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1

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

ClinicalTrials.gov

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

2014-06-17

2

Idiopathic thrombocytopenic purpura  

PubMed Central

Idiopathic thrombocytopenic purpura (ITP) is defined as a hematologic disorder, characterized by isolated thrombocytopenia without a clinically apparent cause. The major causes of accelerated platelet consumption include immune thrombocytopenia, decreased bone marrow production, and increased splenic sequestration. The clinical presentation may be acute with severe bleeding, or insidious with slow development with mild or no symptoms. The initial laboratory tests useful at the first visit to predict future diagnosis were erythrocyte count, leukocyte count, anti-glycoprotein IIb/IIIa antibodies, reticulated platelets, plasma thrombopoietin level. Treatment should be restricted to those patients with moderate or severe thrombocytopenia who are bleeding or at risk of bleeding. We present a case report on ITP with clinical presentation, diagnosis and management.

Kayal, L.; Jayachandran, S.; Singh, Khushboo

2014-01-01

3

Idiopathic thrombocytopenic purpura: predictors of chronic disease.  

PubMed Central

We studied the extent to which patient characteristics influenced outcome in childhood idiopathic thrombocytopenic purpura in a historical cohort of 289 children over a 20 year period (1968-87). Outcome was classified as acute or chronic depending on whether the platelet count had returned to normal (150 X 10(9)/l) by six months after diagnosis. Fifty three cases (18%) had chronic idiopathic thrombocytopenic purpura. The likelihood of chronic disease was determined by logistic regression analysis of five patient variables: age, sex, season of onset of symptoms, history of recent viral illness, and duration of symptoms at presentation. A history of symptoms of greater than 14 days at presentation, adjusted for the other variables, was strongly predictive of chronic idiopathic thrombocytopenic purpura; the other variables did not significantly affect outcome. At 28 days after diagnosis 138 (47%) of the study cohort had normal platelet counts. Children whose platelet counts were less than 150 X 10(9)/l had a threefold risk of progressing to chronic idiopathic thrombocytopenic purpura, which increased to fivefold if counts were less than 50 X 10(9)/l. Two thirds of patients in the chronic group, irrespective of treatment, remained thrombocytopenic two years after diagnosis. We conclude that a history of symptoms for greater than two weeks at presentation is strongly predictive of chronic idiopathic thrombocytopenic purpura. If platelet counts are subnormal 28 days after diagnosis the risk of chronic idiopathic thrombocytopenic purpura is increased with prolonged thrombocytopenia being very likely if platelet counts remain low three months after diagnosis. PMID:2357088

Robb, L G; Tiedeman, K

1990-01-01

4

Thrombotic thrombocytopenic purpura in adult Still's disease.  

PubMed

We describe 2 patients with adult Still's disease who developed thrombotic thrombocytopenic purpura (TTP) and were successfully treated. Although TTP has been associated with autoimmune diseases, usually with systemic lupus erythematosus or various forms of vasculitis, it has rarely been observed in patients with adult Still's disease. This uncommon coexistence of 2 clinical entities may indicate similar pathogenetic mechanisms. PMID:8882053

Boki, K A; Tsirantonaki, M J; Markakis, K; Moutsopoulos, H M

1996-02-01

5

Thrombotic thrombocytopenic purpura mimicking acute ischemic stroke  

Microsoft Academic Search

Thrombotic thrombocytopenic purpura (TTP) is an autoimmune disorder characterised by thrombocytopenia, haemolytic anemia, fluctuating neurological deficits, fever, and renal impairment. This case report is about a young man who presented with acute onset right sided paralysis, dysarthria, and central facial paralysis, suggestive of cerebrovascular accident, but eventually diagnosed as TTP. In addition, the clinical presentation of TTP is discussed and

E Aksay; S Kiyan; M Ersel; O Hudaverdi

2006-01-01

6

Pitfalls in the Diagnosis of Immune Thrombocytopenic Purpura in Children: 4 Case Reports  

Microsoft Academic Search

Acute idiopathic thrombocytopenic purpura is the most common cause of thrombocytopenia in childhood, and diagnosis of idiopathic thrombocytopenic purpura is made clinically based on the exclusion of other causes of thrombocytopenia. Patients with diverse causes of thrombocytopenia are sometimes erroneously diagnosed as having idiopathic thrombocytopenic purpura. However, for the prevention of misdiagnoses, careful inspection of peripheral blood smear is of

Betül Biner; Ömer Devecio?lu; Muzaffer Demir

2007-01-01

7

Priapism and penile gangrene due to thrombotic thrombocytopenic purpura.  

