTP during TIP chemotherapy. Following the third cycle of TIP chemotherapy, the patient developed fever, anemia, thrombocytopenia and confusion. A diagnosis of TTP was established. Plasmapheresis was initiated as daily treatment in the first week, then continued every other day for 4 weeks. TIP chemotherapy was discontinued. The patient's clinical and neurological symptoms improved markedly after a week. Renal function and hemolysis improved, and the patient was discharged in a stable condition. The patient did not develop any complications and has been in remission for 5 months. The Naranjo adverse drug reaction probability scale indicated a likely association between TTP and the TIP chemotherapy regimen in this patient. This case is also investigated with regard to the associated literature to increase the awareness of TTP following chemotherapy.

  19. Long-term remission induced by low-dose rituximab for relapsed and refractory thrombotic thrombocytopenic purpura: A report of two cases

    PubMed Central

    TONG, HONG-YAN; YE, LI; YE, XING-NONG; LU, DE-MIN; LI, YING

    2015-01-01

    Thrombotic thrombocytopenic purpura (TTP) is acquired in the majority of cases. Traditional therapy consists of plasma exchange (PEX), as well as the administration of certain immunosuppressive agents including steroids. A standard dose of rituximab (RTX) at 375 mg/m2 weekly for 4 consecutive weeks was recently demonstrated to have significant activity in patients with acquired TTP. To date, clinicians have limited experience using low-dose RTX. In the present study, 2 patients were treated with low-dose RTX at 100 mg weekly for 4 consecutive weeks as a salvage therapy following failure to respond to PEX and other immunosuppressive agents. Prior to RTX therapy, the patients had severely deficient ADAMTS13 activity and detectable anti-ADAMTS13 inhibitors. The patients achieved complete remission and presented long-term stabilization during follow-up. Repeated detection during follow-up demonstrated that the patients had 100% ADAMTS13 activity and undetectable anti-ADAMTS13 antibodies. Although further investigation in a prospective clinical trial is required, the use of low-dose RTX seems to be as effective as a standard dose for patients with relapsing or refractory acquired TTP.

  20. Anti-D (WinRho SD) treatment of children with chronic autoimmune thrombocytopenic purpura stimulates transient cytokine/chemokine production.

    PubMed

    Semple, J W; Allen, D; Rutherford, M; Woloski, M; David, M; Wakefield, C; Butchart, S; Freedman, J; Blanchette, V

    2002-03-01

    Intravenous anti-D is often used in the treatment of autoimmune thrombocytopenic purpura (AITP), but little is known about its mechanisms of action. To investigate anti-D's potential in vivo mechanism(s) of action, a small group (N = 7) of children with chronic AITP was studied. The children initially received either 25 or 50 microg/kg of WinRho-SD in a four-cycle cross-over trial, and peripheral blood samples from the first and third cycles were assessed for cytokine levels at pre-treatment, 3 hr, 1 day, and 8 days post-treatment. Results showed that platelet counts significantly increased in all the children by day 8 post-treatment. Analysis of serum by ELISA showed that there was a significant but transient rise in both pro- and anti-inflammatory cytokine/chemokine levels (e.g., IL1RA, IL6, GM-CSF, MCP-1 alpha, TNF-alpha and MCP-1) by 3 hr post-treatment in both cycles which returned to baseline levels by 8 days post-treatment. These results suggest that anti-D administration may initially activate the RES in the form of cytokine/chemokine secretion, which is subsequently followed by an increase in platelet counts. It is possible that the induced cytokine/chemokine storm may have an effect on several physiological processes such as those mediating either adverse effects or potentially RES phagocytic activity. PMID:11891813

  1. Metastatic Breast Cancer with Extensive Osseous Metastasis Presenting with Symptomatic Immune Thrombocytopenic Purpura and Anemia: A Case Report and Review of the Literature

    PubMed Central

    Niu, Jiaxin; Goldin, Teresa; Markman, Maurie; Kundranda, Madappa N.

    2015-01-01

    Background Immune thrombocytopenic purpura (ITP) is a rare acquired bleeding disorder with an estimated incidence of 1 in 10,000 people in the general population. The association of ITP with breast cancer is an even rarer entity with very limited reports in the English literature. Case Presentation We report a case of a 51-year-old female with no significant past medical history who presented with sudden onset of malaise, syncope, gingival bleed and epistaxis. She was found to have severe thrombocytopenia (platelet count 6,000/?l) and anemia (hemoglobin 7.2 g/dl). Her workup led to the diagnosis of metastatic ductal breast cancer with extensive bone metastasis. Bone marrow biopsy demonstrated myelophthisis which was initially thought to be consistent with her presentation of thrombocytopenia and anemia. Therefore, the patient was started on hormonal therapy for the treatment of her metastatic breast cancer. After 3 months of therapy, she did not improve and developed severe mucosal bleeding. Her clinical presentation was suspicious for ITP and immune-mediated anemia, and hence she was started on steroids and intravenous immunoglobulin. The patient had a dramatic response to therapy with normalization of her platelet count and hemoglobin within 2 weeks. Conclusion To our knowledge, this is the first reported case of metastatic breast cancer presenting with symptomatic ITP and anemia, and both symptoms are postulated to be immune-mediated. PMID:26120311

  2. The D173G mutation in ADAMTS-13 causes a severe form of congenital thrombotic thrombocytopenic purpura. A clinical, biochemical and in silico study.

    PubMed

    Lancellotti, Stefano; Peyvandi, Flora; Pagliari, Maria Teresa; Cairo, Andrea; Abdel-Azeim, Safwat; Chermak, Edrisse; Lazzareschi, Ilaria; Mastrangelo, Stefano; Cavallo, Luigi; Oliva, Romina; De Cristofaro, Raimondo

    2015-12-22

    Congenital thrombotic thrombocytopenic purpura (TTP) is a rare form of thrombotic microangiopathy, inherited with autosomal recessive mode as a dysfunction or severe deficiency of ADAMTS-13 (A Disintegrin And Metalloprotease with ThromboSpondin 1 repeats Nr. 13), caused by mutations in the ADAMTS-13 gene. About 100 mutations of the ADAMTS-13 gene were identified so far, although only a few characterised by in vitro expression studies. A new Asp to Gly homozygous mutation at position 173 of ADAMTS-13 sequence was identified in a family of Romanian origin, with some members affected by clinical signs of TTP. In two male sons, this mutation caused a severe (

  3. The complex differential diagnosis between thrombotic thrombocytopenic purpura and the atypical hemolytic uremic syndrome: Laboratory weapons and their impact on treatment choice and monitoring.

    PubMed

    Mannucci, P M; Cugno, M

    2015-11-01

    Thrombocytopenia and microangiopathic hemolytic anemia are the hallmark of the thrombotic microangiopathies (TMAs) thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). TTP, inherited or autoimmune, is mainly caused by the plasma deficiency of the von Willebrand factor cleaving protease ADAMTS13, owing to gene mutations or autoantibodies. Typical HUS is often caused by infections with Shiga-Toxin-producing Escherichia coli and thus is called STEC-HUS. The rarer atypical form of HUS is often associated with complement dysregulation, owing to the inherited deficiency or dysfunction of factor H or other complement proteins. In the past the distinction between these TMAs was almost exclusively based on clinical grounds, the term TTP being used for cases with predominant neurological involvement, STEC HUS for cases presenting with bloody diarrhea and atypical HUS identifying patients with severe renal damage. However the clinical presentation may not easily distinguish TTP from atypical HUS. A more accurate differential diagnosis has clinical implications, because plasma exchange (the treatment of choice in TTP) is much less effective in atypical HUS, which shows dramatic short- and long-term therapeutic benefits from eculizumab, a monoclonal antibody that inhibits complement activation. This article will point out that the measurement of ADAMTS13 is able to diagnose accurately the majority of TTP cases, and that very simple tests such as the platelet count and serum creatinine can predict the deficiency of the protease with a good degree of accuracy. In atypical HUS, new methods were recently developed that not only demonstrate the activation of the complement system, i.e., the main disease mechanism, but also help to tailor the short- and long-term treatment with eculizumab. PMID:26386489

  4. Efficacy, safety, and dose response of intravenous anti-D immune globulin (WinRho SDF) for the treatment of idiopathic thrombocytopenic purpura in children.

    PubMed

    Freiberg, A; Mauger, D

    1998-01-01

    We analyzed data from 20 children treated for acute or chronic idiopathic (immune) thrombocytopenic purpura (ITP) at a single institution to determine the relationship between dose of intravenous anti-D immune globulin (WinRho SDF; Nabi, Boca Raton, FL), increase in platelet count, and decrease in hemoglobin in the therapy of ITP. Higher doses of anti-D were clearly associated with a greater therapeutic response in the platelet count, with no increase in hemolysis for both acute and chronic ITP. A significant correlation was found between dose and peak increase in platelet count measured in the 14 days following administration. This effect was present for both acute ITP (17 infusions, P = .0001) and chronic ITP (30 infusions, P = .038). Although hemolysis was seen in nearly all infusions, with a median hemoglobin fall of 1.9 g/dL (range, 0 to 4.2), the decrease in hemoglobin was greater than 2.5 for only three infusions, and the largest fall in hemoglobin (4.2) was in a child with an underlying hemolytic anemia. Furthermore, for both acute and chronic ITP there was no relationship between the decrease in hemoglobin and the dose given (P = .22), nor between the increase in platelet count and fall in hemoglobin (P = .27). This analysis supports the use of higher doses of anti-D for the treatment of ITP, and demonstrates the need for a trial of high-dose anti-D (>100 microg/kg) in acute and chronic ITP. PMID:9523746

  5. Evaluation of the effects of and earliest response rate to anti-D treatment in children with chronic idiopathic thrombocytopenic purpura: a pilot study.

    PubMed

    Yetgin, Sevgi; Aytaç, Selin; Olcay, Lale; Tunç, Bahattin; Ozbek, Namik; Aydinok, Ye?im

    2010-01-01

    In this pilot study, 30 (14 male, 16 female; median age: 8 years, range: 2-18) chronic non-splenectomized idiopathic thrombocytopenic purpura (ITP) patients with Rh+ blood group and their 49 attacks were evaluated after intravenous (i.v.) anti-D (WinRho SDF, Cangene Corporation, Winnipeg, MB, Canada) treatment at a dose of 50 microg/kg x 3 days (n = 21 cases; 35 attacks) or a single dose of 75 microg/kg (n = 9 cases; 14 attacks) to define the hemostatic dose of anti-D. Five of 30 patients (22/49 attacks) were resistant to steroid, intravenous immunoglobulin (IVIG) and vincristine treatment. Hemoglobin (Hb), white blood cells (WBC), platelets (plt) and reticulocytes (ret) were evaluated before and after treatment during the follow-up in sequences on the 1st, 7th, 14th and 21st days after anti-D treatment if the patients had no symptom. All patients, even the resistant ones, experienced an increase in plt count to provide protection from bleeding (> or = 20 x 10(9)/L in patients with symptoms, > or = 10 x 10(9)/L in patients without symptoms). The plt responses of one resistant and five non-resistant patients treated with a single 75 microg/kg dose of i.v. anti-D in 8 attacks were monitored at the 2nd, 4th, 8th, 24th and 48th hours of the treatment. A protective plt level was attained within 2 hours in 6 attacks of five non-resistant cases and in 24 hours in the remaining 2 attacks of one resistant case. This pilot study suggests that anti-D treatment in ITP patients is effective and can increase plt to a level adequate enough to protect from hemorrhage within 2 hours, when given in a 75 microg/kg dose. A few adverse events (i.e. chills, hemolysis and hemoglobinuria) resolved without intervention. PMID:20560246

  6. Intravenous anti-D treatment of immune thrombocytopenic purpura: analysis of efficacy, toxicity, and mechanism of effect.

    PubMed

    Bussel, J B; Graziano, J N; Kimberly, R P; Pahwa, S; Aledort, L M

    1991-05-01

    The efficacy, toxicity, and mechanism of effect of intravenous Anti-D (Winrho) were studied in 43 Rh+ patients with immune thrombocytopenia purpura (ITP) who had not undergone splenectomy and in three already splenectomized patients. The mean platelet increase for the 43 nonsplenectomized patients was 95,000/microL (median 43,000/microL). Children had greater acute platelet responses than did adults. Human immunodeficiency virus status and duration of thrombocytopenia did not affect response. Maintenance treatment was given to patients as needed: the average interval between infusions was 24 days. The three splenectomized patients had no platelet response whatsoever. Toxicity was minimal; infusions were completed in less than 5 minutes. The generally accepted mechanism of effect of Anti-D has been Fc receptor blockade by substitution of antibody-coated red blood cells for antibody-coated platelets. Evidence is presented suggesting that the effect of IV Anti-D is not limited to Fc receptor blockade, including: (1) no correlation of parameters of hemolysis with platelet increase; (2) a 48- to 72-hour delay before platelet increase; (3) a tendency of the change in monocyte Fc receptor I expression to correlate with platelet increase; and (4) increased in vitro production of antibodies to sheep red blood cells following IV Anti-D infusion. PMID:1850307

  7. What Causes Thrombotic Thrombocytopenic Purpura?

    MedlinePLUS

    ... is involved in blood clotting. Not having enough enzyme activity causes overactive blood clotting. In TTP, blood clots ... make a normal ADAMTS13 enzyme. As a result, enzyme activity is lacking or changed. "Inherited" means that the ...

  8. A phase-II sequential case-series study of all patients presenting to four plasma exchange centres with presumed relapsed/refractory thrombotic thrombocytopenic purpura treated with rituximab.

    PubMed

    Clark, William F; Rock, Gail; Barth, David; Arnold, Donald M; Webert, Kathyrn E; Yenson, Paul R; Kelton, John G; Li, Lihua; Foley, Steven R

    2015-07-01

    The primary objective of this phase II study was to evaluate the efficacy of rituximab in the management of adult patients with physician-diagnosed presumed thrombotic thrombocytopenic purpura (TTP); relapsed or refractory. We conducted a multicentre study in four Canadian hospital-based apheresis units. Forty patients with presumed TTP (20 refractory and 20 relapsing) were sequentially enrolled and all received rituximab in a standardized manner. A complete response was documented in 14 of 19 refractory patients by week 8 and 15/16 were alive and in remission at 52 weeks (one patient was lost to follow-up, one was a non-responder, and three died). Among relapsing patients, 16/18 had a complete response at week 8 and 18/18 at week 52 (one patient lost to follow-up and one withdrew). At 1 year, all relapsing and 85% of refractory patients survived. Of 38/40 patients who had ADMATS13 testing at study entry, 13/19 refractory and 10/19 relapsing patients had ADAMTS13 < 10% (typical TTP); whereas 6/19 refractory and 9/19 relapsing cases had ADAMTS13 > 10% (other thrombotic microangiopathy; TMA). Refractory-typical TTP in contrast to refractory-other TMA and all relapsing patients treated with plasma exchange and rituximab, were less likely to be responsive and more likely to die or relapse. PMID:25855259

  9. Investigation of whether the acute hemolysis associated with Rho(D) immune globulin intravenous (human) administration for treatment of immune thrombocytopenic purpura is consistent with the acute hemolytic transfusion reaction model

    PubMed Central

    Gaines, Ann Reed; Lee-Stroka, Hallie; Byrne, Karen; Scott, Dorothy E.; Uhl, Lynne; Lazarus, Ellen; Stroncek, David F.

    2012-01-01

    BACKGROUND Immune thrombocytopenic purpura and secondary thrombocytopenia patients treated with Rho(D) immune globulin intravenous (human; anti-D IGIV) have experienced acute hemolysis, which is inconsistent with the typical presentation of extravascular hemolysis—the presumed mechanism of action of anti-D IGIV. Although the mechanism of anti-D-IGIV–associated acute hemolysis has not been established, the onset, signs/symptoms, and complications appear consistent with the intravascular hemolysis of acute hemolytic transfusion reactions (AHTRs). In transfusion medicine, the red blood cell (RBC) antigen-antibody incompatibility(-ies) that precipitate AHTRs can be detected in vitro with compatibility testing. Under the premise that anti-D-IGIV–associated acute hemolysis results from RBC antigen-antibody–mediated complement activation, this study evaluated whether the incompatibility(-ies) could be detected in vitro with a hemolysin assay, which would support the AHTR model as the hemolytic mechanism. STUDY DESIGN AND METHODS Seven anti-D IGIV lots were tested to determine the RBC antibody identities in those lots, including four lots that had been implicated in acute hemolytic episodes. Hemolysin assays were performed that tested each of 73 RBC specimens against each lot, including the RBCs of one patient who had experienced acute hemolysis after anti-D IGIV administration. RESULTS Only two anti-D IGIV lots contained RBC antibodies beyond those expected. No hemolysis endpoint was observed in any of the hemolysin assays. CONCLUSION Although the findings did not support the AHTR model, the results are reported to contribute knowledge about the mechanism of anti-D-IGIV–associated acute hemolysis and to prompt continued investigation into cause(s), prediction, and prevention of this potentially serious adverse event. PMID:19220820

  10. How Is Thrombotic Thrombocytopenic Purpura Diagnosed?

    MedlinePLUS

    ... blood test measures a protein called lactate dehydrogenase (LDH). For this test, a sample of blood is ... red blood cells to break down and release LDH into the blood. LDH also is released from ...

  11. How Is Thrombotic Thrombocytopenic Purpura Treated?

    MedlinePLUS

    ... plasma for people who have inherited TTP Plasma exchange for people who have acquired TTP Plasma therapy ... replace the missing or changed ADAMTS13 enzyme. Plasma exchange (also called plasmapheresis) is used to treat acquired ...

  12. Safety and Efficacy Study of Romiplostim to Treat ITP in Pediatric Subjects

    ClinicalTrials.gov

    2015-07-13

    Idiopathic Thrombocytopenic Purpura; Thrombocytopenia; Thrombocytopenia in Pediatric Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP); Thrombocytopenia in Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP); Thrombocytopenic Purpura; Immune Thrombocytopenia

  13. Local leukocyte proliferation as a target for cyclophosphamide in the treatment of Henoch-Schönlein purpura nephritis grade VI.

    PubMed

    Kaneko, Masahiro; Ikezumi, Yohei; Yamada, Takeshi; Hasegawa, Hiroya; Kaneko, Utako; Saitoh, Akihiko

    2016-01-01

    Henoch-Schönlein purpura nephritis (HSPN) is one of the most common types of chronic glomerulonephritis in children; however, there have been few reports on the pathogenesis and management of grade VI HSPN. We present the case of a 6-year-old boy with grade VI HSPN accompanied by severe nephrotic syndrome and hypocomplementaemia. Immunohistological studies revealed profound glomerular accumulation of CD45- and CD68-positive inflammatory cells. Moreover, some cells expressed the proliferating marker proliferating cell nuclear antigen. His proteinuria and general oedema persisted despite repeated high-dose steroid therapy; however, these clinical symptoms immediately improved after beginning treatment with cyclophosphamide (CyP). Grade VI HSPN was successfully treated with steroids and immunosuppressants. Among immunosuppressive drugs, CyP was considered the most effective. PMID:26693846

  14. Assessment of Regulatory T Cells in Childhood Immune Thrombocytopenic Purpura

    PubMed Central

    Mazzucco, Karina L. M.; Junior, Lauro M.; Lemos, Natália E.; Wieck, Andréa; Pezzi, Annelise; Laureano, Alvaro M.; Amorin, Bruna; Valim, Vanessa; Silla, Lucia; Daudt, Liane E.; Marostica, Paulo J. C.

    2013-01-01

    This study had the objective to assess the frequency of Tregs in children newly diagnosed with ITP and ascertain whether an association exists between Tregs and platelet counts, by means of a comparison with healthy controls. This case-control study included 19 patients newly diagnosed with ITP—whose blood samples were collected at four points in time: before any therapy and 1, 3, and 6 months after diagnosis—and 19 healthy controls. Tregs (CD4+ CD25+Foxp3 T cells) were evaluated by flow cytometry. There was a statistically significant difference in platelet count between the case and control groups. There were no significant differences in Treg counts between cases and controls at any point during the course of the study and no difference in Treg counts between the chronic and nonchronic groups and no significant correlation between Tregs and platelet counts in the case and control groups. The findings of this study did not show any statistically significant correlation between Tregs and number of platelets in the case and control groups. Treg cells did not play a role in the regulation of autoimmunity in children with ITP. PMID:24298390

  15. Cryoglobulinaemia in Henoch-Schönlein purpura.

    PubMed

    Garcia-Fuentes, M; Chantler, C; Williams, D G

    1977-07-16

    Sera from patients with Henoch-Schönlein purpura were examined for cryoglobulinaemia. Thirty patients had acute Henoch-Schönlein purpura, with or without renal diseas; 14 had chronic nephritis after a previous episode of purpura; and 17 were well, without urinary abnormalities, after recovering from Henoch-Schönlen purpura. Raised concentrations of cryoglobulins were present in 14 (47%) of those with acute purpura, nine (64%) of those with chronic nephritis, but none of those who had recovered completely from Henoch-Schönlein purpura. This suggests that acute Henoch-Schönlein purpura and the chronic nephritis that sometimes follows it have an immune-complex pathogenesis. IgA and properdin were found in several cryoglobulins, which suggested that complement had been activated via the alternative pathway, but isolated cryoglobulins capable of splitting C3 in vitro did so via the classical pathway. PMID:871825

  16. Ocular purpura in a swimmer.

    PubMed Central

    Jowett, N. I.; Jowett, S. G.

    1997-01-01

    Swimming goggles are increasingly being worn by children during swimming lessons to protect their eyes, although reports of ocular damage associated with their use is becoming more common. We describe a new injury, 'purpura gogglorum', caused by overtight application of faulty goggles. Whilst no permanent harm to the eyes resulted in this case, other swimmers have sustained more serious ocular damage, including loss of sight, from goggle-associated injury. Images Figure PMID:9497956

  17. How we use WinRho in patients with idiopathic thrombocytopenic purpura.

    PubMed

    Stotler, Brie A; Schwartz, Joseph

    2015-11-01

    Primary immune thrombocytopenia (ITP) is an autoimmune disease that affects children and adults. WinRho SDF is a D immune globulin product that is Food and Drug Administration approved for the treatment of ITP in D+ pediatric and adult patients. WinRho is a plasma-derived biologic product dispensed from blood banks. Transfusion medicine physicians serve as a resource to health care providers regarding blood component and derivative usage and, as such, should be familiar with the use of WinRho for ITP, including the dosage, administration, and contraindications. This report details the transfusion medicine consultation practice and guidelines at a tertiary care academic medical center for the usage of WinRho SDF in patients with ITP. PMID:26094894

  18. Thrombotic thrombocytopenic purpura and its look-alikes: a single institution experience.

    PubMed

    Bellone, Michael; Chiang, Jason; Ahmed, Tahmeena; Galanakis, Dennis; Senzel, Lisa

    2012-02-01

    At presentation, variant or "look-alike" conditions can resemble TTP. We reviewed charts of 26 consecutive patients treated for presumed TTP. Of 15 classic TTP patients, 11 were tested for ADAMTS13; all showed severe deficiency, and inhibitor levels correlated with probability of relapse. The variant TMA group consisted of 8 patients who had active clinical disorders which overlapped with TTP. Variant TMA patients had higher creatinine and worse prognosis than classic TTP patients. "Look-alike" disorders included ITP with intravascular hemolysis following administration of WinRho™, and human granulocytic anaplasmosis. These conditions had not been previously described as TTP look-alikes. PMID:22154043

  19. Psychogenic Purpura (Gardner-Diamond Syndrome)

    PubMed Central

    Bhattacharya, Gaurav

    2015-01-01

    Psychogenic purpura, also known as Gardner-Diamond syndrome or autoerythrocyte sensitization syndrome, is a rare condition characterized by spontaneous development of painful edematous skin lesions progressing to ecchymosis over the next 24 hours. Severe stress and emotional trauma always precede the skin lesions. The condition is most commonly seen in women, but isolated cases have been reported in adolescents and in males. Psychodermatologic evaluation and dermatology and psychiatry liaison have been successful in the treatment of these patients. This report provides an overview of psychogenic purpura and presents the case of a 15-year-old girl. PMID:26137346

  20. Henoch-Schönlein Purpura with Posterior Reversible Encephalopathy Syndrome.

    PubMed

    Stefek, Bryan; Beck, Michael; Ioffreda, Michael; Gardner, Lyndsay; Stefanski, Michael

    2015-11-01

    Henoch-Schönlein purpura is a common small-vessel vasculitis that presents in children as nonthrombocytopenic, nontender, and palpable purpura, arthritis/arthralgia, and abdominal pain. Central nervous system involvement is a reported, but likely, under-recognized complication. We present an 8-year-old boy with Henoch-Schönlein purpura and posterior reversible encephalopathy syndrome, after proposed mechanism and treatment considerations. PMID:26323197

  1. Drug-related Henoch-Schönlein Purpura.

    PubMed

    Escudero, A; Lucas, E; Vidal, J B; Sánchez-Guerrero, I; Martínez, A; Illán, F; Ramos, J

    1996-01-01

    We report the case of a patient with Henoch-Schönlein Purpura related to a treatment with cefuroxime and diclofenac who presented important systemic manifestations including a glomerulonephritis with IgA mesangial deposits. Skin testing with beta lactam antibiotics and diclofenac were negative in immediate and late reaction as well as RAST test to penicillins G and V. No cautious administration of drugs was done because of the illness severity. Although a reaction to diclofenac could not be excluded we thought that the more probably implicated drug was cefuroxime because the patient referred a purpuric rash after the intake of cephradine for a mastitis, ten years ago. PMID:8882757

  2. Coagulopathy and functional hyposplenism during an episode of thrombotic thrombocytopenic purpura in a HgbS/?+-thalassemia patient

    PubMed Central

    Gangemi, Andrew J; Pickens, Peter V

    2015-01-01

    Key Clinical Message We report a case of TTP in a sickle cell/?+-thalassemia heterozygote with nonspecific complaints and a evidence of hemolysis, initially attributed to sickle crisis. Included in this case is a discussion of the development of functional hyposplenism, a rarely reported complication, limitation of ADAMTS-13 in diagnosis, and the use of platelet transfusion. PMID:26273433

  3. Rituximab treatment for adult purpura nephritis with nephrotic syndrome.

    PubMed

    Ishiguro, Hiroaki; Hashimoto, Tatsuo; Akata, Mariko; Suzuki, Shota; Azushima, Kengo; Kobayashi, Yusuke; Kanaoka, Tomohiko; Yoshida, Shinichiro; Wakui, Hiromichi; Oshikawa, Jin; Nagahama, Kiyotaka; Inayama, Yoshiaki; Tamura, Kouichi; Toya, Yoshiyuki; Umemura, Satoshi

    2013-01-01

    The case of a 68-year-old woman with purpura nephritis associated with nephrotic syndrome is herein described. The patient's clinical course and the findings of a renal biopsy study revealed purpura nephritis. Following treatment with corticosteroids and intravenous cyclophosphamide accompanied by an angiotensin II type I receptor-blocker, an anti-platelet drug and an hydroxymethylglutaryl (HMG)-CoA, the proteinuria mildly decreased. Additional rituximab therapy led to a complete remission. This report describes our successful experience using rituximab to treat refractory nephrotic syndrome of purpura nephritis. Further studies are required to confirm the efficacy of rituximab as an alternative therapy for nephrotic syndrome. PMID:23676594

  4. Retiform purpura: a new stigmata of illicit drug use?

    PubMed

    Geller, Lauren; Whang, Talley B; Mercer, Stephen E; Phelps, Robert

    2011-01-01

    We report a 50-year-old woman who presented with a six-month history of recurrent retiform purpura of uncertain etiology. Laboratory findings included neutropenia, positive anticardiolipin IgM antibody, and a weakly positive p-ANCA. Histopathology revealed a leukocytoclastic vasculitis with intravascular thrombi. Urine toxicology screen was positive for cocaine. These findings are similar to recent reports of agranulocytosis and purpura induced by levamisole-tainted cocaine. A review of the clinical and histopathological findings associated with levamisole-induced purpura will be discussed. PMID:21382290

  5. Purpura Fulminans Secondary to Rickettsial Infection: A Case Report

    PubMed Central

    Holyachi, Renuka; Kadeli, Deepak K

    2015-01-01

    Purpura fulminans is an acute life threatening disorder characterized by cutaneous haemorrhagic manifestations and necrosis caused by disseminated intravascular coagulation and dermal vascular thrombosis. In this case a 60-year-old male presented with purpuric lesions over both upper and lower limbs and consumption coagulopathy following rickettsial infection. It was diagnosed as purpura fulminans secondary to rickettsial infection with disseminated intravascular coagulation and treated with replacement of platelets and coagulation factors along with antibiotics and doxycycline. PMID:26673422

  6. Endoscopy in neutropenic and/or thrombocytopenic patients

    PubMed Central

    Tong, Michelle C; Tadros, Micheal; Vaziri, Haleh

    2015-01-01

    AIM: To evaluate the safety of endoscopic procedures in neutropenic and/or thrombocytopenic cancer patients. METHODS: We performed a literature search for English language studies in which patients with neutropenia and/or thrombocytopenia underwent endoscopy. Studies were included if endoscopic procedures were used as part of the evaluation of neutropenic and/or thrombocytopenic patients, yielding 13 studies. Two studies in which endoscopy was not a primary evaluation tool were excluded. Eleven relevant studies were identified by two independent reviewers on PubMed, Scopus, and Ovid databases. RESULTS: Most of the studies had high diagnostic yield with relatively low complication rates. Therapeutic endoscopic interventions were performed in more than half the studies, including high-risk procedures, such as sclerotherapy. Platelet transfusion was given if counts were less than 50000/mm3 in four studies and less than 10000/mm3 in one study. Other thrombocytopenic precautions included withholding of biopsy if platelet count was less than 30000/mm3 in one study and less than 20000/mm3 in another study. Two of the ten studies which examined thrombocytopenic patient populations reported bleeding complications related to endoscopy, none of which caused major morbidity or mortality. All febrile neutropenic patients received prophylactic broad-spectrum antibiotics in the studies reviewed. Regarding afebrile neutropenic patients, prophylactic antibiotics were given if absolute neutrophil count was less than 1000/mm3 in one study, if the patient was undergoing colonoscopy and had a high inflammatory condition without clear definition of significance in another study, and if the patient was in an aplastic phase in a third study. Endoscopy was also withheld in one study for severe pancytopenia. CONCLUSION: Endoscopy can be safely performed in patients with thrombocytopenia/neutropenia. Prophylactic platelet transfusion and/or antibiotic administration prior to endoscopy may be considered in some cases and should be individualized. PMID:26674926

  7. Staphylococcal Purpura Fulminans: Report of a Case.

    PubMed

    Honarpisheh, Hedieh; Camp, Robert; Lazova, Rossitza

    2015-08-01

    Purpura fulminans (PF) is associated with several infections and most commonly with meningococcemia. However, there are only a few reports of this entity in association with toxic shock syndrome toxin-1-producing Staphylococcus aureus. We report a 53-year-old man who presented with fever, progressive hemodynamic instability, multiorgan failure, and thrombocytopenia following lobectomy for a solitary lung metastasis from rectal adenocarcinoma. He developed progressive generalized eruption of nonblanching red, purple, and black macules, papules, and plaques on the trunk and extremities consistent with PF. He died on postadmission day 3. Autopsy examination revealed purulent pleural exudate, which grew toxic shock syndrome toxin-1-producing S. aureus. Premortem and autopsy skin biopsies demonstrated epidermal necrosis, subepidermal bullae, and fibrin thrombi within small cutaneous vessels with minimal perivascular lymphocytic inflammation and without accompanying vasculitis. With this case report, we would like to draw attention to the fact that staphylococcal toxic shock syndrome-associated PF may be highly underrecognized and much more common than reflected in the literature. PMID:25099358

  8. Acute Esophageal Necrosis Presenting With Henoch-Schönlein Purpura.

    PubMed

    Iorio, Natalya; Bernstein, Gregory R; Malik, Zubair; Schey, Ron

    2015-10-01

    A 63-year-old woman with abdominal pain and melena developed a palpable, purpuric rash and acute kidney injury. Skin and kidney biopsy confirmed Henoch-Schönlein purpura. Upper endoscopy revealed diffuse, circumferential, black-appearing mucosa of the esophagus consistent with acute esophageal necrosis (AEN), also known as black esophagus. AEN is a very rare cause of gastrointestinal hemorrhage with a high mortality risk. To our knowledge, there have been no prior reports of AEN associated with Henoch-Schonlein purpura or other vasculitis. PMID:26504868

  9. Acute Esophageal Necrosis Presenting With Henoch-Schönlein Purpura

    PubMed Central

    Bernstein, Gregory R.; Malik, Zubair; Schey, Ron

    2015-01-01

    A 63-year-old woman with abdominal pain and melena developed a palpable, purpuric rash and acute kidney injury. Skin and kidney biopsy confirmed Henoch-Schönlein purpura. Upper endoscopy revealed diffuse, circumferential, black-appearing mucosa of the esophagus consistent with acute esophageal necrosis (AEN), also known as black esophagus. AEN is a very rare cause of gastrointestinal hemorrhage with a high mortality risk. To our knowledge, there have been no prior reports of AEN associated with Henoch-Schonlein purpura or other vasculitis. PMID:26504868

  10. Purpura Fulminans Due to Acquired Protein C Deficiency

    PubMed Central

    Mukherjee, Devdeep; Pal, Priyankar; Kundu, Ritabrata

    2015-01-01

    Purpura fulminans (PF) may be the presenting symptom in a patient with protein C (PC) deficiency. It is a hematological emergency and presents with extensive areas of hemorrhagic necrosis of the skin. PC deficiency is usually genetically inherited. However, we report a 1 year and 4 months boy, who presented with acquired PC deficiency possibly of postinfectious etiology and developed PF. PMID:26677306

  11. [Skin lesions and joint involvement in purpura fulminans (author's transl)].

    PubMed

    Allouis, M; Catier, P; Bracq, H; Babut, J M

    1980-10-01

    Until recently, purpura fulminans had a very prognosis. It can now be treated and the patient may survive but extensive skin necrosis may lead to septic arthritis. The authors have observed 4 cases of this disease. 3 had to suffer amputation of a lower limb. They describe the type of care recommended in order to limit the extent of the necrosis. PMID:6450996

  12. "Benign" hypergammaglobulinemic purpura is not benign in pregnancy.

    PubMed

    Jolly, Elaine C; Hunt, Beverley J; Ellis, Spencer; Griffiths, Malcolm; Farrington, Ken

    2009-06-01

    A woman presented at 25 weeks gestation in her first pregnancy with severe preeclampsia and an intrauterine death. It later emerged that she had Waldenstrom's benign hypergammaglobulinemic purpura. We discuss the implications of this diagnosis in pregnancy and explore possible management options during subsequent pregnancies. PMID:19057848

  13. Vasculitic purpura in vinyl chloride disease: a case report

    SciTech Connect

    Magnavita, N.; Bergamaschi, A.; Garcovich, A.; Giuliano, G.

    1986-05-01

    Vinyl chloride (VC), a volatile substance mostly used for polyvinyl chloride (PVC) synthesis, is a systemic toxicant particularly noxious to endothelium. Angiosarcoma of the liver, Raynaud's phenomenon, scleroderma-like lesions, acroosteolysis and neuritis are known to be typical vinyl chloride-associated manifestations (VC disease). A so far unknown feature of the disease is purpura. This was first observed by the authors in a worker of a PVC-producing plant. The skin eruption was characterized by small purpuric maculae with tiny, palpable spots and papulae, mostly concentrated on the lower part of the legs, changing into bullae, pustules and crusts and tending to spontaneous regression after withdrawal from VC exposure. A skin biopsy revealed marked inflammatory reaction with a mostly lymphocytic and histiocytic infiltration around and in the walls of dermal arterioles. The finding of increased circulating immune complexes and anti-smooth muscle autoantibodies strengthens the hypothesis that immunologic changes play a role in the appearance of ''vinylic purpura.''

  14. [Mild hemophilia A fortuitously discovered during Henoch-Schönlein purpura].

    PubMed

    Joly, B; d'Oiron, R; Desconclois, C; Bendelac, L; Rafowicz, A; Meyzer, C; Labrune, P; Veyradier, A

    2015-11-01

    Henoch-Schönlein purpura is a common form of immunological vasculitis in children. Hemophilia A is a genetic disorder, inherited in a X-linked recessive pattern, and characterized by spontaneous hemorrhage or prolonged bleeding due to factor VIII deficiency. The clinical signs depend on the severity of factor VIII deficiency. We herein report the case of a 4-year-old boy admitted to the emergency room for typical rheumatoid purpura, associated with a lengthening of aPTT, whose exploration had uncovered mild hemophilia A. Laboratory assays should explore lengthening of aPTT: firstly the presence of lupus anticoagulant without bleeding risk, in an inflammatory context; secondly a deficiency of VWF and one of the factors involved in the extrinsic coagulation pathway associated with bleeding risk. PMID:26412326

  15. Retiform purpura in a patient with a history of cocaine use.

    PubMed

    Fthenakis, A; Klein, P A

    2011-01-01

    There have been rare published cases of retiform purpura related to cocaine use. Levamisole, a common adulterant, has been implicated as the etiologic agent. We describe a female patient, aged 48 years, with cocaine-related retiform purpura involving her face, abdomen, and legs and alert physicians to the dangers of levamisole-contaminated cocaine. PMID:21549087

  16. Relationship between chronic tonsillitis and Henoch-Schonlein purpura

    PubMed Central

    Yan, Min; Wang, Zhan; Niu, Na; Zhao, Jianxia; Peng, Jian

    2015-01-01

    The aim of this study was to explore the relationship between children’s chronic tonsillitis and Henoch-Schonlein purpura (HSP). We randomly selected 56 cases of HSP children with chronic tonsillitis during December 2009 to December 2012, 26 cases for surgery group and 30 cases for non-surgery. The duration of abdominal pain and rash, 24 hours urine protein quantity, urine red blood cell count, titre of anti streptolysin O (ASO) and complement C3 (C3) were compared and analyzed with statistical method. Compared with the non-surgery group, the duration of abdominal pain and rash, overcast days of urine protein and occult blood in the surgery group were improved significantly (P < 0.05). 24 hours urine protein quantity and urine red blood cell count of the surgery group were improved significantly after surgery (P < 0.01). Chronic tonsillitis was one of the important factors leading to recurrent rash and inducing Henoch-Schonlein purpura nephritis. Tonsillectomy was an alternative mean to treat HSP children with chronic tonsillitis. PMID:26550368

  17. Do the acute platelet responses of patients with immune thrombocytopenic purpura (ITP) to IV anti-D and to IV gammaglobulin predict response to subsequent splenectomy?

    PubMed

    Bussel, J B; Kaufmann, C P; Ware, R E; Woloski, B M

    2001-05-01

    The acute platelet response to Intravenous Gammaglobulin (IVIG) has been reported to predict response to subsequent splenectomy of patients with ITP. The current study was undertaken to determine if the platelet response to IV anti-D (Winrho-SDF) predicts response to subsequent splenectomy. The 61 HIV-uninfected children and adults in this study had taken part in the pre-licensing studies of IV anti-D and were all those who not only had evaluable platelet responses to IV anti-D but also had undergone splenectomy and had information available describing its 1-year outcome. Results of treatment with IVIG were available in 38 of these 61 patients. Neither response to the initial infusion of IV anti-D, nor response to the initial or last IVIG, predicted the response in either children or adults to subsequent splenectomy. However, response to the last anti-D infusion in adults was strongly correlated (P = 0.003) to response to subsequent splenectomy as was hemolysis >/=2.0 gm/dl after IV anti-D (P = 0.03). There was no overall relationship between response to IV anti-D or IVIG, and response to subsequent splenectomy. However, a good platelet response in adults to the last IV anti-D and a hemoglobin decrease >/=2.0 gm/dl both appeared to predict response to subsequent splenectomy. PMID:11279654

  18. Intestinal infarction and portal vein thrombosis in a patient with henoch schonlein purpura.

    PubMed

    Abebe, Mekdess; Patnaik, Asha; Miller, Frederick; Roppelt, Heidi; Wadhwa, Nand K; Abate, Mersema; Nord, Edward P

    2012-01-01

    Henoch Schonlein purpura is a systemic vasculitis that commonly affects children and teenagers but also affects adults of all ages. In most instances it has a benign course. Organ involvement, particularly in adults, and notably the kidneys and gastrointestinal tract may require therapeutic intervention and may have a less favorable outcome. We report a case of a 58-year-old man who presented with purpura and who rapidly developed catastrophic intestinal vasculitis, leading to his demise. PMID:23097737

  19. A case study of thrombotic thrombocytopaenic purpura: a 'powerful poison'.

    PubMed

    Cox, Dani; Coyer, Fiona

    2004-05-01

    This paper presents the case of a previously well 72 year old man who spent 86 days in the intensive care unit (ICU) following a remarkable and explosive presentation of the rare condition thrombotic thrombocytopaenic purpura (TTP). TTP is an intravascular platelet aggregation disorder that, without treatment, is associated with significantly high mortality rates. This paper discusses TTP in terms of its presentation, pathophysiology, diagnosis and management. In addition to TTP, the patient developed a number of comorbidities during his stay in ICU. Particular attention is given to two major problems: acute renal failure and prolonged encephalopathy. These issues, along with the initial diagnosis of TTP, resulted in the patient remaining in ICU for a longer period than otherwise might have been expected. Despite many obstacles, the patient recovered and was discharged from hospital 116 days after initial presentation. PMID:15218818

  20. Severe Henoch-Schönlein purpura with infliximab for ulcerative colitis

    PubMed Central

    Song, Yang; Shi, Yan-Hong; He, Chong; Liu, Chang-Qin; Wang, Jun-Shan; Zhao, Yu-Jie; Guo, Yan-Min; Wu, Rui-Jin; Feng, Xiao-Yue; Liu, Zhan-Ju

    2015-01-01

    Infliximab (IFX) is an anti-tumor necrosis factor chimeric antibody that is effective for treatment of autoimmune disorders such as Crohn’s disease and ulcerative colitis (UC). IFX is well tolerated with a low incidence of adverse effects such as infections, skin reactions, autoimmunity, and malignancy. Dermatological manifestations can appear as infusion reaction, vasculitis, cutaneous infections, psoriasis, eczema, and skin cancer. Here, we present an unusual case of extensive and sporadic subcutaneous ecchymosis in a 69-year-old woman with severe UC, partial colectomy and cecostomy, following her initial dose of IFX. The reaction occurred during infliximab infusion, and withdrawal of IFX led to gradual alleviation of her symptoms. We concluded that Henoch-Schönlein purpura, a kind of leukocytoclastic vasculitis, might have contributed to the development of the bruising. Although the precise mechanisms of the vasculitis are still controversial, such a case highlights the importance of subcutaneous adverse effects in the management of UC with IFX. PMID:26019477

  1. Severe Henoch-Schönlein purpura with infliximab for ulcerative colitis.

    PubMed

    Song, Yang; Shi, Yan-Hong; He, Chong; Liu, Chang-Qin; Wang, Jun-Shan; Zhao, Yu-Jie; Guo, Yan-Min; Wu, Rui-Jin; Feng, Xiao-Yue; Liu, Zhan-Ju

    2015-05-21

    Infliximab (IFX) is an anti-tumor necrosis factor chimeric antibody that is effective for treatment of autoimmune disorders such as Crohn's disease and ulcerative colitis (UC). IFX is well tolerated with a low incidence of adverse effects such as infections, skin reactions, autoimmunity, and malignancy. Dermatological manifestations can appear as infusion reaction, vasculitis, cutaneous infections, psoriasis, eczema, and skin cancer. Here, we present an unusual case of extensive and sporadic subcutaneous ecchymosis in a 69-year-old woman with severe UC, partial colectomy and cecostomy, following her initial dose of IFX. The reaction occurred during infliximab infusion, and withdrawal of IFX led to gradual alleviation of her symptoms. We concluded that Henoch-Schönlein purpura, a kind of leukocytoclastic vasculitis, might have contributed to the development of the bruising. Although the precise mechanisms of the vasculitis are still controversial, such a case highlights the importance of subcutaneous adverse effects in the management of UC with IFX. PMID:26019477

  2. Expansion of Circulating T Follicular Helper Cells in Children with Acute Henoch-Schönlein Purpura

    PubMed Central

    Xie, Jue; Liu, Yan; Wang, Lei; Ruan, Guoxiang; Yuan, Huiming; Fang, Hong; Wu, Jianyong; Cui, Dawei

    2015-01-01

    Henoch-Schönlein purpura (HSP) is a common systemic small vessel vasculitis in children with disorder autoimmune responses. T follicular helper (TFH) cells play crucial roles in regulating immune responses. The aim of our study was to investigate the probable role of TFH cells in the pathogenesis of children with HSP. In this study, the frequency of circulating CXCR5+CD4+TFH cells with inducible costimulator (ICOS) expression in the children with acute HSP was significantly higher than that in healthy controls (HCs) but not CXCR5+CD4+TFH cells with programmed death-1 (PD-1) expression. Moreover, serum levels of IL-21 and IL-6 cytokines, IgA, and C3 in HSP children were also significantly higher than those in HCs. A positive correlation was observed between the frequencies of circulating ICOS+CXCR5+CD4+TFH cells and the serum IL-21 or IgA levels of acute HSP children, respectively. Additionally, the mRNA expression levels of interleukin- (IL-) 21, IL-6, and transcriptional factors (B-cell lymphoma-6, Bcl-6) were also significantly increased in peripheral blood from acute HSP children compared to HCs. Taken together, these findings suggest that TFH cells and associated molecules might play critical roles in the pathogenesis of HSP, which are possible therapeutic targets in HSP children. PMID:26491701

  3. Pneumatosis intestinalis associated with Henoch-Schönlein purpura.

    PubMed

    Fatima, Ayesha; Gibson, Donald Paul

    2014-09-01

    Henoch-Schönlein purpura (HSP) is the most common vasculitis in children. It is a disorder of the inflammatory cascade leading to immunoglobulin A deposition and leukocytoclastic vasculitis of small vessels of skin, kidneys, joints, and gastrointestinal (GI) tract. A wide variety of GI manifestations are seen in ?50% to 75% of patients with HSP. Diffuse colicky abdominal pain is the most common GI symptom. The small bowel is the most frequently involved GI site. Intussusception is rare but is the most common surgical complication. We report the case of a 2-year-old girl with a 5-day history of abdominal pain followed by a palpable purpuric rash. Her urinalysis, complete blood cell count, and tests of renal function were normal. An acute abdominal series was unremarkable initially, and abdominal ultrasound imaging showed ascites and thickened small bowel loops. She was diagnosed with HSP. The abdominal pain worsened, and an abdominal computed tomography scan demonstrated distal small bowel wall thickening and pneumatosis intestinalis in the descending colon. She was started on total parenteral nutrition and antibiotics and placed on bowel rest. She was given 2 mg/kg of intravenous immunoglobulin. Her abdominal pain gradually improved over the next week, and a repeat computed tomography scan showed significant improvement of the small bowel wall thickening and pneumatosis. The purpuric rash improved, and her abdominal pain resolved. We report a case of HSP and pneumatosis intestinalis, an association that has not been reported previously. PMID:25157006

  4. Parallel-ridge pattern on dermatoscopy: observation in a case of purpura traumatica pedis

    PubMed Central

    Feci, Luca; Fimiani, Michele; Rubegni, Pietro

    2015-01-01

    Dermatologists are often referred urgent cases of acral hematoma by general practitioners and sports medicine specialists for the purpose of excluding warts, nevi or melanoma. Acral hematoma is often a cause of anxiety to patients and their families. Here, we report a case of purpura traumatica pedis, referred to us as suspected plantar melanoma because of the finding of parallel-ridge pattern on dermatoscopic examination. To avoid unnecessary and costly procedures, doctors should inquire about any episode of physical exertion before the onset of purpura, recording the lesion’s anatomic site (e.g., unilateral vs. bilateral involvement) and clinical features. PMID:26693086

  5. Pneumococcal sepsis-induced purpura fulminans in an asplenic adult patient without disseminated intravascular coagulation.

    PubMed

    Saraceni, Christine; Schwed-Lustgarten, Daniel

    2013-12-01

    Acute perturbations in the hemostatic balance of anticoagulation and procoagulation antecede the manifestation of purpura fulminans, a rare syndrome of intravascular thrombosis and hemorrhagic infarction of the skin. Hallmarks include small vessel thrombosis, tissue necrosis and disseminated intravascular thrombosis. The course may be rapidly fulminant resulting in multiorgan failure with thrombotic occlusion of the vasculature, leading to distal extremity ischemia and necrosis. Depletion of protein C (PC) has been emphasized in the pathogenesis. Early intravenous antibiotic administration and hemodynamic support are cornerstones in management. Herein, we report a case of pneumococcal sepsis-induced purpura fulminans limited to the skin in an asplenic adult patient without the development disseminated intravascular coagulation. PMID:24185261

  6. Thromboelastometric Monitoring of the Hemostatic Effect of Platelet Concentrates Transfusion in Thrombocytopenic Children Undergoing Chemotherapy.

    PubMed

    Ziegler, Bernhard; Solomon, Cristina; Cadamuro, Janne; Jones, Neil

    2015-09-01

    Prophylactic platelet concentrates transfusion represents a therapeutic choice in patients with chemotherapy-induced thrombocytopenia. This prospective, non-interventional study evaluated the effects of platelet concentrates transfusion on thromboelastometric parameters of platelet function in 36 transfusion occasions for 11 thrombocytopenic children undergoing chemotherapy. Pre- and posttransfusion (1-2 hours) blood samples were analyzed using standard coagulation tests and thromboelastometry (ROTEM) measurements (EXTEM and FIBTEM tests). Platelet component of the clot was calculated based on the EXTEM and FIBTEM maximum clot elasticity (MCE) results. After transfusion, mean platelet count increased from 16.5 × 10(9)/L to 43.0 × 10(9)/L (P < .001) and platelet component increased from 34.1 to 73.0 (P < .001). Statistically significant increases for posttransfusion EXTEM parameters A10, A20, and maximum clot firmness (MCF) were observed compared to pretransfusion values (P < .001). The EXTEM ?-angle values increased posttransfusion (P < .05). The FIBTEM measurements were comparable pre- and posttransfusion. The study showed that platelet concentrates transfusion in thrombocytopenic children undergoing chemotherapy improves platelet-related coagulation pattern. PMID:25525046

  7. Thromboelastometric Monitoring of the Hemostatic Effect of Platelet Concentrates Transfusion in Thrombocytopenic Children Undergoing Chemotherapy

    PubMed Central

    Solomon, Cristina; Cadamuro, Janne; Jones, Neil

    2015-01-01

    Prophylactic platelet concentrates transfusion represents a therapeutic choice in patients with chemotherapy-induced thrombocytopenia. This prospective, non-interventional study evaluated the effects of platelet concentrates transfusion on thromboelastometric parameters of platelet function in 36 transfusion occasions for 11 thrombocytopenic children undergoing chemotherapy. Pre- and posttransfusion (1-2 hours) blood samples were analyzed using standard coagulation tests and thromboelastometry (ROTEM) measurements (EXTEM and FIBTEM tests). Platelet component of the clot was calculated based on the EXTEM and FIBTEM maximum clot elasticity (MCE) results. After transfusion, mean platelet count increased from 16.5 × 109/L to 43.0 × 109/L (P < .001) and platelet component increased from 34.1 to 73.0 (P < .001). Statistically significant increases for posttransfusion EXTEM parameters A10, A20, and maximum clot firmness (MCF) were observed compared to pretransfusion values (P < .001). The EXTEM ?-angle values increased posttransfusion (P < .05). The FIBTEM measurements were comparable pre- and posttransfusion. The study showed that platelet concentrates transfusion in thrombocytopenic children undergoing chemotherapy improves platelet-related coagulation pattern. PMID:25525046

  8. Antigenic Complementarity in the Origins of Autoimmunity: A General Theory Illustrated With a Case Study of Idiopathic Thrombocytopenia Purpura

    PubMed Central

    Root-Bernstein, Robert; Couturier, Jacob

    2006-01-01

    We describe a novel, testable theory of autoimmunity, outline novel predictions made by the theory, and illustrate its application to unravelling the possible causes of idiopathic thrombocytopenia purpura (ITP). Pairs of stereochemically complementary antigens induce complementary immune responses (antibody or T-cell) that create loss of regulation and civil war within the immune system itself. Antibodies attack antibodies creating circulating immune complexes; T-cells attack T-cells creating perivascular cuffing. This immunological civil war abrogates the self-nonself distinction. If at least one of the complementary antigens mimics a self antigen, then this unregulated immune response will target host tissues as well. Data demonstrating that complementary antigens are found in some animal models of autoimmunity and may be present in various human diseases, especially ITP, are reviewed. Specific mechanisms for preventing autoimmunity or suppressing existing autoimmunity are derived from the theory, and critical tests proposed. Finally, we argue that Koch's postulates are inadequate for establishing disease causation for multiple-antigen diseases and discuss the possibility that current research has failed to elucidate the causes of human autoimmune diseases because we are using the wrong criteria. PMID:16603444

  9. [Meningococcal purpura fulminans: treatment with recombinant protein C activator in 3 cases].

    PubMed

    Salinas, U; Unzueta, J; Vidarte, M A; Rodrigo, M P; Gómez, J J; Aguilera, L

    2007-10-01

    Purpura fulminans is a serious disease associated with high rates of morbidity and mortality. It usually leads to disseminated intravascular coagulation and septic shock related to reduced levels of protein C. Recombinant protein C (rPC) activator has been used successfully to inhibit this process. Intracranial hemorrhages are the most important, life-threatening adverse effects of treatment with rPC activator. We report 3 cases of patients with meningococcal purpura fulminans who developed septic shock and multiorgan dysfunction. They were treated with the protocol for septic shock, antibiotics and rPC activator from the time of admission, and improvement in hemodynamic dysfunction was observed within hours in all patients. All received platelet replacement transfusions. Subarachnoid bleeding complications occurred in 2 patients. One patient died 5 days after admission and 2 were discharged from the intensive recovery care unit 28 days after admission. PMID:17993100

  10. Spontaneous Bacterial Peritonitis and Henoch-Schönlein Purpura in a Patient with Liver Cirrhosis

    PubMed Central

    Gupta, Neil; Kim, Joyce; Njei, Basile

    2015-01-01

    Henoch-Schönlein purpura (HSP) is a small vessel systemic vasculitis, predominantly affecting children, characterized by a tetrad of manifestations, specifically palpable purpura, arthralgia, abdominal pain, and renal disease. HSP in the adult population is rare, and no case has been described of HSP in liver cirrhosis with spontaneous bacterial peritonitis (SBP). We present the case of a 58-year-old male with liver cirrhosis, who was subsequently diagnosed with SBP and later HSP. In this patient, the diagnosis of HSP was demonstrated clinically by his palpable purpura, diarrhea, hematuria, and abdominal pain and confirmed pathologically by his renal and skin biopsies demonstrating leukocytoclastic vasculitis and IgA complexes. We believe that this is an example of altered IgA processing in cirrhosis leading to the development of IgA immune complexes and ultimately HSP. The patient additionally had SBP, which may have increased his risk for developing HSP given antigen processing by mucosa-associated lymphoid tissues leading to immune complex deposition, which may not have been effectively cleared in the context of his liver disease. The patient unfortunately died of gastrointestinal hemorrhage, which is unclear to be due to his underlying cirrhosis or a gastrointestinal manifestation of HSP itself. PMID:26064127

  11. Sirolimus for Autoimmune Disease of Blood Cells

    ClinicalTrials.gov

    2015-10-20

    Autoimmune Pancytopenia; Autoimmune Lymphoproliferative Syndrome (ALPS); Evans Syndrome; Idiopathic Thrombocytopenic Purpura; Anemia, Hemolytic, Autoimmune; Autoimmune Neutropenia; Lupus Erythematosus, Systemic; Inflammatory Bowel Disease; Rheumatoid Arthritis

  12. Anaphylactoid Purpura Manifested after Acute Gastroenteritis with Severe Dehydration in an 8-Year-Old Male Child: A Case Report.

    PubMed

    Thakkar, Umang G; Vanikar, Aruna V; Trivedi, Hargovind L

    2015-12-01

    Anaphylactoid purpura, also known as Henoch-Schönleinpurpura (HSP), is an IgA-mediated vasculitis that tends to be a benign disease of childhood. Up to 50% of cases are preceded by an upper tract respiratory infection caused by group-A beta-hemolytic streptococcus and present with the common tetrad of abdominal pain, arthritis, purpuric rash, and renal involvement. The majority of patients recover completely. Here we document a rare case of anaphylactoid purpura which manifested with skin lesions in the form of palpable purpura following about of acute gastroenteritis with severe dehydration; it was treated with a short regimen of steroid therapy, which resulted in the complete remission of the disease. We conclude that prompt diagnosis and multidisciplinary intervention will lead to appropriate management-consisting of the installation of early short-course steroid therapy and thus, prevent further complications and the recurrence of the disease. PMID:26602584

  13. Purpura Fulminans Associated with Hemiparesis Following Measles Infection in a Nigerian Girl: A Case Report

    PubMed Central

    Ibrahim, Aliyu

    2013-01-01

    Purpura fulminans is a life-threatening hematologic emergency characterized by extensive skin necrosis with hemorrhagic infarction, hypotension and gangrene which may arise from severe sepsis; mostly gram negative sepsis though also associated with some gram positive organisms, similarly viral infections like varicella and measles have been implicated; it may also arise from congenital deficiency of the anticoagulants protein C, S, and antithrombin III; and it may also be idiopathic. Its clinical manifestation may be quite extensive resulting in multiorgan failure. Treatment will require aggressive management with use of fresh frozen plasma, heparin, antibiotics, and surgical debridement of necrotic tissue.

  14. [Videocapsule endoscopy used for diagnosis of Henoch-Schönlein purpura with gastrointestinal complications].

    PubMed

    Sivayogajeyam, Sivakaran; Christensen, Kent Dencker

    2013-09-16

    Henoch-Schönlein purpura (HSP) is primarily a childhood disease and is less common in adults where the incidence varies from 3.4 to 14.3 cases per million. We describe a case of adult HSP and discuss the role of videocapsule endoscopy, which is a non-invasive and safe method to evaluate the typical mucosa changes in especially small bowel. Medical doctors should be aware of HSP in adults and pay attention to the fact that in an unusual presentation with gastrointestinal manifestation videocapsule endoscopy may play a safe diagnostic role. PMID:24044543

  15. Successful treatment of hemorrhagic bullous henoch-schönlein purpura with oral corticosteroid: a case report.

    PubMed

    Kocaoglu, Celebi; Ozturk, Ramazan; Unlu, Yasar; Akyurek, Fatma Tuncez; Arslan, Sukru

    2013-01-01

    Henoch-Schönlein purpura (HSP) is a vasculitis of small-sized blood vessels, resulting from immunoglobulin-A-mediated inflammation. It is the most common acute systemic vasculitis in childhood and mainly affects skin, gastrointestinal tract, joints, and kidneys. The characteristic rash of HSP consists of palpable purpuric lesions 2 to 10?mm in diameter concentrating in the buttocks and lower extremities. The occurrence of hemorrhagic bullae in children with HSP is rarely encountered. This report describes a 4.5-year-old female patient with HSP associated with hemorrhagic bullous lesions. PMID:23691409

  16. Schönlein-henoch purpura in children and adults: diagnosis, pathophysiology and management.

    PubMed

    Rostoker, G

    2001-01-01

    Schönlein-Henoch syndrome is a form of systemic small-vessel vasculitis, characterised by vascular and/or mesangial immunoglobulin A1 deposits. The main clinical manifestations are vascular purpura, predominating on the lower limbs, and articular, gastrointestinal and renal symptoms. Pulmonary, cardiac, genital and neurological symptoms have also be observed. The syndrome usually affects children, whereas it is rare in adults. The frequency of renal involvement varies between individual studies (from 20 to 100%). Renal manifestations are usually mild and transient, although chronic nephropathies may occur. Overall, an estimated 2% of children with Schönlein-Henoch purpura progress to renal failure and up to 20% of children with nephritis treated in specialised centres require haemodialysis. The renal prognosis appears to be worse in adults. Aetiological investigations are required, as a triggering factor is found in approximately half the patients (e.g. viral, bacterial and parasitic infections, drugs, toxins, systemic diseases and cancer). Dapsone has beneficial effects on cutaneous, gastrointestinal and articular manifestations in adults, especially those with chronic forms. Corticosteroids may be useful for refractory abdominal pain. Methylprednisolone pulse therapy, immunosuppressive drugs (e.g. cyclophosphamide and azathioprine), plasma exchange and polyclonal immunoglobulin therapy are beneficial in very rare life-threatening forms of the disease and in rare instances where renal function is compromised. PMID:11437679

  17. [Neonatal purpura fulminans without sepsis due to a severe congenital protein C deficiency].

    PubMed

    Hmami, F; Cherrabi, H; Oulmaati, A; Bouabdallah, Y; Bouharrou, A

    2015-10-01

    Severe congenital protein C deficiency is a rare life-threatening coagulopathy. In the early hours of life, the neonate presents with extensive purpura fulminans and substantial skin necrosis contrasting with a preserved general state and a negative infectious exam. Disseminated intravascular coagulation sets in secondarily. Prenatal outset of thrombotic events is a rare situation that worsens the prognosis, especially protein C replacement in utero is not available. We report a case of a male newborn of consanguineous parents who were asymptomatic carriers of heterozygous protein C deficiency. This infant presented prenatal ventricular hemorrhage with hydrocephalus and rapidly extensive postnatal skin necrosis that was not regressive in spite of fresh frozen plasma administrated after 24h of life. Prenatal diagnosis, early recognition, and urgent therapy with protein C replacement and anticoagulant treatment are crucial to improve the prognosis, avoid further damage after delivery, and prevent the devastating consequences of severe protein C deficiency. PMID:26228809

  18. Self-limiting recurrent bullous Henoch-Schonlein purpura with lupus anticoagulant.

    PubMed

    Gration, Betty; Osakwe, Edwin

    2015-01-01

    Henoch-Schonlein purpura (HSP) is the most common acute systemic vasculitis of childhood with an incidence of approximately 1:10,000. It commonly presents with skin, gastrointestinal tract, joints and renal system signs and symptoms. We present a case of recurrent self-limiting HSP with lupus anticoagulant presenting with haemorrhagic bullous skin lesions and scrotal swelling. The initial presentation resolved within 4 weeks but over the next 6 months, a few self-limiting but milder skin lesions occurred. Some institutions have advocated the use of steroids in these cases but our case showed that the use of steroids may not be required. This atypical presentation of HSP led to unnecessary investigations that this case report aims to prevent in the future by raising its awareness. PMID:25604501

  19. Thrombocytosis following splenectomy and aortic valve replacement for idiopathic thrombocytopaenic purpura with bicuspid aortic valve

    PubMed Central

    Katiyar, Sarika; Ganjsinghani, Payal Kamlesh; Jain, Rajnish Kumar

    2015-01-01

    Idiopathic thrombocytopaenic purpura (ITP) patients are at high risk for complications during and after cardiac surgeries involving cardiopulmonary bypass. The main clinical problem of primary ITP is an increased risk of bleeding although bleeding may not always be present. More recently, thrombosis has become appreciated as another potential complication of the procedure. We report a 22-year-old female patient with ITP with bicuspid aortic valve and splenomegaly, who underwent uncomplicated aortic valve replacement and splenectomy simultaneously. She was readmitted with chest pain due to coronary thrombosis following splenectomy which made the management difficult. We describe our experience in managing this patient who presented with thrombotic complication rather than bleeding in post-operative period and the challenges met in maintaining appropriate anticoagulation for aortic valve replacement as well as thrombosis, post-splenectomy PMID:26379295

  20. Anesthetic management of a patient with Henoch-Schonlein purpura for drainage of cervical lymphadenitis: A case report.

    PubMed

    Hasija, Neha; Taxak, Susheela; Bhardwaj, Mamta; Vashist, Kirti

    2014-04-01

    Henoch-Schonlein purpura (HSP) is a multisystem disease and immunoglobulin A-mediated vasculitis with a self-limited course affecting the skin, joints, gastrointestinal tract, and kidneys. Severe renal and central nervous system disease may lead to life-threatening conditions, and immunosuppressive agents and plasmapheresis may be needed. We report successful management of a 6-year-old patient with HSP for drainage of cervical lymphadenitis. PMID:24843348

  1. Urinary excretion and renal production of hepatocyte growth factor in children with Henoch-Schönlein purpura.

    PubMed

    Ding, W; Sun, S; Zhen, J; Yu, Y

    2010-01-01

    This study measured urinary excretion and renal levels of hepatocyte growth factor (HGF) in children with Henoch-Schönlein purpura (HSP), examining the relationship between HGF, proteinuria and renal pathological changes. Seventy-eight patients with HSP aged 6 - 18 years were divided into three groups, based on urinary albumin excretion rate. Urinary HGF concentration was measured by enzyme-linked immunosorbent assay. Renal biopsies were performed in 22 patients; renal levels of HGF protein were determined immunohistochemically. Compared with controls, urinary HGF was significantly increased in patients with normoalbuminuria and microalbuminuria, especially in those with microalbuminuria; no differences were observed between patients with macroalbuminuria and controls. Little or no HGF was present in normal kidney, but HGF was present in renal tissue in all HSP patients, particularly those with microalbuminuria. Urinary HGF was strongly correlated with the presence of renal HGF. These results suggest that HGF is associated with proteinuria and renal pathological changes in children with HSP. The detection of urinary HGF in children with HSP may be a non-invasive, effective, method for early diagnosis of renal injury. PMID:21226996

  2. Skin Necrosis and Purpura Fulminans in Children With and Without Thrombophilia-A Tertiary Center's Experience.

    PubMed

    Fruchtman, Yariv; Strauss, Tzipora; Rubinstein, Marina; Ben Harush, Miriam; Revel-Vilk, Shoshana; Kapelushmik, Joseph; Paret, Gideon; Kenet, Gili

    2015-10-01

    Purpura fulminans (PF) is a very rare clinicopathologic skin disorder comprising dermal microvascular thrombosis associated with perivascular hemorrhage of multiple origins. It may occur as the presenting symptom of severe congenital deficiency of protein C (PC) or protein S (PS) during the newborn period, or later in life following oral anticoagulant therapy with vitamin K antagonists, or of sepsis that may be associated with disseminated intravascular coagulation. Treatment consists of anticoagulants and PC concentrates during acute episodes. We report our experience in the diagnosis and management of pediatric PF. The medical records of the 6 children aged 2-16 years (median: 5 years) who presented with PF to our tertiary care center between 1996 and 2013 were studied. The thrombophilia workup revealed either the presence of congenital homozygous PC deficiency, prothrombotic polymorphisms (factor V Leiden and FIIG20210A heterozygosity), acquired PC/PS deficiency, or no discernible thrombophilia. The skin necrosis resolved following conservative fresh-frozen plasma/anticoagulant therapy in 2 cases, whereas 3 children required interventional plastic surgery. The sixth case, a 10-year-old child with severe PC deficiency, heterozygous factor V Leiden, and FIIG20210A, received recombinant activated PC. PF in childhood is rare and has multiple etiologies. Understanding of the variable pathogenesis and risk factors will facilitate diagnosis and appropriate clinical management. PMID:26436558

  3. Acute penile pain and swelling in a 4-year-old child with Henoch-Schönlein purpura.

    PubMed

    Tewary, Kishor Kumar; Khodaghalian, Bernadette; Narchi, Hassib

    2015-01-01

    Henoch-Schönlein purpura (HSP) is the most common vasculitis found in children. It usually affects the small vessels of the skin, joints, gastrointestinal tract and, more rarely, kidneys, brain, lungs and genitalia. Apart from classical presentation with purpuric rashes around buttocks and lower extremities, features such as arthralgia, abdominal pain, haematuria and proteinuria as well as scrotal swelling have been described in the literature. Penile involvement is rare and is not commonly described. We describe a child with HSP who developed penile involvement. We review the literature of all the cases reported in detail, in order to highlight useful clinical presentation, management and prognosis of this rare manifestation. PMID:25858918

  4. Elevated plasma advanced oxidation protein products in children with Henoch-Schonlein purpura.

    PubMed

    Keskin, Nurcan; Civilibal, Mahmut; Elevli, Murat; Koldas, Macit; Duru, Nilgun Selcuk; Ozturk, Humeyra

    2011-11-01

    Henoch-Schonlein purpura (HSP) is a systemic vasculitis characterized by involvement of skin, joints, gastrointestinal tract (GIT), and kidney; its pathogenesis is still controversial. The aim of our study was to investigate the role of oxidative stress in the pathogenesis of HSP. Plasma advanced oxidation protein products (AOPP) level was measured in 29 children with HSP at the onset of the disease and during remission in comparison with 30 healthy subjects. Patients at the active stage had significantly higher AOPP levels than those at the remission stage of HSP and the controls (42.9?±?25.7, 30.6?±?11.8, 27.9?±?11.2 mmol/l; P?=?0.027 and P?=?0.023 respectively). The mean AOPP levels of the patients with arthritis and/or arthralgia were significantly higher those than without joint involvement (48.3?±?26.0 and 22.3?±?9.3, P?=?0.036 respectively). However, AOPP levels were similar in patients with and without gastrointestinal involvement. Plasma AOPP levels were positively correlated with leukocyte and thrombocyte count at disease onset, whereas they were found to be negatively correlated with serum glucose and sodium levels. The mean thrombocyte count was the only independent predictor of increased level of AOPP in regression analysis (??=?0.407; P?=?0.029). In conclusion, this study showed that increased oxidative stress may play an important role in the pathogenesis of HSP. Also, we suggest that higher platelet count might be an indirect indicator of oxidative stress in these patients. Further research is required to identify the potential association between oxidative stress and increased thrombocyte count in children with HSP. PMID:21553322

  5. Mycophenolate mofetil plus prednisone for inducing remission of Henoch-Schönlein purpura nephritis: a retrospective study*

    PubMed Central

    Han, Fei; Chen, Liang-liang; Ren, Ping-ping; Le, Jing-yun; Choong, Pei-jing; Wang, Hong-ju; Xu, Ying; Chen, Jiang-hua

    2015-01-01

    Objective: The treatment of Henoch-Schönlein purpura (HSP) with moderate proteinuria remains controversial. We retrospectively analyzed the efficacy of immune suppressants, with a particular emphasis on mycophenolate mofetil (MMF). Methods: Ninety-five HSP patients with moderate proteinuria (1.0–3.5 g/24 h) after at least three months of therapy with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) were divided into three groups: an MMF group (n=33) that received MMF 1.0–1.5 g/d combined with prednisone (0.4–0.5 mg/(kg·d)), a corticosteroid (CS) group (n=31) that received full-dose prednisone (0.8–1.0 mg/(kg·d)), and a control group (n=31). Patients in the MMF and CS groups continued to take ACEI or ARB at the original dose. The patients in the control group continued to take ACEI or ARB but the dose was increased by (1.73±0.58)-fold. The patients were followed up for 6–78 months (median 28 months). Results: The baseline proteinuria was higher in the MMF group ((2.1±0.9) g/24 h) than in the control group ((1.6±0.8) g/24 h) (P=0.039). The proteinuria decreased significantly in all groups during follow-up, but only in the MMF group did it decrease significantly after the first month. At the end of follow-up, the proteinuria was (0.4±0.7) g/24 h in the MMF group and (0.4±0.4) g/24 h in the CS group, significantly lower than that in the control group ((0.9±1.1) g/24 h). The remission rates in the MMF group, CS group, and control group were respectively 72.7%, 71.0%, and 48.4% at six months and 72.7%, 64.5%, and 45.2% at the end of follow-up. The overall number of reported adverse events was 17 in the MMF group, 30 in the CS group, and 6 in the control group (P<0.001). Conclusions: MMF with low-dose prednisone may be as effective as full-dose prednisone and tend to have fewer adverse events. Therefore, it is probably superior to conservative treatments of adult HSP patients with moderate proteinuria. PMID:26365119

  6. Joint effusions and purpura in multiply-transfused adult beta-thalassemia- clinical pointers to diagnosis of scurvy.

    PubMed

    Prakash, A; Pandey, A K

    2013-01-01

    Periodic transfusions and effective chelation have ensured that thalassemics survive in to adulthood but their life is punctuated by peculiar problems in adulthood. Three cases of scurvy are being reported presenting uniquely as purpura, right hip joint effusion and right knee joint effusion with haemorrhage in prepatellar and retropatellar bursae, respectively over an 18 month period (2009-2010). The first two cases did give a history of gum bleed. None had any coagulation disturbance or transfusion-transmitted infections or connective tissue disorder. All the three cases responded dramatically to vitamin C supplementation. It is imperative to keep in mind that recurrent blood transfusions are associated with a state of subclinical vitamin C deficiency and overt scurvy may manifest as cumulative number of transfusions increase, as in adult thalassemics. PMID:24899338

  7. Expression of acid-sensing ion channels of gastric mucosa from patients with Henoch-Schönlein purpura.

    PubMed

    Yuan, Li-ping; Bo, Yan; Ming, Gui; Zhou, Qi-lian

    2012-04-01

    Acid-sensing ion channels (ASICs) are members of the voltage-insensitive, amiloride-sensitive degenerin/epithelial Na channel family of cation channels and have been shown to mediate pain associated with tissue acidosis after inflammation or injury; however, the expression and role of ASICs in gastrointestinal tract of Henoch-Schönlein purpura (HSP) patients were still uncertain. The present study was designed to examine the expression and localization of ASICs in gastric mucosa from patients with HSP using immunochemical techniques. The results showed that there was a significant increase in the mean relative optical density of ASIC2 and ASIC3 but not ASIC1a in the lining epithelium and glandular tubes of gastric mucosa from HSP patients with HSP. This finding suggested that ASICs may be related to the pathogenesis of gastrointestinal manifestations in patients with HSP. PMID:22157923

  8. A rare association of acute bacterial endocarditis with Henoch-Schönlein purpura (HSP) in an adult patient.

    PubMed

    Ilyas, Shahid; Salim, Sumera

    2014-12-01

    Henoch-Schönlein purpura (HSP) is a systemic, small vessel vasculitic disorder that mainly affects joint, skin, gastrointestinal tract and kidneys. It is primarily a disease of children that is typically self-limited, but 10 percent of cases occur in adults where features and outcomes may vary. The underlying pathogenesis of HSP remains unknown. We report a case of HSP that occurred with the onset of acute bacterial endocarditis (ABE) in an otherwise healthy 37-year-old Native American male. The patient presented with fevers, fatigue, abdominal pain and renal failure and was found to have acute left-sided staphylococcal endocarditis. He subsequently developed small bowel perforation and purpuric rash. Initially he was treated with broad spectrum antibiotics and small bowel resection. However, resolution of HSP and the associated signs and symptoms was only achieved after treatment with oral steroids and plasmapheresis. PMID:25571618

  9. Penile Skin Involvement as the First Presentation of Henoch-Schonlein Purpura Report of Nine Cases and Review of Literature

    PubMed Central

    Paydary, Koosha; Emamzadeh Fard, Sahra; Mahboubi, Amir Hassan; Ziaee, Vahid; Moradinejad, Mohammad Hassan; Kajbafzadeh, Abdol-Mohammad

    2015-01-01

    Introduction: Involvement of penis is a rare presentation in henoch-schonlein purpura (HSP). The presentations are mainly due to the deposition of immunoglobulin A (IgA) into the vessel walls. In this report, we present the clinical history of nine HSP cases that presented with penile skin involvement. Case Presentation: All patients were referred in the acute phase of HSP. Penile skin involvement was evident as erythema, edema, ecchymosis, or induration of prepuce and/or penile shaft, that appeared simultaneously with skin rash in seven patients. Gastrointestinal involvement was positive in six patients. Patients were treated with steroids and follow up visits were normal except for one patient that developed crescentic glomerulonephritis. Conclusions: We present nine cases of HSP with penile involvement in order to indicate another rare aspect of HSP and its possible complications as well as its appropriate treatment. PMID:26396696

  10. Romiplostim Injection

    MedlinePLUS

    ... clot) in order to decrease the risk of bleeding in people who have chronic idiopathic thrombocytopenic purpura ( ... ongoing condition that may cause easy bruising or bleeding due to an abnormally low number of platelets ...

  11. Haematology and neurology

    PubMed Central

    Austin, Steven; Cohen, Hannah; Losseff, Nick

    2007-01-01

    This review aims to update the reader on advances in the understanding of haematological conditions that may arise in neurological practice. Thrombophilia, antiphospholipid antibody syndrome, thrombotic thrombocytopenic purpura, sickle cell and clonal disorders associated with neuropathy are discussed. PMID:17369588

  12. Autologous Peripheral Blood Stem Cell Transplantation in Patients With Life Threatening Autoimmune Diseases

    ClinicalTrials.gov

    2005-06-23

    Purpura, Schoenlein-Henoch; Graft Versus Host Disease; Anemia, Hemolytic, Autoimmune; Rheumatoid Arthritis; Churg-Strauss Syndrome; Hypersensitivity Vasculitis; Wegener's Granulomatosis; Systemic Lupus Erythematosus; Giant Cell Arteritis; Pure Red Cell Aplasia; Juvenile Rheumatoid Arthritis; Polyarteritis Nodosa; Autoimmune Thrombocytopenic Purpura; Takayasu Arteritis

  13. Similar disturbances in B cell activity and regulatory T cell function in Henoch-Schonlein purpura and systemic lupus erythematosus

    SciTech Connect

    Beale, M.G.; Nash, G.S.; Bertovich, M.J.; MacDermott, R.P.

    1982-01-01

    The immunoglobulin synthesizing activities of peripheral mononuclear cells (MNC) from five patients with Henoch-Schonlein purpura (HSP) and eight patients with active systemic lupus erythematosus (SLE) were compared. Cumulative amounts of IgM, IgG, and IgA synthesized and secreted by unstimulated and PWM-stimulated patient cells over a 12-day period were determied in a solid-phase radioimmunoassay. In unstimulated control cultures mean rates of IgM, IgG, and IgA synthesis were less than 250 ng/ml. The synthetic activities of patient MNC were markedly increased. In HSP cultures IgA was the major immunoglobulin class produced (2810 x/divide 1.33 ng/ml) followed by IgG (1754 x/divide 1.32 ng/ml) and IgM (404 x/divide 1.16 ng/ml). In SLE cultures IgA and IgG syntheses were equally elevated (4427 x/divide 1.20 and 4438 x/divide 1.49 ng/ml, respectively) whereas IgM synthesis averaged 967 x/divide 1.66 ng/ml. PWM stimulation of pateient MNC caused a sharp decline in the synthesis of all three immunoglobulin classes. After T cell depletion B cell-enriched fractions from HSP and SLE patients maintained high levels of IgA and IgG synthesis that were inhibited by PWM and by normal allogeneic but not autologous T cells. In PWM-stimulted co-cultures, patient T cells nonspecifically suppressed the synthetic activities of autologous and control B cells. in contrast patient B cells achieved normal levels of immunoglobulin synthesis when cultured with control T cells plus PWM. In longitudinal studies patient B and T cell disturbances persisted despite clinical improvement.

  14. Association between toll-like receptor 6 expression and auxiliary T cells in the peripheral blood of pediatric patients with allergic purpura

    PubMed Central

    CHANG, HONG; CAO, YONGXIAN; LIN, YI; ZHU, HAIYAN; FU, YUAN; CHEN, XIUXIA; ZHANG, QIUYE

    2015-01-01

    The aim of the present study was to investigate the correlations between toll-like receptor 6 (TLR6) expression in the peripheral blood mononuclear cells (PBMCs) and auxiliary T cells of children with purpura. A total of 42 children with acute Henoch-Schönlein purpura (HSP) were selected for the study, and a further 30 healthy children were selected as a control group. Enzyme-linked immunosorbent assays were performed to detect the levels of plasma interferon (IFN)-?, interleukin (IL)-4 and IL-17, and flow cytometry was performed to detect the TLR6 protein expression levels in PBMCs. The plasma levels of IL-4, IFN-? and IL-17 in the HSP group were significantly higher compared with those in the normal control group. TLR6 protein expression was significantly increased in the PBMCs of the HSP patients. The TLR6 protein expression levels in the monocytes of the HSP group significantly positively correlated with the serum IL-4 and IL-17 levels, but not with the serum levels of IFN-?. Therefore, the results of the present study suggest that the activation of TLR6 may be involved in the immunopathogenesis of HSP, and that the activated TLR6 may mediate this process by upregulating the immune responses of type 2 T helper (Th2) and Th17 cells. PMID:26622521

  15. Henoch-Schönlein purpura in northern Spain: clinical spectrum of the disease in 417 patients from a single center.

    PubMed

    Calvo-Río, Vanesa; Loricera, Javier; Mata, Cristina; Martín, Luis; Ortiz-Sanjuán, Francisco; Alvarez, Lino; González-Vela, M Carmen; González-Lamuño, Domingo; Rueda-Gotor, Javier; Fernández-Llaca, Héctor; González-López, Marcos A; Armesto, Susana; Peiró, Enriqueta; Arias, Manuel; González-Gay, Miguel A; Blanco, Ricardo

    2014-03-01

    The severity of clinical features and the outcomes in previous series of patients reported with Henoch-Schönlein purpura (HSP) vary greatly, probably due to selection bias. To establish the actual clinical spectrum of HSP in all age groups using an unselected and wide series of patients diagnosed at a single center, we performed a retrospective review of 417 patients classified as having HSP according to the criteria proposed by Michel et al. Of 417 patients, 240 were male and 177 female, with a median age at the time of disease diagnosis of 7.5 years (interquartile range [IQR], 5.3-20.1 yr). Three-quarters of the patients were children or young people aged 20 years or younger (n = 315), and one-quarter were adults (n = 102). The most frequent precipitating events were a previous infection (38%), usually an upper respiratory tract infection, and/or drug intake (18.5%) shortly before the onset of the vasculitis. At disease onset the most common manifestations were skin lesions (55.9%), nephropathy (24%), gastrointestinal involvement (13.7%), joint symptoms (9.1%), and fever (6.2%). Cutaneous involvement occurring in all patients, mainly purpuric skin lesion, was the most common manifestation when the vasculitis was fully established, followed by gastrointestinal (64.5%), joint (63.1%), and renal involvement (41.2%). The main laboratory findings were leukocytosis (36.7%), anemia (8.9%), and increased serum IgA levels (31.7%). The most frequent therapies used were corticosteroids (35%), nonsteroidal antiinflammatory drugs (14%), and cytotoxic agents (5%). After a median follow-up of 12 months (IQR, 2-38 mo), complete recovery was observed in most cases (n = 346; 83.2%), while persistent, usually mild, nephropathy was observed in only 32 (7.7%) cases. Relapses were observed in almost a third of patients (n = 133; 31.9%).In conclusion, although HSP is a typical vasculitis affecting children and young people, it is not uncommon in adults. The prognosis is favorable in most cases, depending largely on renal involvement. PMID:24646467

  16. Henoch-Schönlein Purpura

    MedlinePLUS

    ... the urine sample. Patches on the dipstick change color when blood or protein are present in urine. [ ... by the NIDDK is carefully reviewed by NIDDK scientists and other experts. The NIDDK would like to ...

  17. PlayStation purpura.

    PubMed

    Robertson, Susan J; Leonard, Jane; Chamberlain, Alex J

    2010-08-01

    A 16-year-old boy presented with a number of asymptomatic pigmented macules on the volar aspect of his index fingers. Dermoscopy of each macule revealed a parallel ridge pattern of homogenous reddish-brown pigment. We propose that these lesions were induced by repetitive trauma from a Sony PlayStation 3 (Sony Corporation, Tokyo, Japan) vibration feedback controller. The lesions completely resolved following abstinence from gaming over a number of weeks. Although the parallel ridge pattern is typically the hallmark for early acral lentiginous melanoma, it may be observed in a limited number of benign entities, including subcorneal haematoma. PMID:20695869

  18. Progressive Pigmentary Purpura

    MedlinePLUS

    ... 2/2017 2017 AOCD Spring Current Concepts in Dermatology Meeting more Latest News 4/3/2014 The Burning Truth 12/19/2013 Osteopathic Training Statement 7/2/2013 The Truth About Tanning 4/24/2013 Sun Safety IQ Online Surveys About AOCD The AOCD was recognized in ...

  19. Sputter target

    DOEpatents

    Gates, Willard G. (Kansas City, MO); Hale, Gerald J. (Overland Park, KS)

    1980-01-01

    The disclosure relates to an improved sputter target for use in the deposition of hard coatings. An exemplary target is given wherein titanium diboride is brazed to a tantalum backing plate using a gold-palladium-nickel braze alloy.

  20. Targeted Audio

    NASA Astrophysics Data System (ADS)

    Olszewski, Dirk

    Targeted audio aims at creating personal listening zones by utilizing adequate measurements. A person inside this listening zone shall be able to perceive acoustically submitted information without disturbing other persons outside the desired listening zone. In order to fulfill this demand, the use of a highly directional audible sound beam is favored. The sound beam shall be aimed at the respective listening zone target, thus implicating the expression targeted audio.

  1. Targeted metabolomics.

    PubMed

    Roberts, Lee D; Souza, Amanda L; Gerszten, Robert E; Clish, Clary B

    2012-04-01

    The metabolome is the terminal downstream product of the genome and consists of the total complement of all the low-molecular-weight molecules (metabolites) in a cell, tissue, or organism. Metabolomics aims to measure a wide breadth of small molecules in the context of physiological stimuli or disease states. Metabolomics methodologies fall into two distinct groups: untargeted metabolomics, an intended comprehensive analysis of all the measurable analytes in a sample including chemical unknowns, and targeted metabolomics, the measurement of defined groups of chemically characterized and biochemically annotated metabolites. The methodologies considered in this unit focus on the processes of conducting targeted metabolomics experiments, and the advantages of this general approach are highlighted herein. This unit outlines procedures for extracting nitrogenous metabolites (including amino acids), lipids, and intermediary metabolites (including TCA cycle oxoacids) from blood plasma. Specifically, protocols are described for analyzing these metabolites using targeted metabolomics experiments based on liquid chromatography-mass spectrometry. PMID:22470063

  2. Target: Lifestyle.

    ERIC Educational Resources Information Center

    Poehlman, Eric T.

    1985-01-01

    "Target: Lifestyle" is a physical education curriculum adopted by Detroit Country Day School which incorporates instruction in nutrition, physical fitness, first aid, and lifetime sports. This curriculum aims to influence student attitudes and lifestyles in health and physical fitness. Four levels of instruction are described. (DF)

  3. Target assembly

    DOEpatents

    Lewis, Richard A. (Falls Church, VA)

    1980-01-01

    A target for a proton beam which is capable of generating neutrons for absorption in a breeding blanket includes a plurality of solid pins formed of a neutron emissive target material disposed parallel to the path of the beam and which are arranged axially in a plurality of layers so that pins in each layer are offset with respect to pins in all other layers, enough layers being used so that each proton in the beam will strike at least one pin with means being provided to cool the pins. For a 300 mA, 1 GeV beam (300 MW), stainless steel pins, 12 inches long and 0.23 inches in diameter are arranged in triangular array in six layers with one sixth of the pins in each layer, the number of pins being such that the entire cross sectional area of the beam is covered by the pins with minimum overlap of pins.

  4. Deorbit targeting

    NASA Technical Reports Server (NTRS)

    Tempelman, W. H.

    1973-01-01

    The navigation and control of the space shuttle during atmospheric entry are discussed. A functional flow diagram presenting the basic approach to the deorbit targeting problem is presented. The major inputs to be considered are: (1) vehicle state vector, (2) landing site location, (3) entry interface parameters, (4) earliest desired time of landing, and (5) maximum cross range. Mathematical models of the navigational procedures based on controlled thrust times are developed.

  5. The effect of antiviral therapy on hepatitis C virus-related thrombocytopenia: a case report

    PubMed Central

    2014-01-01

    Background Autoimmune thrombocytopenic purpura is an immunological disorder characterized by increased platelet destruction due to presence of anti-platelet autoantibodies. Hepatitis C virus infection, which is one of the most common chronic viral infections worldwide, may cause secondary chronic immune thrombocytopenic purpura. Case presentation We report a case of a 51-year-old Caucasian female with hepatitis C virus infection who developed a severe, reversible, immune thrombocytopenia. Platelet count was as low as 56.000/mm3, hepatitis C virus serology was positive, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase and gamma-glutamyltransferase serum levels were elevated. Disorders potentially associated with autoimmune thrombocytopenic purpura were ruled out. A corticosteroid treatment was started and led to an increase in platelet count. The patient was then treated with pegylated-interferon alpha 2a and ribavirin. After four weeks of treatment hepatitis C virus - ribonucleic acid became undetectable and steroid treatment was discontinued. Six months of antiviral therapy achieved a sustained biochemical and virological response together with persistence of normal platelet count. Conclusion In our case report hepatitis C virus seemed to play a pathogenic role in autoimmune thrombocytopenic purpura. Moreover, the successful response (negative hepatitis C virus - ribonucleic acid) to tapered steroids and antiviral therapy was useful to revert thrombocytopenia. PMID:24457056

  6. 76 FR 36367 - National Vaccine Injury Compensation Program: Revisions to the Vaccine Injury Table

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-22

    ...period prescribed. V. Vaccines containing measles A...Thrombocytopenic 7-30 days. virus (e.g., MMR, MR, M). purpura. B. Vaccine-Strain 6 months. Measles...period prescribed. VI. Vaccines containing polio A...live virus (OPV). --in a...

  7. INVITED REVIEW Biology and physics of von Willebrand factor concatamers

    E-print Network

    Springer, Timothy A.

    haemostasis by activating binding of the A1 domain to platelet GPIba, and over longer time periods, regulate: biosynthesis, secretion, shear flow, thrombotic thrombocytopenic purpura, von Willebrand disease, weibel palade, collagen, platelet glycoprotein Ib (GPIb), and integrins aIIbb3 and aVb3 (Fig. 1A). VWF multimers

  8. How Do I Talk to My Family about Gaucher?

    MedlinePLUS

    ... sent to a specialized medical center for analysis. Diagnosis can take a long time because signs and symptoms of Gaucher are often shared with other disorders, such as: • Leukemia or lymphoma • Multiple myeloma • Idiopathic thrombocytopenic purpura (ITP) • Neimann-Pick disease TALKING ...

  9. Accelerator target

    SciTech Connect

    Schlyer, D.J.; Ferrieri, R.A.; Koehler, C.

    1999-06-29

    A target includes a body having a depression in a front side for holding a sample for irradiation by a particle beam to produce a radioisotope. Cooling fins are disposed on a backside of the body opposite the depression. A foil is joined to the body front side to cover the depression and sample therein. A perforate grid is joined to the body atop the foil for supporting the foil and for transmitting the particle beam therethrough. A coolant is circulated over the fins to cool the body during the particle beam irradiation of the sample in the depression. 5 figs.

  10. Accelerator target

    SciTech Connect

    Schlyer, David J.; Ferrieri, Richard A.; Koehler, Conrad

    1999-01-01

    A target includes a body having a depression in a front side for holding a sample for irradiation by a particle beam to produce a radioisotope. Cooling fins are disposed on a backside of the body opposite the depression. A foil is joined to the body front side to cover the depression and sample therein. A perforate grid is joined to the body atop the foil for supporting the foil and for transmitting the particle beam therethrough. A coolant is circulated over the fins to cool the body during the particle beam irradiation of the sample in the depression.