PubMed

A 51-year-old man presented with 4 days of idiopathic ischemic priapism. Partial detumescence was achieved with aspiration and injection with intracorporeal adrenaline. On further evaluation, the patient was diagnosed with thrombotic thrombocytopenic purpura. This was treated with plasma exchange and steroids. The penis was initially observed for 3 weeks, which subsequently became necrotic and infected, requiring debridement. After debridement of penile shaft skin, it became apparent that the entire penis was necrotic, necessitating total penectomy. The wound was closed secondarily 2 weeks later. Gangrene of the penis after priapism is very rare. Priapism associated with thrombotic thrombocytopenic purpura has not been reported previously in published data. PMID:19896177

Kwok, Benjamin; Varol, Celi

2010-01-01

8

Thrombocytopenic purpura as adverse reaction to recombinant hepatitis B vaccine  

Microsoft Academic Search

Three cases of immune thrombocytopenic purpura after the first dose of recombinant hepatitis B vaccine occurred in infants under 6 months of age. Other possible causes of this condition were excluded. Antiplatelet antibodies were present. A defect in platelet production was excluded in two children. Corticosteroid treatment was effective. Subsequent administration of other vaccines (against polio, diphtheria, and tetanus) did

F Ronchi; P Cecchi; F Falcioni; A Marsciani; G Minak; G Muratori; P L Tazzari; S Beverini

1998-01-01

9

Thrombotic thrombocytopenic purpura: MR demonstration of reversible brain abnormalities  

SciTech Connect

We report a case of thrombotic thrombocytopenic purpura evaluated by MR, Multiple hyperintense foci on the TS-weighted images, observed principally in the brain stem and in the region of the basal nuclei, and neurologic signs disappeared after 15 days of therapy. 6 refs., 2 figs.

D'Aprile, P.; Carella, A.; Pagliarulo, R. (Univ. of Bari (Italy)); Farchi, G. (Oncology Institute, Bari (Italy))

1994-01-01

10

Congenital ADAMTS13 Deficiency: A Rare Mimicker of Immune Thrombocytopenic Purpura.  

PubMed

Congenital ADAMTS13 deficiency is a rare disease that leads to recurrent episodes of thrombotic thrombocytopenic purpura. We report a case that mimicked a recurring immune thrombocytopenic purpura in a child. Mild cases of ADAMTS13 deficiency may be initially confused with immune thrombocytopenic purpura if hemolytic anemia is not severe and renal or neurological symptoms are not present. Fresh frozen plasma is the treatment of choice in acute thrombotic thrombocytopenic purpura in ADAMTS13-deficient patients. The best long-term treatment for slightly symptomatic cases remains to be elucidated. Recombinant human ADAMTS13 factor will be a promising option when commercially available. PMID:24942015

Quintero, Victor; Garcia-Pose, Araceli; Barrios-Tascon, Ana; Pacheco-Cumani, Monica

2014-11-01

11

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. ...

12

Thrombotic Thrombocytopenic Purpura-Haemolytic Uremic Syndrome and pregnancy  

PubMed Central

Thrombotic Thrombocytopenic Purpura-Haemolytic Uremic Syndrome (TTP-HUS) is a rare pregnancy and postpartum complication that may simulate the more common obstetric complications, preeclampsia and the syndrome of haemolysis, elevated liver functions tests, low platelets (HELLP). We describe a 26 years old patient who presented with peri-partum TTP-HUSand was initially treated as a case of HELLP syndrome without any improvement. A brief review of the current TTP-HUS treatment options in pregnancy is also presented.

Mwita, Julius Chacha; Vento, Sandro; Benti, Tadele

2014-01-01

13

Perioperative Care of a Patient with Refractory Idiopathic Thrombocytopenic Purpura Undergoing Total Knee Arthroplasty  

PubMed Central

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder leading to low platelet count and an increased risk of bleeding. Major joint replacement surgery in a patient with ITP can be associated with severe postoperative bleeding. We present our experience of perioperative management in a patient with severe refractory chronic idiopathic thrombocytopenic purpura who successfully underwent a cemented total knee replacement. PMID:23269964

Gudimetla, Veera; Stewart, Andrew; Luscombe, Karen L; Charalambous, Charalambos P

2012-01-01

14

Perioperative care of a patient with refractory idiopathic thrombocytopenic purpura undergoing total knee arthroplasty.  