  11. Neutrino Factory Target Vessel

    E-print Network

    McDonald, Kirk

    Neutrino Factory Target Vessel Concept V. Graves Target Studies EVO April 11, 2012 #12;2 Managed by UT-Battelle for the U.S. Department of Energy Target Vessel Concept 11 Apr 2012 Target Vessel;3 Managed by UT-Battelle for the U.S. Department of Energy Target Vessel Concept 11 Apr 2012 Starting Point

  12. Neutrino Factory Target Vessel

    E-print Network

    McDonald, Kirk

    Neutrino Factory Target Vessel Concept Update V. Graves T. Lessard Target Studies EVO June 26, 2012 #12;2 Managed by UT-Battelle for the U.S. Department of Energy Target Vessel Update 26 June 2012 of Energy Target Vessel Update 26 June 2012 Review - Mercury Module Extraction #12;4 Managed by UT

  13. Neutrino Factory Target Vessel

    E-print Network

    McDonald, Kirk

    Neutrino Factory Target Vessel Concepts Updated 4/16/12 V. Graves Target Studies EVO April 11, 2012 #12;2 Managed by UT-Battelle for the U.S. Department of Energy Target Vessel Concept 16 Apr 2012 Target Vessel Requirements · Accurate jet placement · Jet/beam dump pool · Double containment of mercury

  14. Neutrino Factory Target Vessel

    E-print Network

    McDonald, Kirk

    Neutrino Factory Target Vessel Concept Update V. Graves Target Studies EVO June 12, 2012 #12;2 Managed by UT-Battelle for the U.S. Department of Energy Target Vessel Update 12 June 2012 Review ­ IPAC #12;3 Managed by UT-Battelle for the U.S. Department of Energy Target Vessel Update 12 June 2012 Inner

  15. Neutrino Factory Target Vessel

    E-print Network

    McDonald, Kirk

    Neutrino Factory Target Vessel Concept V. Graves Target Studies EVO May 1, 2012 #12;2 Managed by UT-Battelle for the U.S. Department of Energy Target Vessel Concept 1 May 2012 Review ­ Two Target Vessel Ideas · Solid-Battelle for the U.S. Department of Energy Target Vessel Concept 1 May 2012 #12;4 Managed by UT-Battelle for the U

  16. Electrically charged targets

    DOEpatents

    Goodman, Ronald K. (Livermore, CA); Hunt, Angus L. (Alamo, CA)

    1984-01-01

    Electrically chargeable laser targets and method for forming such charged targets in order to improve their guidance along a predetermined desired trajectory. This is accomplished by the incorporation of a small amount of an additive to the target material which will increase the electrical conductivity thereof, and thereby enhance the charge placed upon the target material for guidance thereof by electrostatic or magnetic steering mechanisms, without adversely affecting the target when illuminated by laser energy.

  17. Polarized internal target apparatus

    DOEpatents

    Holt, R.J.

    1984-10-10

    A polarized internal target apparatus with a polarized gas target of improved polarization and density (achieved by mixing target gas atoms with a small amount of alkali metal gas atoms, and passing a high intensity polarized light source into the mixture to cause the alkali metal gas atoms to become polarized which interact in spin exchange collisions with target gas atoms yielding polarized target gas atoms) is described.

  18. Organelle targeting: third level of drug targeting

    PubMed Central

    Sakhrani, Niraj M; Padh, Harish

    2013-01-01

    Drug discovery and drug delivery are two main aspects for treatment of a variety of disorders. However, the real bottleneck associated with systemic drug administration is the lack of target-specific affinity toward a pathological site, resulting in systemic toxicity and innumerable other side effects as well as higher dosage requirement for efficacy. An attractive strategy to increase the therapeutic index of a drug is to specifically deliver the therapeutic molecule in its active form, not only into target tissue, nor even to target cells, but more importantly, into the targeted organelle, ie, to its intracellular therapeutic active site. This would ensure improved efficacy and minimize toxicity. Cancer chemotherapy today faces the major challenge of delivering chemotherapeutic drugs exclusively to tumor cells, while sparing normal proliferating cells. Nanoparticles play a crucial role by acting as a vehicle for delivery of drugs to target sites inside tumor cells. In this review, we spotlight active and passive targeting, followed by discussion of the importance of targeting to specific cell organelles and the potential role of cell-penetrating peptides. Finally, the discussion will address the strategies for drug/DNA targeting to lysosomes, mitochondria, nuclei and Golgi/endoplasmic reticulum. PMID:23898223

  19. Clinical uses of radiolabeled platelets

    SciTech Connect

    Datz, F.L.; Christian, P.E.; Baker, W.J.

    1985-12-01

    Platelets were first successfully radiolabeled in 1953. At that time, investigators were primarily interested in developing a technique to accurately measure platelet life span in both normal and thrombocytopenic patients. Studies using platelets labeled with /sup 51/Cr have shown shortened platelet survival times in a number of diseases including idiopathic thrombocytopenic purpura, coronary artery disease, and diabetes mellitus. More recently, labels such as /sup 111/In have been developed that allow in vivo imaging of platelets. Indium-111 platelets are being used to better understand the pathophysiology of atherosclerosis, thrombophlebitis, pulmonary embolism and clotting disorders, and to improve the clinical diagnosis of these diseases.

  20. Magnetically attached sputter targets

    DOEpatents

    Makowiecki, D.M.; McKernan, M.A.

    1994-02-15

    An improved method and assembly for attaching sputtering targets to cathode assemblies of sputtering systems which includes a magnetically permeable material is described. The magnetically permeable material is imbedded in a target base that is brazed, welded, or soldered to the sputter target, or is mechanically retained in the target material. Target attachment to the cathode is achieved by virtue of the permanent magnets and/or the pole pieces in the cathode assembly that create magnetic flux lines adjacent to the backing plate, which strongly attract the magnetically permeable material in the target assembly. 11 figures.

  1. Magnetically attached sputter targets

    DOEpatents

    Makowiecki, Daniel M. (Livermore, CA); McKernan, Mark A. (Livermore, CA)

    1994-01-01

    An improved method and assembly for attaching sputtering targets to cathode assemblies of sputtering systems which includes a magnetically permeable material. The magnetically permeable material is imbedded in a target base that is brazed, welded, or soldered to the sputter target, or is mechanically retained in the target material. Target attachment to the cathode is achieved by virtue of the permanent magnets and/or the pole pieces in the cathode assembly that create magnetic flux lines adjacent to the backing plate, which strongly attract the magnetically permeable material in the target assembly.

  2. Molecular Targets Laboratory

    Cancer.gov

    Group Mission: Develops, adapts, evaluates, and applies novel screening assays, protocols and emerging technologies for molecular target validation, molecularly targeted lead discovery and research; Provides screening support for bioassay-guided lead isol

  3. FLIR target screening

    NASA Technical Reports Server (NTRS)

    Aggarwal, R.

    1982-01-01

    Methods for the segmentation and recognition of individual targets sensed with forward looking infrared detectors are discussed. Particular attention is given to an adaptive multi-scenario target screener.

  4. DTP - Molecular Targets

    Cancer.gov

    Thousands of molecular targets have been measured in the NCI panel of 60 human tumor cell lines. Measurements include protein levels, RNA measurements, mutation status and enzyme activity levels. You can choose to search for a target of interest, or you may browse through a list of targets.

  5. Using TARGET Data

    Cancer.gov

    The TARGET Initiative produces large-scale genomic data for a selected set of pediatric cancers and provides the research community access to those data. The goal for broadly sharing TARGET data is to facilitate the discovery of therapeutic targets for childhood cancers and catalyze the translation of these discoveries into clinical applications.

  6. Targets for Precision Measurements

    NASA Astrophysics Data System (ADS)

    Loveland, W.; Yao, L.; Asner, D. M.; Baker, R. G.; Bundgaard, J.; Burgett, E.; Cunningham, M.; Deaven, J.; Duke, D. L.; Greife, U.; Grimes, S.; Heffner, M.; Hill, T.; Isenhower, D.; Klay, J. L.; Kleinrath, V.; Kornilov, N.; Laptev, A. B.; Massey, T. N.; Meharchand, R.; Qu, H.; Ruz, J.; Sangiorgio, S.; Selhan, B.; Snyder, L.; Stave, S.; Tatishvili, G.; Thornton, R. T.; Tovesson, F.; Towell, D.; Towell, R. S.; Watson, S.; Wendt, B.; Wood, L.

    2014-05-01

    The general properties needed in targets (sources) for high precision, high accuracy measurements are reviewed. The application of these principles to the problem of developing targets for the Fission TPC is described. Longer term issues, such as the availability of actinide materials, improved knowledge of energy losses and straggling and the stability of targets during irradiation are also discussed.

  7. Plasma sheath driven targets

    SciTech Connect

    Brownell, J.H.; Freeman, B.L.

    1980-02-01

    Plasma focus driven target implosions are simulated using hydrodynamic-burn codes. Support is given to the idea that the use of a target in a plasma focus should allow ''impedance matching'' between the fuel and gun, permitting larger fusion yields from a focus-target geometry than the scaling laws for a conventional plasma focus would predict.

  8. Graphite targets at LAMPF

    SciTech Connect

    Brown, R.D.; Grisham, D.L.

    1983-01-01

    Rotating polycrystalline and stationary pyrolytic graphite target designs for the LAMPF experimental area are described. Examples of finite element calculations of temperatures and stresses are presented. Some results of a metallographic investigation of irradiated pyrolytic graphite target plates are included, together with a brief description of high temperature bearings for the rotating targets.

  9. High Power Cryogenic Targets

    SciTech Connect

    Gregory Smith

    2011-08-01

    The development of high power cryogenic targets for use in parity violating electron scattering has been a crucial ingredient in the success of those experiments. As we chase the precision frontier, the demands and requirements for these targets have grown accordingly. We discuss the state of the art, and describe recent developments and strategies in the design of the next generation of these targets.

  10. Kepler Target Pixel Files

    NASA Astrophysics Data System (ADS)

    Thompson, Susan E.; McCauliff, S.; Bryson, S.; Still, M.; van Cleve, J.; Dotson, J.; Twicken, J.; Klaus, T.; Cote, M.; Fanelli, M.

    2011-01-01

    In early 2011, the Kepler Mission will make available the pixel data for all observed targets, in addition to the aperture photometry light curves currently provided at the Multi-mission Archive at STScI (MAST). These target pixel files will contain images of the calibrated flux, the subtracted background, and the removed cosmic rays for the target at each cadence. Certain targets, such as highly variable stars, non-stellar targets, or saturated targets, require an analysis beyond fixed, optimal aperture photometry in order to retrieve all the information from the data. For a few cases we demonstrate the utility of the target pixel files in understanding the quality of the data and in performing specialized aperture photometry. Kepler was selected as the 10th mission of the Discovery Program. Funding for this mission is provided by NASA, Science Mission Directorate.

  11. Magnetized Target Fusion: Improving the plasma target

    NASA Astrophysics Data System (ADS)

    Intrator, T.; Magnetized Target Fusion Collaboration

    2011-10-01

    Magneto Inertial Fusion (MIF) inertial adiabatic compression of a plasma fuel target takes advantage of embedded magnetic field to reduce thermal conduction and enhance alpha-particle heating. Magnetized Target Fusion (MTF) is a subset of MIF, requiring target plasma formation plus ejection into a solid flux conserving compressor shell or liner that implodes and compresses a plasma target. The liner has much larger mass than the compressed fuel, which increases the dwell time because it scales as the square root of the total mass. It appears possible to exceed the typical figure of merit eta*G > 10 which is the product of (high) driver efficiency eta and (small) fusion gain G. We describe our efforts to improve the plasma target lifetime by using plasma guns. We also show recent data including experimental engineering test shots in a collaboration with Kirtland Air Force Research Laboratory to realize a physics demonstration of MTF. DOE, Office of Science, Office of Fusion Energy Sciences, under LANS Contract No. DE-AC52-06NA25396.

  12. Bar coded retroreflective target

    DOEpatents

    Vann, Charles S. (Fremont, CA)

    2000-01-01

    This small, inexpensive, non-contact laser sensor can detect the location of a retroreflective target in a relatively large volume and up to six degrees of position. The tracker's laser beam is formed into a plane of light which is swept across the space of interest. When the beam illuminates the retroreflector, some of the light returns to the tracker. The intensity, angle, and time of the return beam is measured to calculate the three dimensional location of the target. With three retroreflectors on the target, the locations of three points on the target are measured, enabling the calculation of all six degrees of target position. Until now, devices for three-dimensional tracking of objects in a large volume have been heavy, large, and very expensive. Because of the simplicity and unique characteristics of this tracker, it is capable of three-dimensional tracking of one to several objects in a large volume, yet it is compact, light-weight, and relatively inexpensive. Alternatively, a tracker produces a diverging laser beam which is directed towards a fixed position, and senses when a retroreflective target enters the fixed field of view. An optically bar coded target can be read by the tracker to provide information about the target. The target can be formed of a ball lens with a bar code on one end. As the target moves through the field, the ball lens causes the laser beam to scan across the bar code.

  13. Effective neutron targets

    SciTech Connect

    Gao, H.

    1997-07-01

    Because of the lack of a free neutron target, deuterium targets have been used extensively in studying the neutron structure. The unique spin structure of the {sup 3}He ground state wave function and the recent developments in laser technologies made polarized {sup 3}He targets widely used in many experiments from neutron electromagnetic form factor studies to nucleon spin structure function measurements at all major electron accelerator facilities. In this talk, the current status of the polarized {sup 3}He targets will be reviewed. The author will focus on neutron electromagnetic form factor studies using polarized {sup 3}He targets. The polarized nucleon spin structure function measurements using polarized {sup 3}He targets will also be discussed.

  14. Targeting the tumor microenvironment

    SciTech Connect

    Kenny, P.A.; Lee, G.Y.; Bissell, M.J.

    2006-11-07

    Despite some notable successes cancer remains, for the most part, a seemingly intractable problem. There is, however, a growing appreciation that targeting the tumor epithelium in isolation is not sufficient as there is an intricate mutually sustaining synergy between the tumor epithelial cells and their surrounding stroma. As the details of this dialogue emerge, new therapeutic targets have been proposed. The FDA has already approved drugs targeting microenvironmental components such as VEGF and aromatase and many more agents are in the pipeline. In this article, we describe some of the 'druggable' targets and processes within the tumor microenvironment and review the approaches being taken to disrupt these interactions.

  15. GWAS and drug targets

    PubMed Central

    2014-01-01

    Background Genome wide association studies (GWAS) have revealed a large number of links between genome variation and complex disease. Among other benefits, it is expected that these insights will lead to new therapeutic strategies, particularly the identification of new drug targets. In this paper, we evaluate the power of GWAS studies to find drug targets by examining how many existing drug targets have been directly 'rediscovered' by this technique, and the extent to which GWAS results may be leveraged by network information to discover known and new drug targets. Results We find that only a very small fraction of drug targets are directly detected in the relevant GWAS studies. We investigate two possible explanations for this observation. First, we find evidence of negative selection acting on drug target genes as a consequence of strong coupling with the disease phenotype, so reducing the incidence of SNPs linked to the disease. Second, we find that GWAS genes are substantially longer on average than drug targets and than all genes, suggesting there is a length related bias in GWAS results. In spite of the low direct relationship between drug targets and GWAS reported genes, we found these two sets of genes are closely coupled in the human protein network. As a consequence, machine-learning methods are able to recover known drug targets based on network context and the set of GWAS reported genes for the same disease. We show the approach is potentially useful for identifying drug repurposing opportunities. Conclusions Although GWA studies do not directly identify most existing drug targets, there are several reasons to expect that new targets will nevertheless be discovered using these data. Initial results on drug repurposing studies using network analysis are encouraging and suggest directions for future development. PMID:25057111

  16. First SNS Target Replacement

    E-print Network

    McDonald, Kirk

    Servo-Manipulator ·The servo-manipulator is the defining feature of the SNS hot cell: ­ Dual-arm, high Environment ­ Target Service Bay ­ Maintenance Equipment ­ Target Process Configuration ­ Radiation several key functions: ­ Enclosure of the mercury process ­ Maintenance of the mercury process equipment

  17. Step tracking shrinking targets

    NASA Technical Reports Server (NTRS)

    Johnson, Walter W.; Hart, Sandra G.

    1987-01-01

    Four models describing how people might acquire targets that dynamically vary in size were examined; two that described movement speed as a simple function of target size (either initial or final) and two that described movement speed as a function of the predicted size of the targets at a fixed time in the future (one was referenced to the beginning of the reaction time phase, and the other to the end of this phase). It was found that movement time was best described as a function of a size prediction made at the end, rather than the start, of the reaction time phase. Subjective workload ratings primarily reflected the total amount of time needed to acquire the targets rather than the time pressure imposed by the diminishing size of these targets.

  18. Targeted therapy in lymphoma

    PubMed Central

    2010-01-01

    Discovery of new treatments for lymphoma that prolong survival and are less toxic than currently available agents represents an urgent unmet need. We now have a better understanding of the molecular pathogenesis of lymphoma, such as aberrant signal transduction pathways, which have led to the discovery and development of targeted therapeutics. The ubiquitin-proteasome and the Akt/mammalian target of rapamycin (mTOR) pathways are examples of pathological mechanisms that are being targeted in drug development efforts. Bortezomib (a small molecule protease inhibitor) and the mTOR inhibitors temsirolimus, everolimus, and ridaforolimus are some of the targeted therapies currently being studied in the treatment of aggressive, relapsed/refractory lymphoma. This review will discuss the rationale for and summarize the reported findings of initial and ongoing investigations of mTOR inhibitors and other small molecule targeted therapies in the treatment of lymphoma. PMID:21092307

  19. Production Target Design Report

    SciTech Connect

    Woloshun, Keith Albert; Dale, Gregory E.; Olivas, Eric Richard

    2015-07-28

    The Northstar 99Mo production target, a cylindrical length of 100Mo rod, has evolved considerably since its first conception.  The cylinder was very early sliced into disks to increase the heat transfer area, first to 1 mm thick disks then to the current 0.5 mm thick.  The coolant was changed early in the target development from water to helium to eliminate corrosion and dissolution.  The diameter has increased from initially 6 mm to 12 mm, the current diameter of the test target now at ANL, to nominally 28 mm (26-30.6 mm, depending upon optimal beam spot size and shape).  The length has also changed to improve the production to cost ratio, so now the target is nominally 41 mm long (excluding coolant gaps between disks), and irradiated on both ends.  This report summarizes the current status of the plant target design.

  20. Targeted delivery of nanomedicines.

    PubMed

    Kumar Khanna, Vinod

    2012-01-01

    The role of targeting of the diseased region by a drug is emphasized. The rationale for resorting to nanomaterials as drug carriers is explained. A clear understanding of the biological environment, its degradation in diseased condition, and the interaction of the drug with it in normal condition and during illness lie at the core of successful drug delivery. Passive and active drug targeting approaches are differentiated. Commonly used drug targets, targeting ligands, and nanoscale systems are elaborated. Mechanisms of internalization of nanomedicines and circumventing P-glycoprotein mediated resistance are outlined. The paper presents an overview of the current scenario of targeted transportation of nanomedicines to the affected organ and suggests future research directions. PMID:22577576

  1. Internal polarized targets

    SciTech Connect

    Kinney, E.R.; Coulter, K.; Gilman, R.; Holt, R.J.; Kowalczyk, R.S.; Napolitano, J.; Potterveld, D.H.; Young, L. ); Mishnev, S.I.; Nikolenko, D.M.; Popov, S.G.; Rachek, I.A.; Temnykh, A.B.; Toporkov, D.K.; Tsentalovich, E.P.; Wojtsekhowski, B.B. . Inst. Yadernoj Fiziki)

    1989-01-01

    Internal polarized targets offer a number of advantages over external targets. After a brief review of the basic motivation and principles behind internal polarized targets, the technical aspects of the atomic storage cell will be discussed in particular. Sources of depolarization and the means by which their effects can be ameliorated will be described, especially depolarization by the intense magnetic fields arising from the circulating particle beam. The experience of the Argonne Novosibirsk collaboration with the use of a storage cell in a 2 GeV electron storage ring will be the focus of this technical discussion. 17 refs., 11 figs.

  2. Molecular Targets Laboratory

    Cancer.gov

    The MTL provides an outstanding training environment for qualified predoctoral and postdoctoral individuals interested in furthering their skills and experiences in the multidisciplinary sciences of assay development, target validation, drug discovery res

  3. Molecular Targets Laboratory

    Cancer.gov

    Group Mission: Provides chemistry support for bioassay-guided fractionation, isolation, purification and structural characterization of novel, molecularly targeted nonproteinaceous leads from natural products; Reisolates bioactive compounds of interest fo

  4. CDRP - Target Populations

    Cancer.gov

    Home About CDRP Background The Challenge Ahead Health Disparities Cooperative Planning Grant Objective and Scope U56 Award Mechanism Target Populations Funded Institutions Funded Institutions Programs' Presentations CDRP Symposium Presentations Clinical

  5. Molecular Targets Laboratory

    Cancer.gov

    Date Investigator Title  Project Manager(s) December 18, 2000 Philipp Kaldis Cyclin Dependent Kinases as Potential Screening Targets O'Keefe   August 8, 2001 Chem Akin Diana Linnekin Mastocytosis: The Disease, Therapeutic Challenges and Potential Opportun

  6. Ampliseq Targeted Resequencing

    Cancer.gov

    Exome Sequencing frequently identifies regions of interest for further exploration or validation of variants. Targeted resequencing, either as a follow-up to exome sequencing, or as a stand-alone project, can be done using Life Technologies' Ion Ampliseq

  7. Targeted Cancer Therapies

    MedlinePLUS

    ... of cells in the body. Cancer vaccines and gene therapy are sometimes considered targeted therapies because they interfere ... see Help Finding NCI-Supported Clinical Trials . Hormone therapy Signal transduction inhibitors Gene ... inhibitors Immunotherapy Monoclonal ...

  8. Molecular Targets Laboratory

    Cancer.gov

    The MTL provides leadership for the translation of basic science advances into drug leads, bioprobes and reagents for molecular target evaluation. exploits chemical and biodiversity repositories, including the NCI Natural Products Repository, for molecula

  9. Molecular Targets Laboratory

    Cancer.gov

    Mission The MTL provides leadership for the translation of basic science advances into drug leads, bioprobes and reagents for molecular target evaluation.  We exploit chemical and biodiversity repositories, including the NCI Natural Products Repository, f

  10. Molecular Targets Laboratory

    Cancer.gov

    In addition to the intramural community of world-class scientists comprising the CCR, there are other unique resources available at the NCI that provide extraordinary opportunities for intramural collaborations in molecular target elucidation, validation

  11. Molecular Targets Laboratory

    Cancer.gov

    Background Recent advances and insights into the molecular pathogenesis of cancer provide unprecedented opportunities for discovery and development of novel, molecularly targeted diagnostic, therapeutic and preventative strategies and agents. The pivotal

  12. Target classification strategies

    NASA Astrophysics Data System (ADS)

    Schachter, Bruce J.

    2015-05-01

    Target classification algorithms have generally kept pace with developments in the academic and commercial sectors since the 1970s. However, most recently, investment into object classification by internet companies and various Human Brain Projects have far outpaced that of the defense sector. Implications are noteworthy. There are some unique characteristics of the military classification problem. Target classification is not solely an algorithm design problem, but is part of a larger system design task. The design flows down from a concept of operations (ConOps) and key performance parameters (KPPs). Inputs are image and/or signal data and time-synchronized metadata. The operation is real-time. The implementation minimizes size, weight and power (SWaP). The output must be conveyed to a time-strapped operator who understands the rules of engagement. It is assumed that the adversary is actively trying to defeat recognition. The target list is often mission dependent, not necessarily a closed set, and may change on a daily basis. It is highly desirable to obtain sufficiently comprehensive training and testing data sets, but costs of doing so are very high and data on certain target types are scarce. The training data may not be representative of battlefield conditions suggesting the avoidance of highly tuned designs. A number of traditional and emerging target classification strategies are reviewed in the context of the military target problem.

  13. Mitochondria-targeted antioxidants.

    PubMed

    Oyewole, Anne O; Birch-Machin, Mark A

    2015-12-01

    Redox homeostasis is maintained by the antioxidant defense system, which is responsible for eliminating a wide range of oxidants, including reactive oxygen species (ROS), lipid peroxides, and metals. Mitochondria-localized antioxidants are widely studied because the mitochondria, the major producers of intracellular ROS, have been linked to the cause of aging and other chronic diseases. Mitochondria-targeted antioxidants have shown great potential because they cross the mitochondrial phospholipid bilayer and eliminate ROS at the heart of the source. Growing evidence has identified mitochondria-targeted antioxidants, such as MitoQ and tiron, as potentially effective antioxidant therapies against the damage caused by enhanced ROS generation. This literature review summarizes the current knowledge on mitochondria-targeted antioxidants and their contribution to the body's antioxidant defense system. In addition to addressing the concerns surrounding current antioxidant strategies, including difficulties in targeting antioxidant treatment to sites of pathologic oxidative damage, we discuss promising therapeutic agents and new strategic approaches.-Oyewole, A. O., Birch-Machin, M. A. Mitochondria-targeted antioxidants. PMID:26253366

  14. Burglar Target Selection

    PubMed Central

    Townsley, Michael; Bernasco, Wim; Ruiter, Stijn; Johnson, Shane D.; White, Gentry; Baum, Scott

    2015-01-01

    Objectives: This study builds on research undertaken by Bernasco and Nieuwbeerta and explores the generalizability of a theoretically derived offender target selection model in three cross-national study regions. Methods: Taking a discrete spatial choice approach, we estimate the impact of both environment- and offender-level factors on residential burglary placement in the Netherlands, the United Kingdom, and Australia. Combining cleared burglary data from all study regions in a single statistical model, we make statistical comparisons between environments. Results: In all three study regions, the likelihood an offender selects an area for burglary is positively influenced by proximity to their home, the proportion of easily accessible targets, and the total number of targets available. Furthermore, in two of the three study regions, juvenile offenders under the legal driving age are significantly more influenced by target proximity than adult offenders. Post hoc tests indicate the magnitudes of these impacts vary significantly between study regions. Conclusions: While burglary target selection strategies are consistent with opportunity-based explanations of offending, the impact of environmental context is significant. As such, the approach undertaken in combining observations from multiple study regions may aid criminology scholars in assessing the generalizability of observed findings across multiple environments. PMID:25866418

  15. Targeted assets risk analysis.

    PubMed

    Bouwsema, Barry

    2013-01-01

    Risk assessments utilising the consolidated risk assessment process as described by Public Safety Canada and the Centre for Security Science utilise the five threat categories of natural, human accidental, technological, human intentional and chemical, biological, radiological, nuclear or explosive (CBRNE). The categories of human intentional and CBRNE indicate intended actions against specific targets. It is therefore necessary to be able to identify which pieces of critical infrastructure represent the likely targets of individuals with malicious intent. Using the consolidated risk assessment process and the target capabilities list, coupled with the CARVER methodology and a security vulnerability analysis, it is possible to identify these targeted assets and their weaknesses. This process can help emergency managers to identify where resources should be allocated and funding spent. Targeted Assets Risk Analysis (TARA) presents a new opportunity to improve how risk is measured, monitored, managed and minimised through the four phases of emergency management, namely, prevention, preparation, response and recovery. To reduce risk throughout Canada, Defence Research and Development Canada is interested in researching the potential benefits of a comprehensive approach to risk assessment and management. The TARA provides a framework against which potential human intentional threats can be measured and quantified, thereby improving safety for all Canadians. PMID:23615063

  16. High power density targets

    NASA Astrophysics Data System (ADS)

    Pellemoine, Frederique

    2013-12-01

    In the context of new generation rare isotope beam facilities based on high-power heavy-ion accelerators and in-flight separation of the reaction products, the design of the rare isotope production targets is a major challenge. In order to provide high-purity beams for science, high resolution is required in the rare isotope separation. This demands a small beam spot on the production target which, together with the short range of heavy ions in matter, leads to very high power densities inside the target material. This paper gives an overview of the challenges associated with this high power density, discusses radiation damage issues in targets exposed to heavy ion beams, and presents recent developments to meet some of these challenges through different projects: FAIR, RIBF and FRIB which is the most challenging. Extensive use of Finite Element Analysis (FEA) has been made at all facilities to specify critical target parameters and R&D work at FRIB successfully retired two major risks related to high-power density and heavy-ion induced radiation damage.

  17. Setting reference targets

    SciTech Connect

    Ruland, R.E.

    1997-04-01

    Reference Targets are used to represent virtual quantities like the magnetic axis of a magnet or the definition of a coordinate system. To explain the function of reference targets in the sequence of the alignment process, this paper will first briefly discuss the geometry of the trajectory design space and of the surveying space, then continue with an overview of a typical alignment process. This is followed by a discussion on magnet fiducialization. While the magnetic measurement methods to determine the magnetic centerline are only listed (they will be discussed in detail in a subsequent talk), emphasis is given to the optical/mechanical methods and to the task of transferring the centerline position to reference targets.

  18. Phoenix Color Targets

    NASA Technical Reports Server (NTRS)

    2008-01-01

    These images of three Phoenix color targets were taken on sols 1 and 2 by the Surface Stereo Imager (SSI) on board the Phoenix lander. The bottom target was imaged in approximate color (SSI's red, green, and blue filters: 600, 530, and 480 nanometers), while the others were imaged with an infrared filter (750 nanometers). All of them will be imaged many times over the mission to monitor the color calibration of the camera. The two at the top show grains 2 to 3 millimeters in size that were likely lifted to the Phoenix deck during landing. Each of the large color chips on each target contains a strong magnet to protect the interior material from Mars' magnetic dust.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  19. Targeted polypeptide degradation

    DOEpatents

    Church, George M. (Brookline, MA); Janse, Daniel M. (Brookline, MA)

    2008-05-13

    This invention pertains to compositions, methods, cells and organisms useful for selectively localizing polypeptides to the proteasome for degradation. Therapeutic methods and pharmaceutical compositions for treating disorders associated with the expression and/or activity of a polypeptide by targeting these polypeptides for degradation, as well as methods for targeting therapeutic polypeptides for degradation and/or activating therapeutic polypeptides by degradation are provided. The invention provides methods for identifying compounds that mediate proteasome localization and/or polypeptide degradation. The invention also provides research tools for the study of protein function.

  20. Integrin Targeted Therapeutics

    PubMed Central

    Millard, Melissa; Odde, Srinivas; Neamati, Nouri

    2011-01-01

    Integrins are heterodimeric, transmembrane receptors that function as mechanosensors, adhesion molecules and signal transduction platforms in a multitude of biological processes. As such, integrins are central to the etiology and pathology of many disease states. Therefore, pharmacological inhibition of integrins is of great interest for the treatment and prevention of disease. In the last two decades several integrin-targeted drugs have made their way into clinical use, many others are in clinical trials and still more are showing promise as they advance through preclinical development. Herein, this review examines and evaluates the various drugs and compounds targeting integrins and the disease states in which they are implicated. PMID:21547158

  1. Foam encapsulated targets

    DOEpatents

    Nuckolls, John H. (Livermore, CA); Thiessen, Albert R. (Livermore, CA); Dahlbacka, Glen H. (Livermore, CA)

    1983-01-01

    Foam encapsulated laser-fusion targets wherein a quantity of thermonuclear fuel is embedded in low density, microcellular foam which serves as an electron conduction channel for symmetrical implosion of the fuel by illumination of the target by one or more laser beams. The fuel, such as DT, is contained within a hollow shell constructed of glass, for example, with the foam having a cell size of preferably no greater than 2 .mu.m, a density of 0.065 to 0.6.times.10.sup.3 kg/m.sup.3, and external diameter of less than 200 .mu.m.

  2. Comet and Target Ghost: Techniques for Selecting Moving Targets

    E-print Network

    Comet and Target Ghost: Techniques for Selecting Moving Targets Khalad Hasan1 , Tovi Grossman2 that assist in selecting moving targets. We present Comet, a technique that enhances tar- gets based of the target, while leaving the motion uninterrupted. We found a speed benefit for the Comet in a 1D selection

  3. Targeted cancer immunotherapy

    PubMed Central

    Müller, Dafne

    2012-01-01

    Under physiological conditions, the trans-presentation of interleukin-15 (IL-15) by the IL-15 receptor ? on the cell surface allows to confine and tune the IL-15-mediated immune responses. Therefore, targeting strategies that mimic this situation at the tumor sites appear especially promising for anticancer immunotherapy. PMID:23170284

  4. Microenvironmental Targets in Sarcoma

    PubMed Central

    Ehnman, Monika; Larsson, Olle

    2015-01-01

    Sarcomas are rare malignant tumors affecting all age groups. They are typically classified according to their resemblance to corresponding normal tissue. Their heterogeneous features, for example, in terms of disease-driving genetic aberrations and body location, complicate both disease classification and development of novel treatment regimens. Many years of failure of improved patient outcome in clinical trials has led to the conclusion that novel targeted therapies are likely needed in combination with current multimodality regimens. Sarcomas have not, in contrast to the common carcinomas, been the subject of larger systematic studies on how tumor behavior relates to characteristics of the tumor microenvironment. There is consequently an urgent need for identifying suitable molecular targets, not only in tumor cells but also in the tumor microenvironment. This review discusses preclinical and clinical data about potential molecular targets in sarcomas. Studies on targeted therapies involving the tumor microenvironment are prioritized. A greater understanding of the biological context is expected to facilitate more successful design of future clinical trials in sarcoma. PMID:26583076

  5. Targeted radionuclide therapy

    PubMed Central

    Williams, Lawrence E.; DeNardo, Gerald L.; Meredith, Ruby F.

    2008-01-01

    Targeted radionuclide therapy (TRT) seeks molecular and functional targets within patient tumor sites. A number of agents have been constructed and labeled with beta, alpha, and Auger emitters. Radionuclide carriers spanning a broad range of sizes; e.g., antibodies, liposomes, and constructs such as nanoparticles have been used in these studies. Uptake, in percent-injected dose per gram of malignant tissue, is used to evaluate the specificity of the targeting vehicle. Lymphoma (B-cell) has been the primary clinical application. Extension to solid tumors will require raising the macroscopic absorbed dose by several-fold over values found in present technology. Methods that may effect such changes include multistep targeting, simultaneous chemotherapy, and external sequestration of the agent. Toxicity has primarily involved red marrow so that marrow replacement can also be used to enhance future TRT treatments. Correlation of toxicities and treatment efficiency has been limited by relatively poor absorbed dose estimates partly because of using standard (phantom) organ sizes. These associations will be improved in the future by obtaining patient-specific organ size and activity data with hybrid SPECT?CT and PET?CT scanners. PMID:18697529

  6. Molecular Targets Laboratory

    Cancer.gov

    2016 T. Masaoka, H. Zhao, D. R. Hirsch, M. P. D'Erasmo, C. Meck, B. Vardano, M. J. Meyers, J. Baines, J. A. Beutler, R. P. Murelli, L. Tang, S. F. J. Le Grice, Characterization of the C-terminal nuclease domain of herpes simplex virus pUL15 as a target of

  7. Target Heart Rates

    MedlinePLUS

    ... you’re ready to determine your target training heart rate. As you exercise, periodically: Take your pulse on the inside of ... safer than others. Learn more: Blood Pressure Vs. Heart Rate The AHA Recommendations ... Receive healthy living tips every month! First Name ( ...

  8. Target Heart Rate Calculator

    MedlinePLUS

    ... workout Enter your age to find a target heart rate during exercise. You'll get the most out of your activities by staying within this range of heartbeats/minute. What is your age? years. How to Check Your Heart Rate Right after you stop exercising, take your pulse: ...

  9. High purity tungsten targets

    NASA Technical Reports Server (NTRS)

    1975-01-01

    High purity tungsten, which is used for targets in X-ray tubes was considered for space processing. The demand for X-ray tubes was calculated using the growth rates for dental and medical X-ray machines. It is concluded that the cost benefits are uncertain.

  10. Opportunity Spies Its Target

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This is a forward-looking view of the Meridiani Planum plains that lie between the Mars Exploration Rover Opportunity and its primary drive target, 'Endurance Crater.' The images in this image mosaic were taken by the rover's panoramic camera on sol 88.

  11. Target fragmentation in radiobiology

    NASA Technical Reports Server (NTRS)

    Wilson, John W.; Cucinotta, Francis A.; Shinn, Judy L.; Townsend, Lawrence W.

    1993-01-01

    Nuclear reactions in biological systems produce low-energy fragments of the target nuclei seen as local high events of linear energy transfer (LET). A nuclear-reaction formalism is used to evaluate the nuclear-induced fields within biosystems and their effects within several biological models. On the basis of direct ionization interaction, one anticipates high-energy protons to have a quality factor and relative biological effectiveness (RBE) of unity. Target fragmentation contributions raise the effective quality factor of 10 GeV protons to 3.3 in reasonable agreement with RBE values for induced micronuclei in bean sprouts. Application of the Katz model indicates that the relative increase in RBE with decreasing exposure observed in cell survival experiments with 160 MeV protons is related solely to target fragmentation events. Target fragment contributions to lens opacity given an RBE of 1.4 for 2 GeV protons in agreement with the work of Lett and Cox. Predictions are made for the effective RBE for Harderian gland tumors induced by high-energy protons. An exposure model for lifetime cancer risk is derived from NCRP 98 risk tables, and protraction effects are examined for proton and helium ion exposures. The implications of dose rate enhancement effects on space radiation protection are considered.

  12. Future Fixed Target Facilities

    SciTech Connect

    Melnitchouk, Wolodymyr

    2009-01-01

    We review plans for future fixed target lepton- and hadron-scattering facilities, including the 12 GeV upgraded CEBAF accelerator at Jefferson Lab, neutrino beam facilities at Fermilab, and the antiproton PANDA facility at FAIR. We also briefly review recent theoretical developments which will aid in the interpretation of the data expected from these facilities.

  13. Solid Target Options S. Childress

    E-print Network

    McDonald, Kirk

    geometry to spread energy deposition over a large target area #12;Solid Target Options NuFACT'00 S power is higher than for existing solid target designs - but not by a large factor. · NuMI graphite target design (400 kW beam) has similar energy deposition density as a 1 MW neutrino source. Recent

  14. Plastids and protein targeting.

    PubMed

    McFadden, G I

    1999-01-01

    Plastids with two bounding membranes--as exemplified by red algae, green algae, plants, and glaucophytes--derive from primary endosymbiosis; a process involving engulfment and retention of a cyanobacterium by a phagotrophic eukaryote. Plastids with more than two bounding membranes (such as those of euglenoids, dinoflagellates, heterokonts, haptopytes, apicomplexa, cryptomonads, and chlorarachniophytes) probably arose by secondary endosymbiosis, in which a eukaryotic alga (itself the product of primary endosymbiosis) was engulfed and retained by a phagotroph. Secondary endosymbiosis transfers photosynthetic capacity into heterotrophic lineages, has apparently occurred numerous times, and has created several major eukaryotic lineages comprising upwards of 42,600 species. Plastids acquired by secondary endosymbiosis are sometimes referred to as "second-hand." Establishment of secondary endosymbioses has involved transfer of genes from the endosymbiont nucleus to the secondary host nucleus. Limited gene transfer could initially have served to stabilise the endosymbioses, but it is clear that the transfer process has been extensive, leading in many cases to the complete disappearance of the endosymbiont nucleus. One consequence of these gene transfers is that gene products required in the plastid must be targeted into the organelle across multiple membranes: at least three for stromal proteins in euglenoids and dinoflagellates, and across five membranes in the case of thylakoid lumen proteins in plastids with four bounding membranes. Evolution of such targeting mechanisms was obviously a key step in the successful establishment of each different secondary endosymbiosis. Analysis of targeted proteins in the various organisms now suggests that a similar system is used by each group. However, rather than interpreting this similarity as evidence of an homologous origin, I believe that targeting has evolved convergently by combining and recycling existing protein trafficking mechanisms already existing in the endosymbiont and host. Indeed, by analyzing the multiple motifs in targeting sequences of some genes it is possible to infer that they originated in the plastid genome, transferred from there into the primary host nucleus, and subsequently moved into the secondary host nucleus. Thus, each step of the targeting process in "second-hand" plastids recapitulates the gene's previous intracellular transfers. PMID:10461382

  15. Mitochondria-targeting particles

    PubMed Central

    Wongrakpanich, Amaraporn; Geary, Sean M; Joiner, Mei-ling A; Anderson, Mark E; Salem, Aliasger K

    2015-01-01

    Mitochondria are a promising therapeutic target for the detection, prevention and treatment of various human diseases such as cancer, neurodegenerative diseases, ischemia-reperfusion injury, diabetes and obesity. To reach mitochondria, therapeutic molecules need to not only gain access to specific organs, but also to overcome multiple barriers such as the cell membrane and the outer and inner mitochondrial membranes. Cellular and mitochondrial barriers can be potentially overcome through the design of mitochondriotropic particulate carriers capable of transporting drug molecules selectively to mitochondria. These particulate carriers or vectors can be made from lipids (liposomes), biodegradable polymers, or metals, protecting the drug cargo from rapid elimination and degradation in vivo. Many formulations can be tailored to target mitochondria by the incorporation of mitochondriotropic agents onto the surface and can be manufactured to desired sizes and molecular charge. Here, we summarize recently reported strategies for delivering therapeutic molecules to mitochondria using various particle-based formulations. PMID:25490424

  16. Targeted Therapy for Melanoma.

    PubMed

    Wong, Deborah J L; Ribas, Antoni

    2016-01-01

    Vemurafenib and dabrafenib, two potent tyrosine kinase inhibitors (TKIs) of the BRAF(V600E) kinase, are highly effective in the treatment of a BRAF (V600) -mutant metastatic melanoma. These are selective type I inhibitors (functional against the active conformation of the kinase) of the RAF kinases, which are key players in the mitogen-activated protein kinase (MAPK) pathway. BRAF (V600) mutations are present in approximately 7 % of all cancers, including high frequencies of mutations reported in 50 % of advanced melanomas and 100 % of hairy cell leukemias. As with most targeted therapies, resistance to BRAF inhibitors is an issue, and mechanisms of resistance are varied. Combining BRAF inhibitors with MEK inhibitors such as trametinib delays the development of resistance. Rationally combining targeted therapies to address the mechanism of resistance or combining BRAF inhibitors with other effective therapies such as immunotherapy may result in further improvement in outcomes for patients. PMID:26601866

  17. Targeting biodefense markets.

    PubMed

    Olinger, Gene Garrard

    2009-10-01

    The "World Vaccine Congress 2009" held in Washington D.C. (April 20-23, 2009) sponsored several sessions focused on the vaccine market targeting biodefense. On day one of the congress, a panel discussion outlined the federal progress in medical countermeasure preparedness that included emerging infections, influenza, and biodefense focuses. The second day, a session focused on the biodefense vaccine market with both government and industry members discussing the opportunities and challenges associated with the budding market. PMID:19855169

  18. Apparatus for forming targets

    DOEpatents

    Woerner, Robert L. (Livermore, CA)

    1980-01-01

    Apparatus and method for cryoinduced uniform deposition of cryogenic materials, such as deuterium-tritium (DT) mixtures, on the inner surface of hollow spherical members, such as inertially imploded targets. By vaporizing and quickly refreezing cryogenic materials contained within a hollow spherical member, a uniform layer of the materials is formed on the inner surface of the spherical member. Heating of the cryogenic material, located within a non-isothermal compact freezing cell, is accomplished by an electrical heat pulse, whereafter the material is quickly frozen forming a uniform layer on the inner surface of the spherical member. The method is not restricted to producing a frozen layer on only the inner surface of the innermost hollow member, but where multiple concentric hollow spheres are involved, such as in multiple shell targets for lasers, electron beams, etc., layers of cryogenic material may also be formed on the inner surface of intermediate or outer spherical members, thus providing the capability of forming targets having multiple concentric layers or shells of frozen DT.

  19. Bromodomains as therapeutic targets

    PubMed Central

    Muller, Susanne; Filippakopoulos, Panagis; Knapp, Stefan

    2011-01-01

    Acetylation of lysine residues is a post-translational modification with broad relevance to cellular signalling and disease biology. Enzymes that ‘write’ (histone acetyltransferases, HATs) and ‘erase’ (histone deacetylases, HDACs) acetylation sites are an area of extensive research in current drug development, but very few potent inhibitors that modulate the ‘reading process’ mediated by acetyl lysines have been described. The principal readers of ?-N-acetyl lysine (Kac) marks are bromodomains (BRDs), which are a diverse family of evolutionary conserved protein-interaction modules. The conserved BRD fold contains a deep, largely hydrophobic acetyl lysine binding site, which represents an attractive pocket for the development of small, pharmaceutically active molecules. Proteins that contain BRDs have been implicated in the development of a large variety of diseases. Recently, two highly potent and selective inhibitors that target BRDs of the BET (bromodomains and extra-terminal) family provided compelling data supporting targeting of these BRDs in inflammation and in an aggressive type of squamous cell carcinoma. It is likely that BRDs will emerge alongside HATs and HDACs as interesting targets for drug development for the large number of diseases that are caused by aberrant acetylation of lysine residues. PMID:21933453

  20. Nanocrystal targeting in vivo

    NASA Astrophysics Data System (ADS)

    Åkerman, Maria E.; Chan, Warren C. W.; Laakkonen, Pirjo; Bhatia, Sangeeta N.; Ruoslahti, Erkki

    2002-10-01

    Inorganic nanostructures that interface with biological systems have recently attracted widespread interest in biology and medicine. Nanoparticles are thought to have potential as novel intravascular probes for both diagnostic (e.g., imaging) and therapeutic purposes (e.g., drug delivery). Critical issues for successful nanoparticle delivery include the ability to target specific tissues and cell types and escape from the biological particulate filter known as the reticuloendothelial system. We set out to explore the feasibility of in vivo targeting by using semiconductor quantum dots (qdots). Qdots are small (<10 nm) inorganic nanocrystals that possess unique luminescent properties; their fluorescence emission is stable and tuned by varying the particle size or composition. We show that ZnS-capped CdSe qdots coated with a lung-targeting peptide accumulate in the lungs of mice after i.v. injection, whereas two other peptides specifically direct qdots to blood vessels or lymphatic vessels in tumors. We also show that adding polyethylene glycol to the qdot coating prevents nonselective accumulation of qdots in reticuloendothelial tissues. These results encourage the construction of more complex nanostructures with capabilities such as disease sensing and drug delivery.

  1. Follicular penetration and targeting.

    PubMed

    Lademann, Jürgen; Otberg, Nina; Jacobi, Ute; Hoffman, Robert M; Blume-Peytavi, Ulrike

    2005-12-01

    In the past, intercellular penetration was assumed to be the most important penetration pathway of topically applied substances. First hints that follicular penetration needs to be taken into consideration were confirmed by recent investigations, presented during the workshop "Follicular Penetration and Targeting" at the 4th Intercontinental Meeting of Hair Research Societies", in Berlin 2004. Hair follicles represent an efficient reservoir for the penetration of topically applied substances with subsequent targeting of distinct cell populations, e.g., nestin-expressing follicular bulge cells. The volume of this reservoir can be determined by differential stripping technology. The follicular penetration processes are significantly influenced by the state of the follicular infundibulum; recent experimental investigations could demonstrate that it is essential to distinguish between open and closed hair follicles. Topically applied substances can only penetrate into open hair follicle. Knowledge of follicular penetration is of high clinical relevance for functional targeting of distinct follicular regions. Human hair follicles show a hair-cycle-dependent variation of the dense neuronal and vascular network. Moreover, during hair follicle cycling with initiation of anagen, newly formed vessels occur. Thus, the potential of nestin-expressing hair follicle stem cells to form neurons and blood vessels was investigated. PMID:16382687

  2. Radiation calibration targets

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Several prominent features of Mars Pathfinder and surrounding terrain are seen in this image, taken by the Imager for Mars Pathfinder on July 4 (Sol 1), the spacecraft's first day on the Red Planet. Portions of a lander petal are at the lower part of the image. At the left, the mechanism for the high-gain antenna can be seen. The dark area along the right side of the image represents a portion of the low-gain antenna. The radiation calibration target is at the right. The calibration target is made up of a number of materials with well-characterized colors. The known colors of the calibration targets allow scientists to determine the true colors of the rocks and soils of Mars. Three bull's-eye rings provide a wide range of brightness for the camera, similar to a photographer's grayscale chart. In the middle of the bull's-eye is a 5-inch tall post that casts a shadow, which is distorted in this image due to its location with respect to the lander camera.

    A large rock is located at the near center of the image. Smaller rocks and areas of soil are strewn across the Martian terrain up to the horizon line.

    Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C.

  3. Interferon ?-targeted therapy.

    PubMed

    Hanaoka, Hironari; Takeuchi, Tsutomu

    2013-01-01

    Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the production of autoantibodies to various cellular components. Although many of therapies have shown great efficacy, they often associate with adverse effects. The development of safer therapies for SLE has led to recent emphasis on targeting selected pathways that can be important in the inflammatory process in SLE. The cytokine family of type I interferons (IFNs), and especially the IFN? subtypes, are implicated in pathogenesis of SLE. Genetic polymorphisms of several components of the IFN signaling pathway have been associated with an increased risk of SLE. Therefore, IFN? subtypes have been identified as a potential target for drug development in SLE. There have been developed three agents, IFN?-targeted therapy, Sifalimumab, Rontalizumab and NNC 0152-0000-0001. They are anti-IFN? monoclonal antibodies that bind to and specifically neutralizes most IFN? subtypes, preventing signaling through the type I IFN receptor. The safety and dose-proportional pharmacokinetics of those agents were demonstrated. A larger study is currently ongoing, further safety profile will be evaluated. This review provides an update on the ongoing clinical trials of anti-IFN? therapy and the promise and obstacles in the use of biologics in SLE. PMID:23994795

  4. Internal targets at storage rings

    NASA Astrophysics Data System (ADS)

    Grigoryev, Kirill

    2015-11-01

    Internal targets play an important role in nuclear and high energy physics research. After many decades of development, these targets have become very common and highly complex devices. Different types of polarized and unpolarized targets, such as atomic beam, gaseous-, liquid- and solid-state targets, are used in various experiments at storage rings all over the world. The choice and usage of devices (both current and those in development) for internal experiments are strongly dependent on the many parameters of stored beams (e.g. dimensions, lifetime, cooling availability and polarization) and design parameters of the target (areal density, dimensions of the interaction point, target cooling, the gas load to the target chamber and time structure of the target). All these parameters are tightly coupled and must be considered together. The different internal targets are presented in this paper.

  5. Fecal microbiota transplantation broadening its application beyond intestinal disorders

    PubMed Central

    Xu, Meng-Que; Cao, Hai-Long; Wang, Wei-Qiang; Wang, Shan; Cao, Xiao-Cang; Yan, Fang; Wang, Bang-Mao

    2015-01-01

    Intestinal dysbiosis is now known to be a complication in a myriad of diseases. Fecal microbiota transplantation (FMT), as a microbiota-target therapy, is arguably very effective for curing Clostridium difficile infection and has good outcomes in other intestinal diseases. New insights have raised an interest in FMT for the management of extra-intestinal disorders associated with gut microbiota. This review shows that it is an exciting time in the burgeoning science of FMT application in previously unexpected areas, including metabolic diseases, neuropsychiatric disorders, autoimmune diseases, allergic disorders, and tumors. A randomized controlled trial was conducted on FMT in metabolic syndrome by infusing microbiota from lean donors or from self-collected feces, with the resultant findings showing that the lean donor feces group displayed increased insulin sensitivity, along with increased levels of butyrate-producing intestinal microbiota. Case reports of FMT have also shown favorable outcomes in Parkinson’s disease, multiple sclerosis, myoclonus dystonia, chronic fatigue syndrome, and idiopathic thrombocytopenic purpura. FMT is a promising approach in the manipulation of the intestinal microbiota and has potential applications in a variety of extra-intestinal conditions associated with intestinal dysbiosis. PMID:25574083

  6. Non-Targeted Analysis Challenge (Non-targeted screening workshop)

    EPA Science Inventory

    This brief presentation is intended to motivate discussion of the "Non-Targeted Analysis Challenge" at the Advancing Non-Targeted Analyses of Xenobiotics in Environmental and Biological Media workshop held at the EPA RTP campus.

  7. Targeted therapy in gastrointestinal malignancies

    PubMed Central

    Chhatrala, Ravi; Thanavala, Yasmin; Iyer, Renuka

    2014-01-01

    Increased understanding of cancer pathogenesis has identified several pathways that serve as potential targets for novel targeted agents in development. The selection of targeted cancer therapy based on biomarkers has instigated a new era of personalized medicine and changed the way we practice oncology. Many targeted agents are approved for treatment of gastrointestinal malignancies most targeting tumor angiogenesis, and many more are in different phases of development. Here we briefly summarize nine different targeted agents that are approved currently in the U.S. and several other agents currently being studied in various gastrointestinal cancers. PMID:24737952

  8. Targeting Breast Cancer Metastasis

    PubMed Central

    Jin, Xin; Mu, Ping

    2015-01-01

    Metastasis is the leading cause of breast cancer-associated deaths. Despite the significant improvement in current therapies in extending patient life, 30–40% of patients may eventually suffer from distant relapse and succumb to the disease. Consequently, a deeper understanding of the metastasis biology is key to developing better treatment strategies and achieving long-lasting therapeutic efficacies against breast cancer. This review covers recent breakthroughs in the discovery of various metastatic traits that contribute to the metastasis cascade of breast cancer, which may provide novel avenues for therapeutic targeting. PMID:26380552

  9. Targeted therapy for sarcomas

    PubMed Central

    Forscher, Charles; Mita, Monica; Figlin, Robert

    2014-01-01

    Sarcomas are tumors of mesenchymal origin that make up approximately 1% of human cancers. They may arise as primary tumors in either bone or soft tissue, with approximately 11,280 soft tissue tumors and 2,650 bone tumors diagnosed each year in the United States. There are at least 50 different subtypes of soft tissue sarcoma, with new ones described with ever-increasing frequency. One way to look at sarcomas is to divide them into categories on the basis of their genetic make-up. One group of sarcomas has an identifiable, relatively simple genetic signature, such as the X:18 translocation seen in synovial sarcoma or the 11:22 translocation seen in Ewing’s sarcoma. These specific abnormalities often lead to the presence of fusion proteins, such as EWS-FLI1 in Ewing’s sarcoma, which are helpful as diagnostic tools and may become therapeutic targets in the future. Another group of sarcomas is characterized by complex genetic abnormalities as seen in leiomyosarcoma, osteosarcoma, and undifferentiated sarcoma. It is important to keep these distinctions in mind when contemplating the development of targeted agents for sarcomas. Different abnormalities in sarcoma could be divided by tumor subtype or by the molecular or pathway abnormality. However, some existing drugs or drugs in development may interfere with or alter more than one of the presented pathways. PMID:24669185

  10. Liquid Hydrogen: Target, Detector

    SciTech Connect

    Mulholland, G.T.; Harigel, G.G.

    2004-06-23

    In 1952 D. Glaser demonstrated that a radioactive source's radiation could boil 135 deg. C superheated-diethyl ether in a 3-mm O glass vessel and recorded bubble track growth on high-speed film in a 2-cm3 chamber. This Bubble Chamber (BC) promised improved particle track time and spatial resolution and cycling rate. Hildebrand and Nagle, U of Chicago, reported Liquid Hydrogen minimum ionizing particle boiling in August 1953. John Wood created the 3.7-cm O Liquid Hydrogen BC at LBL in January 1954. By 1959 the Lawrence Berkley Laboratory (LBL) Alvarez group's '72-inch' BC had tracks in liquid hydrogen. Within 10 years bubble chamber volumes increased by a factor of a million and spread to every laboratory with a substantial high-energy physics program. The BC, particle accelerators and special separated particle beams created a new era of High Energy Physics (HEP) experimentation. The BC became the largest most complex cryogenic installation at the world's HEP laboratories for decades. The invention and worldwide development, deployment and characteristics of these cryogenic dynamic target/detectors and related hydrogen targets are described.

  11. Magnetized Target Fusion

    NASA Technical Reports Server (NTRS)

    Griffin, Steven T.

    2002-01-01

    Magnetized target fusion (MTF) is under consideration as a means of building a low mass, high specific impulse, and high thrust propulsion system for interplanetary travel. This unique combination is the result of the generation of a high temperature plasma by the nuclear fusion process. This plasma can then be deflected by magnetic fields to provide thrust. Fusion is initiated by a small traction of the energy generated in the magnetic coils due to the plasma's compression of the magnetic field. The power gain from a fusion reaction is such that inefficiencies due to thermal neutrons and coil losses can be overcome. Since the fusion reaction products are directly used for propulsion and the power to initiate the reaction is directly obtained from the thrust generation, no massive power supply for energy conversion is required. The result should be a low engine mass, high specific impulse and high thrust system. The key is to successfully initiate fusion as a proof-of-principle for this application. Currently MSFC is implementing MTF proof-of-principle experiments. This involves many technical details and ancillary investigations. Of these, selected pertinent issues include the properties, orientation and timing of the plasma guns and the convergence and interface development of the "pusher" plasma. Computer simulations of the target plasma's behavior under compression and the convergence and mixing of the gun plasma are under investigation. This work is to focus on the gun characterization and development as it relates to plasma initiation and repeatability.

  12. Rotating Target Development for SNS Second Target Station

    SciTech Connect

    McManamy, Thomas J; Rennich, Mark J; Crawford, Roy K; Geoghegan, Patrick J; Janney, Jim G

    2010-01-01

    A rotating target for the second target station (STS) at SNS has been identified as an option along with a mercury target. Evaluation of the rotating target alternative for STS has started at 1.5 MW which is considered an upper bound for the power. Previous preconceptual design work for a 3 MW rotating target is being modified for the lower power level. Transient thermal analysis for a total loss of active water cooling has been done for a simplified 2D model of the target and shielding monolith which shows that peak temperatures are well below the level at which tungsten vaporization by steam could exceed site boundary dose limits. Design analysis and integration configuration studies have been done for the target-moderator-reflector assembly which maximizes the number of neutron beam lines and provides for replacement of the target and moderators. Target building hot cell arrangement for this option will be described. An option for operation in rough vacuum without a proton beam window using Ferro fluid seals on a vertical shaft is being developed. A full scale prototypic drive module based on the 3 MW preconceptual design has been fabricated and successfully tested with a shaft and mock up target supplied by the ESS-Bilbao team. Overall planning leading to decision between mercury and the rotating target in 2011 will be discussed

  13. ORION laser target diagnostics.

    PubMed

    Bentley, C D; Edwards, R D; Andrew, J E; James, S F; Gardner, M D; Comley, A J; Vaughan, K; Horsfield, C J; Rubery, M S; Rothman, S D; Daykin, S; Masoero, S J; Palmer, J B; Meadowcroft, A L; Williams, B M; Gumbrell, E T; Fyrth, J D; Brown, C R D; Hill, M P; Oades, K; Wright, M J; Hood, B A; Kemshall, P

    2012-10-01

    The ORION laser facility is one of the UK's premier laser facilities which became operational at AWE in 2010. Its primary mission is one of stockpile stewardship, ORION will extend the UK's experimental plasma physics capability to the high temperature, high density regime relevant to Atomic Weapons Establishment's (AWE) program. The ORION laser combines ten laser beams operating in the ns regime with two sub ps short pulse chirped pulse amplification beams. This gives the UK a unique combined long pulse/short pulse laser capability which is not only available to AWE personnel but also gives access to our international partners and visiting UK academia. The ORION laser facility is equipped with a comprehensive suite of some 45 diagnostics covering optical, particle, and x-ray diagnostics all able to image the laser target interaction point. This paper focuses on a small selection of these diagnostics. PMID:23126904

  14. ORION laser target diagnosticsa)

    NASA Astrophysics Data System (ADS)

    Bentley, C. D.; Edwards, R. D.; Andrew, J. E.; James, S. F.; Gardner, M. D.; Comley, A. J.; Vaughan, K.; Horsfield, C. J.; Rubery, M. S.; Rothman, S. D.; Daykin, S.; Masoero, S. J.; Palmer, J. B.; Meadowcroft, A. L.; Williams, B. M.; Gumbrell, E. T.; Fyrth, J. D.; Brown, C. R. D.; Hill, M. P.; Oades, K.; Wright, M. J.; Hood, B. A.; Kemshall, P.

    2012-10-01

    The ORION laser facility is one of the UK's premier laser facilities which became operational at AWE in 2010. Its primary mission is one of stockpile stewardship, ORION will extend the UK's experimental plasma physics capability to the high temperature, high density regime relevant to Atomic Weapons Establishment's (AWE) program. The ORION laser combines ten laser beams operating in the ns regime with two sub ps short pulse chirped pulse amplification beams. This gives the UK a unique combined long pulse/short pulse laser capability which is not only available to AWE personnel but also gives access to our international partners and visiting UK academia. The ORION laser facility is equipped with a comprehensive suite of some 45 diagnostics covering optical, particle, and x-ray diagnostics all able to image the laser target interaction point. This paper focuses on a small selection of these diagnostics.

  15. ORION laser target diagnostics

    SciTech Connect

    Bentley, C. D.; Edwards, R. D.; Andrew, J. E.; James, S. F.; Gardner, M. D.; Comley, A. J.; Vaughan, K.; Horsfield, C. J.; Rubery, M. S.; Rothman, S. D.; Daykin, S.; Masoero, S. J.; Palmer, J. B.; Meadowcroft, A. L.; Williams, B. M.; Gumbrell, E. T.; Fyrth, J. D.; Brown, C. R. D.; Hill, M. P.; Oades, K.; and others

    2012-10-15

    The ORION laser facility is one of the UK's premier laser facilities which became operational at AWE in 2010. Its primary mission is one of stockpile stewardship, ORION will extend the UK's experimental plasma physics capability to the high temperature, high density regime relevant to Atomic Weapons Establishment's (AWE) program. The ORION laser combines ten laser beams operating in the ns regime with two sub ps short pulse chirped pulse amplification beams. This gives the UK a unique combined long pulse/short pulse laser capability which is not only available to AWE personnel but also gives access to our international partners and visiting UK academia. The ORION laser facility is equipped with a comprehensive suite of some 45 diagnostics covering optical, particle, and x-ray diagnostics all able to image the laser target interaction point. This paper focuses on a small selection of these diagnostics.

  16. [Molecular targeted therapy].

    PubMed

    Stenner-Liewen, F; Zippelius, A; Pestalozzi, B C; Knuth, A

    2006-12-01

    Until recently, cancer therapy was based on three modalities: surgery, radiotherapy, and cytostatic chemotherapy. In most instances treatment of solid tumors was a surgical domain. For patients with incomplete resection or relapse after surgery, radiotherapy and chemotherapy usually offered only partial response and mostly of limited duration. By the mid-1990s visions of antibody-based therapies, vaccination strategies, and even gene-specific therapies existed but seemed far from clinical practice. United States Federal Drug Administration approval of the humanized antibody rituximab (1997) and the tyrosine kinase inhibitor imatinib (2001) has changed perceptions of oncologic treatment. These drugs turned visions into reality and led the pharmaceutical industry, clinicians, and patients to new perspectives. This article gives an overview of the development of this fourth modality in cancer therapy, so-called targeted therapy. PMID:17109101

  17. Stroke Neuroprotection: Targeting Mitochondria

    PubMed Central

    Talley Watts, Lora; Lloyd, Reginald; Justin Garling, Richard; Duong, Timothy

    2013-01-01

    Stroke is the fourth leading cause of death and the leading cause of long-term disability in the United States. Blood flow deficit results in an expanding infarct core with a time-sensitive peri-infarct penumbra that is considered salvageable and is the primary target for treatment strategies. The only current FDA-approved drug for treating ischemic stroke is recombinant tissue plasminogen activator (rt-PA). However, this treatment is limited to within 4.5 h of stroke onset in a small subset of patients. The goal of this review is to focus on mitochondrial-dependent therapeutic agents that could provide neuroprotection following stroke. Dysfunctional mitochondria are linked to neurodegeneration in many disease processes including stroke. The mechanisms reviewed include: (1) increasing ATP production by purinergic receptor stimulation, (2) decreasing the production of ROS by superoxide dismutase, or (3) increasing antioxidant defenses by methylene blue, and their benefits in providing neuroprotection following a stroke. PMID:24961414

  18. Electromagnetic targeting of guns

    SciTech Connect

    Pogue, E.W.; Boat, R.M.; Holden, D.N.; Lopez, J.R.

    1996-10-01

    This is the final report of a one-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). Electromagnetic pulse (EMP) signals produced from explosives being fired have been reported in the literature for fifty years. When a gun is fired it produces an EMP muzzle blast signal. The strength and nature of these signals was first analyzed in the early 1970s, while the results were interesting, no follow-up studies were conducted. With modern detection and signal processing technology, we believe that these signals could be used to instantaneously locate guns of virtually all calibers as they fire. The objective of our one-year project was to establish the basic nature of these signals and their utility in the concept of electromagnetic targeting of guns.

  19. Target detection portal

    DOEpatents

    Linker, Kevin L. (Albuquerque, NM); Brusseau, Charles A. (Tijeras, NM)

    2002-01-01

    A portal apparatus for screening persons or objects for the presence of trace amounts of target substances such as explosives, narcotics, radioactive materials, and certain chemical materials. The portal apparatus can have a one-sided exhaust for an exhaust stream, an interior wall configuration with a concave-shape across a horizontal cross-section for each of two facing sides to result in improved airflow and reduced washout relative to a configuration with substantially flat parallel sides; air curtains to reduce washout; ionizing sprays to collect particles bound by static forces, as well as gas jet nozzles to dislodge particles bound by adhesion to the screened person or object. The portal apparatus can be included in a detection system with a preconcentrator and a detector.

  20. Using the Nova target chamber for high-yield targets

    SciTech Connect

    Pitts, J.H.

    1987-09-28

    The existing 2.2-m-radius Nova aluminum target chamber, coated and lined with boron-seeded carbon shields, is proposed for use with 1000-MJ-yield targets in the next laser facility. The laser beam and diagnostic holes in the target chamber are left open and the desired 10/sup -2/ Torr vacuum is maintained both inside and outside the target chamber; a larger target chamber room is the vacuum barrier to the atmosphere. The hole area available is three times that necessary to maintain a maximum fluence below 12 J/cm/sup 2/ on optics placed at a radius of 10 m. Maximum stress in the target chamber wall is 73 MPa, which complies with the intent of the ASME Pressure Vessel Code. However, shock waves passing through the inner carbon shield could cause it to comminute. We propose tests and analyses to ensure that the inner carbon shield survives the environment. 13 refs.

  1. Target support for inertial confinement fusion

    SciTech Connect

    Schultz, K.R.

    1995-08-01

    General Atomics (GA) plays an important industrial support role for the US Inertial Confinement Fusion (ICF) program in the area of target technology. This includes three major activities: target fabrication support, target handling systems development, and target chamber design. The work includes target fabrication for existing ICF experiments, target and target system development for future experiments, and target research and target chamber design for experiments on future machines, such as the National Ignition Facility (NIF).

  2. Immunotherapy Targets in Pediatric Cancer

    PubMed Central

    Orentas, Rimas J.; Lee, Daniel W.; Mackall, Crystal

    2011-01-01

    Immunotherapy for cancer has shown increasing success and there is ample evidence to expect that progress gleaned in immune targeting of adult cancers can be translated to pediatric oncology. This manuscript reviews principles that guide selection of targets for immunotherapy of cancer, emphasizing the similarities and distinctions between oncogene-inhibition targets and immune targets. It follows with a detailed review of molecules expressed by pediatric tumors that are already under study as immune targets or are good candidates for future studies of immune targeting. Distinctions are made between cell surface antigens that can be targeted in an MHC independent manner using antibodies, antibody derivatives, or chimeric antigen receptors versus intracellular antigens which must be targeted with MHC restricted T cell therapies. Among the most advanced immune targets for childhood cancer are CD19 and CD22 on hematologic malignancies, GD2 on solid tumors, and NY-ESO-1 expressed by a majority of synovial sarcomas, but several other molecules reviewed here also have properties which suggest that they too could serve as effective targets for immunotherapy of childhood cancer. PMID:22645714

  3. Facility target insert shielding assessment

    SciTech Connect

    Mocko, Michal

    2015-10-06

    Main objective of this report is to assess the basic shielding requirements for the vertical target insert and retrieval port. We used the baseline design for the vertical target insert in our calculations. The insert sits in the 12”-diameter cylindrical shaft extending from the service alley in the top floor of the facility all the way down to the target location. The target retrieval mechanism is a long rod with the target assembly attached and running the entire length of the vertical shaft. The insert also houses the helium cooling supply and return lines each with 2” diameter. In the present study we focused on calculating the neutron and photon dose rate fields on top of the target insert/retrieval mechanism in the service alley. Additionally, we studied a few prototypical configurations of the shielding layers in the vertical insert as well as on the top.

  4. Oxide Fiber Targets at ISOLDE

    E-print Network

    Köster, U; Carminati, D; Catherall, R; Cederkäll, J; Correia, J G; Crepieux, B; Dietrich, M; Elder, K; Fedosseev, V; Fraile-Prieto, L M; Franchoo, S; Fynbo, H O U; Georg, U; Giles, T; Joinet, A; Jonsson, O C; Kirchner, R; Lau, C; Lettry, Jacques; Maier, H J; Mishin, V I; Oinonen, M; Peräjärvi, K; Ravn, H L; Rinaldi, T; Santana-Leitner, M; Wahl, U; Weissman, L

    2003-01-01

    Many elements are rapidly released from oxide matrices. Some oxide powder targets show a fast sintering, thus losing their favorable release characteristics. Loosely packed oxyde fiber targets are less critical since they may maintain their open structure even when starting to fuse together at some contact points. The experience with various oxyde fiber targets (titania, zirconia, ceria and thoria) used in the last years at ISOLDE is reviewed. For short-lived isotopes of Cu, Ga and Xe the zirconia and ceria targets respectively provided significantly higher yields than any other target (metal foils, oxide powders, etc.) tested before. Titania fibers, which were not commercially available, were produced in a relic process by impregnation of a rayon felt in a titanium chloride solution and subsequent calcination by heating the dried felt in air. Thoria fibers were obtained either by the same process or by burning commercial gas lantern mantle cloth. In the future a beryllia fiber target could be used to produce...

  5. Multiple target laser ablation system

    DOEpatents

    Mashburn, D.N.

    1996-01-09

    A laser ablation apparatus and method are provided in which multiple targets consisting of material to be ablated are mounted on a movable support. The material transfer rate is determined for each target material, and these rates are stored in a controller. A position detector determines which target material is in a position to be ablated, and then the controller controls the beam trigger timing and energy level to achieve a desired proportion of each constituent material in the resulting film. 3 figs.

  6. Targeted Nanotechnology for Cancer Imaging

    PubMed Central

    Toy, Randall; Bauer, Lisa; Hoimes, Christopher; Ghaghada, Ketan B.; Karathanasis, Efstathios

    2014-01-01

    Targeted nanoparticle imaging agents provide many benefits and new opportunities to facilitate accurate diagnosis of cancer and significantly impact patient outcome. Due to the highly engineerable nature of nanotechnology, targeted nanoparticles exhibit significant advantages including increased contrast sensitivity, binding avidity and targeting specificity. Considering the various nanoparticle designs and their adjustable ability to target a specific site and generate detectable signals, nanoparticles can be optimally designed in terms of biophysical interactions (i.e., intravascular and interstitial transport) and biochemical interactions (i.e., targeting avidity towards cancer-related biomarkers) for site-specific detection of very distinct microenvironments. This review seeks to illustrate that the design of a nanoparticle dictates its in vivo journey and targeting of hard-to-reach cancer sites, facilitating early and accurate diagnosis and interrogation of the most aggressive forms of cancer. We will report various targeted nanoparticles for cancer imaging using X-ray computed tomography, ultrasound, magnetic resonance imaging, nuclear imaging and optical imaging. Finally, to realize the full potential of targeted nanotechnology for cancer imaging, we will describe the challenges and opportunities for the clinical translation and widespread adaptation of targeted nanoparticles imaging agents. PMID:25116445

  7. Target engagement in lead generation.

    PubMed

    Durham, Timothy B; Blanco, Maria-Jesus

    2015-03-01

    The pharmaceutical industry is currently facing multiple challenges, in particular the low number of new drug approvals in spite of the high level of R&D investment. In order to improve target selection and assess properly the clinical hypothesis, it is important to start building an integrated drug discovery approach during Lead Generation. This should include special emphasis on evaluating target engagement in the target tissue and linking preclinical to clinical readouts. In this review, we would like to illustrate several strategies and technologies for assessing target engagement and the value of its application to medicinal chemistry efforts. PMID:25630223

  8. Inferring Gene Regulatory Relationships by Combining TargetTarget Pattern

    E-print Network

    Minnesota, University of

    Inferring Gene Regulatory Relationships by Combining Target­Target Pattern Recognition.interscience.wiley.com). DOI: 10.1002/bit.20305 Abstract: Although microarray data have been success- fully used for gene clustering and classification, the use of time series microarray data for constructing gene regu- latory

  9. Type of Cancer Treatment: Targeted Therapy

    Cancer.gov

    Information about the role that targeted therapies play in cancer treatment. Includes how targeted therapies work against cancer, who receives targeted therapies, common side effects, and what to expect when having targeted therapies.

  10. The Kepler Dropped Target Program

    NASA Astrophysics Data System (ADS)

    Haas, Michael Robert; Dotson, J. L.; Batalha, N.; Gilliland, R. L.; Walkowicz, L.; Gautier, T. N.; Cochran, W. D.

    2010-01-01

    Kepler provides high-precision optical photometry of over 160000 stars on a 30-min cadence and 512 stars on a 1-min cadence. During the nominal 3.5-year mission, the target list will be updated at regular intervals to eliminate misclassified giants and highly variable stars and, late in the mission, the target list will be trimmed to accommodate decreased bandwidth. The data from these dropped targets will provide a unique and valuable legacy for stellar astrophysics. After commissioning and one-month of science data collection, Kepler has already dropped more than 8400 targets and posted the available data to the Multi-mission Archive at STScI (MAST). This treasure of dropped targets will continue to grow over the life of the mission. Since this data becomes public 60 days after the targets are officially dropped, it provides a unique opportunity for early community involvement. This presentation describes how the data can be accessed to exploit this legacy and provides some examples of dropped target light curves. Dropped targets of particular interest can be proposed for further observation through Kepler's Guest Observer Program on an annual basis. Kepler was selected as the 10th mission of the Discovery Program. Funding for this mission is provided by NASA, Science Mission Directorate.

  11. Targeted Specular Photons Michelle Laprade

    E-print Network

    Montréal, Université de

    Targeted Specular Photons Michelle Laprade Département d'Informatique et de Recherche in the resulting image which are not captured using traditional photon map- ping algorithms. This method uses a separate group of photons ­ targeted specular photons ­ which are shot specifically towards

  12. Cancer Cell Targeting Androgen Receptor

    E-print Network

    Liu, Xiaole Shirley

    Cancer Cell Article Targeting Androgen Receptor in Estrogen Receptor-Negative Breast Cancer Min Ni therapies for breast cancer that target the estrogen receptor (ER) are ineffective in the 25%­30% of cases status. How androgens and AR regulate breast cancer growth remains largely unknown. We find that AR

  13. GLYCOSYLATION: DISEASE TARGETS AND THERAPY

    E-print Network

    Gaucher, Tay-Sachs, Fabry, Sandhoff and GM1 gangliosidosis. GSL storage diseases occur at a collective1 GLYCOSYLATION: DISEASE TARGETS AND THERAPY Nicole Zitzmann1, Timothy Block2, Anund Methta2 illustrate strategies for providing therapy inffff disease targets. Two of these are to develop antiviral

  14. Targeted marketing and public health.

    PubMed

    Grier, Sonya A; Kumanyika, Shiriki

    2010-01-01

    Targeted marketing techniques, which identify consumers who share common needs or characteristics and position products or services to appeal to and reach these consumers, are now the core of all marketing and facilitate its effectiveness. However, targeted marketing, particularly of products with proven or potential adverse effects (e.g., tobacco, alcohol, entertainment violence, or unhealthful foods) to consumer segments defined as vulnerable raises complex concerns for public health. It is critical that practitioners, academics, and policy makers in marketing, public health, and other fields recognize and understand targeted marketing as a specific contextual influence on the health of children and adolescents and, for different reasons, ethnic minority populations and other populations who may benefit from public health protections. For beneficial products, such understanding can foster more socially productive targeting. For potentially harmful products, understanding the nature and scope of targeted marketing influences will support identification and implementation of corrective policies. PMID:20070196

  15. TARGETING POLYMER THERAPEUTICS TO BONE

    PubMed Central

    Low, Stewart; Kope?ek, Jind?ich

    2012-01-01

    An aging population in the developing world has led to an increase in musculoskeletal diseases such as osteoporosis and bone metastases. Left untreated many bone diseases cause debilitating pain and in the case of cancer, death. Many potential drugs are effective in treating diseases but result in side effects preventing their efficacy in the clinic. Bone, however, provides an unique environment of inorganic solids, which can be exploited in order to effectively target drugs to diseased tissue. By integration of bone targeting moieties to drug-carrying water-soluble polymers, the payload to diseased area can be increased while side effects decreased. The realization of clinically relevant bone targeted polymer therapeutics depends on (1) understanding bone targeting moiety interactions, (2) development of controlled drug delivery systems, as well as (3) understanding drug interactions. The latter makes it possible to develop bone targeted synergistic drug delivery systems. PMID:22316530

  16. Target migration path morphology of moving targets in spotlight SAR

    NASA Astrophysics Data System (ADS)

    Garren, David A.; Scrofani, James W.; Tummala, Murali; McEachen, John C.

    2013-05-01

    This paper examines the signature characteristics of moving targets in spotlight synthetic aperture radar (SAR) image data. This analysis considers the special case in which the radar sensor is assumed to move with constant speed and heading on a level flight path with broadside imaging geometry. It is shown that the resulting defocused smear signature in the spotlight SAR image exhibits range migration effects, as has been shown previously for strip map SAR analysis. In particular, cases of uniform target motion exhibit simply curved range migration paths, whereas non-uniform target motion can cause complicated smear shapes.

  17. Aided targeting system simulation evaluation

    NASA Technical Reports Server (NTRS)

    Demaio, Joe; Becker, Curtis

    1994-01-01

    Simulation research was conducted at the Crew Station Research and Development Facility on the effectiveness and ease of use of three targeting systems. A manual system required the aviator to scan a target array area with a simulated second generation forward looking infrared (FLIR) sensor, locate and categorize targets, and construct a target hand-off list. The interface between the aviator and the system was like that of an advanced scout helicopter (manual mode). Two aided systems detected and categorized targets automatically. One system used only the FLIR sensor and the second used FLIR fused with Longbow radar. The interface for both was like that of an advanced scout helicopter aided mode. Exposure time while performing the task was reduced substantially with the aided systems, with no loss of target hand-off list accuracy. The fused sensor system showed lower time to construct the target hand-off list and a slightly lower false alarm rate than the other systems. A number of issues regarding system sensitivity and criterion, and operator interface design are discussed.

  18. Targeted Therapies for Lung Cancer

    PubMed Central

    Larsen, Jill E.; Cascone, Tina; Gerber, David E.; Heymach, John V.; Minna, John D.

    2012-01-01

    Although lung cancer remains the leading cancer killer in the United States, recently a number of developments indicate future clinical benefit. These include evidence that computed tomography–based screening decreases lung cancer mortality, the use of stereotactic radiation for early-stage tumors, the development of molecular methods to predict chemotherapy sensitivity, and genome-wide expression and mutation analysis data that have uncovered oncogene “addictions” as important therapeutic targets. Perhaps the most significant advance in the treatment of this challenging disease is the introduction of molecularly targeted therapies, a term that currently includes monoclonal antibodies and small-molecule tyrosine kinase inhibitors. The development of effective targeted therapeutics requires knowledge of the genes and pathways involved and how they relate to the biologic behavior of lung cancer. Drugs targeting the epidermal growth factor receptor, anaplastic lymphoma kinase, and vascular endothelial growth factor are now U.S. Food and Drug Administration approved for the treatment of advanced non-small cell lung cancer. These agents are generally better tolerated than conventional chemotherapy and show dramatic efficacy when their use is coupled with a clear understanding of clinical data, mechanism, patient selection, drug interactions, and toxicities. Integrating genome-wide tumor analysis with drug- and targeted agent-responsive phenotypes will provide a wealth of new possibilities for lung cancer–targeted therapeutics. Ongoing research efforts in these areas as well as a discussion of emerging targeted agents being evaluated in clinical trials are the subjects of this review. PMID:22157296

  19. Behavioral Targeting—Consumer Tracking

    NASA Astrophysics Data System (ADS)

    Srimani, P. K.; Srinivas, A.

    2011-12-01

    Behavioral targeting is an online marketing method that collects data on the browsing activities of consumers, in order to `target' more relevant online advertising. Behavioral targeting enables marketers to reach in-market consumers and increases the value of publisher inventory. At the heart of behavioral targeting is a learning-based investigation of consumer behaviors. It helps marketers understand consumers' purchase patterns over time, mapping out a customer's activities based not only on a single purchase but also on an annual or even lifetime basis. As marketers increasingly appreciate the importance of customer lifetime value, behavioral targeting can be a foundation for creating a continuous analytical study of consumer trends and patterns. But as behavioural-targeting systems become more sophisticated and invasive, it is vital that the companies behind them are open with users about what is going on, and give them control over their personal information. The aim of this paper is to explore the various tools and techniques of behavioral targeting and its benefits to online marketing. A multiple—case study approach was used for exploring the effectiveness and acceptance of online marketing in the area of the online marketing.

  20. Auditory target detection in reverberation.

    PubMed

    Zurek, Patrick M; Freyman, Richard L; Balakrishnan, Uma

    2004-04-01

    Measurements and theoretical predictions of auditory target detection in simulated reverberant conditions are reported. The target signals were pulsed 1/3-octave bands of noise and the masker signal was a continuous wideband noise. Target and masker signals were passed through a software simulation of a reverberant room with a rigid sphere modeling a listener's head. The location of the target was fixed while the location of the masker was varied in the simulated room. Degree of reverberation was controlled by varying the uniform acoustic absorption of the simulated room's surfaces. The resulting target and masker signals were presented to the listeners over headphones in monaural-left, monaural-right, or binaural listening modes. Changes in detection performance in the monaural listening modes were largely predictable from the changes in target-to-masker ratio in the target band, but with a few dB of extra masking in reverberation. Binaural detection performance was generally well predicted by applying Durlach's [in Foundations of Modern Auditory Theory (Academic, New York, 1972)] equalization-cancellation theory to the direct-plus-reverberant ear signals. Predictions in all cases were based on a statistical description of room acoustics and on acoustic diffraction by a sphere. The success of these detection models in the present well-controlled reverberant conditions suggests that they can be used to incorporate listening mode and source location as factors in speech-intelligibility predictions. PMID:15101640

  1. Auditory target detection in reverberation

    NASA Astrophysics Data System (ADS)

    Zurek, Patrick M.; Freyman, Richard L.; Balakrishnan, Uma

    2004-04-01

    Measurements and theoretical predictions of auditory target detection in simulated reverberant conditions are reported. The target signals were pulsed 13-octave bands of noise and the masker signal was a continuous wideband noise. Target and masker signals were passed through a software simulation of a reverberant room with a rigid sphere modeling a listener's head. The location of the target was fixed while the location of the masker was varied in the simulated room. Degree of reverberation was controlled by varying the uniform acoustic absorption of the simulated room's surfaces. The resulting target and masker signals were presented to the listeners over headphones in monaural-left, monaural-right, or binaural listening modes. Changes in detection performance in the monaural listening modes were largely predictable from the changes in target-to-masker ratio in the target band, but with a few dB of extra masking in reverberation. Binaural detection performance was generally well predicted by applying Durlach's [in Foundations of Modern Auditory Theory (Academic, New York, 1972)] equalization-cancellation theory to the direct-plus-reverberant ear signals. Predictions in all cases were based on a statistical description of room acoustics and on acoustic diffraction by a sphere. The success of these detection models in the present well-controlled reverberant conditions suggests that they can be used to incorporate listening mode and source location as factors in speech-intelligibility predictions.

  2. Versatile cold atom target apparatus

    SciTech Connect

    Goetz, Simone; Hoeltkemeier, Bastian; Hofmann, Christoph S.; Litsch, Dominic; DePaola, Brett D.; Weidemueller, Matthias

    2012-07-15

    We report on a compact and transportable apparatus that consists of a cold atomic target at the center of a high resolution recoil ion momentum spectrometer. Cold rubidium atoms serve as a target which can be operated in three different modes: in continuous mode, consisting of a cold atom beam generated by a two-dimensional magneto-optical trap, in normal mode in which the atoms from the beam are trapped in a three-dimensional magneto-optical trap (3D MOT), and in high density mode in which the 3D MOT is operated in dark spontaneous optical trap configuration. The targets are characterized using photoionization.

  3. ORNL gas-jet target

    SciTech Connect

    Thornton, S.T.; Parks, R.L.; Shapira, D.; Ford, J.L.C. Jr.; Shivakumar, B.; Novotny, R.

    1984-01-01

    A supersonic gas jet target built for studying heavy-ion induced nuclear reactions with high energy resolution is described. The device is installed as part of a magnetic spectrograph and has produced image sizes in the focal plane as small as 0.4 mm using 100 MeV /sup 16/O beams collimated to an area of about 1 mm/sup 2/. Target densities of 30 ..mu..g/cm/sup 2/ (/sup 40/Ar) and 15 ..mu..g/cm/sup 2/ (/sup 14/N) have easily been obtained. The target has already been used for two nuclear reaction experiments. 9 references, 8 figures.

  4. A variable optical target simulator

    NASA Technical Reports Server (NTRS)

    Kulas, C. E.; Crosswhite, E. D.

    1979-01-01

    A crucial experiment, relative to determining the ability of an imaging seeker to track a target and generate accurate terminal guidance, requires an optical device which can provide imagery that grows in size as a real-time estimate of true missile flight conditions. The basic components of an Optical Contrast TV Imaging Seeker are reviewed to establish the need for an optical target simulator. An optomechanical device called a Variable Optical Target Simulator (VOTS) which generates end game scene situations is discussed. The organization of optical components and their control for providing an image which grows in size as a linear estimate of real world situations is presented.

  5. Cancer Target Discovery and Development

    Cancer.gov

    Published on Office of Cancer Genomics (https://ocg.cancer.gov) Home > CTD² Cancer Target Discovery and Development [1] Program Body:  Network Centers The CTD2 Network Centers work both independently and collaboratively to advance the understanding of

  6. Tumor Targeting, Trifunctional Dendritic Wedge

    PubMed Central

    2015-01-01

    We report in vitro and in vivo evaluation of a newly designed trifunctional theranostic agent for targeting solid tumors. This agent combines a dendritic wedge with high boron content for boron neutron capture therapy or boron MRI, a monomethine cyanine dye for visible-light fluorescent imaging, and an integrin ligand for efficient tumor targeting. We report photophysical properties of the new agent, its cellular uptake and in vitro targeting properties. Using live animal imaging and intravital microscopy (IVM) techniques, we observed a rapid accumulation of the agent and its retention for a prolonged period of time (up to 7 days) in fully established animal models of human melanoma and murine mammary adenocarcinoma. This macromolecular theranostic agent can be used for targeted delivery of high boron load into solid tumors for future applications in boron neutron capture therapy. PMID:25350602

  7. Target Article Epigenetic Perspectives on

    E-print Network

    Champagne, Frances A.

    Target Article Epigenetic Perspectives on Development: Evolving Insights on the Origins of the meeting: ``Epigenetics and Behavioral Development Within and Across Generations'' included discussion. The contributions to this special section highlight the importance of the epigenetic regulation of gene expression

  8. Cavitation in a Mercury Target

    SciTech Connect

    West, C.D.

    2000-09-01

    Recent theoretical work on the formation of bubble nucleation centers by energetic particles leads to some reasonably credible calculations of the maximum negative pressure that might be sustained without bubble formation in the mercury target of the Spallation Neutron Source.

  9. Cancer Target Discovery and Development

    Cancer.gov

    Published on Office of Cancer Genomics (http://ocg.cancer.gov) Home > CTD² Cancer Target Discovery and Development [1] Program Body:  Network Centers The CTD2 Network Centers work both independently and collaboratively to advance the understanding of

  10. "Cavitation in a Mercury Target"

    SciTech Connect

    West, C.D.

    2000-09-06

    Recent theoretical work on the formation of bubble nucleation centers by energetic particles leads to some reasonably credible calculations of the maximum negative pressure that might be sustained without bubble formation in the mercury target of the Spallation Neutron Source.

  11. Nanoparticles for Targeted Drug Delivery

    E-print Network

    Chow, Gan-Moog

    Nanoparticles were synthesized and modified for target drug delivery. The research involved the aqueous synthesis of near infrared (NIR) sensitive Au-Au2S nanoparticles. An anti-cancer drug (cis-platin) ...

  12. Tumor targeting, trifunctional dendritic wedge.

    PubMed

    Dubey, Ramin; Kushal, Swati; Mollard, Alexis; Vojtovich, Lesya; Oh, Philip; Levin, Michael D; Schnitzer, Jan E; Zharov, Ilya; Olenyuk, Bogdan Z

    2015-01-21

    We report in vitro and in vivo evaluation of a newly designed trifunctional theranostic agent for targeting solid tumors. This agent combines a dendritic wedge with high boron content for boron neutron capture therapy or boron MRI, a monomethine cyanine dye for visible-light fluorescent imaging, and an integrin ligand for efficient tumor targeting. We report photophysical properties of the new agent, its cellular uptake and in vitro targeting properties. Using live animal imaging and intravital microscopy (IVM) techniques, we observed a rapid accumulation of the agent and its retention for a prolonged period of time (up to 7 days) in fully established animal models of human melanoma and murine mammary adenocarcinoma. This macromolecular theranostic agent can be used for targeted delivery of high boron load into solid tumors for future applications in boron neutron capture therapy. PMID:25350602

  13. Targeting ubiquitination for cancer therapies.

    PubMed

    Morrow, John Kenneth; Lin, Hui-Kuan; Sun, Shao-Cong; Zhang, Shuxing

    2015-11-01

    Ubiquitination, the structured degradation and turnover of cellular proteins, is regulated by the ubiquitin-proteasome system (UPS). Most proteins that are critical for cellular regulations and functions are targets of the process. Ubiquitination is comprised of a sequence of three enzymatic steps, and aberrations in the pathway can lead to tumor development and progression as observed in many cancer types. Recent evidence indicates that targeting the UPS is effective for certain cancer treatment, but many more potential targets might have been previously overlooked. In this review, we will discuss the current state of small molecules that target various elements of ubiquitination. Special attention will be given to novel inhibitors of E3 ubiquitin ligases, especially those in the SCF family. PMID:26630263

  14. Oral targeted therapy for cancer

    PubMed Central

    Carrington, Christine

    2015-01-01

    SUMMARY Oral targeted therapies are increasingly being used to treat cancer. They work by interfering with specific molecules or pathways involved in tumour growth. It is essential that health professionals managing patients taking these drugs have appropriate training and skills. They should be aware of potential adverse effects and drug interactions, and be able to manage toxicities when they occur. Despite the selectivity of these targeted therapies, they still have serious adverse effects including skin reactions, diarrhoea and altered organ function. PMID:26648656

  15. Target identification using laser imaging

    SciTech Connect

    Jennings, J.; Baker, M.; Barrett, J.; Ellis, B.N.; Kacerek, J.; Yee, J.