PubMed

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder leading to low platelet count and an increased risk of bleeding. Major joint replacement surgery in a patient with ITP can be associated with severe postoperative bleeding. We present our experience of perioperative management in a patient with severe refractory chronic idiopathic thrombocytopenic purpura who successfully underwent a cemented total knee replacement. PMID:23269964

Singhal, Rohit; Gudimetla, Veera; Stewart, Andrew; Luscombe, Karen L; Charalambous, Charalambos P

2012-12-01

15

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

PubMed Central

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

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

2014-01-01

16

Two novel ADAMTS13 gene mutations in thrombotic thrombocytopenic purpura\\/hemolytic-uremic syndrome (TTP\\/HUS)  

Microsoft Academic Search

Two novel ADAMTS13 gene mutations in thrombotic thrombocytopenic purpura\\/hemolytic-uremic syndrome (TTP\\/HUS).BackgroundThrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS) are now considered to be variants of one single syndrome called thrombotic thrombocytopenic purpura\\/hemolytic-uremic syndrome (TTP\\/HUS). Key features are thrombocytopenia, hemolytic anemia, and subsequently impaired function of different organs, especially the kidneys and the central nervous system (CNS). One possible reason is

CHRISTOPH LICHT; LUDWIG STAPENHORST; THORSTEN SIMON; ULRICH BUDDE; REINHARD SCHNEPPENHEIM; BERND HOPPE

2004-01-01

17

Platelet antibody in prolonged remission of childhood idiopathic thrombocytopenic purpura  

SciTech Connect

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.

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

1985-11-01

18

Platelet antibody in idiopathic thrombocytopenic purpura and other thrombocytopenias  

SciTech Connect

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.

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

1980-10-01

19

Gemcitabine-associated thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.  

PubMed

A patient being treated for metastatic adenocarcinoma of the pancreas presents to the clinic for a routine appointment. A complete blood count reveals hemoglobin of 6.5 g/dl and a platelet count of 30,000 K/mm3 thought to be from the last of many doses of gemcitabine. On assessment, the only complaint was fatigue with no evidence of bleeding or other abnormal physical findings other than pallor. Past medical history includes hypertension managed with three antihypertensive agents. Additional laboratory tests reveal elevated blood urea nitrogen (69 mg/dl), creatinine (2.76 mg/dl), and lactic dehydrogenase (LDH), was well as indirect bilirubin (2.1 mg/dl). The patient is admitted and transfused with packed red blood cells (pRBCs). The next day, the platelet count drops to 9,000 K/mm3 and the hemoglobin increases, appropriately, to 8.9 g/dl. Urinalysis is positive for hemoglobin (+ 3). The peripheral blood smear is positive for schistocytes (fragmented RBCs). A pheresis catheter is placed after the patient was evaluated by a hematologist and a nephrologist. A presumptive diagnosis of thrombotic thrombocytopenic purpura (TTP) with hemolytic uremic syndrome (HUS) was made. PMID:25158661

Held-Warmkessel, Jeanne

2014-09-01

20

Acute and fatal thrombocytopenic thrombotic purpura after a single dose of pemetrexed.  

PubMed

Case Thrombocytopenic thrombotic purpura (TTP), a life-threatening event consisting of disseminated vascular thrombosis, has never been described before as a possible side effect of the anticancer drug pemetrexed. A 70 years old patient affected by a poorly differentiated non small cell lung cancer, subjected to his first pemetrexed administration, developed an acute thrombocytopenic thrombotic purpura, fatal in a few hours. Conclusions Pemetrexed can cause TTP. Clinicians have to be alert for the rapid onset and aggressiveness of this possible side effect. It is difficult to recognise the first signs and symptoms. PMID:25370901

Alabiso, Irene; Baratelli, Chiara; Brizzi, Maria Pia; Bitossi, Raffaella; Ottone, Azzurra; Tampellini, Marco