    1994-12-31

    Solid state lasers have been utilized for many varied applications. This application describes how the high peak power, short pulse capability of an alexandrite laser, in combination with a generation 3 image intensified receiver can solve the problem of very long range target identification. Applications have relevance to both commercial and military uses where day/night all weather imaging is required. Wavelength diversity provides single and multispectral system capability, therefore allowing discrimination of targets against varied backgrounds.

  16. The JLab Frozen Spin Target

    SciTech Connect

    Keith, C. D.

    2009-08-04

    A polarized, frozen spin target has been designed and constructed at Jefferson Lab for use inside the CEBAF Large Acceptance Spectrometer. Protons in TEMPO-doped butanol are polarized via dynamic nuclear polarization (DNP) to approximately 90% using microwaves and an external, 5 T solenoid magnet. The target sample is then cooled to approximately 30 mK while an internal 0.56 T superconducting magnet is used to maintain the polarization. Relaxation times in excess of 3500 hours have been observed.

  17. Target template precision is unaffected by target-distractor similarity.

    PubMed

    Wyland, Hannah; Vecera, Shaun

    2015-09-01

    It is well supported that target templates held in visual short-term memory guide visual search (Desimone & Duncan, 1995; Wolfe, 1994). We investigated how template precision is affected by search context. Following previous research, participants searched RSVP streams for an orange letter and reported its presence or absence (Anderson, 2014). In different blocks, distractor letters were either similar to the target color (red, gold, green and blue) or dissimilar to the target color (white, purple, green and blue). If template precision is affected by search difficulty, accuracy differences should be found between the two distractor conditions. In Experiments 1-3, the RSVP stream consisted of eight frames of four letters each. Targets in Experiment 1 could appear at any location on the 2nd-6th frames. Compared to the distractor dissimilar condition, accuracy in the similar distractor condition was significantly worse. This difference, however, may reflect insufficient time for selection and consolidation processes, not template precision. To test this, targets in Experiment 2 appeared on screens 4-8. While subsequent displays may interrupt processing of the 4th-7th screens, the 8th (final) screen allows adequate time for selection and consolidation. Here, a significant interaction was found between distractor color and target position with follow-up tests indicating significantly better performance at the 8th position in the similar distractor condition. For Experiment 3, additional time was added between each RSVP display to allow selection and consolidation of each display. Although the main effect of distractor color was significant, the accuracy difference between the conditions was greatly reduced. To remove the need for selection processes, Experiment 4 presented a single stream of 16 frames. Accuracy for this experiment did not differ between conditions. The results of these experiments suggest that target identification is limited by selection, consolidation, and comparison processes, but not by template precision. Meeting abstract presented at VSS 2015. PMID:26326134

  18. Targeted therapy in gastric cancer.

    PubMed

    Thiel, Alexandra; Ristimäki, Ari

    2015-05-01

    Gastric cancer is often diagnosed at an advanced stage. Although chemotherapy prolongs survival and improves quality of life, the survival of gastric cancer patients with advanced disease is short. Thanks to recent insights into the molecular pathways involved in gastric carcinogenesis, new targeted treatment options have become available for gastric cancer patients. Trastuzumab, an antibody targeted to HER-2, was shown to improve survival of advanced gastric cancer patients harboring HER-2 overexpression due to gene amplification in their tumor cells, and is currently also explored in adjuvant and neoadjuvant settings. Another agent with promising results in clinical trials is ramucirumab, an antibody targeting VEGFR-2. No clear survival benefit, however, were experienced with agents targeting EGFR (cetuximab, panitumumab), VEGF-A (bevacizumab), or mTOR (everolimus). Drugs targeting c-MET/HGF are currently under investigation in biomarker-selected cohorts, with promising results in early clinical trials. This review will summarize the current status of targeted treatment options in gastric cancer. PMID:25706252

  19. Killing cells by targeting mitosis

    PubMed Central

    Manchado, E; Guillamot, M; Malumbres, M

    2012-01-01

    Cell cycle deregulation is a common feature of human cancer. Tumor cells accumulate mutations that result in unscheduled proliferation, genomic instability and chromosomal instability. Several therapeutic strategies have been proposed for targeting the cell division cycle in cancer. Whereas inhibiting the initial phases of the cell cycle is likely to generate viable quiescent cells, targeting mitosis offers several possibilities for killing cancer cells. Microtubule poisons have proved efficacy in the clinic against a broad range of malignancies, and novel targeted strategies are now evaluating the inhibition of critical activities, such as cyclin-dependent kinase 1, Aurora or Polo kinases or spindle kinesins. Abrogation of the mitotic checkpoint or targeting the energetic or proteotoxic stress of aneuploid or chromosomally instable cells may also provide further benefits by inducing lethal levels of instability. Although cancer cells may display different responses to these treatments, recent data suggest that targeting mitotic exit by inhibiting the anaphase-promoting complex generates metaphase cells that invariably die in mitosis. As the efficacy of cell–cycle targeting approaches has been limited so far, further understanding of the molecular pathways modulating mitotic cell death will be required to move forward these new proposals to the clinic. PMID:22223105

  20. Radiation target analysis of RNA.

    PubMed Central

    Benstein, S L; Kempner, E

    1996-01-01

    Ribozymes are polynucleotide molecules with intrinsic catalytic activity, capable of cleaving nucleic acid substrates. Large RNA molecules were synthesized containing a hammerhead ribozyme moiety of 52 nucleotides linked to an inactive leader sequence, for total lengths of either 262 or 1226 nucleotides. Frozen RNAs were irradiated with high energy electrons. Surviving ribozyme activity was determined using the ability of the irradiated ribozymes to cleave a labeled substrate. The amount of intact RNA remaining was determined from the same irradiated samples by scanning the RNA band following denaturing gel electrophoresis. Radiation target analyses of these data revealed a structural target size of 80 kDa and a ribozyme activity target size of 15 kDa for the smaller ribozyme, and 319 kDa and 16 kDa, respectively, for the larger ribozyme. The disparity in target size for activity versus structure indicates that, in contrast to proteins, there is no spread of radiation damage far from the primary site of ionization in RNA molecules. The smaller target size for activity indicates that only primary ionizations occurring in the specific active region are effective. This is similar to the case for oligosaccharides. We concluded that the presence of the ribose sugar in the polymer chain restricts radiation damage to a small region and prevents major energy transfer throughout the molecule. Radiation target analysis should be a useful technique for evaluating local RNA:RNA and RNA:protein interactions in vitro. Images Fig. 2 PMID:8692828

  1. MARS Target Yield Studies University of Warwick

    E-print Network

    McDonald, Kirk

    ), shielding (brown), iron plug (purple). John Back Oxford target meeting 1 May 2008 #12;4 On-axis Bz field z1 MARS Target Yield Studies John Back University of Warwick 1st May 2008 John Back Oxford target.5 cm. Parabolic beam: r=0.15 cm. John Back Oxford target meeting 1 May 2008 #12;3 Target Geometry: (z

  2. Unification of automatic target tracking and automatic target recognition

    NASA Astrophysics Data System (ADS)

    Schachter, Bruce J.

    2014-06-01

    The subject being addressed is how an automatic target tracker (ATT) and an automatic target recognizer (ATR) can be fused together so tightly and so well that their distinctiveness becomes lost in the merger. This has historically not been the case outside of biology and a few academic papers. The biological model of ATT?ATR arises from dynamic patterns of activity distributed across many neural circuits and structures (including retina). The information that the brain receives from the eyes is "old news" at the time that it receives it. The eyes and brain forecast a tracked object's future position, rather than relying on received retinal position. Anticipation of the next moment - building up a consistent perception - is accomplished under difficult conditions: motion (eyes, head, body, scene background, target) and processing limitations (neural noise, delays, eye jitter, distractions). Not only does the human vision system surmount these problems, but it has innate mechanisms to exploit motion in support of target detection and classification. Biological vision doesn't normally operate on snapshots. Feature extraction, detection and recognition are spatiotemporal. When vision is viewed as a spatiotemporal process, target detection, recognition, tracking, event detection and activity recognition, do not seem as distinct as they are in current ATT and ATR designs. They appear as similar mechanism taking place at varying time scales. A framework is provided for unifying ATT and ATR.

  3. Targets and methods for target preparation for radionuclide production

    DOEpatents

    Zhuikov, Boris L; Konyakhin, Nicolai A; Kokhanyuk, Vladimir M; Srivastava, Suresh C

    2012-10-16

    The invention relates to nuclear technology, and to irradiation targets and their preparation. One embodiment of the present invention includes a method for preparation of a target containing intermetallic composition of antimony Ti--Sb, Al--Sb, Cu--Sb, or Ni--Sb in order to produce radionuclides (e.g., tin-117 m) with a beam of accelerated particles. The intermetallic compounds of antimony can be welded by means of diffusion welding to a copper backing cooled during irradiation on the beam of accelerated particles. Another target can be encapsulated into a shell made of metallic niobium, stainless steel, nickel or titanium cooled outside by water during irradiation. Titanium shell can be plated outside by nickel to avoid interaction with the cooling water.

  4. Thrombocytopenia-Associated Multiple Organ Failure and Acute Kidney Injury.

    PubMed

    Nguyen, Trung C; Cruz, Miguel A; Carcillo, Joseph A

    2015-10-01

    Thrombocytopenia-associated multiple organ failure (TAMOF) is a clinical phenotype that encompasses a spectrum of syndromes associated with disseminated microvascular thromboses, such as the thrombotic microangiopathies thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) and disseminated intravascular coagulation (DIC). Autopsies findings in TTP, HUS, or DIC reveal specific findings that can differentiate these 3 entities. Von Willebrand factor and ADAMTS-13 play a central role in TTP. Shiga toxins and the complement pathway are vital in the development of HUS. Tissue factor is the major protease that drives the pathology of DIC. Acute kidney injury (AKI) is a common feature in patients with TAMOF. PMID:26410136

  5. Breast Cancer Presenting as Paraneoplastic Erythroderma: An Extremely Rare Case

    PubMed Central

    Katsantonis, Ioannis; Roussos, Nikolaos; Manoludaki, Kassiani; Antonopoulos, Stavros

    2014-01-01

    The skin may exhibit the first clinical evidence of a systemic disease and may provide the first clues to a diagnosis in malignancies. Erythroderma is defined as generalized redness and scaling and it is a clinical manifestation of a variety of underlying diseases including, rarely, solid tumors. Breast cancer is associated with a variety of skin paraneoplastic manifestations like acanthosis nigricans, erythromelalgia, thrombotic thrombocytopenic purpura, acrokeratosis paraneoplastica, dermatomyositis, systemic sclerosis, and scleroderma. However, in the literature, the correlation of erythroderma with breast cancer is quite infrequent. Here, we describe a case of a 76-year-old woman who presented with a paraneoplastic manifestation of erythroderma due to breast cancer. PMID:25295062

  6. Thermal Targets for Satellite Calibration

    SciTech Connect

    Villa-Aleman, E.

    2001-01-10

    The Savannah River Technology Center (SRTC) is currently calibrating the Multispectral Thermal Imager (MTI) satellite sponsored by the Department of Energy. The MTI imager is a research and development project with 15 wavebands in the visible, near-infrared, short-wave infrared, mid-wave infrared and long-wave infrared spectral regions. A plethora of targets with known temperatures such as power plant heated lakes, volcano lava vents, desert playas and aluminized Mylar tarps are being used in the validation of the five thermal bands of the MTI satellite. SRTC efforts in the production of ''cold targets'' with aluminized Mylar tarps will be described. Visible and thermal imagery and wavelength dependent radiance measurements of the calibration targets will be presented.

  7. A Cryogenic Infrared Calibration Target

    NASA Technical Reports Server (NTRS)

    Wollack, E. J.; Kinzer, R. E., Jr.; Rinehart, S. A.

    2014-01-01

    A compact cryogenic calibration target is presented that has a peak diffuse reflectance, R < or = 0.003, from 800 to 4800/cm (12 - 2 microns ). Upon expanding the spectral range under consideration to 400-10,000/ cm-1 (25 - 1 microns) the observed performance gracefully degrades to R < or = 0.02 at the band edges. In the implementation described, a high-thermal-conductivity metallic substrate is textured with a pyramidal tiling and subsequently coated with a thin lossy dielectric coating that enables high absorption and thermal uniformity across the target. The resulting target assembly is lightweight, has a low-geometric profile, and has survived repeated thermal cycling from room temperature to approx.4 K. Basic design considerations, governing equations, and test data for realizing the structure described are provided. The optical properties of selected absorptive materials-Acktar Fractal Black, Aeroglaze Z306, and Stycast 2850 FT epoxy loaded with stainless steel powder-are characterized and presented

  8. Antibiotic drugs targeting bacterial RNAs

    PubMed Central

    Hong, Weiling; Zeng, Jie; Xie, Jianping

    2014-01-01

    RNAs have diverse structures that include bulges and internal loops able to form tertiary contacts or serve as ligand binding sites. The recent increase in structural and functional information related to RNAs has put them in the limelight as a drug target for small molecule therapy. In addition, the recognition of the marked difference between prokaryotic and eukaryotic rRNA has led to the development of antibiotics that specifically target bacterial rRNA, reduce protein translation and thereby inhibit bacterial growth. To facilitate the development of new antibiotics targeting RNA, we here review the literature concerning such antibiotics, mRNA, riboswitch and tRNA and the key methodologies used for their screening.

  9. Antiproton stopping in atomic targets

    NASA Astrophysics Data System (ADS)

    Bailey, J. J.; Kadyrov, A. S.; Abdurakhmanov, I. B.; Fursa, D. V.; Bray, I.

    2015-08-01

    Stopping powers of antiprotons in H, He, Ne, Ar, Kr, and Xe targets are calculated using a semiclassical time-dependent convergent close-coupling method. The helium target is treated using both frozen-core and multiconfiguration approximations. The electron-electron correlation of the target is fully accounted for in both cases. Double ionization and ionization with excitation channels are taken into account using an independent-event model. The Ne, Ar, Kr, and Xe atom wave functions are described in a model of six p -shell electrons above a frozen Hartree-Fock core with only one-electron excitations from the outer p shell allowed. Results obtained for helium in the multiconfiguration treatment are in better agreement with experimental measurements than other theories.

  10. A cryogenic infrared calibration target

    NASA Astrophysics Data System (ADS)

    Wollack, E. J.; Kinzer, R. E.; Rinehart, S. A.

    2014-04-01

    A compact cryogenic calibration target is presented that has a peak diffuse reflectance, R ? 0.003, from 800 to 4800 cm-1 (12 - 2 ?m). Upon expanding the spectral range under consideration to 400-10 000 cm-1 (25 - 1 ?m) the observed performance gracefully degrades to R ? 0.02 at the band edges. In the implementation described, a high-thermal-conductivity metallic substrate is textured with a pyramidal tiling and subsequently coated with a thin lossy dielectric coating that enables high absorption and thermal uniformity across the target. The resulting target assembly is lightweight, has a low-geometric profile, and has survived repeated thermal cycling from room temperature to ˜4 K. Basic design considerations, governing equations, and test data for realizing the structure described are provided. The optical properties of selected absorptive materials—Acktar Fractal Black, Aeroglaze Z306, and Stycast 2850 FT epoxy loaded with stainless steel powder—are characterized and presented.

  11. A cryogenic infrared calibration target.

    PubMed

    Wollack, E J; Kinzer, R E; Rinehart, S A

    2014-04-01

    A compact cryogenic calibration target is presented that has a peak diffuse reflectance, R ? 0.003, from 800?to?4800?cm(-1) (12 - 2??m). Upon expanding the spectral range under consideration to 400-10,000?cm(-1) (25 - 1??m) the observed performance gracefully degrades to R ? 0.02 at the band edges. In the implementation described, a high-thermal-conductivity metallic substrate is textured with a pyramidal tiling and subsequently coated with a thin lossy dielectric coating that enables high absorption and thermal uniformity across the target. The resulting target assembly is lightweight, has a low-geometric profile, and has survived repeated thermal cycling from room temperature to ?4 K. Basic design considerations, governing equations, and test data for realizing the structure described are provided. The optical properties of selected absorptive materials-Acktar Fractal Black, Aeroglaze Z306, and Stycast 2850 FT epoxy loaded with stainless steel powder-are characterized and presented. PMID:24784638

  12. Observations of Spacecraft Targets, Unusual Asteroids, and Targets of Opportunity

    NASA Technical Reports Server (NTRS)

    Tholen, David J.

    1998-01-01

    Obtain physical and astrometric observations of: (1) spacecraft targets to support mission operations; (2) known asteroids with unusual orbits to help determine their origin; and (3) newly discovered minor planets (including both asteroids and comets) that represent a particular opportunity to add significant new knowledge of the Solar System.

  13. High-efficiency target-ion sources for RIB generation

    SciTech Connect

    Alton, G.D.

    1993-12-31

    A brief review is given of high-efficiency ion sources which have been developed or are under development at ISOL facilities which show particular promise for use at existing, future, or radioactive ion beam (RIB) facilities now under construction. Emphasis will be placed on those sources which have demonstrated high ionization efficiency, species versatility, and operational reliability and which have been carefully designed for safe handling in the high level radioactivity radiation fields incumbent at such facilities. Brief discussions will also be made of the fundamental processes which affect the realizable beam intensities in target-ion sources. Among the sources which will be reviewed will be selected examples of state-of-the-art electron-beam plasma-type ion sources, thermal-ionization, surface-ionization, ECR, and selectively chosen ion source concepts which show promise for radioactive ion beam generation. A few advanced, chemically selective target-ion sources will be described, such as sources based on the use of laser-resonance ionization, which, in principle, offer a more satisfactory solution to isobaric contamination problems than conventional electromagnetic techniques. Particular attention will be given to the sources which have been selected for initial or future use at the Holifield Radioactive Ion Beam Facility now under construction at the Oak Ridge National Laboratory.

  14. Materials considerations in accelerator targets

    SciTech Connect

    Peacock, H.B. Jr.; Iyer, N.C.; Louthan, M.R. Jr.

    1994-08-01

    Future nuclear materials production and/or the burn-up of long lived radioisotopes may be accomplished through the capture of spallation produced neutrons in accelerators. Aluminum clad-lead and/or lead alloys has been proposed as a spallation target. Aluminum was the cladding choice because of the low neutron absorption cross section, fast radioactivity decay, high thermal conductivity, and excellent fabricability. Metallic lead and lead oxide powders were considered for the target core with the fabrication options being casting or powder metallurgy (PM). Scoping tests to evaluate gravity casting, squeeze casting, and casting and swaging processes showed that, based on fabricability and heat transfer considerations, squeeze casting was the preferred option for manufacture of targets with initial core cladding contact. Thousands of aluminum clad aluminum-lithium alloy core targets and control rods for tritium production have been fabricated by coextrusion processes and successfully irradiated in the SRS reactors. Tritium retention in, and release from the coextruded product was modeled from experimental and operational data. Newly produced tritium atoms were trapped by lithium atoms to form a lithium tritide. The effective tritium pressure required for trap or tritide stability was the equilibrium decomposition pressure of tritium over a lithium tritide-aluminum mixture. The temperature dependence of tritium release was determined by the permeability of the cladding to tritium and the local equilibrium at the trap sites. The model can be used to calculate tritium release from aluminum clad, aluminum-lithium alloy targets during postulated accelerator operational and accident conditions. This paper describes the manufacturing technologies evaluated and presents the model for tritium retention in aluminum clad, aluminum-lithium alloy tritium production targets.

  15. Target detection in SLAR images

    NASA Astrophysics Data System (ADS)

    Sita, D.

    1994-06-01

    Methods for automatic detection of target areas from SAR images have been investigated. Algorithms have been developed for extraction of regions such as lakes and urban areas and linear features such as roads, rivers, bridges. These methods, at present, are mostly based on gray level and gradient thresholding schemes. A comparision of the experimental results is presented.

  16. Other targeted drugs in melanoma.

    PubMed

    González-Cao, María; Rodón, Jordi; Karachaliou, Niki; Sánchez, Jesús; Santarpia, Mariacarmela; Viteri, Santiago; Pilotto, Sara; Teixidó, Cristina; Riso, Aldo; Rosell, Rafael

    2015-10-01

    Targeted therapy drugs are developed against specific molecular alterations on cancer cells. Because they are "targeted" to the tumor, these therapies are more effective and better tolerated than conventional therapies such as chemotherapy. In the last decade, great advances have been made in understanding of melanoma biology and identification of molecular mechanisms involved in malignant transformation of cells. The identification of oncogenic mutated kinases involved in this process provides an opportunity for development of new target therapies. The dependence of melanoma on BRAF-mutant kinase has provided an opportunity for development of mutation-specific inhibitors with high activity and excellent tolerance that are now being used in clinical practice. This marked a new era in the treatment of metastatic melanoma and much research is now ongoing to identify other "druggable" kinases and transduction signaling networking. It is expected that in the near future the spectrum of target drugs for melanoma treatment will increase. Herein, we review the most relevant potential novel drugs for melanoma treatment based on preclinical data and the results of early clinical trials. PMID:26605312

  17. Foam shell cryogenic ICF target

    DOEpatents

    Darling, Dale H. (Pleasanton, CA)

    1987-01-01

    A uniform cryogenic layer of DT fuel is maintained in a fusion target having a low density, small pore size, low Z rigid foam shell saturated with liquid DT fuel. Capillary action prevents gravitational slumping of the fuel layer. The saturated shell may be cooled to produce a solid fuel layer.

  18. RADIATION ONCOLOGY TARGET YOUR FUTURE

    E-print Network

    Tobar, Michael

    RADIATION ONCOLOGY TARGET YOUR FUTURE #12;A Career in Radiation Oncology YOUR CHOICE SAVE LIVES Take the first step towards a career in Radiation Oncology Visit www.acareerinradiationoncology.com.au 2 What is Radiation Oncology? Radiation Oncology is made up of three unique medical specialties

  19. Mercury Intense Target (MERIT) Update

    E-print Network

    McDonald, Kirk

    ) Syringe Pump - Syringe pump design replaced the original centrifugal pump due to the high pressure OF ENERGY Muon Collaboration Friday Mtg. Oct. 28, 2005 Overall Plan · Pump equipment and target delivery · Up to 100 pulses for the CERN test, >500 operating cycles for system testing · The pump equipment

  20. Target Homework to Maximize Learning

    ERIC Educational Resources Information Center

    Heitzmann, Ray

    2007-01-01

    Targeted homework is based upon the belief that homework can make a significant contribution to student achievement in the areas of knowledge, skills, and values. It centers on the notion that homework achieves maximum effectiveness when teachers share the school's homework policy as well as their policy with students and parents or guardians. The…

  1. Targeted Event Detection Werner Stuetzlea

    E-print Network

    Percival, Don

    Targeted Event Detection Werner Stuetzlea Donald B. Percival b,a, Caren Marzbana,b a of event detection based upon a (typically multivariate) data stream characterizing some system. Most of the time the system is quiescent ­ nothing of interest is happening ­ but occasionally events of interest

  2. Target Article Epigenetic Influence of

    E-print Network

    Champagne, Frances A.

    and behavior will be explored. ß 2010 Wiley Periodicals, Inc. Dev Psychobiol Keywords: epigenetic; maternalTarget Article Epigenetic Influence of Social Experiences Across the Lifespan Frances A. Champagne expression as one possible route through which these long-term outcomes are achieved. These epigenetic

  3. Guide to Accessing TARGET Data

    Cancer.gov

    Published on Office of Cancer Genomics (https://ocg.cancer.gov) Home > Guide to Accessing TARGET Data   New user?                     Approved user?                [1] [2] [3] What type of data do you want to download: open and/or controlled access data? OPEN

  4. Guide to Accessing TARGET Data

    Cancer.gov

    Published on Office of Cancer Genomics (http://ocg.cancer.gov) Home > Guide to Accessing TARGET Data   New user?                     Approved user?                [1] [2] [3] What type of data do you want to download: open and/or controlled access data? OPEN

  5. Other targeted drugs in melanoma

    PubMed Central

    Rodón, Jordi; Karachaliou, Niki; Sánchez, Jesús; Santarpia, Mariacarmela; Viteri, Santiago; Pilotto, Sara; Teixidó, Cristina; Riso, Aldo; Rosell, Rafael

    2015-01-01

    Targeted therapy drugs are developed against specific molecular alterations on cancer cells. Because they are “targeted” to the tumor, these therapies are more effective and better tolerated than conventional therapies such as chemotherapy. In the last decade, great advances have been made in understanding of melanoma biology and identification of molecular mechanisms involved in malignant transformation of cells. The identification of oncogenic mutated kinases involved in this process provides an opportunity for development of new target therapies. The dependence of melanoma on BRAF-mutant kinase has provided an opportunity for development of mutation-specific inhibitors with high activity and excellent tolerance that are now being used in clinical practice. This marked a new era in the treatment of metastatic melanoma and much research is now ongoing to identify other “druggable” kinases and transduction signaling networking. It is expected that in the near future the spectrum of target drugs for melanoma treatment will increase. Herein, we review the most relevant potential novel drugs for melanoma treatment based on preclinical data and the results of early clinical trials. PMID:26605312

  6. TARGETED DELIVERY OF INHALED PROTEINS

    EPA Science Inventory

    ETD-02-047 (Martonen) GPRA # 10108

    TARGETED DELIVERY OF INHALED PROTEINS
    T. B. Martonen1, J. Schroeter2, Z. Zhang3, D. Hwang4, and J. S. Fleming5
    1Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Research Triangle Park...

  7. Target Audience: Health care professionals

    E-print Network

    Hitchcock, Adam P.

    Target Audience: Health care professionals Workshop Facilitator: Valerie Spironello, MSW, RSW Valerie has been a social worker for over 20 years working in a variety of settings including health care provided workshops and presentations to health care providers on a variety of topics such as compassion

  8. Tumor Targeting via Integrin Ligands

    PubMed Central

    Marelli, Udaya Kiran; Rechenmacher, Florian; Sobahi, Tariq Rashad Ali; Mas-Moruno, Carlos; Kessler, Horst

    2013-01-01

    Selective and targeted delivery of drugs to tumors is a major challenge for an effective cancer therapy and also to overcome the side-effects associated with current treatments. Overexpression of various receptors on tumor cells is a characteristic structural and biochemical aspect of tumors and distinguishes them from physiologically normal cells. This abnormal feature is therefore suitable for selectively directing anticancer molecules to tumors by using ligands that can preferentially recognize such receptors. Several subtypes of integrin receptors that are crucial for cell adhesion, cell signaling, cell viability, and motility have been shown to have an upregulated expression on cancer cells. Thus, ligands that recognize specific integrin subtypes represent excellent candidates to be conjugated to drugs or drug carrier systems and be targeted to tumors. In this regard, integrins recognizing the RGD cell adhesive sequence have been extensively targeted for tumor-specific drug delivery. Here we review key recent examples on the presentation of RGD-based integrin ligands by means of distinct drug-delivery systems, and discuss the prospects of such therapies to specifically target tumor cells. PMID:24010121

  9. Solid Targets for Neutron Spallation Sources

    E-print Network

    McDonald, Kirk

    targets produce higher neutron fluxes than liquid metal targets · Neutron flux ~ neutron production is less than 30%, solid tungsten targets will generate equal or greater neutron flux than liquid metal · Liquid metal targets distribute the decay heat within the total liquid metal volume, typically ~100x

  10. Beam Pulse Structure and Targets Roger Bennett

    E-print Network

    McDonald, Kirk

    that there is permanent distortion or failure - shock. Short high intensity beam pulses will give rise to shock in a target. The shock wave travels through matter at the speed of sound, where E is Young's modulus energy goes into the target in this time and the shock wave in the target is reduced. If the target

  11. Tyrosine kinase inhibitors: Multi-targeted or single-targeted?

    PubMed Central

    Broekman, Fleur; Giovannetti, Elisa; Peters, Godefridus J

    2011-01-01

    Since in most tumors multiple signaling pathways are involved, many of the inhibitors in clinical development are designed to affect a wide range of targeted kinases. The most important tyrosine kinase families in the development of tyrosine kinase inhibitors are the ABL, SCR, platelet derived growth factor, vascular endothelial growth factor receptor and epidermal growth factor receptor families. Both multi-kinase inhibitors and single-kinase inhibitors have advantages and disadvantages, which are related to potential resistance mechanisms, pharmacokinetics, selectivity and tumor environment. In different malignancies various tyrosine kinases are mutated or overexpressed and several resistance mechanisms exist. Pharmacokinetics is influenced by interindividual differences and differs for two single targeted inhibitors or between patients treated by the same tyrosine kinase inhibitor. Different tyrosine kinase inhibitors have various mechanisms to achieve selectivity, while differences in gene expression exist between tumor and stromal cells. Considering these aspects, one type of inhibitor can generally not be preferred above the other, but will depend on the specific genetic constitution of the patient and the tumor, allowing personalized therapy. The most effective way of cancer treatment by using tyrosine kinase inhibitors is to consider each patient/tumor individually and to determine the strategy that specifically targets the consequences of altered (epi)genetics of the tumor. This strategy might result in treatment by a single multi kinase inhibitor for one patient, but in treatment by a couple of single kinase inhibitors for other patients. PMID:21603317

  12. Multishell inertial confinement fusion target

    DOEpatents

    Holland, James R. (Butler, PA); Del Vecchio, Robert M. (Vandergrift, PA)

    1984-01-01

    A method of fabricating multishell fuel targets for inertial confinement fusion usage. Sacrificial hemispherical molds encapsulate a concentric fuel pellet which is positioned by fiber nets stretched tautly across each hemispherical mold section. The fiber ends of the net protrude outwardly beyond the mold surfaces. The joint between the sacrificial hemispheres is smoothed. A ceramic or glass cover is then deposited about the finished mold surfaces to produce an inner spherical surface having continuously smooth surface configuration. The sacrificial mold is removed by gaseous reaction accomplished through the porous ceramic cover prior to enclosing of the outer sphere by addition of an outer coating. The multishell target comprises the inner fuel pellet concentrically arranged within a surrounding coated cover or shell by fiber nets imbedded within the cover material.

  13. Hox Targets and Cellular Functions

    PubMed Central

    Sánchez-Herrero, Ernesto

    2013-01-01

    Hox genes are a group of genes that specify structures along the anteroposterior axis in bilaterians. Although in many cases they do so by modifying a homologous structure with a different (or no) Hox input, there are also examples of Hox genes constructing new organs with no homology in other regions of the body. Hox genes determine structures though the regulation of targets implementing cellular functions and by coordinating cell behavior. The genetic organization to construct or modify a certain organ involves both a genetic cascade through intermediate transcription factors and a direct regulation of targets carrying out cellular functions. In this review I discuss new data from genome-wide techniques, as well as previous genetic and developmental information, to describe some examples of Hox regulation of different cell functions. I also discuss the organization of genetic cascades leading to the development of new organs, mainly using Drosophila melanogaster as the model to analyze Hox function. PMID:24490109

  14. Targeted therapies for bone sarcomas

    PubMed Central

    Heymann, Dominique; Rédini, Françoise

    2013-01-01

    Bone sarcomas include a very large number of tumour subtypes, which originate form bone and more particularly from mesenchymal stem cell lineage. Osteosarcoma, Ewing's sarcoma and chondrosarcoma, the three main bone sarcoma entities develop in a favourable microenvironment composed by bone cells, blood vessels, immune cells, based on the ‘seed and soil theory'. Current therapy associates surgery and chemotherapy, however, bone sarcomas remain diseases with high morbidity and mortality especially in children and adolescents. In the past decade, various new therapeutic approaches emerged and target the tumour niche or/and directly the tumour cells by acting on signalling/metabolic pathways involved in cell proliferation, apoptosis or drug resistance. The present review gives a brief overview from basic to clinical assessment of the main targeted therapies of bone sarcoma cells. PMID:24422100

  15. Multishell inertial confinement fusion target

    DOEpatents

    Holland, James R. (Butler, PA); Del Vecchio, Robert M. (Vandergrift, PA)

    1987-01-01

    A method of fabricating multishell fuel targets for inertial confinement fusion usage. Sacrificial hemispherical molds encapsulate a concentric fuel pellet which is positioned by fiber nets stretched tautly across each hemispherical mold section. The fiber ends of the net protrude outwardly beyond the mold surfaces. The joint between the sacrificial hemispheres is smoothed. A ceramic or glass cover is then deposited about the finished mold surfaces to produce an inner spherical surface having continuously smooth surface configuration. The sacrificial mold is removed by gaseous reactions accomplished through the porous ceramic cover prior to enclosing of the outer sphere by addition of an outer coating. The multishell target comprises the inner fuel pellet concentrically arranged within a surrounding coated cover or shell by fiber nets imbedded within the cover material.

  16. Remote moving target indication assessment

    SciTech Connect

    Canavan, G.H.

    1996-10-01

    The objective of this project was to design and test key components of a sensor to be used on remotely piloted vehicles, aircraft, or satellites for the detection of moving vehicles in cluttered backgrounds. The proposed sensor uses modern large-array focal planes to provide multiple infrared observations of moving targets and capable on-board computers to integrate multiple observations to detect moving targets in background clutter. This combination reduces the size, weight, and cost of the sensor to levels that can be flown on many small unmanned platforms. This effort selected the actual components, integrated them into a test bed, tested the performance of the sensor against realistic generated scenes, and designed a proof-of-concept prototype.

  17. Coherent Communications, Imaging and Targeting

    SciTech Connect

    Stappaerts, E; Baker, K; Gavel, D; Wilks, S; Olivier, S; Brase, J; Olivier, S; Brase, J

    2003-10-03

    Laboratory and field demonstration results obtained as part of the DARPA-sponsored Coherent Communications, Imaging and Targeting (CCIT) program are reviewed. The CCIT concept uses a Phase Conjugation Engine based on a quadrature receiver array, a hologram processor and a spatial light modulator (SLM) for high-speed, digital beam control. Progress on the enabling MEMS SLM, being developed by a consortium consisting of LLNL, academic institutions and small businesses, is presented.

  18. Targeting inflammation in metabolic syndrome.

    PubMed

    Welty, Francine K; Alfaddagh, Abdulhamied; Elajami, Tarec K

    2016-01-01

    The metabolic syndrome (MetS) is comprised of a cluster of closely related risk factors, including visceral adiposity, insulin resistance, hypertension, high triglyceride, and low high-density lipoprotein cholesterol; all of which increase the risk for the development of type 2 diabetes and cardiovascular disease. A chronic state of inflammation appears to be a central mechanism underlying the pathophysiology of insulin resistance and MetS. In this review, we summarize recent research which has provided insight into the mechanisms by which inflammation underlies the pathophysiology of the individual components of MetS including visceral adiposity, hyperglycemia and insulin resistance, dyslipidemia, and hypertension. On the basis of these mechanisms, we summarize therapeutic modalities to target inflammation in the MetS and its individual components. Current therapeutic modalities can modulate the individual components of MetS and have a direct anti-inflammatory effect. Lifestyle modifications including exercise, weight loss, and diets high in fruits, vegetables, fiber, whole grains, and low-fat dairy and low in saturated fat and glucose are recommended as a first line therapy. The Mediterranean and dietary approaches to stop hypertension diets are especially beneficial and have been shown to prevent development of MetS. Moreover, the Mediterranean diet has been associated with reductions in total and cardiovascular mortality. Omega-3 fatty acids and peroxisome proliferator-activated receptor ? agonists lower high levels of triglyceride; their role in targeting inflammation is reviewed. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone blockers comprise pharmacologic therapies for hypertension but also target other aspects of MetS including inflammation. Statin drugs target many of the underlying inflammatory pathways involved in MetS. PMID:26207884

  19. Novel anticancer therapeutics targeting telomerase.

    PubMed

    Ruden, Maria; Puri, Neelu

    2013-08-01

    Telomeres are protective caps at the ends of human chromosomes. Telomeres shorten with each successive cell division in normal human cells whereas, in tumors, they are continuously elongated by human telomerase reverse transcriptase (hTERT). Telomerase is overexpressed in 80-95% of cancers and is present in very low levels or is almost undetectable in normal cells. Because telomerase plays a pivotal role in cancer cell growth it may serve as an ideal target for anticancer therapeutics. Inhibition of telomerase may lead to a decrease of telomere length resulting in cell senescence and apoptosis in telomerase positive tumors. Several strategies of telomerase inhibition are reviewed, including small molecule inhibitors, antisense oligonucleotides, immunotherapies and gene therapies, targeting the hTERT or the ribonucleoprotein subunit hTER. G-quadruplex stabilizers, tankyrase and HSP90 inhibitors targeting telomere and telomerase assembly, and T-oligo approach are also covered. Based on this review, the most promising current telomerase targeting therapeutics are the antisense oligonucleotide inhibitor GRN163L and immunotherapies that use dendritic cells (GRVAC1), hTERT peptide (GV1001) or cryptic peptides (Vx-001). Most of these agents have entered phase I and II clinical trials in patients with various tumors, and have shown good response rates as evidenced by a reduction in tumor cell growth, increased overall disease survival, disease stabilization in advanced staged tumors and complete/partial responses. Most therapeutics have shown to be more effective when used in combination with standard therapies, resulting in concomitant telomere shortening and tumor mass shrinkage, as well as preventing tumor relapse and resistance to single agent therapy. PMID:22841437

  20. Fixed target flammable gas upgrades

    SciTech Connect

    Schmitt, R.; Squires, B.; Gasteyer, T.; Richardson, R.

    1996-12-01

    In the past, fixed target flammable gas systems were not supported in an organized fashion. The Research Division, Mechanical Support Department began to support these gas systems for the 1995 run. This technical memo describes the new approach being used to supply chamber gasses to fixed target experiments at Fermilab. It describes the engineering design features, system safety, system documentation and performance results. Gas mixtures provide the medium for electron detection in proportional and drift chambers. Usually a mixture of a noble gas and a polyatomic quenching gas is used. Sometimes a small amount of electronegative gas is added as well. The mixture required is a function of the specific chamber design, including working voltage, gain requirements, high rate capability, aging and others. For the 1995 fixed target run all the experiments requested once through gas systems. We obtained a summary of problems from the 1990 fixed target run and made a summary of the operations logbook entries from the 1991 run. These summaries primarily include problems involving flammable gas alarms, but also include incidents where Operations was involved or informed. Usually contamination issues were dealt with by the experimenters. The summaries are attached. We discussed past operational issues with the experimenters involved. There were numerous incidents of drift chamber failure where contaminated gas was suspect. However analyses of the gas at the time usually did not show any particular problems. This could have been because the analysis did not look for the troublesome component, the contaminant was concentrated in the gas over the liquid and vented before the sample was taken, or that contaminants were drawn into the chambers directly through leaks or sub-atmospheric pressures. After some study we were unable to determine specific causes of past contamination problems, although in argon-ethane systems the problems were due to the ethane only.

  1. Promising therapeutic targets in neuroblastoma

    PubMed Central

    Matthay, Katherine K.; George, Rani E.; Yu, Alice L.

    2012-01-01

    Neuroblastoma, the most common extra- cranial solid tumor in children, is derived from neural crest cells. Nearly half of patients present with metastatic disease, and have 5-year EFS of less than 50%. New approaches with targeted therapy may improve efficacy without increased toxicity. The current review will evaluate three promising targeted therapies, including 131I-metaiodobenzylguanidine (MIBG), a radiopharmaceutical taken up by the human norepinephrine transporter expressed in 90% of neuroblastomas, immunotherapy with monoclonal antibodies targeting the GD2 ganglioside, expressed on 98% of neuroblastoma cells, and inhibitors of ALK, a tyrosine kinase which is mutated or amplified in approximately 10% of neuroblastoma and expressed on the surface of most neuroblastoma cells. Early phase trials have confirmed the activity of 131I-MIBG in relapsed neuroblastoma, with response rates of about 30%, but the technical aspects of administration of large amounts of radioactivity in young children and the limited access have hindered incorporation into treatment of newly diagnosed patients. Anti-GD2 antibodies have also demonstrated activity in relapsed disease, and a recent phase III randomized trial showed a significant improvement in event-free survival for patients receiving chimeric anti-GD2 (ch14.18) combined with cytokines and isotretinoin after myeloablative consolidation therapy. A recently approved small molecule inhibitor of ALK has promising pre-clinical activity for neuroblastoma, and is currently in phase I and II trials. This is the first agent directed to a specific mutation in neuroblastoma, and marks a new step toward personalized therapy for neuroblastoma. Further clinical development of targeted treatments offers new hope for children with neuroblastoma. PMID:22589483

  2. Targeting immunosuppression for cancer therapy

    PubMed Central

    Ghirelli, Cristina; Hagemann, Thorsten

    2013-01-01

    Failing immunity has been acknowledged for its contribution to cancer development and progression. Recent clinical findings have provided payoffs for significant preclinical evaluation and refinement over the last 20 years, but many questions remain to be answered. In this issue of the JCI, Marabelle et al. describe a novel method for targeting the Tregs that infiltrate tumors, demonstrating that dampening the tumor immunosuppressive environment while activating innate antitumor immunity may be an effective approach to cancer treatment. PMID:23728169

  3. Preparation of thick molybdenum targets

    NASA Technical Reports Server (NTRS)

    Singh, J. J.

    1974-01-01

    Thick natural molybdenum deposits on nickel plated copper substrates were prepared by thermal decomposition of molybdenum hexacarbonyl vapors on a heated surface in an inert gas atmosphere. The molybdenum metal atoms are firmly bonded to the substrate atoms, thus providing an excellent thermal contact across the junction. Molybdenum targets thus prepared should be useful for internal bombardment in a cyclotron where thermal energy inputs can exceed 10 kW.

  4. Renal Toxicities of Targeted Therapies.

    PubMed

    Abbas, Anum; Mirza, Mohsin M; Ganti, Apar Kishor; Tendulkar, Ketki

    2015-12-01

    With the incorporation of targeted therapies in routine cancer therapy, it is imperative that the array of toxicities associated with these agents be well-recognized and managed, especially since these toxicities are distinct from those seen with conventional cytotoxic agents. This review will focus on these renal toxicities from commonly used targeted agents. This review discusses the mechanisms of these side effects and management strategies. Anti-vascular endothelial growth factor (VEGF) agents including the monoclonal antibody bevacizumab, aflibercept (VEGF trap), and anti-VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs) all cause hypertension, whereas some of them result in proteinuria. Monoclonal antibodies against the human epidermal growth factor receptor (HER) family of receptors, such as cetuximab and panitumumab, cause electrolyte imbalances including hypomagnesemia and hypokalemia due to the direct nephrotoxic effect of the drug on renal tubules. Cetuximab may also result in renal tubular acidosis. The TKIs, imatinib and dasatinib, can result in acute or chronic renal failure. Rituximab, an anti-CD20 monoclonal antibody, can cause acute renal failure following initiation of therapy because of the onset of acute tumor lysis syndrome. Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, can result in proteinuria. Discerning the renal adverse effects resulting from these agents is essential for safe treatment strategies, particularly in those with pre-existing renal disease. PMID:25922090

  5. Aluminum-lithium target behavior

    SciTech Connect

    McDonell, W.R.

    1989-10-01

    Information on physical properties and irradiation behavior of aluminum-lithium target alloys employed for the production of tritium in Savannah River reactors has been reviewed to support development of technology for the New Production Reactor (NPR). Phase compositions and microstructures, thermal conductivity, mechanical properties, and constituent diffusion phenomena of the alloys, established in prior site studies, are presented. Irradiation behavior, including distributions of product tritium and helium and related exposure limits due to swelling and cracking of the target alloys is discussed, along with gas release processes occurring during subsequent product recovery operations. The property review supports designation of the aluminum-lithium alloys as ideally well-suited target materials for low-temperature, tritium-producing reactors, demonstrated over 35 years of Savannah River reactor operation. Low temperature irradiation and reaction with lithium in the alloy promotes tritium retention during reactor exposure, and the aluminum provides a matrix from which the product is readily recovered on heating following irradiation. 33 refs., 26 figs., 8 tabs.

  6. Improving Prospects for Targeting RAS.

    PubMed

    Singh, Harshabad; Longo, Dan L; Chabner, Bruce A

    2015-11-01

    RAS mutations are among the most common oncogenic drivers in human cancers, affecting nearly a third of all solid tumors and around a fifth of common myeloid malignancies, but they have evaded therapeutic interventions, despite being the focus of intense research over the last three decades. Recent discoveries lend new understanding about the structure, function, and signaling of RAS and have opened new avenues for development of much needed new therapies. We discuss the various approaches under investigation to target mutant RAS proteins. The recent development of direct RAS inhibitors specific to KRAS G12C mutations represents a landmark discovery that promises to change the perception about RAS's druggability. Multiple clinical trials targeting synthetically lethal partners and/or downstream signaling partners of RAS are underway. Novel inhibitors targeting various arms of RAS processing and signaling have yielded encouraging results in the laboratory, but refinement of the drug-like properties of these molecules is required before they will be ready for the clinic. PMID:26371146

  7. Thomson scattering on inhomogeneous targets

    NASA Astrophysics Data System (ADS)

    Thiele, R.; Sperling, P.; Chen, M.; Bornath, Th.; Fäustlin, R. R.; Fortmann, C.; Glenzer, S. H.; Kraeft, W.-D.; Pukhov, A.; Toleikis, S.; Tschentscher, Th.; Redmer, R.

    2010-11-01

    The introduction of brilliant free-electron lasers enables new pump-probe experiments to characterize warm dense matter states. For instance, a short-pulse optical laser irradiates a liquid hydrogen jet that is subsequently probed with brilliant soft x-ray radiation. The strongly inhomogeneous plasma prepared by the optical laser is characterized with particle-in-cell simulations. The interaction of the soft x-ray probe radiation for different time delays between pump and probe with the inhomogeneous plasma is also taken into account via radiative hydrodynamic simulations. We calculate the respective scattering spectrum based on the Born-Mermin approximation for the dynamic structure factor considering the full density and temperature-dependent Thomson scattering cross section throughout the target. We can identify plasmon modes that are generated in different target regions and monitor their temporal evolution. Therefore, such pump-probe experiments are promising tools not only to measure the important plasma parameters density and temperature but also to gain valuable information about their time-dependent profile through the target. The method described here can be applied to various pump-probe scenarios by combining optical lasers and soft x ray, as well as x-ray sources.

  8. A Cryogenic Infrared Calibration Target

    E-print Network

    Wollack, Edward J; Rinehart, Stephan A

    2014-01-01

    A compact cryogenic calibration target is presented that has a peak diffuse reflectance, $R \\le 0.003$, from $800-4,800\\,{\\rm cm}^{-1}$ $(12-2\\,\\mu$m). Upon expanding the spectral range under consideration to $400-10,000\\,{\\rm cm}^{-1}$ $(25-1\\,\\mu$m) the observed performance gracefully degrades to $R \\le 0.02$ at the band edges. In the implementation described, a high-thermal-conductivity metallic substrate is textured with a pyramidal tiling and subsequently coated with a thin lossy dielectric coating that enables high absorption and thermal uniformity across the target. The resulting target assembly is lightweight, has a low-geometric profile, and has survived repeated thermal cycling from room temperature to $\\sim4\\,$K. Basic design considerations, governing equations, and test data for realizing the structure described are provided. The optical properties of selected absorptive materials -- Acktar Fractal Black, Aeroglaze Z306, and Stycast 2850 FT epoxy loaded with stainless steel powder -- are character...

  9. LIFE Target Fabrication Research Plan Sept 2008

    SciTech Connect

    Miles, R; Biener, J; Kucheyev, S; Montesanti, R; Satcher, J; Spadaccini, C; Rose, K; Wang, M; Hamza, A; Alexander, N; Brown, L; Hund, J; Petzoldt, R; Sweet, W; Goodin, D

    2008-11-10

    The target-system for the baseline LIFE fast-ignition target was analyzed to establish a preliminary estimate for the costs and complexities involved in demonstrating the technologies needed to build a prototype LIFE plant. The baseline fast-ignition target upon which this analysis was developed is shown in Figure 1.0-1 below. The LIFE target-system incorporates requirements for low-cost, high throughput manufacture, high-speed, high accuracy injection of the target into the chamber, production of sufficient energy from implosion and recovery and recycle of the imploded target material residue. None of these functions has been demonstrated to date. Existing target fabrication techniques which lead to current 'hot spot' target costs of {approx}$100,000 per target and at a production rate of 2/day are unacceptable for the LIFE program. Fabrication techniques normally used for low-cost, low accuracy consumer products such as toys must be adapted to the high-accuracy LIFE target. This will be challenge. A research program resulting is the demonstration of the target-cycle technologies needed for a prototype LIFE reactor is expected to cost {approx}$51M over the course of 5 years. The effort will result in targets which will cost an estimated $0.23/target at a rep-rate of 20 Hz or about 1.73M targets/day.

  10. Properties of Protein Drug Target Classes

    PubMed Central

    Bull, Simon C.; Doig, Andrew J.

    2015-01-01

    Accurate identification of drug targets is a crucial part of any drug development program. We mined the human proteome to discover properties of proteins that may be important in determining their suitability for pharmaceutical modulation. Data was gathered concerning each protein’s sequence, post-translational modifications, secondary structure, germline variants, expression profile and drug target status. The data was then analysed to determine features for which the target and non-target proteins had significantly different values. This analysis was repeated for subsets of the proteome consisting of all G-protein coupled receptors, ion channels, kinases and proteases, as well as proteins that are implicated in cancer. Machine learning was used to quantify the proteins in each dataset in terms of their potential to serve as a drug target. This was accomplished by first inducing a random forest that could distinguish between its targets and non-targets, and then using the random forest to quantify the drug target likeness of the non-targets. The properties that can best differentiate targets from non-targets were primarily those that are directly related to a protein’s sequence (e.g. secondary structure). Germline variants, expression levels and interactions between proteins had minimal discriminative power. Overall, the best indicators of drug target likeness were found to be the proteins’ hydrophobicities, in vivo half-lives, propensity for being membrane bound and the fraction of non-polar amino acids in their sequences. In terms of predicting potential targets, datasets of proteases, ion channels and cancer proteins were able to induce random forests that were highly capable of distinguishing between targets and non-targets. The non-target proteins predicted to be targets by these random forests comprise the set of the most suitable potential future drug targets, and should therefore be prioritised when building a drug development programme. PMID:25822509

  11. Kidney–targeted drug delivery systems

    PubMed Central

    Zhou, Peng; Sun, Xun; Zhang, Zhirong

    2014-01-01

    Kidney-targeted drug delivery systems represent a promising technology to improve drug efficacy and safety in the treatment of renal diseases. In this review, we summarize the strategies that have been employed to develop kidney-targeted drug delivery systems. We also describe how macromolecular carriers and prodrugs play crucial roles in targeting drugs to particular target cells in the kidney. New technologies render it possible to create renal targeting conjugates and other delivery systems including nanoparticles and liposomes present promising strategies to achieve the goal of targeting drugs to the kidney.

  12. Bioengineering Strategies for Designing Targeted Cancer Therapies

    PubMed Central

    Wen, Xuejun

    2014-01-01

    The goals of bioengineering strategies for targeted cancer therapies are (1) to deliver a high dose of an anticancer drug directly to a cancer tumor, (2) to enhance drug uptake by malignant cells, and (3) to minimize drug uptake by nonmalignant cells. Effective cancer-targeting therapies will require both passive- and active targeting strategies and a thorough understanding of physiologic barriers to targeted drug delivery. Designing a targeted therapy includes the selection and optimization of a nanoparticle delivery vehicle for passive accumulation in tumors, a targeting moiety for active receptor-mediated uptake, and stimuli-responsive polymers for control of drug release. The future direction of cancer targeting is a combinatorial approach, in which targeting therapies are designed to use multiple targeting strategies. The combinatorial approach will enable combination therapy for delivery of multiple drugs and dual ligand targeting to improve targeting specificity. Targeted cancer treatments in development and the new combinatorial approaches show promise for improving targeted anticancer drug delivery and improving treatment outcomes. PMID:23768509

  13. Targeting Cancer with Antisense Oligomers

    SciTech Connect

    Hnatowich, DJ

    2008-10-28

    With financial assistance from the Department of Energy, we have shown definitively that radiolabeled antisense DNAs and other oligomers will accumulate in target cancer cells in vitro and in vivo by an antisense mechanism. We have also shown that the number of mRNA targets for our antisense oligomers in the cancer cell types that we have investigated so far is sufficient to provide and antisense image and/or radiotherapy of cancer in mice. These studies have been reported in about 10 publications. However our observation over the past several years has shown that radiolabeled antisense oligomers administered intravenously in their native and naked form will accumulate and be retained in target xenografts by an antisense mechanism but will also accumulate at high levels in normal organs such as liver, spleen and kidneys. We have investigated unsuccessfully several commercially available vectors. Thus the use of radiolabeled antisense oligomers for the imaging of cancer must await novel approaches to delivery. This laboratory has therefore pursued two new paths, optical imaging of tumor and Auger radiotherapy. We are developing a novel method of optical imaging tumor using antisense oligomers with a fluorophore is administered while hybridized with a shorter complementary oligomer with an inhibitor. In culture and in tumored mice that the duplex remains intact and thus nonfluorescent until it encounters its target mRNA at which time it dissociates and the antisense oligomer binds along with its fluorophore to the target. Simultaneous with the above, we have also observed, as have others, that antisense oligomers migrate rapidly and quantitatively to the nucleus upon crossing cell membranes. The Auger electron radiotherapy path results from this observation since the nuclear migration properties could be used effectively to bring and to retain in the nucleus an Auger emitting radionuclide such as 111In or 125I bound to the antisense oligomer. Since the object becomes radiotherapy rather than imaging, the delivery problem may be obviated by attaching the antisense oligomer to an antitumor antibody to improve delivery following intravenous administration. Since many antibodies are trapped in endosomes following internalization, a cell penetrating peptide such as tat will also be included to ensure transport of the complex without entrapment. Rather than covalent conjugation of the three entities, we are using streptavidin as linker after biotinylated each component. Our recent efforts have concentrated on establishing the influence of the streptavidin linker on the properties of each component within the delivery nanoparticle. Thus, we have shown that the Herceptin antibody, when linked to a labeled oligomer via streptavidin, remains capable of directing the label oligomer to Her2+ tumor cells in vitro and Her2+ tumor xenografts in mice. In addition, we have demonstrated that a labeled antisense oligomer within the nanoparticle remains capable of migrating to the nucleus and binding to its target mRNA in vitro and in vivo. We have shown that the tat peptide also preserves its properties of cell transport when incubated as one component of the nanoparticle. Most recently, we have addressed another of our concerns, namely whether the streptavidin would adversely effect the biodistribution of the antisense oligomer. We were pleased to find that the 99mTc-labeled antisense MORF within the Herceptin three component and two component nanoparticles accumulated and was retained in tumor in a manner suggestive of radiolabeled Herceptin itself. Thus the preserved properties within the streptavidin delivery nanoparticle of the Herceptin antibody, the tat peptide and the 111In labeled antisense MORF oligomer will explain why we have successfully demonstrated an Auger electron-mediated, antisense-mediated radiotherapy in cells in culture. One remaining concern is that the delivery nanoparticle may deliver the Auger electron emitting radionuclide to the nucleus of normal cells as well as tumor cells. We have now performed tumored mice stu

  14. Hematological targets of radiation damage.

    PubMed

    Kulkarni, Shilpa; Ghosh, Sanchita P; Hauer-Jensen, Martin; Kumar, K Sree

    2010-11-01

    Radiation-induced myelosuppression remains a rate-limiting factor of radiotherapy and chemotherapy. Therefore, hematological targets of radiation damage are of great significance for radiation oncology and normal tissue injury and protection. Protection of hematopoietic stem and progenitor cells is pivotal. In order to develop therapeutic targets, it is necessary to understand the mechanisms of stem cell renewal and differentiation. Recent advances in the molecular pathology of hematopoietic stem cells indicate a fine balance between various extrinsic and intrinsic signaling pathways in preserving the self-renewal and proliferative capacity of stem cells. Extrinsic signaling involves a microenvironment niche factors such as neighboring stromal cells, osteoblasts, and adipocytes secreting cytokines, chemokines, and metalloproteinases; intrinsic regulation involves Wnt/hedgehog/Notch signaling, DNA damage-induced epigenetic alterations, telomere shortening, and early senescence. Various drugs including synthetic cytokine mimetics, cytokine stimulators, and DNA repair modulators are being tested as radioprotectants. Colony-stimulating factors are routinely used in clinics to treat neutropenia induced by chemotherapy and radiotherapy as well as to mobilize and expand progenitors used in autologous transplantation. However, toxicity has limited their use. The vitamin E isoforms gamma tocotrienol, a potent free radical scavenger that has displayed promising anticarcinogenic properties, was recently shown to protect bone marrow (BM) from radiation injury and to stimulate hematopoiesis in a murine model. This chapter focuses on the potential targets of radiation damage in BM and speculates on the mechanisms of protection by ?-tocotrienol and how these mechanisms can contribute to radioprotection in general and to protection of BM during chemotherapy and radiotherapy in particular. PMID:20583980

  15. Targeted therapy for gastric cancer.

    PubMed

    Smyth, Elizabeth C; Cunningham, David

    2012-09-01

    For patients with advanced gastric cancer, traditional double or triplet cytotoxic chemotherapy regimens result in a median survival of 9-11 months. As combination therapy is associated with increased survival, but also increased toxicity in a patient population whose performance status often compromised by their malignancy, development of more effective and less toxic treatment choices is mandated. Emerging data from gene expression profiling suggests that differences in pathological appearance and clinical behavior may be due the presence of unique molecular phenotypes. Characterization of the gastric cancer genomic landscape reveals the presence of multiple alterations in expression of receptor tyrosine kinases, which in conjunction with their ligands and downstream effector molecules represent potentially druggable pathways for future drug development. Treatment of HER2 positive gastric cancer with trastuzumab has led to significant gains in overall survival, and further manipulation of this pathway using the novel anti-HER2 directed agents pertuzumab and T-DM1 in addition to dual EGFR/HER2 blockade with lapatinib may yield positive results. In contrast, targeting of the EGFR pathway in combination with chemotherapy in unselected patients has not been fruitful to date, with no significant gains over standard chemotherapy yet demonstrated. Similarly, use of the anti-angiogenic monoclonal antibody bevacizumab was not successful in a large global randomized trial; however intriguing regional variations were seen with respect to efficacy of this drug, leading to calls for a second, regionally stratified study. Careful selection of patient subsets will become a key factor in future clinical trials, as novel targeted agents such as those targeting the MET/HGF and FGFR axes move forward into clinical development. It is hoped that treatment of patients in such molecularly defined groups is will lead to significant gains in survival compared to current treatment paradigms. PMID:22552927

  16. Myxochelins target human 5-lipoxygenase.

    PubMed

    Schieferdecker, Sebastian; König, Stefanie; Koeberle, Andreas; Dahse, Hans-Martin; Werz, Oliver; Nett, Markus

    2015-02-27

    Extracts of the predatory myxobacterium Pyxidicoccus fallax HKI 727 showed antiproliferative effects on leukemic K-562 cells. Bioactivity-guided fractionation led to the isolation of the bis-catechol myxochelin A and two new congeners. The biosynthetic origin of myxochelins C and D was confirmed by feeding studies with isotopically labeled precursors. Pharmacological testing revealed human 5-lipoxygenase (5-LO) as a molecular target of the myxochelins. In particular, myxochelin A efficiently inhibited 5-LO activity with an IC50 of 1.9 ?M and reduced the proliferation of K-562 cells at similar concentrations. PMID:25686392

  17. Approaching Rock Target No. 1

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This 3-D stereo anaglyph image was taken by the Mars Exploration Rover Spirit front hazard-identification camera after the rover's first post-egress drive on Mars Sunday. Engineers drove the rover approximately 3 meters (10 feet) from the Columbia Memorial Station toward the first rock target, seen in the foreground. The football-sized rock was dubbed Adirondack because of its mountain-shaped appearance. Scientists plan to use instruments at the end of the rover's robotic arm to examine the rock and understand how it formed.

  18. Conotoxins: Molecular and Therapeutic Targets

    NASA Astrophysics Data System (ADS)

    Lewis, Richard J.

    Marine molluscs known as cone snails produce beautiful shells and a complex array of over 50,000 venom peptides evolved for prey capture and defence. Many of these peptides selectively modulate ion channels and transporters, making them a valuable source of new ligands for studying the role these targets play in normal and disease physiology. A number of conopeptides reduce pain in animal models, and several are now in pre-clinical and clinical development for the treatment of severe pain often associated with diseases such as cancer. Less than 1% of cone snail venom peptides are pharmacologically characterised.

  19. Pfizer targets genomics through Pfizergen

    SciTech Connect

    Glaser, V.

    1995-06-01

    Recently, Pfizer (New York) formed Pfizergen to develop and commercialize genomics. For starters, Pfizergen involves investments by Pfizer of more than $115 million - excluding milestone payments and royalties on future products - in four biotech firms. Seeking a strong foothold in genomics, Pfizer is piecing together a multifaceted network of technologies. Through its alliance with Incyte, Pfizer has already accessed gene databases, high-throughput gene sequencing, and transcription analysis. Through Pfizergen, it will access expertise in microbial genetic engineering and combinatorial chemistry, as well as antiviral, antisense, and gene therapy capabilities. Future investments could target firms specializing in such products as positional cloning and bioinformatics.

  20. Electromagnetic Scattering from Realistic Targets

    NASA Technical Reports Server (NTRS)

    Lee, Shung- Wu; Jin, Jian-Ming

    1997-01-01

    The general goal of the project is to develop computational tools for calculating radar signature of realistic targets. A hybrid technique that combines the shooting-and-bouncing-ray (SBR) method and the finite-element method (FEM) for the radiation characterization of microstrip patch antennas in a complex geometry was developed. In addition, a hybridization procedure to combine moment method (MoM) solution and the SBR method to treat the scattering of waveguide slot arrays on an aircraft was developed. A list of journal articles and conference papers is included.

  1. Targeting ECM Disrupts Cancer Progression

    PubMed Central

    Venning, Freja A.; Wullkopf, Lena; Erler, Janine T.

    2015-01-01

    Metastatic complications are responsible for more than 90% of cancer-related deaths. The progression from an isolated tumor to disseminated metastatic disease is a multistep process, with each step involving intricate cross talk between the cancer cells and their non-cellular surroundings, the extracellular matrix (ECM). Many ECM proteins are significantly deregulated during the progression of cancer, causing both biochemical and biomechanical changes that together promote the metastatic cascade. In this review, the influence of several ECM proteins on these multiple steps of cancer spread is summarized. In addition, we highlight the promising (pre-)clinical data showing benefits of targeting these ECM macromolecules to prevent cancer progression. PMID:26539408

  2. Cascaded target normal sheath acceleration

    SciTech Connect

    Wang, W. P.; Shen, B. F.; Zhang, X. M.; Wang, X. F.; Xu, J. C.; Zhao, X. Y.; Yu, Y. H.; Yi, L. Q.; Shi, Y.; Zhang, L. G.; Xu, T. J.; Xu, Z. Z.

    2013-11-15

    A cascaded target normal sheath acceleration (TNSA) scheme is proposed to simultaneously increase energy and improve energy spread of a laser-produced mono-energetic proton beam. An optimum condition that uses the maximum sheath field to accelerate the center of the proton beam is theoretically found and verified by two-dimensional particle-in-cell simulations. An initial 10 MeV proton beam is accelerated to 21 MeV with energy spread decreased from 5% to 2% under the optimum condition during the process of the cascaded TNSA. The scheme opens a way to scale proton energy lineally with laser energy.

  3. TargetRNA2: identifying targets of small regulatory RNAs in bacteria

    PubMed Central

    Kery, Mary Beth; Feldman, Monica; Livny, Jonathan; Tjaden, Brian

    2014-01-01

    Many small, noncoding RNAs (sRNAs) in bacteria act as posttranscriptional regulators of messenger RNAs. TargetRNA2 is a web server that identifies mRNA targets of sRNA regulatory action in bacteria. As input, TargetRNA2 takes the sequence of an sRNA and the name of a sequenced bacterial replicon. When searching for targets of RNA regulation, TargetRNA2 uses a variety of features, including conservation of the sRNA in other bacteria, the secondary structure of the sRNA, the secondary structure of each candidate mRNA target and the hybridization energy between the sRNA and each candidate mRNA target. TargetRNA2 outputs a ranked list of likely regulatory targets for the input sRNA. When evaluated on a comprehensive set of sRNA-target interactions, TargetRNA2 was found to be both accurate and efficient in identifying targets of sRNA regulatory action. Furthermore, TargetRNA2 has the ability to integrate RNA-seq data, if available. If an sRNA is differentially expressed in two or more RNA-seq experiments, TargetRNA2 considers co-differential gene expression when searching for regulatory targets, significantly improving the accuracy of target identifications. The TargetRNA2 web server is freely available for use at http://cs.wellesley.edu/?btjaden/TargetRNA2. PMID:24753424

  4. 40 CFR 35.9020 - Planning targets.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...AND LOCAL ASSISTANCE Financial Assistance for the National Estuary Program § 35.9020 Planning targets. The EPA Assistant...targets are broad budgetary goals for total expenditures by each estuary program and are directly related to the activities that are...

  5. 40 CFR 35.9020 - Planning targets.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...AND LOCAL ASSISTANCE Financial Assistance for the National Estuary Program § 35.9020 Planning targets. The EPA Assistant...targets are broad budgetary goals for total expenditures by each estuary program and are directly related to the activities that are...

  6. 40 CFR 35.9020 - Planning targets.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...AND LOCAL ASSISTANCE Financial Assistance for the National Estuary Program § 35.9020 Planning targets. The EPA Assistant...targets are broad budgetary goals for total expenditures by each estuary program and are directly related to the activities that are...

  7. 40 CFR 35.9020 - Planning targets.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...AND LOCAL ASSISTANCE Financial Assistance for the National Estuary Program § 35.9020 Planning targets. The EPA Assistant...targets are broad budgetary goals for total expenditures by each estuary program and are directly related to the activities that are...

  8. 40 CFR 35.9020 - Planning targets.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...AND LOCAL ASSISTANCE Financial Assistance for the National Estuary Program § 35.9020 Planning targets. The EPA Assistant...targets are broad budgetary goals for total expenditures by each estuary program and are directly related to the activities that are...

  9. Nanoparticles for targeting the infarcted heart

    E-print Network

    Dvir, Tal

    We report a nanoparticulate system capable of targeting the heart after myocardial infarction (MI). Targeting is based on overexpression of angiotensin II type 1 (AT1) receptor in the infarcted heart. Liposomes 142 nm in ...

  10. 28 CFR 55.17 - Targeting.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...PROVISIONS OF THE VOTING RIGHTS ACT REGARDING LANGUAGE MINORITY GROUPS Minority Language Materials and Assistance § 55.17 Targeting...Targeting” refers to a system in which the minority language materials or assistance required by...

  11. 28 CFR 55.17 - Targeting.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...PROVISIONS OF THE VOTING RIGHTS ACT REGARDING LANGUAGE MINORITY GROUPS Minority Language Materials and Assistance § 55.17 Targeting...Targeting” refers to a system in which the minority language materials or assistance required by...

  12. 28 CFR 55.17 - Targeting.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...PROVISIONS OF THE VOTING RIGHTS ACT REGARDING LANGUAGE MINORITY GROUPS Minority Language Materials and Assistance § 55.17 Targeting...Targeting” refers to a system in which the minority language materials or assistance required by...

  13. 28 CFR 55.17 - Targeting.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...PROVISIONS OF THE VOTING RIGHTS ACT REGARDING LANGUAGE MINORITY GROUPS Minority Language Materials and Assistance § 55.17 Targeting...Targeting” refers to a system in which the minority language materials or assistance required by...

  14. 28 CFR 55.17 - Targeting.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...PROVISIONS OF THE VOTING RIGHTS ACT REGARDING LANGUAGE MINORITY GROUPS Minority Language Materials and Assistance § 55.17 Targeting...Targeting” refers to a system in which the minority language materials or assistance required by...

  15. Targets and processes for fabricating same

    SciTech Connect

    Cowna, Thomas; Malekos, Steven; Korgan, Grant; Adams, Jesse; Sentoku, Yasuhiko; LeGalloudec, Nathalie

    2014-06-10

    In particular embodiments, the present disclosure provides targets including a metal layer and defining a hollow inner surface. The hollow inner surface has an internal apex. The distance between at least two opposing points of the internal apex is less than about 15 .mu.m. In particular examples, the distance is less than about 1 .mu.m. Particular implementations of the targets are free standing. The targets have a number of disclosed shaped, including cones, pyramids, hemispheres, and capped structures. The present disclosure also provides arrays of such targets. Also provided are methods of forming targets, such as the disclosed targets, using lithographic techniques, such as photolithographic techniques. In particular examples, a target mold is formed from a silicon wafer and then one or more sides of the mold are coated with a target material, such as one or more metals.

  16. Targets and processes for fabricating same

    DOEpatents

    Cowan, Thomas (Dresden, DE); Malekos, Steven (Reno, NV); Korgan, Grant (Reno, NV); Adams, Jesse (Reno, NV); Sentoku, Yasuhiko (Reno, NV); Le Galloudec, Nathalie (Reno, NV); Fuchs, Julien (Paris, FR)

    2012-07-24

    In particular embodiments, the present disclosure provides targets including a metal layer and defining a hollow inner surface. The hollow inner surface has an internal apex. The distance between at least two opposing points of the internal apex is less than about 15 .mu.m. In particular examples, the distance is less than about 1 .mu.m. Particular implementations of the targets are free standing. The targets have a number of disclosed shaped, including cones, pyramids, hemispheres, and capped structures. The present disclosure also provides arrays of such targets. Also provided are methods of forming targets, such as the disclosed targets, using lithographic techniques, such as photolithographic techniques. In particular examples, a target mold is formed from a silicon wafer and then one or more sides of the mold are coated with a target material, such as one or more metals.

  17. Policies for Online Target Date Assignment Problems

    E-print Network

    Grötschel, Martin

    Policies for Online Target Date Assignment Problems: Competitive Analysis versus Expected Analysis Methods for Optimization with Dynamic Input Data 7 2.1 Online Optimization.3 Reviewing both Analysis Methods . . . . . . . . . . . . . . . . . . . . . . . . . . 16 3 The Online Target

  18. Purity of targets prepared on Cu substrates

    NASA Astrophysics Data System (ADS)

    Méens, A.; Rossini, I.; Sens, J. C.

    1993-09-01

    The purity of several elemental self-supporting targets usually prepared by evaporation onto soluble Cu substrates has been studied. The targets were analysed by Rutherford backscattering and instrumental neutron activation analysis. Because of the high percentage of Cu observed in some Si targets, further measurements, including transmission electron microscopy, have been performed on Si targets deposited by e-gun bombardment onto Cu and ion-beam sputtering onto betaine.

  19. Current progress in NIF target concepts

    SciTech Connect

    Gobby, P.L.; Foreman, L.R.; Thoma, D.J.; Jacobson, L.A.; Hollis, R.V.; Barrera, J.; Mitchell, M.A.; Salazar, M.A.; Salzer, L.J.

    1996-10-01

    Target concepts for the National Ignition Facility (NIF) require progress in the art and science of target fabrication. Three distinct issues are addressed: beryllium fuel capsules, foam-buffered direct drive, and high-density gas-filled hohlraums. In all cases experiments on the existing Nova laser at LLNL are either in progress or planned for the near future to test the various concepts. Consequently, target fabrication must be able to deliver targets appropriate for each.

  20. Fat Targets for Skeletal Health

    PubMed Central

    Kawai, Masanobu; Devlin, Maureen J; Rosen, Clifford J

    2013-01-01

    Emerging evidence points to a critical role for the skeleton in several homeostatic processes including energy balance. The connection between fuel utilization and skeletal remodeling begins in the bone marrow with lineage allocation of mesenchymal stromal cells into adipocytes or osteoblasts. Mature bone cells secrete factors that influence insulin sensitivity and fat cells synthesize cytokines that regulate osteoblast differentiation. The emerging importance of the bone-fat interaction suggests that novel molecules could be used as targets to enhance bone formation and possibly prevent fractures. In this review, we discuss three pathways that could favor pharmacologic intervention with the ultimate goal of enhancing bone mass and reducing osteoporotic fracture risk. Not surprisingly, because of the complex interactions across homeostatic networks, other pathways will likely be activated by this targeting and these could prove to be beneficial or detrimental for the organism. Hence a more complete picture of energy utilization and skeletal remodeling will be required to bring these potential agents into any future clinical armamentarium. PMID:19468288

  1. String theory in target space

    E-print Network

    Rutger H. Boels; Tobias Hansen

    2014-02-25

    It is argued that the complete S-matrix of string theory at tree level in a flat background can be obtained from a small set of target space properties, without recourse to the worldsheet description. The main non-standard inputs are (generalised) Britto-Cachazo-Feng-Witten shifts, as well as the monodromy relations for open string theory and the Kawai-Lewellen-Tye relations for closed string theory. The roots of the scattering amplitudes and especially their appearance in the residues at the kinematic poles are central to the story. These residues determine the amplitudes through on-shell recursion relations. Several checks of the formalism are presented, including a computation of the Koba-Nielsen amplitude in the bosonic string. Furthermore the question of target space unitarity is (re-)investigated. For the Veneziano amplitude this question is reduced by Poincare invariance, unitarity and locality to that of positivity of a particular numerical sum. Interestingly, this analysis produces the main conditions of the no-ghost theorem on dimension and intercept from the first three poles of this amplitude.

  2. Learning to track multiple targets.

    PubMed

    Liu, Xiao; Tao, Dacheng; Song, Mingli; Zhang, Luming; Bu, Jiajun; Chen, Chun

    2015-05-01

    Monocular multiple-object tracking is a fundamental yet under-addressed computer vision problem. In this paper, we propose a novel learning framework for tracking multiple objects by detection. First, instead of heuristically defining a tracking algorithm, we learn that a discriminative structure prediction model from labeled video data captures the interdependence of multiple influence factors. Given the joint targets state from the last time step and the observation at the current frame, the joint targets state at the current time step can then be inferred by maximizing the joint probability score. Second, our detection results benefit from tracking cues. The traditional detection algorithms need a nonmaximal suppression postprocessing to select a subset from the total detection responses as the final output and a large number of selection mistakes are induced, especially under a congested circumstance. Our method integrates both detection and tracking cues. This integration helps to decrease the postprocessing mistake risk and to improve performance in tracking. Finally, we formulate the entire model training into a convex optimization problem and estimate its parameters using the cutting plane optimization. Experiments show that our method performs effectively in a large variety of scenarios, including pedestrian tracking in crowd scenes and vehicle tracking in congested traffic. PMID:25051561

  3. Bayesian Spectroscopy and Target Tracking

    SciTech Connect

    Cunningham, C

    2001-05-01

    Statistical analysis gives a paradigm for detection and tracking of weak-signature sources that are moving among a network of detectors. The detector platforms compute and exchange information with near-neighbors in the form of Bayesian probabilities for possible sources. This can shown to be an optimal scheme for the use of detector information and communication resources. Here, we apply that paradigm to the detection and discrimination of radiation sources using multi-channel gamma-ray spectra. We present algorithms for the reduction of detector data to probability estimates and the fusion of estimates among multiple detectors. A primary result is the development of a goodness-of-fit metric, similar to {chi}{sup 2}, for template matching that is statistically valid for spectral channels with low expected counts. Discrimination of a target source from other false sources and detection of imprecisely known spectra are the main applications considered. We use simulated NaI spectral data to demonstrate the Bayesian algorithm compare it to other techniques. Results of simulations of a network of spectrometers are presented, showing its capability to distinguish intended targets from nuisance sources.

  4. Target Detection Using Fractal Geometry

    NASA Technical Reports Server (NTRS)

    Fuller, J. Joseph

    1991-01-01

    The concepts and theory of fractal geometry were applied to the problem of segmenting a 256 x 256 pixel image so that manmade objects could be extracted from natural backgrounds. The two most important measurements necessary to extract these manmade objects were fractal dimension and lacunarity. Provision was made to pass the manmade portion to a lookup table for subsequent identification. A computer program was written to construct cloud backgrounds of fractal dimensions which were allowed to vary between 2.2 and 2.8. Images of three model space targets were combined with these backgrounds to provide a data set for testing the validity of the approach. Once the data set was constructed, computer programs were written to extract estimates of the fractal dimension and lacunarity on 4 x 4 pixel subsets of the image. It was shown that for clouds of fractal dimension 2.7 or less, appropriate thresholding on fractal dimension and lacunarity yielded a 64 x 64 edge-detected image with all or most of the cloud background removed. These images were enhanced by an erosion and dilation to provide the final image passed to the lookup table. While the ultimate goal was to pass the final image to a neural network for identification, this work shows the applicability of fractal geometry to the problems of image segmentation, edge detection and separating a target of interest from a natural background.

  5. Seismoelectric imaging of shallow targets

    USGS Publications Warehouse

    Haines, S.S.; Pride, S.R.; Klemperer, S.L.; Biondi, B.

    2007-01-01

    We have undertaken a series of controlled field experiments to develop seismoelectric experimental methods for near-surface applications and to improve our understanding of seismoelectric phenomena. In a set of off-line geometry surveys (source separated from the receiver line), we place seismic sources and electrode array receivers on opposite sides of a man-made target (two sand-filled trenches) to record separately two previously documented seismoelectric modes: (1) the electromagnetic interface response signal created at the target and (2) the coseismic electric fields located within a compressional seismic wave. With the seismic source point in the center of a linear electrode array, we identify the previously undocumented seismoelectric direct field, and the Lorentz field of the metal hammer plate moving in the earth's magnetic field. We place the seismic source in the center of a circular array of electrodes (radial and circumferential orientations) to analyze the source-related direct and Lorentz fields and to establish that these fields can be understood in terms of simple analytical models. Using an off-line geometry, we create a multifold, 2D image of our trenches as dipping layers, and we also produce a complementary synthetic image through numerical modeling. These images demonstrate that off-line geometry (e.g., crosswell) surveys offer a particularly promising application of the seismoelectric method because they effectively separate the interface response signal from the (generally much stronger) coseismic and source-related fields. ?? 2007 Society of Exploration Geophysicists.

  6. Optimal target placement for neural communication prostheses.

    PubMed

    Cunningham, John P; Yu, Byron M; Shenoy, Krishna V

    2006-01-01

    Neural prosthetic systems have been designed to estimate continuous reach trajectories as well as discrete reach targets. In the latter case, reach targets are typically decoded from neural activity during an instructed delay period, before the reach begins. We have recently characterized the decoding speed and accuracy achievable by such a system. The results were obtained using canonical target layouts, independent of the tuning properties of the neurons available. Here we seek to increase decode accuracy by judiciously selecting the locations of the reach targets based on the characteristics of the neural population at hand. We present an optimal target placement algorithm that approximately maximizes decode accuracy with respect to target locations. Using maximum likelihood decoding, the optimal target placement algorithm yielded up to 11 and 12% improvement for two and sixteen targets, respectively. For four and eight targets, gains were more modest (5 and 3%, respectively) as the target layouts found by the algorithm closely resembled the canonical layouts. Thus, the algorithm can serve not only to find target layouts that outperform canonical layouts, but it can also confirm or help select among multiple canonical layouts. These results indicate that the optimal target placement algorithm is a valuable tool for designing high-performance prosthetic systems. PMID:17945745

  7. TIME DOMAIN EM PROFILING SHALLOW CONDUCTING TARGET

    E-print Network

    Merriam, James

    . Introduction The target is constructed from three separate 24 gage galvanized steel sheets pop-riveted toTIME DOMAIN EM PROFILING OVER A SHALLOW CONDUCTING TARGET J.B. Merriam University of Saskatchewan-47 profile over a known target at one to three m depth is described here. The response of the highly

  8. 28 CFR 55.17 - Targeting.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... REGARDING LANGUAGE MINORITY GROUPS Minority Language Materials and Assistance § 55.17 Targeting. The term...). “Targeting” refers to a system in which the minority language materials or assistance required by the Act are... targeting system will normally fulfill the Act's minority language requirements if it is designed...

  9. 28 CFR 55.17 - Targeting.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... REGARDING LANGUAGE MINORITY GROUPS Minority Language Materials and Assistance § 55.17 Targeting. The term...). “Targeting” refers to a system in which the minority language materials or assistance required by the Act are... targeting system will normally fulfill the Act's minority language requirements if it is designed...

  10. 28 CFR 55.17 - Targeting.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... REGARDING LANGUAGE MINORITY GROUPS Minority Language Materials and Assistance § 55.17 Targeting. The term...). “Targeting” refers to a system in which the minority language materials or assistance required by the Act are... targeting system will normally fulfill the Act's minority language requirements if it is designed...

  11. 28 CFR 55.17 - Targeting.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... REGARDING LANGUAGE MINORITY GROUPS Minority Language Materials and Assistance § 55.17 Targeting. The term...). “Targeting” refers to a system in which the minority language materials or assistance required by the Act are... targeting system will normally fulfill the Act's minority language requirements if it is designed...

  12. 28 CFR 55.17 - Targeting.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... REGARDING LANGUAGE MINORITY GROUPS Minority Language Materials and Assistance § 55.17 Targeting. The term...). “Targeting” refers to a system in which the minority language materials or assistance required by the Act are... targeting system will normally fulfill the Act's minority language requirements if it is designed...

  13. 75 FR 73987 - Target Date Disclosure

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-30

    ... comprehensive information about TDFs that apply age or target retirement-based asset allocations, described in.../MethodologyDocuments/MethodologyPapers/TargetDateFundSurvey_2010.pdf . Based on the foregoing, the Department... Benefits Security Administration 29 CFR Part 2550 RIN 1210-AB38 Target Date Disclosure AGENCY:...

  14. Target & Capture for PRISM Koji Yoshimura

    E-print Network

    McDonald, Kirk

    Target & Capture for PRISM Koji Yoshimura On behalf of PRISM Target Group Institute of Particle University Contents Targetry for PRISM Solenoid capture Conducting Target Summary #12;NuFACT'03 June 7th, 2003, Columbia University What's PRISM PRISM( Phase Rotation Intense Slow Muon source) A dedicated

  15. Automatic Target Word Disambiguation Using Syntactic Relationships

    E-print Network

    Automatic Target Word Disambiguation Using Syntactic Relationships Ebony Domingo1 and Rachel Edita. Multiple target translations are due to several meanings of source words, and various target word equivalents depending on the context of the source word. Thus, an automated approach is presented

  16. Predicting new molecular targets for known drugs

    E-print Network

    Kaski, Samuel

    ARTICLES Predicting new molecular targets for known drugs Michael J. Keiser1,2 *, Vincent Setola3 drugs are intended to be selective, at least some bind to several physiological targets, explaining side effects and efficacy. Because many drug­target combinations exist, it would be useful to explore possible

  17. Drug-Target Interaction Predicates Combining Similarities

    E-print Network

    Daume III, Hal

    Drug-Target Interaction Predicates DataSet Combining Similarities Collective Inference Collective Inference and Multi-Relational Learning for Drug­Target Interaction Prediction Shobeir Fakhraei1, Bert Huang1 and Lise Getoor1,2 Poly-pharmacology Drug Repurposing Drug-Target Interaction Network Studies

  18. Recognition of Hits in a Target

    NASA Astrophysics Data System (ADS)

    Semerak, Vojtech; Drahansky, Martin

    This paper describes two possible ways of hit recognition in a target. First method is based on frame differencing with use of a stabilization algorithm to eliminate movements of a target. Second method uses flood fill with random seed point definition to find hits in the target scene.

  19. Proprioceptive information about target location suppresses autokinesis

    NASA Technical Reports Server (NTRS)

    Lackner, J. R.; Zabkar, J. J.

    1977-01-01

    An experimental study of autokinesis perceived by subjects who had proprioceptive information about target locations was conducted. When subjects were permitted to grasp the target light mount, their perceptions of autokinesis were found to be fewer and of smaller magnitude than when only visual information about the target location was available. The decrease in autokinesis was correlated with an enhancement of oculomotor control.

  20. Radioactive Target Detection Using Wireless Sensor Network

    E-print Network

    Zhang, Tonglin

    Chapter 31 Radioactive Target Detection Using Wireless Sensor Network Tonglin Zhang Abstract The detection of radioactive target is becoming more important recently in public safety and national security can simultaneously detect and locate the radioactive target in the area. Our simulation results have

  1. Liquid Metal Target for NLC Positron Source

    SciTech Connect

    Sheppard, John C.

    2002-08-19

    Possibility of creating the liquid lead target with parameters, optimum for the NLC positron source, is investigated. Target has a form of titanium vessel, filled with liquid lead, pumped through. The energy deposition in target is characterized by 35 kW average power and up to 250 J/g specific energy at optimum beam sigma 0.6 mm. The use of pumped through liquid lead as target material solves both the problems of power evacuation and target survival. The window for beam exit is made of both temperature and pressure resistive material--the diamond-like ceramic BN.

  2. PLUTONIUM-238 PRODUCTION TARGET DESIGN STUDIES

    SciTech Connect

    Hurt, Christopher J; Wham, Robert M; Hobbs, Randall W; Owens, R Steven; Chandler, David; Freels, James D; Maldonado, G Ivan

    2014-01-01

    A new supply chain is planned for plutonium-238 using existing reactors at the Oak Ridge National Laboratory (ORNL) and Idaho National Laboratory (INL) and existing chemical recovery facilities at ORNL. Validation and testing activities for new irradiation target designs have been conducted in three phases over a 2 year period to provide data for scale-up to production. Target design, qualification, target fabrication, and irradiation of fully-loaded targets have been accomplished. Data from post-irradiation examination (PIE) supports safety analysis and irradiation of future target designs.

  3. Cure of alopecia areata after eradication of Helicobacter pylori: A new association?

    PubMed Central

    Campuzano-Maya, Germán

    2011-01-01

    Alopecia areata is a disease of the hair follicles, with strong evidence supporting autoimmune etiology. Alopecia areata is frequently associated with immune-mediated diseases with skin manifestations such as psoriasis and lichen planus, or without skin manifestations such as autoimmune thyroiditis and idiopathic thrombocytopenic purpura. Helicobacter pylori (H. pylori) infection is present in around 50% of the world’s population and has been associated with a variety of immune-mediated extra-digestive disorders including autoimmune thyroiditis, idiopathic thrombocytopenic purpura, and psoriasis. A case of a 43-year old man with an 8-mo history of alopecia areata of the scalp and beard is presented. The patient was being treated by a dermatologist and had psychiatric support, without any improvement. He had a history of dyspepsia and the urea breath test confirmed H. pylori infection. The patient went into remission from alopecia areata after H. pylori eradication. If such an association is confirmed by epidemiological studies designed for this purpose, new therapeutic options could be available for these patients, especially in areas where infection with H. pylori is highly prevalent. PMID:21912461

  4. Cure of alopecia areata after eradication of Helicobacter pylori: a new association?

    PubMed

    Campuzano-Maya, Germán

    2011-07-14

    Alopecia areata is a disease of the hair follicles, with strong evidence supporting autoimmune etiology. Alopecia areata is frequently associated with immune-mediated diseases with skin manifestations such as psoriasis and lichen planus, or without skin manifestations such as autoimmune thyroiditis and idiopathic thrombocytopenic purpura. Helicobacter pylori (H. pylori) infection is present in around 50% of the world's population and has been associated with a variety of immune-mediated extra-digestive disorders including autoimmune thyroiditis, idiopathic thrombocytopenic purpura, and psoriasis. A case of a 43-year old man with an 8-mo history of alopecia areata of the scalp and beard is presented. The patient was being treated by a dermatologist and had psychiatric support, without any improvement. He had a history of dyspepsia and the urea breath test confirmed H. pylori infection. The patient went into remission from alopecia areata after H. pylori eradication. If such an association is confirmed by epidemiological studies designed for this purpose, new therapeutic options could be available for these patients, especially in areas where infection with H. pylori is highly prevalent. PMID:21912461

  5. Epitope specificity and isotype of monoclonal anti-D antibodies dictate their ability to inhibit phagocytosis of opsonized platelets.

    PubMed

    Kjaersgaard, Mimi; Aslam, Rukhsana; Kim, Michael; Speck, Edwin R; Freedman, John; Stewart, Donald I H; Wiersma, Erik J; Semple, John W

    2007-08-15

    Rh immune globulin (WinRho SDF; Cangene, Mississauga, ON, Canada) is an effective treatment for autoimmune thrombocytopenic purpura; however, maintaining a sustained supply for its use in autoimmune thrombocytopenic purpura and its primary indication, hemolytic disease of the newborn, makes the development of alternative reagents desirable. We compared Rh immune globulin and 6 human monoclonal anti-D antibodies (MoAnti-D) with differing isotypes and specificities for their ability to opsonize erythrocytes and inhibit platelet phagocytosis in an in vitro assay. Results demonstrated that opsonization of erythrocytes with Rh immune globulin significantly (P < .001) reduced phagocytosis of fluorescently labeled opsonized platelets in an Fc-dependent manner. Of the MoAnti-D that shared specificity but differed in isotype, only IgG3 antibodies could significantly (P < .001) inhibit platelet phagocytosis. In contrast, 2 MoAnti-D shared isotypes and differed in specificity; however, only one could significantly (P < .001) inhibit platelet phagocytosis. The results suggest that MoAnti-D epitope specificity and isotypes are critical requirements for optimal inhibition of opsonized platelet phagocytosis. PMID:17456719

  6. Terahertz-based target typing.

    SciTech Connect

    Lyo, Sungkwun Kenneth; Wanke, Michael Clement; Reno, John Louis; Shaner, Eric Arthur; Grine, Albert D.; Barrick, Todd A.

    2008-09-01

    The purpose of this work was to create a THz component set and understanding to aid in the rapid analysis of transient events. This includes the development of fast, tunable, THz detectors, along with filter components for use with standard detectors and accompanying models to simulate detonation signatures. The signature effort was crucial in order to know the spectral range to target for detection. Our approach for frequency agile detection was to utilize plasmons in the channel of a specially designed field-effect transistor called the grating-gate detector. Grating-gate detectors exhibit narrow-linewidth, broad spectral tunability through application of a gate bias, and no angular dependence in their photoresponse. As such, if suitable sensitivity can be attained, they are viable candidates for Terahertz multi-spectral focal plane arrays.

  7. Targeting potassium channels in cancer

    PubMed Central

    2014-01-01

    Potassium channels are pore-forming transmembrane proteins that regulate a multitude of biological processes by controlling potassium flow across cell membranes. Aberrant potassium channel functions contribute to diseases such as epilepsy, cardiac arrhythmia, and neuromuscular symptoms collectively known as channelopathies. Increasing evidence suggests that cancer constitutes another category of channelopathies associated with dysregulated channel expression. Indeed, potassium channel–modulating agents have demonstrated antitumor efficacy. Potassium channels regulate cancer cell behaviors such as proliferation and migration through both canonical ion permeation–dependent and noncanonical ion permeation–independent functions. Given their cell surface localization and well-known pharmacology, pharmacological strategies to target potassium channel could prove to be promising cancer therapeutics. PMID:25049269

  8. Synchronous identification of friendly targets

    SciTech Connect

    Telle, John M.; Roger, Stutz A.

    1998-01-01

    A synchronous communication targeting system for use in battle. The present invention includes a transceiver having a stabilizing oscillator, a synchronous amplifier and an omnidirectional receiver, all in electrical communication with each other. A remotely located beacon is attached to a blackbody radiation source and has an amplitude modulator in electrical communication with a optical source. The beacon's amplitude modulator is set so that the optical source transmits radiation frequency at approximately the same or lower amplitude than that of the blackbody radiation source to which the beacon is attached. The receiver from the transceiver is adapted to receive frequencies approximately at or below blackbody radiation signals and sends such signals to the synchronous amplifier. The synchronous amplifier then rectifies and amplifies those signals which correspond to the predetermined frequency to therefore identify whether the blackbody radiation source is friendly or not.

  9. Fabrication of boron sputter targets

    DOEpatents

    Makowiecki, Daniel M. (Livermore, CA); McKernan, Mark A. (Livermore, CA)

    1995-01-01

    A process for fabricating high density boron sputtering targets with sufficient mechanical strength to function reliably at typical magnetron sputtering power densities and at normal process parameters. The process involves the fabrication of a high density boron monolithe by hot isostatically compacting high purity (99.9%) boron powder, machining the boron monolithe into the final dimensions, and brazing the finished boron piece to a matching boron carbide (B.sub.4 C) piece, by placing aluminum foil there between and applying pressure and heat in a vacuum. An alternative is the application of aluminum metallization to the back of the boron monolithe by vacuum deposition. Also, a titanium based vacuum braze alloy can be used in place of the aluminum foil.

  10. Reprofiled drug targets ancient protozoans

    PubMed Central

    Debnath, Anjan; Ndao, Momar; Reed, Sharon L.

    2013-01-01

    Recently, we developed a novel automated, high throughput screening (HTS) methodology for the anaerobic intestinal parasite Entamoeba histolytica. We validated this HTS platform by screening a chemical library containing US Food and Drug Administration (FDA)-approved drugs and bioactive compounds. We identified an FDA-approved drug, auranofin, as most active against E. histolytica both in vitro and in vivo. Our cell culture and animal studies indicated that thioredoxin reductase, an enzyme involved in reactive oxygen species detoxification, was the target for auranofin in E. histolytica. Here, we discuss the rationale for drug development for three parasites which are major causes of diarrhea worldwide, E. histolytica, Giardia lamblia and Cryptosporidium parvum and extend our current finding of antiparasitic activity of auranofin to Entamoeba cysts, G. lamblia and C. parvum. These studies support the use of HTS assays and reprofiling FDA-approved drugs for new therapy for neglected tropical diseases. PMID:23137963

  11. Targeting epigenetic regulations in cancer.

    PubMed

    Ning, Bo; Li, Wenyuan; Zhao, Wei; Wang, Rongfu

    2016-01-01

    Epigenetic regulation of gene expression is a dynamic and reversible process with DNA methylation, histone modifications, and chromatin remodeling. Recently, groundbreaking studies have demonstrated the importance of DNA and chromatin regulatory proteins from different aspects, including stem cell, development, and tumor genesis. Abnormal epigenetic regulation is frequently associated with diseases and drugs targeting DNA methylation and histone acetylation have been approved for cancer therapy. Although the network of epigenetic regulation is more complex than people expect, new potential druggable chromatin-associated proteins are being discovered and tested for clinical application. Here we review the key proteins that mediate epigenetic regulations through DNA methylation, the acetylation and methylation of histones, and the reader proteins that bind to modified histones. We also discuss cancer associations and recent progress of pharmacological development of these proteins. PMID:26508480

  12. Pharmacotherapeutic targets in Alzheimer's disease

    PubMed Central

    Biran, Yif'at; Masters, Colin L; Barnham, Kevin J; Bush, Ashley I; Adlard, Paul A

    2009-01-01

    Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disorder which is characterized by an increasing impairment in normal memory and cognitive processes that significantly diminishes a person's daily functioning. Despite decades of research and advances in our understanding of disease aetiology and pathogenesis, there are still no effective disease-modifying drugs available for the treatment of AD. However, numerous compounds are currently undergoing pre-clinical and clinical evaluations. These candidate pharma-cotherapeutics are aimed at various aspects of the disease, such as the microtubule-associated ?-protein, the amyloid-? (A?) peptide and metal ion dyshomeostasis – all of which are involved in the development and progression of AD. We will review the way these pharmacological strategies target the biochemical and clinical features of the disease and the investigational drugs for each category. PMID:19040415

  13. Targeted therapy using alpha emitters

    NASA Astrophysics Data System (ADS)

    Vaidyanathan, Ganesan; Zalutsky, Michael R.

    1996-10-01

    Radionuclides such as and which decay by the emission of -particles are attractive for certain applications of targeted radiotherapy. The tissue penetration of and -particles is equivalent to only a few cell diameters, offering the possibility of combining cell-specific targeting with radiation of similar range. Unlike the -particles emitted by radionuclides such as and , -particles are radiation of high linear energy transfer and thus greater biological effectiveness. Several approaches have been explored for targeted radiotherapy with - and -labelled substances including colloids, monoclonal antibodies, metabolic precursors, receptor-avid ligands and other lower molecular weight molecules. An additional agent which exemplifies the promise of -emitting radiopharmaceuticals is meta-[]astatobenzylguanidine. The toxicity of this compound under single-cell conditions, determined both by []thymidine incorporation and by limiting dilution clonogenic assays, for human neuroblastoma cells is of the order of 1000 times higher than that of meta-[]iodobenzylguanidine. For meta-[]astatobenzylguanidine, the value was equivalent to only atoms bound per cell. These results suggest that meta-[]astatobenzylguanidine might be valuable for the targeted radiotherapy of micrometastatic neuroblastomas.

  14. Fabrication of boron sputter targets

    DOEpatents

    Makowiecki, D.M.; McKernan, M.A.

    1995-02-28

    A process is disclosed for fabricating high density boron sputtering targets with sufficient mechanical strength to function reliably at typical magnetron sputtering power densities and at normal process parameters. The process involves the fabrication of a high density boron monolithe by hot isostatically compacting high purity (99.9%) boron powder, machining the boron monolithe into the final dimensions, and brazing the finished boron piece to a matching boron carbide (B{sub 4}C) piece, by placing aluminum foil there between and applying pressure and heat in a vacuum. An alternative is the application of aluminum metallization to the back of the boron monolithe by vacuum deposition. Also, a titanium based vacuum braze alloy can be used in place of the aluminum foil. 7 figs.

  15. Therapeutic target for protozoal diseases

    DOEpatents

    Rathore, Dharmendar (Blacksburg, VA); Jani, Dewal (Blacksburg, VA); Nagarkatti, Rana (Blacksburg, VA)

    2008-10-21

    A novel Fasciclin Related Adhesive Protein (FRAP) from Plasmodium and related parasites is provided as a target for therapeutic intervention in diseases caused by the parasites. FRAP has been shown to play a critical role in adhesion to, or invasion into, host cells by the parasite. Furthermore, FRAP catalyzes the neutralization of heme by the parasite, by promoting its polymerization into hemozoin. This invention provides methods and compositions for therapies based on the administration of protein, DNA or cell-based vaccines and/or antibodies based on FRAP, or antigenic epitopes of FRAP, either alone or in combination with other parasite antigens. Methods for the development of compounds that inhibit the catalytic activity of FRAP, and diagnostic and laboratory methods utilizing FRAP are also provided.

  16. Dendritic Cell-Targeted Vaccines

    PubMed Central

    Cohn, Lillian; Delamarre, Lélia

    2014-01-01

    Despite significant effort, the development of effective vaccines inducing strong and durable T-cell responses against intracellular pathogens and cancer cells has remained a challenge. The initiation of effector CD8+ T-cell responses requires the presentation of peptides derived from internalized antigen on class I major histocompatibility complex molecules by dendritic cells (DCs) in a process called cross-presentation. A current strategy to enhance the effectiveness of vaccination is to deliver antigens directly to DCs. This is done via selective targeting of antigen using monoclonal antibodies directed against endocytic receptors on the surface of the DCs. In this review, we will discuss considerations relevant to the design of such vaccines: the existence of DC subsets with specialized functions, the impact of the antigen intracellular trafficking on cross-presentation, and the influence of maturation signals received by DCs on the outcome of the immune response. PMID:24910635

  17. Molecular targeting to treat gastric cancer.

    PubMed

    Aoyagi, Keishiro; Kouhuji, Kikuo; Kizaki, Junya; Isobe, Taro; Hashimoto, Kousuke; Shirouzu, Kazuo

    2014-10-14

    Trastuzumab that targets human epidermal growth factor receptor 2 (HER2) protein is the only approved molecular targeting agent for treating gastric cancer in Japan and the outcomes have been favorable. However, trastuzumab is effective for only 10% to 20% of the population with gastric cancer that expresses HER2 protein. Molecular targeting therapy with bevacizumab against vascular endothelial growth factors (VEGF) and with cetuximab and panitumumab against the epidermal growth factors pathway that have been approved for treating colorectal cancer are not considered effective for treating gastric cancer according to several clinical trials. However, ramucirumab that targets VEGF receptor-2 prolonged overall survival in a large phase III clinical trial and it might be an effective molecular targeting therapy for gastric cancer. The significance of molecular targeting therapy for gastric cancer remains controversial. A large-scale randomized clinical trial of novel molecular targeting agents with which to treat gastric cancer is needed. PMID:25320512

  18. Infrared signature generation of airborne targets

    NASA Astrophysics Data System (ADS)

    Whalen, Michael R.

    1993-08-01

    This report proposes a generic methodology for generating infrared signatures of airborne targets. The various issues, assumptions and simplifications utilized in signature studies are outlines to insure baseline consistency among future models and evaluation tools. More specifically, the target is characterized on a component level, and the at-aperture signature is generated by the correct inclusion of atmospheric transmission. While the technique and general concepts may apply to all airborne targets, this study places emphasis on cruise missiles and related targets due to their low contrast. For these targets, the background signature becomes more important as both the emitted target radiance and the reflected background radiance contribute to the overall signature. Example target signatures generated using the proposed methodology will be presented following the discussion of signature modeling.

  19. Liquid Hydrogen Target Experience at SLAC

    SciTech Connect

    Weisend, J.G.; Boyce, R.; Candia, A.; Kaminskas, W.; Mark, J.; Racine, M.; St. Lorant, S.; Weber, T.; Arnold, R.; Bosted, P.; Carr, R.; Gao, J.; Jones, C.E.; McKeown, R.; /Caltech

    2005-08-29

    Liquid hydrogen targets have played a vital role in the physics program at SLAC for the past 40 years. These targets have ranged from small ''beer can'' targets to the 1.5 m long E158 target that was capable of absorbing up to 800 W without any significant density changes. Successful use of these targets has required the development of thin wall designs, liquid hydrogen pumps, remote positioning and alignment systems, safety systems, control and data acquisition systems, cryogenic cooling circuits and heat exchangers. Detailed operating procedures have been created to ensure safety and operational reliability. This paper surveys the evolution of liquid hydrogen targets at SLAC and discusses advances in several of the enabling technologies that made these targets possible.

  20. Ignition of deuterium-trtium fuel targets

    DOEpatents

    Musinski, Donald L. (Saline, MI); Mruzek, Michael T. (Britton, MI)

    1991-01-01

    A method of igniting a deuterium-tritium ICF fuel target to obtain fuel burn in which the fuel target initially includes a hollow spherical shell having a frozen layer of DT material at substantially uniform thickness and cryogenic temperature around the interior surface of the shell. The target is permitted to free-fall through a target chamber having walls heated by successive target ignitions, so that the target is uniformly heated during free-fall to at least partially melt the frozen fuel layer and form a liquid single-phase layer or a mixed liquid/solid bi-phase layer of substantially uniform thickness around the interior shell surface. The falling target is then illuminated from exteriorly of the chamber while the fuel layer is at substantially uniformly single or bi-phase so as to ignite the fuel layer and release energy therefrom.

  1. Air target models for fuzing simulations

    NASA Astrophysics Data System (ADS)

    Dammann, J. F., Jr.

    1982-09-01

    Radar backscatter models for air targets suitable for computer simulation of radar fuze-air target encounters are described. These models determine the characteristics of the energy reflected to the fuze when the target is illuminated by a fuze radar. When the target models are coupled with fuze models, the time when the fuze detects the presence of the target can be determined for any arbitrary terminal encounter geometry. Fuze detection times for representative trajectories can be compared with fuze specifications to measure fuze performance or can be used as a part of a simulation of an entire system to determine system performance. Following one basic methodology, target models have been written for the Fishbed, Foxbat, and Flogger fighter aircraft; the Hind-D helicopter; and the Backfire, Blinder, and B-1 bombers. All of the models are specular point models where the major return is assumed to come from a small number of glitter points or specular points on the target.

  2. Targeting tumor suppressor genes for cancer therapy.

    PubMed

    Liu, Yunhua; Hu, Xiaoxiao; Han, Cecil; Wang, Liana; Zhang, Xinna; He, Xiaoming; Lu, Xiongbin

    2015-12-01

    Cancer drugs are broadly classified into two categories: cytotoxic chemotherapies and targeted therapies that specifically modulate the activity of one or more proteins involved in cancer. Major advances have been achieved in targeted cancer therapies in the past few decades, which is ascribed to the increasing understanding of molecular mechanisms for cancer initiation and progression. Consequently, monoclonal antibodies and small molecules have been developed to interfere with a specific molecular oncogenic target. Targeting gain-of-function mutations, in general, has been productive. However, it has been a major challenge to use standard pharmacologic approaches to target loss-of-function mutations of tumor suppressor genes. Novel approaches, including synthetic lethality and collateral vulnerability screens, are now being developed to target gene defects in p53, PTEN, and BRCA1/2. Here, we review and summarize the recent findings in cancer genomics, drug development, and molecular cancer biology, which show promise in targeting tumor suppressors in cancer therapeutics. PMID:26445307

  3. Molecular targeting to treat gastric cancer

    PubMed Central

    Aoyagi, Keishiro; Kouhuji, Kikuo; Kizaki, Junya; Isobe, Taro; Hashimoto, Kousuke; Shirouzu, Kazuo

    2014-01-01

    Trastuzumab that targets human epidermal growth factor receptor 2 (HER2) protein is the only approved molecular targeting agent for treating gastric cancer in Japan and the outcomes have been favorable. However, trastuzumab is effective for only 10% to 20% of the population with gastric cancer that expresses HER2 protein. Molecular targeting therapy with bevacizumab against vascular endothelial growth factors (VEGF) and with cetuximab and panitumumab against the epidermal growth factors pathway that have been approved for treating colorectal cancer are not considered effective for treating gastric cancer according to several clinical trials. However, ramucirumab that targets VEGF receptor-2 prolonged overall survival in a large phase III clinical trial and it might be an effective molecular targeting therapy for gastric cancer. The significance of molecular targeting therapy for gastric cancer remains controversial. A large-scale randomized clinical trial of novel molecular targeting agents with which to treat gastric cancer is needed. PMID:25320512

  4. Target alignment in the National Ignition Facility

    SciTech Connect

    Vann, C.S.; Bliss, E.S.; Murray, J.E.

    1994-06-06

    Accurate placement of hundreds of focused laser beams on target is necessary to achieve success in the National Ignition Facility (NIF). The current system requirement is {le}7 {mu}rad error in output pointing and {le}1 mm error in focusing. To accommodate several system shots per day, a target alignment system must be able to align the target to chamber center, inject an alignment beam to represent each shot beam, and point and focus the alignment beams onto the target in about one hour. At Lawrence Livermore National Laboratory, we have developed a target alignment concept and built a prototype to validate the approach. The concept comprises three systems: the chamber center reference, target alignment sensor, and target alignment beams.

  5. Ignition of deuterium-tritium fuel targets

    DOEpatents

    Musinski, D.L.; Mruzek, M.T.

    1991-08-27

    Disclosed is a method of igniting a deuterium-tritium ICF fuel target to obtain fuel burn in which the fuel target initially includes a hollow spherical shell having a frozen layer of DT material at substantially uniform thickness and cryogenic temperature around the interior surface of the shell. The target is permitted to free-fall through a target chamber having walls heated by successive target ignitions, so that the target is uniformly heated during free-fall to at least partially melt the frozen fuel layer and form a liquid single-phase layer or a mixed liquid/solid bi-phase layer of substantially uniform thickness around the interior shell surface. The falling target is then illuminated from exteriorly of the chamber while the fuel layer is at substantially uniformly single or bi-phase so as to ignite the fuel layer and release energy therefrom. 5 figures.

  6. Accuracy Evaluation Of microTargeting™ Platforms For Deep-Brain Stimulation Using Virtual Targets

    PubMed Central

    Balachandran, Ramya; Mitchell, Jason; Dawant, Benoit M.; Fitzpatrick, J. Michael

    2015-01-01

    Deep-brain-stimulation (DBS) surgery requires implanting stimulators at target positions with submillimetric accuracy. Traditional stereotactic frames can provide such accuracy, but a recent innovation called the microTargeting™ Platform (FHC, Inc.) replaces this large, universal frame with a single-use, miniature, custom-designed platform. Both single-target and dual-target platforms are available for unilateral and bilateral procedures, respectively. In this paper their targeting accuracies are evaluated in vitro. Our approach employs “virtual targets”, which eliminates the problem of collision of the implant with the target. We implement virtual targets by mounting fiducial markers, which are not used in platform targeting, on an artificial skull and defining targets relative to the skull via that fiducial system. The fiducial system is designed to surround the targets, thereby reducing the overall effect of fiducial localization inaccuracies on the evaluation. It also provides the geometrical transformation from image to physical space. Target selection is based on an atlas of stimulation targets from a set of 31 DBS patients. The measured targeting error is the displacement between the phantom implant and the virtual target. Our results show that the microTargeting™ Platform exhibits submillimetric in vitro accuracy with a mean of 0.42 mm and a 99.9% level of 0.90 mm. PMID:19224717

  7. Using the Dual-Target Cost to Explore the Nature of Search Target Representations

    ERIC Educational Resources Information Center

    Stroud, Michael J.; Menneer, Tamaryn; Cave, Kyle R.; Donnelly, Nick

    2012-01-01

    Eye movements were monitored to examine search efficiency and infer how color is mentally represented to guide search for multiple targets. Observers located a single color target very efficiently by fixating colors similar to the target. However, simultaneous search for 2 colors produced a dual-target cost. In addition, as the similarity between…

  8. Rehashable BTB: An Adaptive Branch Target Buffer to Improve the Target Predictability of Java Code

    E-print Network

    John, Lizy Kurian

    Rehashable BTB: An Adaptive Branch Target Buffer to Improve the Target Predictability of Java Code processing and proposes an adaptive branch target buffer (BTB) design to enhance the predictability of the targets. Our characterization shows that a traditional BTB will frequently mispredict polymorphic indirect

  9. 26 CFR 1.430(d)-1 - Determination of target normal cost and funding target.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Determination of target normal cost and funding target. 1.430(d)-1 Section 1.430(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Certain Stock Options § 1.430(d)-1 Determination of target normal cost and funding target....

  10. Double-layered target and identification method of individual target correlated with evaporation residues

    NASA Astrophysics Data System (ADS)

    Kaji, D.; Morimoto, K.

    2015-08-01

    A double-layered target system and an identification method (target ID) for individual targets mounted on a rotating wheel using correlation with evaporation residues were newly developed for the study of superheavy elements (SHE). The target system can be used in three modes: conventional single-layered mode, double-layered mode, and energy-degrader mode. The target ID method can be utilized for masking a target, measuring an excitation function without changing the beam energy from the accelerator, and searching for SHE nuclides using multiple targets during a single irradiation.

  11. Target injection methods for inertial fusion energy

    SciTech Connect

    Petzoldt, R.W.; Moir, R.W.

    1994-06-01

    We have studied four methods to inject IFE targets: the gas gun, electrostatic accelerator, induction accelerator, and rail gun. We recommend a gas gun for indirect drive targets because they can support a gas pressure load on one end and can slide along the gun barrel without damage. With the gas gun, the amount of gas required for each target (about 10 to 100 mg) is acceptable; for other types of targets, a sabot would be necessary. A cam and poppet valve arrangement is recommended for gas flow control. An electrostatic accelerator is attractive for use with lightweight spherical direct drive targets. Since there is no physical contact between the target and the injector, there will be no wear of either component during the injection process. An induction accelerator has an advantage of no electrical contact between the target and the injector. Physical contact is not even necessary, so the wear should be minimal. It requires a cylindrical conductive target sleeve which is a substantial added mass. A rail gun is a simpler device than an electrostatic accelerator or induction accelerator. It requires electrical contact between the target and the rails and may have a significant wear rate. The wear in a vacuum could be reduced by use of a solid lubricant such as MoS{sub 2}. The total required accuracy of target injection, tracking and beam pointing of {plus_minus}0.4 mm appears achievable but will require development and experimental verification.

  12. Fluid mechanics aspects of magnetic drug targeting.

    PubMed

    Odenbach, Stefan

    2015-10-01

    Experiments and numerical simulations using a flow phantom for magnetic drug targeting have been undertaken. The flow phantom is a half y-branched tube configuration where the main tube represents an artery from which a tumour-supplying artery, which is simulated by the side branch of the flow phantom, branches off. In the experiments a quantification of the amount of magnetic particles targeted towards the branch by a magnetic field applied via a permanent magnet is achieved by impedance measurement using sensor coils. Measuring the targeting efficiency, i.e. the relative amount of particles targeted to the side branch, for different field configurations one obtains targeting maps which combine the targeting efficiency with the magnetic force densities in characteristic points in the flow phantom. It could be shown that targeting efficiency depends strongly on the magnetic field configuration. A corresponding numerical model has been set up, which allows the simulation of targeting efficiency for variable field configuration. With this simulation good agreement of targeting efficiency with experimental data has been found. Thus, the basis has been laid for future calculations of optimal field configurations in clinical applications of magnetic drug targeting. Moreover, the numerical model allows the variation of additional parameters of the drug targeting process and thus an estimation of the influence, e.g. of the fluid properties on the targeting efficiency. Corresponding calculations have shown that the non-Newtonian behaviour of the fluid will significantly influence the targeting process, an aspect which has to be taken into account, especially recalling the fact that the viscosity of magnetic suspensions depends strongly on the magnetic field strength and the mechanical load. PMID:26415215

  13. Therapeutic target database update 2016: enriched resource for bench to clinical drug target and targeted pathway information

    PubMed Central

    Yang, Hong; Qin, Chu; Li, Ying Hong; Tao, Lin; Zhou, Jin; Yu, Chun Yan; Xu, Feng; Chen, Zhe; Zhu, Feng; Chen, Yu Zong

    2016-01-01

    Extensive drug discovery efforts have yielded many approved and candidate drugs targeting various targets in different biological pathways. Several freely accessible databases provide the drug, target and drug-targeted pathway information for facilitating drug discovery efforts, but there is an insufficient coverage of the clinical trial drugs and the drug-targeted pathways. Here, we describe an update of the Therapeutic Target Database (TTD) previously featured in NAR. The updated contents include: (i) significantly increased coverage of the clinical trial targets and drugs (1.6 and 2.3 times of the previous release, respectively), (ii) cross-links of most TTD target and drug entries to the corresponding pathway entries of KEGG, MetaCyc/BioCyc, NetPath, PANTHER pathway, Pathway Interaction Database (PID), PathWhiz, Reactome and WikiPathways, (iii) the convenient access of the multiple targets and drugs cross-linked to each of these pathway entries and (iv) the recently emerged approved and investigative drugs. This update makes TTD a more useful resource to complement other databases for facilitating the drug discovery efforts. TTD is accessible at http://bidd.nus.edu.sg/group/ttd/ttd.asp. PMID:26578601

  14. Targeted alpha therapy for cancer

    NASA Astrophysics Data System (ADS)

    Allen, Barry J.; Raja, Chand; Rizvi, Syed; Li, Yong; Tsui, Wendy; Zhang, David; Song, Emma; Qu, Chang Fa; Kearsley, John; Graham, Peter; Thompson, John

    2004-08-01

    Targeted alpha therapy (TAT) offers the potential to inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The practicality and efficacy of TAT is tested by in vitro and in vivo studies in melanoma, leukaemia, colorectal, breast and prostate cancers, and by a phase 1 trial of intralesional TAT for melanoma. The alpha-emitting radioisotope used is Bi-213, which is eluted from the Ac-225 generator and chelated to a cancer specific monoclonal antibody (mab) or protein (e.g. plasminogen activator inhibitor-2 PAI2) to form the alpha-conjugate (AC). Stable alpha-ACs have been produced which have been tested for specificity and cytotoxicity in vitro against melanoma (9.2.27 mab), leukaemia (WM60), colorectal (C30.6), breast (PAI2, herceptin), ovarian (PAI2, herceptin, C595), prostate (PAI2, J591) and pancreatic (PAI2, C595) cancers. Subcutaneous inoculation of 1-1.5 million human cancer cells into the flanks of nude mice causes tumours to grow in all mice. Tumour growth is compared for untreated controls, nonspecific AC and specific AC, for local (subcutaneous) and systemic (tail vein or intraperitoneal) injection models. The 213Bi-9.2.27 AC is injected into secondary skin melanomas in stage 4 patients in a dose escalation study to determine the effective tolerance dose, and to measure kinematics to obtain the equivalent dose to organs. In vitro studies show that TAT is one to two orders of magnitude more cytotoxic to targeted cells than non-specific ACs, specific beta emitting conjugates or free isotopes. In vivo local TAT at 2 days post-inoculation completely prevents tumour formation for all cancers tested so far. Intra-lesional TAT can completely regress advanced sc melanoma but is less successful for breast and prostate cancers. Systemic TAT inhibits the growth of sc melanoma xenografts and gives almost complete control of breast and prostate cancer tumour growth. Intralesional doses up to 450 µCi in human patients are effective in regressing melanomas, with no concomitant complications. These results point to the application of local and systemic TAT in the management of secondary cancer. Results of the phase 1 clinical trial of TAT of subcutaneous, secondary melanoma indicate proof of the principle that TAT can make tumours in patients regress.

  15. Targeting DNA with novel diphenylcarbazoles.

    PubMed

    Dias, Nathalie; Jacquemard, Ulrich; Baldeyrou, Brigitte; Tardy, Christelle; Lansiaux, Amélie; Colson, Pierre; Tanious, Farial; Wilson, W David; Routier, Sylvain; Mérour, Jean-Yves; Bailly, Christian

    2004-12-01

    Double-stranded DNA is a therapeutic target for a variety of anticancer and antimicrobial drugs. Noncovalent interactions of small molecules with DNA usually occur via intercalation of planar compounds between adjacent base pairs or minor-groove recognition by extended crescent-shaped ligands. However, the dynamic and flexibility of the DNA platform provide a variety of conformations that can be targeted by structurally diverse compounds. Here, we propose a novel DNA-binding template for construction of new therapeutic candidates. Four bisphenylcarbazole derivatives, derived from the combined molecular architectures of known antitumor bisphenylbenzimidazoles and anti-infectious dicationic carbazoles, have been designed, and their interaction with DNA has been studied by a combination of biochemical and biophysical methods. The substitutions of the bisphenylcarbazole core with two terminal dimethylaminoalkoxy side chains strongly promote the interaction with DNA, to prevent the heat denaturation of the double helix. The deletion or the replacement of the dimethylamino-terminal groups with hydroxyl groups strongly decreased DNA interaction, and the addition of a third cationic side chain on the carbazole nitrogen reinforced the affinity of the compound for DNA. Although the bi- and tridentate molecules both derive from well-characterized DNA minor-groove binders, the analysis of their binding mode by means of circular and linear dichroism methods suggests that these compounds form intercalation complexes with DNA. Negative-reduced dichroism signals were recorded in the presence of natural DNA and synthetic AT and GC polynucleotides. The intercalation hypothesis was validated by unwinding experiments using topoisomerase I. Prominent gel shifts were observed with the di- and trisubstituted bisphenylcarbazoles but not with the uncharged analogues. These observations, together with the documented stacking properties of such molecules (components for liquid crystals), prompted us to investigate their binding to the human telomeric DNA sequence by means of biosensor surface plasmon resonance. Under conditions favorable to G4 formation, the title compounds showed only a modest interaction with the telomeric quadruplex sequence, comparable to that measured with a double-stranded oligonucleotide. Their sequence preference was explored by DNase I footprinting experiments from which we identified a composite set of binding sequences comprising short AT stretches and a few other mixed AT/GC blocks with no special AT character. The variety of the binding sequences possibly reflects the coexistence of distinct positioning of the chromophore in the intercalation sites. The bisphenylcarbazole unit represents an original pharmacophore for DNA recognition. Its branched structure, with two or three arms suitable to introduce a structural diversity, provides an interesting scaffold to built molecules susceptible to discriminate between the different conformations of nucleic acids. PMID:15568808

  16. Target production for inertial fusion energy

    SciTech Connect

    Woodworth, J.G.; Meier, W.

    1995-03-01

    Inertial fusion energy (IFE) power plants will require the ignition and burn of 5-10 fusion fuel targets every second. The technology to economically mass produce high-quality, precision targets at this rate is beyond the current state of the art. Techniques that are scalable to high production rates, however, have been identified for all the necessary process steps, and many have been tested in laboratory experiments or are similar to current commercial manufacturing processes. In this paper, we describe a baseline target factory conceptual design and estimate its capital and operating costs. The result is a total production cost of {approximately}16{cents} per target. At this level, target production represents about 6% of the estimated cost of electricity from a 1-GW{sub e} IFE power plant. Cost scaling relationships are presented and used to show the variation in target cost with production rate and plant power level.

  17. Systemic targeted radionuclide therapy: Potential new areas

    SciTech Connect

    Wong, Jeffrey Y.C. . E-mail: jwong@coh.org

    2006-10-01

    Radiation oncology is entering an exciting new era with therapies being delivered in a targeted fashion through an increasing number of novel approaches. External beam radiotherapy now integrates functional and anatomic tumor imaging to guide delivery of conformal radiation to the tumor target. Systemic targeted radionuclide therapy (STaRT) adds an important new dimension by making available to Radiation oncologist biologically targeted radiation therapy. Impressive clinical results with antibody-targeted radiotherapy, leading to the Food and Drug Administration's approval of two anti-CD20 radiolabeled antibodies, highlight the potential of STaRT. Optimization strategies will further improve the efficacy of STaRT by improving delivery systems, modifying the tumor microenvironment to increase targeted dose, and maximizing dose effect. Ultimately, the greatest potential for STaRT will not be as monotherapy, but as therapy integrated into established multimodality regimens and used as adjuvant or consolidative therapy in patients with minimal or micrometastatic disease.

  18. Thermal oscillations in liquid helium targets

    NASA Astrophysics Data System (ADS)

    Wang, L.; Jia, L. X.

    2002-05-01

    A liquid helium target for the high-energy physics was built and installed in the proton beam line at the Alternate Gradient Synchrotron of Brookhaven National Laboratory in 2001. The target flask has a liquid volume of 8.25 liters and is made of thin Mylar film. A G-M/J-T cryocooler of five-watts at 4.2 K was used to produce liquid helium and refrigerate the target. A thermosyphon circuit for the target was connected to the J-T circuit by a liquid/gas separator. Because of the large heat load to the target and its long transfer lines, thermal oscillations were observed during the system tests. To eliminate the oscillation, a series of tests and analyses were carried out. This paper describes the phenomena and provides the understanding of the thermal oscillations in the target system.

  19. High power target developments at ISAC

    NASA Astrophysics Data System (ADS)

    Bricault, P.; Dombsky, M.; Dowling, A.; Lane, M.

    2003-05-01

    TRIUMF, Canada's national research facility for particle and nuclear physics is currently operating the ISAC facility. A high-energy proton beam from the H - TRIUMF cyclotron is used to generate short-lived radioactive species in a thick target. An ion source at the target creates a radioactive beam, which is then injected into the ISAC beam lines and accelerator system. The ISAC facility is designed to accept proton beam intensity up to 100 ?A at 500 MeV. At present our target design can only sustains 40 ?A at maximum. Beyond this point the target has to be cooled. A new target equipped with fins has been developed that may sustain proton beam up to 100 ?A. The fined target has been tested off-line and a thermal simulation using ANSYS ® has been conducted and the results are reported here.

  20. Resistance to Antibiotics Mediated by Target Alterations

    NASA Astrophysics Data System (ADS)

    Spratt, Brian G.

    1994-04-01

    The development of resistance to antibiotics by reductions in the affinities of their enzymatic targets occurs most rapidly for antibiotics that inactivate a single target and that are not analogs of substrate. In these cases of resistance (for example, resistance to rifampicin), numerous single amino acid substitutions may provide large decreases in the affinity of the target for the antibiotic, leading to clinically significant levels of resistance. Resistance due to target alterations should occur much more slowly for those antibiotics (penicillin, for example) that inactivate multiple targets irreversibly by acting as close analogs of substrate. Resistance to penicillin because of target changes has emerged, by unexpected mechanisms, only in a limited number of species. However, inactivating enzymes commonly provide resistance to antibiotics that, like penicillin, are derived from natural products, although such enzymes have not been found for synthetic antibiotics. Thus, the ideal antibiotic would be produced by rational design, rather than by the modification of a natural product.

  1. Targeting autophagy in breast cancer

    PubMed Central

    Maycotte, Paola; Thorburn, Andrew

    2014-01-01

    Macroautophagy (referred to as autophagy here) is an intracellular degradation pathway enhanced in response to a variety of stresses and in response to nutrient deprivation. This process provides the cell with nutrients and energy by degrading aggregated and damaged proteins as well as compromised organelles. Since autophagy has been linked to diverse diseases including cancer, it has recently become a very interesting target in breast cancer treatment. Indeed, current clinical trials are trying to use chloroquine or hydroxychloroquine, alone or in combination with other drugs to inhibit autophagy during breast cancer therapy since chemotherapy and radiation, regimens that are used to treat breast cancer, are known to induce autophagy in cancer cells. Importantly, in breast cancer, autophagy has been involved in the development of resistance to chemotherapy and to anti-estrogens. Moreover, a close relationship has recently been described between autophagy and the HER2 receptor. Here, we discuss some of the recent findings relating autophagy and cancer with a particular focus on breast cancer therapy. PMID:25114840

  2. Target Therapy in Lung Cancer.

    PubMed

    Cafarotti, Stefano; Lococo, Filippo; Froesh, Patrizia; Zappa, Francesco; Andrè, Dutly

    2016-01-01

    Lung cancer is an extremely heterogeneous disease, with well over 50 different histological variants recognized under the fourth revision of the World Health Organization (WHO) typing system [1]. Because these variants have differing genetic and biological properties correct classification of lung cancer is necessary to assure that lung cancer patients receive optimum management. Due to the recent understanding that histologic typing and EGFR mutation status are important for target the therapy in lung adenocarcinoma patients [2] there was a great need for a new classification that addresses diagnostic issues and strategic management to allow for molecular testing in small biopsy and cytology specimens. For this reason and in order to address advances in lung cancer treatment an international multidisciplinary classification was proposed by the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS) [3], further increasing the histological heterogeneity and improving the existing WHO-classification. Is now the beginning of personalized therapy era that is ideally finalized to treat each individual case of lung cancer in different way. PMID:26667341

  3. Tensor Target Polarization at TRIUMF

    SciTech Connect

    Smith, G

    2014-10-27

    The first measurements of tensor observables in $\\pi \\vec{d}$ scattering experiments were performed in the mid-80's at TRIUMF, and later at SIN/PSI. The full suite of tensor observables accessible in $\\pi \\vec{d}$ elastic scattering were measured: $T_{20}$, $T_{21}$, and $T_{22}$. The vector analyzing power $iT_{11}$ was also measured. These results led to a better understanding of the three-body theory used to describe this reaction. %Some measurements were also made in the absorption and breakup channels. A direct measurement of the target tensor polarization was also made independent of the usual NMR techniques by exploiting the (nearly) model-independent result for the tensor analyzing power at 90$^\\circ _{cm}$ in the $\\pi \\vec{d} \\rightarrow 2p$ reaction. This method was also used to check efforts to enhance the tensor polarization by RF burning of the NMR spectrum. A brief description of the methods developed to measure and analyze these experiments is provided.

  4. Targeting SGK1 in diabetes

    PubMed Central

    Görlach, Agnes; Vallon, Volker

    2009-01-01

    Compelling evidence is accumulating pointing to a pathophysiological role of the serum-and-glucocorticoid-inducible-kinase-1 (SGK1) in the development and complications of diabetes. SGK1 is ubiquitously expressed with exquisitely high transcriptional volatility. Stimulators of SGK1 expression include hyperglycemia, cell shrinkage, ischemia, glucocorticoids and mineralocorticoids. SGK1 is activated by insulin and growth factors via phosphatidylinositol-3-kinase, 3-phosphoinositide dependent kinase PDK1 and mTOR. SGK1 activates ion channels (including ENaC, TRPV5, ROMK, KCNE1/KCNQ1 and CLCKa/Barttin), carriers (including NCC, NKCC, NHE3, SGLT1 and EAAT3), and the Na+/K+-ATPase. It regulates the activity of several enzymes (e.g. glycogen-synthase-kinase-3, ubiquitin-ligase Nedd4-2, phosphomannose-mutase-2), and transcription factors (e.g. forkhead-transcription-factor FOXO3a, ?-catenin, nuclear-factor-kappa-B NF?B). A common SGK1 gene variant (~3–5% prevalence in Caucasians, ~10% in Africans) is associated with increased blood pressure, obesity and type 2 diabetes. In patients suffering from type 2 diabetes, SGK1 presumably contributes to fluid retention and hypertension, enhanced coagulation, and increased deposition of matrix proteins leading to tissue fibrosis such as diabetic nephropathy. Accordingly, targeting SGK1 may favourably influence occurrence and course of type 2 diabetes. PMID:19764891

  5. Target for diverse chemical modifications.

    PubMed

    Seidler, Norbert W

    2013-01-01

    The chapter begins with an historical perspective of GAPDH isozymes that is juxtaposed to the fact that there is only one somatic functional gene in humans that is virtually identical among the mammalian species. Over the many years of GAPDH research, dozens of labs have reported the existence of multiple forms of GAPDH, which mostly vary as a function of charge with an occasional report of truncated forms. These observations are in part due to GAPDH being a substrate for many enzymatically-controlled post-translational modifications. While target residues have been identified and predictive algorithms have implicated certain residues, this area of research appears to be in its infancy regarding GAPDH. Equally fascinating, the uniquely susceptible nature of GAPDH to non-enzymatic reactions, that typically are associated with cell stress, such as oxidation and nitration, is also discussed. Two metabolic gases, nitric oxide and hydrogen sulfide, which are enzymatically produced, appear to exert their signaling properties through non-enzymatic reaction with GAPDH. Models of cellular decline are also proposed, including the compelling hypothesis that states cell compromise occurs by the physically blocking the function of chaperonins (i.e. dual-ring multiple-subunit molecular chaperones) by the attachment of misfolded GAPDH. PMID:22851450

  6. Drug targeting through pilosebaceous route.

    PubMed

    Chourasia, Rashmi; Jain, Sanjay K

    2009-10-01

    Local skin targeting is of interest for the pharmaceutical and the cosmetic industry. A topically applied substance has basically three possibilities to penetrate into the skin: transcellular, intercellular, and follicular. The transfollicular path has been largely ignored because hair follicles constitute only 0.1% of the total skin. The hair follicle is a skin appendage with a complex structure containing many cell types that produce highly specialised proteins. The hair follicle is in a continuous cycle: anagen is the hair growth phase, catagen the involution phase and telogen is the resting phase. Nonetheless, the hair follicle has great potential for skin treatment, owing to its deep extension into the dermis and thus provides much deeper penetration and absorption of compounds beneath the skin than seen with the transdermal route. In the case of skin diseases and of cosmetic products, delivery to sweat glands or to the pilosebaceous unit is essential for the effectiveness of the drug. Increased accumulation in the pilosebaceous unit could treat alopecia, acne and skin cancer more efficiently and improve the effect of cosmetic substances and nutrients. Therefore, we review herein various drug delivery systems, including liposomes, niosomes, microspheres, nanoparticles, nanoemulsions, lipid nanocarriers, gene therapy and discuss the results of recent researches. We also review the drugs which have been investigated for pilosebaceous delivery. PMID:19663765

  7. Targeting Perciytes for Angiogenic Therapies

    PubMed Central

    Kelly-Goss, Molly R.; Sweat, Rick S.; Stapor, Peter C.; Peirce, Shayn M.; Murfee, Walter L.

    2014-01-01

    In pathological scenarios, such as tumor growth and diabetic retinopathy, blocking angiogenesis would be beneficial. In others, such as myocardial infarction and hypertension, promoting angiogenesis might be desirable. Due to their putative influence on endothelial cells, vascular pericytes have become a topic of growing interest and are increasingly being evaluated as a potential target for angioregulatory therapies. For example, the strategy of manipulating pericyte recruitment to capillaries could result in anti- or pro-angiogenic effects. However, our current understanding of pericytes is limited by knowledge gaps regarding pericyte identity and lineage. To use a music analogy, this review is a “mash-up” that attempts to integrate what we know about pericyte functionality and expression with what is beginning to be elucidated regarding their regenerative potential. We explore the lingering questions regarding pericyte phenotypic identity and lineage. The expression of different pericyte markers (e.g., SMA, Desmin, NG2 and PDGFR-?) varies for different subpopulations and tissues. Previous use of these markers to identify pericytes has suggested potential phenotypic overlaps and plasticity toward other cell phenotypes. Our review chronicles the state of the literature, identifies critical unanswered questions, and motivates future research aimed at understanding this intriguing cell type and harnessing its therapeutic potential. PMID:24267154

  8. Secondary anchor targeted cell release.

    PubMed

    Ansari, Ali; Lee-Montiel, Felipe T; Amos, Jennifer R; Imoukhuede, P I

    2015-11-01

    Personalized medicine offers the promise of tailoring therapy to patients, based on their cellular biomarkers. To achieve this goal, cellular profiling systems are needed that can quickly and efficiently isolate specific cell types without disrupting cellular biomarkers. Here we describe the development of a unique platform that facilitates gentle cell capture via a secondary, surface-anchoring moiety, and cell release. The cellular capture system consists of a glass surface functionalized with APTES, d-desthiobiotin, and streptavidin. Biotinylated mCD11b and hIgG antibodies are used to capture mouse macrophages (RAW 264.7) and human breast cancer (MCF7-GFP) cell lines, respectively. The surface functionalization is optimized by altering assay components, such as streptavidin, d-desthiobiotin, and APTES, to achieve cell capture on 80% of the functionalized surface and cell release upon biotin treatment. We also demonstrate an ability to capture 50% of target cells within a dual-cell mixture. This engineering advancement is a critical step towards achieving cell isolation platforms for personalized medicine. Biotechnol. Bioeng. 2015;112: 2214-2227. © 2015 Wiley Periodicals, Inc. PMID:26010879

  9. Optimum viewing distance for target acquisition

    NASA Astrophysics Data System (ADS)

    Holst, Gerald C.

    2015-05-01

    Human visual system (HVS) "resolution" (a.k.a. visual acuity) varies with illumination level, target characteristics, and target contrast. For signage, computer displays, cell phones, and TVs a viewing distance and display size are selected. Then the number of display pixels is chosen such that each pixel subtends 1 min-1. Resolution of low contrast targets is quite different. It is best described by Barten's contrast sensitivity function. Target acquisition models predict maximum range when the display pixel subtends 3.3 min-1. The optimum viewing distance is nearly independent of magnification. Noise increases the optimum viewing distance.

  10. Target Studies for Surface Muon Production

    E-print Network

    F. Berg; L. Desorgher; A. Fuchs; W. Hajdas; Z. Hodge; P. -R. Kettle; A. Knecht; R. Lüscher; A. Papa; G. Rutar; M. Wohlmuther

    2015-11-04

    Meson factories are powerful drivers of diverse physics programmes. With beam powers already in the MW-regime attention has to be turned to target and beam line design to further significantly increase surface muon rates available for experiments. For this reason we have explored the possibility of using a neutron spallation target as a source of surface muons by performing detailed Geant4 simulations with pion production cross sections based on a parametrization of existing data. While the spallation target outperforms standard targets in the backward direction by more than a factor 7 it is not more efficient than standard targets viewed under 90{\\deg}. Not surprisingly, the geometry of the target plays a large role in the generation of surface muons. Through careful optimization, a gain in surface muon rate of between 30 - 60% over the standard "box-like" target used at the Paul Scherrer Institute could be achieved by employing a rotated slab target. An additional 10% gain could also be possible by utilizing novel target materials such as, e.g., boron carbide.

  11. Structural Basis for microRNA Targeting

    PubMed Central

    Schirle, Nicole T.; Sheu-Gruttadauria, Jessica; MacRae, Ian J.

    2015-01-01

    Summary MicroRNAs (miRNAs) control expression of thousands of genes in plants and animals. miRNAs function by guiding Argonaute proteins to complementary sites in messenger RNAs (mRNAs) targeted for repression. We determined crystal structures of human Argonaute-2 (Ago2) bound to a defined guide RNA with and without target RNAs representing miRNA recognition sites. These structures suggest a stepwise mechanism, in which Ago2 primarily exposes guide nucleotides 2–5 for initial target pairing. Pairing to nt 2–5 promotes conformational changes that expose nt 2–8 and 13–16 for further target recognition. Interactions with the guide-target minor groove allow Ago2 to interrogate target RNAs in a sequence-independent manner, while an adenosine binding-pocket opposite guide nt 1 further facilitates target recognition. Spurious slicing of miRNA targets is avoided through an inhibitory coordination of one catalytic magnesium ion. These results explain the conserved nucleotide pairing patterns in animal miRNA target sites first observed over two decades ago. PMID:25359968

  12. Peptide-Targeted Radionuclide Therapy for Melanoma

    PubMed Central

    Miao, Yubin; Quinn, Thomas P.

    2011-01-01

    Melanocortin-1 receptor (MC1-R) and melanin are two attractive melanoma-specific targets for peptide-targeted radionuclide therapy for melanoma. Radiolabeled peptides targeting MC1-R/melanin can selectively and specifically target cytotoxic radiation generated from therapeutic radionuclides to melanoma cells for cell killing, while sparing the normal tissues and organs. This review highlights the recent advances of peptide-targeted radionuclide therapy of melanoma targeting MC1R and melanin. The promising therapeutic efficacies of 188Re-(Arg11)CCMSH (188Re-[Cys3,4,10, d-Phe7, Arg11]-?-MSH3-13), 177Lu- and 212Pb-labeled DOTA-Re(Arg11)CCMSH (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-[ReO-(Cys3,4,10, d-Phe7, Arg11)]-?-MSH3-13) and 188Re-HYNIC-4B4 (188Re-hydrazinonicotinamide-Tyr-Glu-Arg-Lys-Phe-Trp-His-Gly-Arg-His) in preclinical melanoma-bearing models demonstrate an optimistic outlook for peptide-targeted radionuclide therapy for melanoma. Peptide-targeted radionuclide therapy for melanoma will likely contribute in an adjuvant setting, once the primary tumor has been surgically removed, to treat metastatic deposits and for treatment of end-stage disease. The lack of effective treatments for metastatic melanoma and end stage disease underscores the necessity to develop and implement new treatment strategies, such as peptide-targeted radionuclide therapy. PMID:18387816

  13. Lithium thermal targets shot on PBFA II

    SciTech Connect

    Sawyer, P.S.; Aubert, J.H.; Baca, P.M.; McNamara, W.F.

    1993-09-01

    Recent lithium ion beam experiments on PBFAII have required intricate targets to measure beam performance and to study target physics issues. Because of the stopping power difference between lithium ions and protons, these targets have presented significantly increased challenges for material preparation and handling compared to previous proton shots. The greatest challenges included complex shaped gold hohlraums, CH foams of densities ranging from 3 to 6 mg/cm3 and vacuum seals covering large areas with a thickness under 1 um. Details regarding assembly and characterization of lithium thermal targets will be described in this poster.

  14. A new transfer system for solid targets

    NASA Astrophysics Data System (ADS)

    Klug, J.; Buckley, K. R.; Zeisler, S. K.; Dodd, M.; Tsao, P.; Hoehr, C.; Economou, C.; Corsaut, J.; Appiah, J. P.; Kovacs, M. S.; Valliant, J. F.; Benard, F.; Ruth, T. J.; Schaffer, P.

    2012-12-01

    As part of a collaborative research project funded by Natural Resources Canada, TRIUMF has designed and manufactured solid target and solid target processing systems for the production of technetium-99m using small medical cyclotrons. The system described herein is capable of transporting the target from a hotcell, where the target is loaded and processed, to the cyclotron and back again. The versatility of the transfer system was demonstrated through the successful installation and operation on the ACSI TR 19 at the BC Cancer Agency, the GE PETtrace cyclotrons at Lawson Health Research (LHRI) and the Centre for Probe Development and Commercialization (CDPC).

  15. ALT-3 target design and simulations

    SciTech Connect

    Peterson, Jeffrey H

    2011-01-12

    ALT-3 is an experiment being designed in collaboration between Russian VNIIEF scientists and LANL that aims to conduct high velocity material experiments to measure shock velocities and pressures near 1 TPa. The DEMG (Disck Explosive Magnetic Generator) is used to drive> 60MA currents to accelerate an aluminum liner to speeds in excess of 20 km/s. 1-D and 2-D simulations of the aluminum target are presented with information on the free surface velocity profile, the state of the target, and the shock velocity in the target. 2-D simulations are presented showing the different targets available as well as a scenario with a perturbed liner impacter.

  16. On Training Targets for Supervised Speech Separation

    PubMed Central

    Wang, Yuxuan; Narayanan, Arun; Wang, DeLiang

    2014-01-01

    Formulation of speech separation as a supervised learning problem has shown considerable promise. In its simplest form, a supervised learning algorithm, typically a deep neural network, is trained to learn a mapping from noisy features to a time-frequency representation of the target of interest. Traditionally, the ideal binary mask (IBM) is used as the target because of its simplicity and large speech intelligibility gains. The supervised learning framework, however, is not restricted to the use of binary targets. In this study, we evaluate and compare separation results by using different training targets, including the IBM, the target binary mask, the ideal ratio mask (IRM), the short-time Fourier transform spectral magnitude and its corresponding mask (FFT-MASK), and the Gammatone frequency power spectrum. Our results in various test conditions reveal that the two ratio mask targets, the IRM and the FFT-MASK, outperform the other targets in terms of objective intelligibility and quality metrics. In addition, we find that masking based targets, in general, are significantly better than spectral envelope based targets. We also present comparisons with recent methods in non-negative matrix factorization and speech enhancement, which show clear performance advantages of supervised speech separation. PMID:25599083

  17. Project Plan Remote Target Fabrication Refurbishment Project

    SciTech Connect

    Bell, Gary L; Taylor, Robin D

    2009-08-01

    In early FY2009, the DOE Office of Science - Nuclear Physics Program reinstated a program for continued production of {sup 252}Cf and other transcurium isotopes at the Radiochemical Engineering Development Center (REDC) at Oak Ridge National Laboratory (ORNL). The FY2009 major elements of the workscope are as follows: (1) Recovery and processing of seven transuranium element targets undergoing irradiation at the High Flux Isotope Reactor (HFIR) at ORNL; (2) Development of a plan to manufacture new targets for irradiation beginning in early- to mid-FY10 to supply irradiated targets for processing Campaign 75 (TRU75); and (3) Refurbishment of the target manufacturing equipment to allow new target manufacture in early FY10 The {sup 252}Cf product from processing Campaign 74 (recently processed and currently shipping to customers) is expected to supply the domestic demands for a period of approximately two years. Therefore it is essential that new targets be introduced for irradiation by the second quarter of FY10 (HFIR cycle 427) to maintain supply of {sup 252}Cf; the average irradiation period is {approx}10 HFIR cycles, requiring about 1.5 calendar years. The strategy for continued production of {sup 252}Cf depends upon repairing and refurbishing the existing pellet and target fabrication equipment for one additional target production campaign. This equipment dates from the mid-1960s to the late 1980s, and during the last target fabrication campaign in 2005- 2006, a number of component failures and operations difficulties were encountered. It is expected that following the target fabrication and acceptance testing of the targets that will supply material for processing Campaign 75 a comprehensive upgrade and replacement of the remote hot-cell equipment will be required prior to subsequent campaigns. Such a major refit could start in early FY 2011 and would take about 2 years to complete. Scope and cost estimates for the repairs described herein were developed, and authorization for the work was received in July 2009 under the Remote Target Fabrication Refurbishment Task of the Enhanced Utilization of Isotope Facilities project (Project Identification Code 2005230) funded by the American Recovery and Reinvestment Act of 2009. The goal of this project is to recover the capability to produce 4-5 curium targets for the irradiation period starting with HFIR cycle 427, currently scheduled to begin 2/17/10. Assuming success, the equipment would then be used to fabricate 6-7 additional targets to hold for the next irradiation campaign specified by the program. Specific objectives are the return to functionality of the Cubicle 3 Pellet Fabrication Line; Cubicle 2 Target Assembly equipment; and Cubicle 1 Target Inspection and Final Assembly system.

  18. 3D Printing Utilized In Target Fabrication

    NASA Astrophysics Data System (ADS)

    Klein, Sallee; Deininger, Michael; Gamboa, Eliseo; Manuel, Mario; Satcher, Joe; Young, Rachel; Kuranz, Carolyn; Keiter, Paul; Drake, R. Paul

    2013-10-01

    Targets are used in high-energy-density physics, when, once ablated by lasers, are platforms for experiments that study astrophysical phenomenon, hydrodynamic instabilities and a myriad of other physics. Target fabrication has long suffered from difficulty in the repeatability of features from target to target. At the University of Michigan, micro-machined acrylic structures are often used to mitigate variations in targets for any single campaign. However, there are limitations to what can be conventionally machined. Ever sophisticated target designs are broaching the limitations of our traditional means of creating the acrylic structures that have long been such an integral element to our success in target fabrication. 3D printing has opened up new opportunities to build targets that could never have been machined by conventional means. Here, we present the advantages and limitations of 3D printing when utilized in target fabrication. This work is funded by the NNSA-DS and SC-OFES Joint Program in High-Energy-Density Laboratory Plasmas, grant number DE-NA0001840, and by the National Laser User Facility Program, grant number DE-NA0000850.

  19. Target definition for shipwreck hunting

    PubMed Central

    Kirsner, Kim

    2015-01-01

    The research described in the present article was implemented to define the locations of two World War II shipwrecks, the German raider Kormoran, and the Australian light cruiser HMAS Sydney. The paper describes the long and complex trail that led through inefficient oceanographic prediction to ambiguous historical prediction involving a single report and on to precise cognitive prediction based on nine reports from more than 70 survivors, a process that yielded a single target position or “mean” just 2.7 NM (nautical miles) from the wreck of Kormoran. Prediction for the position of the wreck of Sydney opened with wishful thinking that she had somehow reached the coast more than 100 NM away when cognitive analysis of the survivor's reports actually provided the basis for accurate prediction in a position near to the wreck of Kormoran. In the account provided below, the focus on cognitive procedures emerged from, first, a review of a sample of the shipwreck hunts, and, second, growing awareness of the extraordinarily rich database available for this search, and the extent to which it was open to cognitive analysis. This review touches on both the trans-disciplinary and the cognitive or intra-disciplinary issues that so challenged the political entities responsible for supervising of the search for the wrecks of Kormoran and Sydney. One of the theoretical questions that emerged from these debate concerns the model of expertise advanced by Collins (2013). The decomposability of alleged forms of expertise is revealed as a fundamental problem for research projects that might or might not benefit from trans-disciplinary research. Where expertise can be decomposed for operational purposes, the traditional dividing lines between experts and novices, and fools for that matter, are much harder to discern, and require advanced and scientifically informed review. PMID:26579007

  20. Ovarian cancer: targeting the untargetable.

    PubMed

    Birrer, Michael J

    2014-01-01

    The premise that all tumors are targetable has been met with some controversy in the approach to epithelial ovarian cancer (EOC). Genomic analysis shows that these tumors (specifically, high-grade serous carcinomas) are genomically unstable and lack actionable driver mutations, much like HER2 in breast and gastric cancers. In this paper, Michael Birrer, MD, PhD, Massachusetts General Hospital, argues that the interpretation of genomic data in ovarian cancer requires a more thoughtful approach that necessitates a closer inspection of the data beyond the mere presence or absence of mutations. We must look at the extensive genomic alterations in DNA and, to understand more about the role of those genes affected by these changes, look beyond the tumor to the role of the stroma. As such, Dr. Birrer is arguing for the importance of translational research. This will be the key to precision medicine in ovarian cancer, as we approach drug discovery and improvements in treatment. Dr. Birrer is a world-renowned scientist who has devoted his career to the study of gynecologic cancers. He has published over 200 papers and written over 27 book chapters and reviews, served on numerous leadership positions in gynecologic oncology (including as co-chair of the National Cancer Institute's Gynecologic Cancer Steering Committee), and remains a clinician-scientist with an active lab and an active clinic. His career trajectory has shown me it is possible to be engaged as a researcher and a clinician and the work he has done has already impacted the care of patients with ovarian cancer. Don S. Dizon, MD, ASCO Educational Book Editor. PMID:24857054

  1. Therapeutic targeting of replicative immortality.

    PubMed

    Yaswen, Paul; MacKenzie, Karen L; Keith, W Nicol; Hentosh, Patricia; Rodier, Francis; Zhu, Jiyue; Firestone, Gary L; Matheu, Ander; Carnero, Amancio; Bilsland, Alan; Sundin, Tabetha; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G; Amedei, Amedeo; Amin, Amr; Helferich, Bill; Boosani, Chandra S; Guha, Gunjan; Ciriolo, Maria Rosa; Chen, Sophie; Mohammed, Sulma I; Azmi, Asfar S; Bhakta, Dipita; Halicka, Dorota; Niccolai, Elena; Aquilano, Katia; Ashraf, S Salman; Nowsheen, Somaira; Yang, Xujuan

    2015-12-01

    One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed "senescence," can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite differences in upstream signaling, senescence often involves convergent interdependent activation of tumor suppressors p53 and p16/pRB, but can be induced, albeit with reduced sensitivity, when these suppressors are compromised. Doses of conventional genotoxic drugs required to achieve cancer cell senescence are often much lower than doses required to achieve outright cell death. Additional therapies, such as those targeting cyclin dependent kinases or components of the PI3K signaling pathway, may induce senescence specifically in cancer cells by circumventing defects in tumor suppressor pathways or exploiting cancer cells' heightened requirements for telomerase. Such treatments sufficient to induce cancer cell senescence could provide increased patient survival with fewer and less severe side effects than conventional cytotoxic regimens. This positive aspect is countered by important caveats regarding senescence reversibility, genomic instability, and paracrine effects that may increase heterogeneity and adaptive resistance of surviving cancer cells. Nevertheless, agents that effectively disrupt replicative immortality will likely be valuable components of new combinatorial approaches to cancer therapy. PMID:25869441

  2. In vivo molecular targeted radiotherapy

    PubMed Central

    2005-01-01

    Unsealed radionuclides have been in clinical therapeutic use for well over half a century. Following the early inappropriate clinical administrations of radium salts in the early 20th century, the first real clinical benefits became evident with the use of 131I-sodium iodide for the treatment of hypothyroidism and differentiated thyroid carcinoma and 32P-sodium phosphate for the treatment of polycythaemia vera. In recent years the use of bone seeking agents 89Sr, 153Sm and 186Re for the palliation of bone pain have become widespread and considerable progress has been evident with the use of 131I-MIBG and 90Y-somatostatin receptor binding agents. Although the use of monoclonal antibody based therapeutic products has been slow to evolve, the start of the 21st century has witnessed the first licensed therapeutic antibody conjugates based on 90Y and 131I for the treatment of non-Hodgkin's lymphoma. The future clinical utility of this form of therapy will depend upon the development of radiopharmaceutical conjugates capable of selective binding to molecular targets. The availability of some therapeutic radionuclides such as 188Re produced from the tungsten generator system which can produce activity as required over many months, may make this type of therapy more widely available in some remote and developing countries. Future products will involve cytotoxic radionuclides with appropriate potency, but with physical characteristics that will enable the administration of therapeutic doses with the minimal need for patient isolation. Further developments are likely to involve molecular constructs such as aptamers arising from new developments in biotechnology. Patient trials are still underway and are now examining new methods of administration, dose fractionation and the clinical introduction of alpha emitting radiopharmaceutical conjugates. This review outlines the history, development and future potential of these forms of therapy. PMID:21625282

  3. Target Cueing Provides Support for Target- and Resource-Based Models of the Attentional Blink

    PubMed Central

    Pincham, Hannah L.; Sz?cs, Dénes

    2012-01-01

    The attentional blink (AB) describes a time-based deficit in processing the second of two masked targets. The AB is attenuated if successive targets appear between the first and final target, or if a cueing target is positioned before the final target. Using various speeds of stimulus presentation, the current study employed successive targets and cueing targets to confirm and extend an understanding of target-target cueing in the AB. In Experiment 1, three targets were presented sequentially at rates of 30 msec/item or 90 msec/item. Successive targets presented at 90 msec improved performance compared with non-successive targets. However, accuracy was equivalently high for successive and non-successive targets presented at 30 msec/item, suggesting that–regardless of whether they occurred consecutively–those items fell within the temporally defined attentional window initiated by the first target. Using four different presentation speeds, Experiment 2 confirmed the time-based definition of the AB and the success of target-cueing at 30 msec/item. This experiment additionally revealed that cueing was most effective when resources were not devoted to the cue, thereby implicating capacity limitations in the AB. Across both experiments, a novel order-error measure suggested that errors tend to decrease with an increasing duration between the targets, but also revealed that certain stimulus conditions result in stable order accuracy. Overall, the results are best encapsulated by target-based and resource-sharing theories of the AB, which collectively value the contributions of capacity limitations and optimizing transient attention in time. PMID:22629426

  4. Comprehensive transcriptomic analysis of molecularly targeted drugs in cancer for target pathway evaluation

    PubMed Central

    Mashima, Tetsuo; Ushijima, Masaru; Matsuura, Masaaki; Tsukahara, Satomi; Kunimasa, Kazuhiro; Furuno, Aki; Saito, Sakae; Kitamura, Masami; Soma-Nagae, Taeko; Seimiya, Hiroyuki; Dan, Shingo; Yamori, Takao; Tomida, Akihiro

    2015-01-01

    Targeted therapy is a rational and promising strategy for the treatment of advanced cancer. For the development of clinical agents targeting oncogenic signaling pathways, it is important to define the specificity of compounds to the target molecular pathway. Genome-wide transcriptomic analysis is an unbiased approach to evaluate the compound mode of action, but it is still unknown whether the analysis could be widely applicable to classify molecularly targeted anticancer agents. We comprehensively obtained and analyzed 129 transcriptomic datasets of cancer cells treated with 83 anticancer drugs or related agents, covering most clinically used, molecularly targeted drugs alongside promising inhibitors of molecular cancer targets. Hierarchical clustering and principal component analysis revealed that compounds targeting similar target molecules or pathways were clustered together. These results confirmed that the gene signatures of these drugs reflected their modes of action. Of note, inhibitors of oncogenic kinase pathways formed a large unique cluster, showing that these agents affect a shared molecular pathway distinct from classical antitumor agents and other classes of agents. The gene signature analysis further classified kinome-targeting agents depending on their target signaling pathways, and we identified target pathway-selective signature gene sets. The gene expression analysis was also valuable in uncovering unexpected target pathways of some anticancer agents. These results indicate that comprehensive transcriptomic analysis with our database (http://scads.jfcr.or.jp/db/cs/) is a powerful strategy to validate and re-evaluate the target pathways of anticancer compounds. PMID:25911996

  5. Some effects of representational friction, target size, and memory averaging on memory for vertically moving targets.

    PubMed

    Hubbard, T L

    1998-03-01

    Observers viewed an animated ascending or descending target that varied in size and velocity across trials and appeared either (a) in isolation, (b) to slide along one side of a single larger stationary object, or (c) to slide between two larger stationary objects. Targets vanished without warning, and displacements (i.e., differences between actual and remembered final position) along the axis of motion and orthogonal axis were measured. Forward displacement (a) decreased with increases in implied friction, (b) increased with increases in target size for descending targets, and (c) decreased with increases in target size for ascending targets. When a larger stationary object was to one side of the target, orthogonal displacement was toward that object; when no object or objects on both sides were present, orthogonal displacement was near zero. Results are consistent with previous findings and speculation on the effects of representational friction, memory averaging, and target size on memory. PMID:9655012

  6. Current Drug Targets -Infectious Disorders, 2002, 2, 169-186 169 Antibiotics Targeting Ribosomes: Crystallographic Studies

    E-print Network

    Yonath, Ada E.

    Current Drug Targets - Infectious Disorders, 2002, 2, 169-186 169 Antibiotics Targeting Ribosomes, Germany Abstract: Resistance to antibiotics is a major problem in modern therapeutics. Ribosomes clinically relevant antibiotics. The ribosomes from eubac- teria are excellent pathogen models. High

  7. ISIS Target studies Could a used ISIS target provide fusion relevant

    E-print Network

    McDonald, Kirk

    stainless steel water manifolds on side of target. #12;TS1 energy deposition and FLUKA dpa Target Plate [800) Precision sectioning requiring installation of an EDM Waste disposal PIE then to include Thermal conductivity Mechanical properties Microscopy #12;

  8. Proton Driver Target Station Keith Gollwitzer

    E-print Network

    McDonald, Kirk

    Proton Driver ­ Target Station Interfaces Keith Gollwitzer Fermilab Wednesday May 28, 2014 MAP 2014". What are the effects? #12;Beam ­ The True Interface Beam goes from Proton Driver Realm to Target by the Proton Driver rings (and transport line collimation) One then calculates * Which in turns determines

  9. Possible Target Options Michael A. Green

    E-print Network

    McDonald, Kirk

    by the cooling area, the heat transfer coefficient, and the heat conduction from the center of the target from low Z material. The target material should be ductile, with high thermal conductivity and should. These materials are strong and non- corrosive. The problem with niobium-titanium is its poor thermal conductivity

  10. Characterization of COROT seismology targets Claude Catala

    E-print Network

    Meyer-Vernet, Nicole

    Characterization of COROT seismology targets Claude Catala Observatoire Midi­Pyrâ??enâ??ees, Toulouse seismology programmes. In order to complete our a priori knowledge on each one of these potential targets/SWG/Milestone 2000, eds. E. Michel and A. Hui­Bon­Hoa 2 2. Entry catalogues for seismology The most important

  11. Active Targets For Capacitive Proximity Sensors

    NASA Technical Reports Server (NTRS)

    Jenstrom, Del T.; Mcconnell, Robert L.

    1994-01-01

    Lightweight, low-power active targets devised for use with improved capacitive proximity sensors described in "Capacitive Proximity Sensor Has Longer Range" (GSC-13377), and "Capacitive Proximity Sensors With Additional Driven Shields" (GSC-13475). Active targets are short-distance electrostatic beacons; they generate known alternating electro-static fields used for alignment and/or to measure distances.

  12. Receptor-targeted metalloradiopharmaceuticals. Final technical report

    SciTech Connect

    Green, Mark A.

    2000-03-22

    Copper (II) and platinum (II) coordination complexes were prepared and characterized. These complexes were designed to afford structural homology with steroidal and non-steroidal estrogens for possible use as receptor-targeted radiopharmaceuticals. While weak affinity for the estrogen receptor was detectable, none would appear to have sufficient receptor-affinity for estrogen-receptor-targeted imaging or therapy.

  13. Target Options for a Neutrino Factory

    E-print Network

    McDonald, Kirk

    Target Options for a Neutrino Factory Chris Densham, Otto Caretta, Tristan Davenne, Mike Fitton) pneumatic driving pressure (max 10 bar) 1. Suction / Lift 2. Load Hopper 3. Pressurise Hopper 4. Powder IncreasingDriverPressure #12;Schematic of implementation as a Neutrino Factory target Tungsten powder hopper

  14. Target discrimination strategies in optics detection

    NASA Astrophysics Data System (ADS)

    Sjöqvist, Lars; Allard, Lars; Henriksson, Markus; Jonsson, Per; Pettersson, Magnus

    2013-10-01

    Detection and localisation of optical assemblies used for weapon guidance or sniper rifle scopes has attracted interest for security and military applications. Typically a laser system is used to interrogate a scene of interest and the retro-reflected radiation is detected. Different system approaches for area coverage can be realised ranging from flood illumination to step-and-stare or continuous scanning schemes. Independently of the chosen approach target discrimination is a crucial issue, particularly if a complex scene such as in an urban environment and autonomous operation is considered. In this work target discrimination strategies in optics detection are discussed. Typical parameters affecting the reflected laser radiation from the target are the wavelength, polarisation properties, temporal effects and the range resolution. Knowledge about the target characteristics is important to predict the target discrimination capability. Two different systems were used to investigate polarisation properties and range resolution information from targets including e.g. road signs, optical reflexes, rifle sights and optical references. The experimental results and implications on target discrimination will be discussed. If autonomous operation is required target discrimination becomes critical in order to reduce the number of false alarms.

  15. Remote sensing of liquid water target operations

    SciTech Connect

    Ferrieri, R.A.; Alexoff, D.L.; Schlyer, D.J.

    1993-12-31

    One of the key considerations in the design of automated liquid water target systems for reliable {sup 18}F{sup {minus}} production is the inclusion of adequate sensing devices for remote feedback of individual process operation status. The process operations needed to generate, extract and deliver {sup 18}F{sup {minus}} to the Hot Lab for subsequent chemistry are not very complex. These involve configuring target valves for access during loading of enriched water, filling the target with water, reconfiguring the target valves so that it is sealed during irradiation, and finally emptying the target contents after irradiation. At the lowest level of remote sensing of these operations is the act of determining whether target valves are actually in their correct configuration for a specific step. Sensing the filling or emptying status of the target is perhaps the most crucial feedback for reliable target performance. Sensing the presence, or absence, of liquid water can be accomplished by measuring some physical property of the substance in that phase. The use of electrical conductivity meters is one method we have discussed in the past in relation to the remote sensing of metal cations to determine the presence of water. Likewise, refractive index is another property of water that can be harnessed for sensing the liquid`s presence. The performance of an optical sensor in the BNL JSW beamline for routine production of {sup 18}F{sup {minus}} is discussed.

  16. Update on Simulations of Mercury Targets

    E-print Network

    McDonald, Kirk

    Update on Simulations of Mercury Targets Roman Samulyak, Tongfei Guo AMS Department, Stony Brook simulations of jets interacting with proton beams · Fluid ­ structure interaction with SPH and mercury thimble multicore supercomputers #12;SPH Simulations 6 Disruption of mercury targets interacting with proton pulses

  17. Targets for high power neutral beams

    SciTech Connect

    Kim, J.

    1980-01-01

    Stopping high-power, long-pulse beams is fast becoming an engineering challenge, particularly in neutral beam injectors for heating magnetically confined plasmas. A brief review of neutral beam target technology is presented along with heat transfer calculations for some selected target designs.

  18. Multistatic Radar Imaging of Moving Targets

    E-print Network

    Cheney, Margaret

    Multistatic Radar Imaging of Moving Targets LING WANG, Member, IEEE MARGARET CHENEY, Member, IEEE that in special cases, the theory reduces to: 1) range-Doppler imaging, 2) inverse synthetic aperture radar (ISAR), 3) synthetic aperture radar (SAR), 4) Doppler SAR, and 5) tomography of moving targets. Manuscript

  19. raddis, 103089 THEORY OF RADAR TARGET DISCRIMINATION

    E-print Network

    Rodriguez, Carlos

    1 1 raddis, 10­30­89 THEORY OF RADAR TARGET DISCRIMINATION E. T. Jaynes Wayman Crow Professor of discrimination depends on the noise level, the background hash, the variation of echo with target aspect angles of these variables is calculated and discussed, leading to some new conclusions about optimal radar design

  20. Technical Design Report, Second Target Station

    SciTech Connect

    Galambos, John D.; Anderson, David E.; Bechtol, D.; Bethea, Katie L.; Brown, N.; Carden, W. F.; Chae, Steven M.; Clark, A.; Counce, Deborah M.; Craft, K.; Crofford, Mark T.; Collins, Richard M.; Cousineau, Sarah M.; Curry, Douglas E.; Cutler, Roy I.; Dayton, Michael J.; Dean, Robert A.; Deibele, Craig E.; Doleans, Marc; Dye, T.; Eason, Bob H.; Eckroth, James A.; Fincrock, C.; Fritts, S.; Gallmeier, Franz X.; Gawne, Ken R.; Hartman, Steven M.; Herwig, Kenneth W.; Hess, S.; Holmes, Jeffrey A.; Horak, Charlie M.; Howell, Matthew P.; Iverson, Erik B.; Jacobs, Lorelei L.; Jones, Larry C.; Johnson, B.; Johnson, S.; Kasemir, Kay; Kim, Sang-Ho; Laughon, Gregory J.; Lu, W.; Mahoney, Kelly L.; Mammosser, John; McManamy, T.; Michilini, M.; Middendorf, Mark E.; O'Neal, Ed; Nemec, B.; Peters, Roy Cecil; Plum, Michael A.; Reagan, G.; Remec, Igor; Rennich, Mark J.; Riemer, Bernie; Saethre, Robert B.; Schubert, James Phillip; Shishlo, Andrei P.; Smith, C. Craig; Strong, William Herb; Tallant, Kathie M.; Tennant, David Alan; Thibadeau, Barbara M.; Trumble, S.; Trotter, Steven M.; Wang, Z.; Webb, Steven B.; Williams, Derrick C.; White, Karen S.; Zhao, Jinkui

    2015-01-01

    The Second Target Station (STS) is a proposed upgrade for SNS. It includes a doubling of the accelerator power and an additional instrument hall. The new instrument hall will receive a 467 kW 10 Hz beam. The parameters and preliminary design aspects of the STS are presented for the accelerator, target systems, instrument hall, instruments and civil construction aspects.

  1. Sequential Multiresolution Trajectory Optimization for Moving Targets

    E-print Network

    Tsiotras, Panagiotis

    Sequential Multiresolution Trajectory Optimization for Moving Targets Sachin Jain and Panagiotis sequential multiresolution trajectory optimization algo- rithms for solving problems with moving targets to solve the associated trajectory optimization problem on a non-uniform grid across time that is adapted

  2. Mercury Intense Target (MERIT) Final Design Review

    E-print Network

    McDonald, Kirk

    , and Procurement P.T. Spampinato V.B. Graves T.A. Gabriel MERIT Collaboration Meeting MIT Plasma Science & Fusion Approach (cont.) · Pump equipment and target delivery system are designed at ORNL - Funding is provided equipment and test the system at ORNL/TTF - Characterize operating parameters of the target equipment

  3. Electromagnetic Scattering from Foliage Camouflaged Hard Targets,

    E-print Network

    Sarabandi, Kamal

    Electromagnetic Scattering from Foliage Camouflaged Hard Targets, in VHF-band Mojtaba Dehmollaian@eecs.umich.edu Abstract A hybrid target-foliage model is developed to investigate the scattering be- havior of hard on single scattering theory for propagation through and scattering from the forest [1] and an FDTD technique

  4. Setting conservation targets for sandy beach ecosystems

    NASA Astrophysics Data System (ADS)

    Harris, Linda; Nel, Ronel; Holness, Stephen; Sink, Kerry; Schoeman, David

    2014-10-01

    Representative and adequate reserve networks are key to conserving biodiversity. This begs the question, how much of which features need to be placed in protected areas? Setting specifically-derived conservation targets for most ecosystems is common practice; however, this has never been done for sandy beaches. The aims of this paper, therefore, are to propose a methodology for setting conservation targets for sandy beach ecosystems; and to pilot the proposed method using data describing biodiversity patterns and processes from microtidal beaches in South Africa. First, a classification scheme of valued features of beaches is constructed, including: biodiversity features; unique features; and important processes. Second, methodologies for setting targets for each feature under different data-availability scenarios are described. From this framework, targets are set for features characteristic of microtidal beaches in South Africa, as follows. 1) Targets for dune vegetation types were adopted from a previous assessment, and ranged 19-100%. 2) Targets for beach morphodynamic types (habitats) were set using species-area relationships (SARs). These SARs were derived from species richness data from 142 sampling events around the South African coast (extrapolated to total theoretical species richness estimates using previously-established species-accumulation curve relationships), plotted against the area of the beach (calculated from Google Earth imagery). The species-accumulation factor (z) was 0.22, suggesting a baseline habitat target of 27% is required to protect 75% of the species. This baseline target was modified by heuristic principles, based on habitat rarity and threat status, with final values ranging 27-40%. 3) Species targets were fixed at 20%, modified using heuristic principles based on endemism, threat status, and whether or not beaches play an important role in the species' life history, with targets ranging 20-100%. 4) Targets for processes and 5) important assemblages were set at 50%, following other studies. 6) Finally, a target for an outstanding feature (the Alexandria dunefield) was set at 80% because of its national, international and ecological importance. The greatest shortfall in the current target-setting process is in the lack of empirical models describing the key beach processes, from which robust ecological thresholds can be derived. As for many other studies, our results illustrate that the conservation target of 10% for coastal and marine systems proposed by the Convention on Biological Diversity is too low to conserve sandy beaches and their biota.

  5. Target identification by means of radar

    NASA Astrophysics Data System (ADS)

    Dalle Mese, E.; Mancianti, M.; Verrazzani, L.; Cantoni, A.

    1984-12-01

    Great practical relevance has the problem of target classification and identification by means of radar. A classification procedure consists basically of two main steps, including the acquisition of the information useful for classifying the target frm raw data (feature extraction), and a suitable processing of the infomation obtained in the first step (pattern recognition) to perform the association between the received signal and the unknown object. The work of the international radar community on the subject of target clasification has been focused mainly on the solution of the problems related to the first step. The present overview is concerned with the classification techniques which utilize the properties of the target frequency response, classification techniques which use a spatially coherent processing of the received echoes, and classification techniques which use the properties of the target scattering matrix. Classification techniques which use a near millimeter-wave (NmmW) radar system operating in the imaging mode are also discussed.

  6. The Jefferson Lab Frozen Spin Target

    E-print Network

    Keith, C D; Carlin, C; Comer, S A; Kashy, D; McAndrew, J; Meekins, D G; Pasyuk, E; Pierce, J J; Seely, M L

    2012-01-01

    A frozen spin polarized target, constructed at Jefferson Lab for use inside a large acceptance spectrometer, is described. The target has been utilized for photoproduction measurements with polarized tagged photons of both longitudinal and circular polarization. Protons in TEMPO-doped butanol were dynamically polarized to approximately 90% outside the spectrometer at 5 T and 200--300 mK. Photoproduction data were acquired with the target inside the spectrometer at a frozen-spin temperature of approximately 30 mK with the polarization maintained by a thin, superconducting coil installed inside the target cryostat. A 0.56 T solenoid was used for longitudinal target polarization and a 0.50 T dipole for transverse polarization. Spin-lattice relaxation times as high as 4000 hours were observed. We also report polarization results for deuterated propanediol doped with the trityl radical OX063.

  7. The Jefferson Lab Frozen Spin Target

    E-print Network

    C. D. Keith; J. Brock; C. Carlin; S. A. Comer; D. Kashy; J. McAndrew; D. G. Meekins; E. Pasyuk; J. J Pierce; M. L. Seely

    2012-04-05

    A frozen spin polarized target, constructed at Jefferson Lab for use inside a large acceptance spectrometer, is described. The target has been utilized for photoproduction measurements with polarized tagged photons of both longitudinal and circular polarization. Protons in TEMPO-doped butanol were dynamically polarized to approximately 90% outside the spectrometer at 5 T and 200--300 mK. Photoproduction data were acquired with the target inside the spectrometer at a frozen-spin temperature of approximately 30 mK with the polarization maintained by a thin, superconducting coil installed inside the target cryostat. A 0.56 T solenoid was used for longitudinal target polarization and a 0.50 T dipole for transverse polarization. Spin-lattice relaxation times as high as 4000 hours were observed. We also report polarization results for deuterated propanediol doped with the trityl radical OX063.

  8. The Jefferson Lab frozen spin target

    NASA Astrophysics Data System (ADS)

    Keith, C. D.; Brock, J.; Carlin, C.; Comer, S. A.; Kashy, D.; McAndrew, J.; Meekins, D. G.; Pasyuk, E.; Pierce, J. J.; Seely, M. L.

    2012-08-01

    A frozen spin polarized target, constructed at Jefferson Lab for use inside a large acceptance spectrometer, is described. The target has been utilized for photoproduction measurements with polarized tagged photons of both longitudinal and circular polarization. Protons in TEMPO-doped butanol were dynamically polarized to approximately 90% outside the spectrometer at 5 T and 200-300 mK. Photoproduction data were acquired with the target inside the spectrometer at a frozen-spin temperature of approximately 30 mK with the polarization maintained by a thin, superconducting coil installed inside the target cryostat. A 0.56 T solenoid was used for longitudinal target polarization and a 0.50 T dipole for transverse polarization. Spin-lattice relaxation times as high as 4000 h were observed. We also report polarization results for deuterated propanediol doped with the trityl radical OX063.

  9. Spherical Target Temperature by Extended CFAST Calculation

    SciTech Connect

    Ma, C W

    2009-05-05

    The purpose of this calculation is to evaluate the temperature at the surface of a spherical target made of polyethylene during a room fire. The current calculation is separated into 2 steps: (1) CFAST code calculation--Calculate the air temperature; radiation flux to the target from the fire, surrounding air, and walls; convection flux; and target temperature. (2) Extended model calculation--Calculate the temperature of the target sphere taking into account the density, heat capacity, heat conductivity, and the spherical geometry of the target by solving the coupled finite difference equations. The second step calculation utilizes the air temperature and radiation flux determined by the CFAST code calculation in the first step.

  10. Launch window definition for sky target experiments.

    NASA Technical Reports Server (NTRS)

    Michaud, N. H.

    1973-01-01

    This paper is a brief report on the computer program developed for the Extraterrestrial Physics Barium Ion Cloud (BIC) Project. The mathematical analysis developed for the program along with its programing characteristics are pointed out to show that this program is adaptable to similar sky target projects. Definite viewing constraints are specified so that the chosen ground tracking stations can photograph the behavior of the sky target after its release. Viewing factors include the illumination of the target by the sun, the relative elevation look angle to the target from each tracking station, the solar and lunar depression angles at each tracking station, and the total sky background brightness of the target relative to each tracking station. Numeric values are assigned to each factor through program input. The program output is flexible so that the results of the window calculations can be studied to the depth required.

  11. Target Selection for the TESS Mission

    NASA Astrophysics Data System (ADS)

    Pepper, Joshua; Stassun, Keivan

    2015-12-01

    The goal of the TESS mission is to discover small, rocky planets transiting bright stars. To reach that goal, we have constructed a compiled catalog of stars from which to select TESS targets. The catalog contains all dwarf stars in the sky with spectral types F5 and later, and I < 12, along with selected sets of fainter M stars. Provisions are being made to augment the target list with stars that fall outside the nominal spectral type and magnitude limits, and to permit dynamic updating of the catalog to accommodate new survey data being released (e.g. Gaia). I will describe the overall target selection strategy, the current target catalog, and how we intend to further expand and refine the TESS target lists.

  12. Progress on LMJ targets for ignition

    NASA Astrophysics Data System (ADS)

    Cherfils-Clérouin, C.; Boniface, C.; Bonnefille, M.; Dattolo, E.; Galmiche, D.; Gauthier, P.; Giorla, J.; Laffite, S.; Liberatore, S.; Loiseau, P.; Malinie, G.; Masse, L.; Masson-Laborde, P. E.; Monteil, M. C.; Poggi, F.; Seytor, P.; Wagon, F.; Willien, J. L.

    2009-12-01

    Targets designed to produce ignition on the Laser Megajoule (LMJ) are being simulated in order to set specifications for target fabrication. The LMJ experimental plans include the attempt of ignition and burn of an ICF capsule with 160 laser beams, delivering up to 1.4 MJ and 380 TW. New targets needing reduced laser energy with only a small decrease in robustness have then been designed for this purpose. Working specifically on the coupling efficiency parameter, i.e. the ratio of the energy absorbed by the capsule to the laser energy, has led to the design of a rugby-ball shaped cocktail hohlraum; with these improvements, a target based on the 240-beam A1040 capsule can be included in the 160-beam laser energy-power space. Robustness evaluations of these different targets shed light on critical points for ignition, which can trade off by tightening some specifications or by preliminary experimental and numerical tuning experiments.

  13. The Jefferson Lab Frozen Spin Target

    SciTech Connect

    Christopher Keith, James Brock, Christopher Carlin, Sara Comer, David Kashy, Josephine McAndrew, David Meekins, Eugene Pasyuk, Joshua Pierce, Mikell Seely

    2012-08-01

    A frozen spin polarized target, constructed at Jefferson Lab for use inside a large acceptance spectrometer, is described. The target has been utilized for photoproduction measurements with polarized tagged photons of both longitudinal and circular polarization. Protons in TEMPO-doped butanol were dynamically polarized to approximately 90% outside the spectrometer at 5 T and 200-300 mK. Photoproduction data were acquired with the target inside the spectrometer at a frozen-spin temperature of approximately 30 mK with the polarization maintained by a thin, superconducting coil installed inside the target cryostat. A 0.56 T solenoid was used for longitudinal target polarization and a 0.50 T dipole for transverse polarization. Spin relaxation times as high as 4000 hours were observed. We also report polarization results for deuterated propanediol doped with the trityl radical OX063.

  14. Targeted polymeric nanoparticles for cancer gene therapy

    PubMed Central

    Kim, Jayoung; Wilson, David R.; Zamboni, Camila G.; Green, Jordan J.

    2015-01-01

    In this article, advances in designing polymeric nanoparticles for targeted cancer gene therapy are reviewed. Characterization and evaluation of biomaterials, targeting ligands, and transcriptional elements are each discussed. Advances in biomaterials have driven improvements to nanoparticle stability and tissue targeting, conjugation of ligands to the surface of polymeric nanoparticles enable binding to specific cancer cells, and the design of transcriptional elements has enabled selective DNA expression specific to the cancer cells. Together, these features have improved the performance of polymeric nanoparticles as targeted non-viral gene delivery vectors to treat cancer. As polymeric nanoparticles can be designed to be biodegradable, non-toxic, and to have reduced immunogenicity and tumorigenicity compared to viral platforms, they have significant potential for clinical use. Results of polymeric gene therapy in clinical trials and future directions for the engineering of nanoparticle systems for targeted cancer gene therapy are also presented. PMID:26061296

  15. The influence of blood on targeted microbubbles

    PubMed Central

    Owen, Joshua; Grove, Philip; Rademeyer, Paul; Stride, Eleanor

    2014-01-01

    The ability to successfully target the delivery of drugs and other therapeutic molecules has been a key goal of biomedical research for many decades. Despite highly promising in vitro results, however, successful translation of targeted drug delivery into clinical use has been extremely limited. This study investigates the significance of the characteristics of whole blood, which are rarely accounted for in vitro assays, as a possible explanation for the poor correlation between in vitro and in vivo experiments. It is shown using two separate model systems employing either biochemical or magnetic targeting that blood causes a substantial reduction in targeting efficiency relative to saline under the same flow conditions. This finding has important implications for the design of targeted drug delivery systems and the assays used in their development. PMID:25253034

  16. Target identification strategies in plant chemical biology

    PubMed Central

    Dejonghe, Wim; Russinova, Eugenia

    2014-01-01

    The current needs to understand gene function in plant biology increasingly require more dynamic and conditional approaches opposed to classic genetic strategies. Gene redundancy and lethality can substantially complicate research, which might be solved by applying a chemical genetics approach. Now understood as the study of small molecules and their effect on biological systems with subsequent target identification, chemical genetics is a fast developing field with a strong history in pharmaceutical research and drug discovery. In plant biology however, chemical genetics is still largely in the starting blocks, with most studies relying on forward genetics and phenotypic analysis for target identification, whereas studies including direct target identification are limited. Here, we provide an overview of recent advances in chemical genetics in plant biology with a focus on target identification. Furthermore, we discuss different strategies for direct target identification and the possibilities and challenges for plant biology. PMID:25104953

  17. Radioactive targets for nuclear accelerator experiments

    NASA Astrophysics Data System (ADS)

    Maier, H. J.; Grossmann, R.; Friebel, H. U.

    1991-05-01

    The quality of a nuclear accelerator target is assessed in terms of its purity, mechanical strength, thickness uniformity and microstructure. High vacuum thin film condensation is the preferred production method, because it results in microscopically smooth targets of high purity. Special variants of this technique are used in our hot laboratory to prepare radioactive targets of good macroscopic and microscopic homogeneity while keeping the consumption of isotopic material on a low level. A particular type of carbon backing provides excellent mechanical strength to the targets. New equipment including modern production plants as well as glove boxes and hot cell facilities permits to maintain the service for a long period. In nuclear physics experiments with radioactive targets problems may arise from a possible contamination of the beam line or other equipment. A few protective measures to overcome these difficulties are mentioned.

  18. Brain tumor-targeted drug delivery strategies

    PubMed Central

    Wei, Xiaoli; Chen, Xishan; Ying, Man; Lu, Weiyue

    2014-01-01

    Despite the application of aggressive surgery, radiotherapy and chemotherapy in clinics, brain tumors are still a difficult health challenge due to their fast development and poor prognosis. Brain tumor-targeted drug delivery systems, which increase drug accumulation in the tumor region and reduce toxicity in normal brain and peripheral tissue, are a promising new approach to brain tumor treatments. Since brain tumors exhibit many distinctive characteristics relative to tumors growing in peripheral tissues, potential targets based on continuously changing vascular characteristics and the microenvironment can be utilized to facilitate effective brain tumor-targeted drug delivery. In this review, we briefly describe the physiological characteristics of brain tumors, including blood–brain/brain tumor barriers, the tumor microenvironment, and tumor stem cells. We also review targeted delivery strategies and introduce a systematic targeted drug delivery strategy to overcome the challenges.

  19. Cooperative target convergence using multiple agents

    SciTech Connect

    Kwok, K.S.; Driessen, B.J.

    1997-10-01

    This work considers the problem of causing multiple (100`s) autonomous mobile robots to converge to a target and provides a follow-the-leader approach to the problem. Each robot has only a limited-range sensor for sending the target and also larger but also limited-range robot-to-robot communication capability. Because of the small amount of information available to the robots, a practical approach to improve convergence to the target is to have a robot follow the robot with the best quality of information. Specifically, each robot emits a signal that informs in-range robots what its status is. A robot has a status value of 0 if it is itself in range of the target. A robot has a status of 1 if it is not in range of the target but is in communication range of a robot that is in range of the target. A robot has a status of 2 if it is not in range of the target but is within range of another robot that has status 1, and so on. Of all the mobile robots that any given robot is in range of, it follows the one with the best status. The emergent behavior is the ant-like trails of robots following each other toward the target. If the robot is not in range of another robot that is either in range of the target or following another robot, the robot will assign-1 to its quality-of-information, and will execute an exhaustive search. The exhaustive search will continue until it encounters either the target or another robot with a nonnegative quality-of-information. The quality of information approach was extended to the case where each robot only has two-bit signals informing it of distance to in-range robots.

  20. 26 CFR 1.430(d)-1 - Determination of target normal cost and funding target.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 5 2013-04-01 2013-04-01 false Determination of target normal cost and funding target. 1.430(d)-1 Section 1.430(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Certain Stock Options § 1.430(d)-1 Determination of target normal cost and...