2014-12-01

21

Platelet-associated complement C3 in immune thrombocytopenic purpura  

SciTech Connect

Platelet-associated C3 (PA-C3) was measured with a quantitative immunofluorescence assay. With this assay, PA-C3 levels were determined for 78 normal volunteers, 30 patients with immune thrombocytopenic purpura (ITP), and 20 patients with nonimmune thrombocytopenias. Platelet-associatd IgG (PA-lgG) levels were also measured with our standard quantitative immunofluorescence assay. All patients with nonimmune thrombocytopenias and ITP in remission had normal PA-C3 levels. Twenty-four patients with active ITP wre classified into 3 groups: 9 (38%) with increased PA-IgG and normal PA-C3 levels, 10 (42%) with elevated PA-C3 and PA-IgG levels, and 5 (20%) with increased PA-C3 values only. A direct correlation was found between PA-C3 and PA-IgG levels. PA-IgG levels were higher in the group of patients with elevated PA-C3 levels than in those with normal values. Platelet survival studies showed reduced survival times of 1.5-2.5 days for the 5 patients with elevated PA-C3 levels only. Elevated PA-C3 levels returned to normal in 7 ITP patients whose platelet counts increased in response to corticosteriod therapy or to splenectomy. Therefore, PA-C3 and PA-IgG assays can be used to identify patients with ITP, to follow their response to therapy, and to classify them into immunologic subgroups similar to red cell classifiation by Coombs' testing in immune hemolytic anemia.

Myers, T.J.; Kim, B.K.; Steiner, M.; Baldini, M.G.

1982-05-01

22

Helicobacter pylori eradication in patients with chronic immune thrombocytopenic purpura  

PubMed Central

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

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

2014-01-01

23

Intracranial haemorrhage in idiopathic thrombocytopenic purpura. Paediatric Haematology Forum of the British Society for Haematology  

Microsoft Academic Search

A UK survey was carried out to discover the frequency, circumstances, and outcome of intracranial haemorrhage (ICH) complicating idiopathic thrombocytopenic purpura (ITP) of childhood. A questionnaire was circulated through the membership of the UK Paediatric Haematology Forum, and thence to local paediatricians and haematologists. It sought information on any child with ITP who had had an ICH during the 20

J S Lilleyman

1994-01-01

24

Management of Acute Childhood Idiopathic Thrombocytopenic Purpura according to AIEOP Consensus Guidelines: Assessment of Italian Experience  

Microsoft Academic Search

Background: Consensus guidelines for diagnosis and treatment of acute childhood idiopathic thrombocytopenic purpura (ITP) were published in 2000 by the Italian Association of Pediatric Haematology and Oncology (AIEOP). The assessment of guideline implementation was the primary objective of the present study. Patients and Methods: Information on each newly diagnosed case of ITP referring to centres conforming with the guidelines was

Giovanni Carlo Del Vecchio; Attilio De Santis; Paola Giordano; Giovanni Amendola; Carlo Baronci; Domenico Del Principe; Bruno Nobili; Momcilo Jankovic; Ugo Ramenghi; Giovanna Russo; Marco Zecca; Domenico De Mattia

2008-01-01

25

Elevated platelet microparticle levels after acute ischemic stroke with concurrent idiopathic thrombocytopenic purpura.  

PubMed

We report a 60-year-old woman with idiopathic thrombocytopenic purpura who experienced acute infarction of the middle cerebral artery. She was treated with an antiplatelet agent and prednisolone to limit platelet activation and destruction. In parallel with clinical amelioration, levels of plasma platelet microparticles (PMPs), a procoagulant factor in platelet activation, decreased after treatment but increased after reduction of the prednisolone dose, resulting in progression of vascular stenosis. Immunosuppressive therapy with cyclosporine normalized plasma PMP levels, and no additional vascular events occurred during the 3-month follow-up period. Immunosuppressive therapy to decrease plasma PMP levels is warranted after acute ischemic stroke in the context of idiopathic thrombocytopenic purpura. PMID:23747179

Ichijo, Masahiko; Ishibashi, Satoru; Ohkubo, Takuya; Nomura, Shosaku; Sanjo, Nobuo; Yokota, Takanori; Mizusawa, Hidehiro

2014-03-01

26

Upshaw-Schulman Syndrome Revisited: A Concept of Congenital Thrombotic Thrombocytopenic Purpura  

Microsoft Academic Search

Upshaw-Schulman syndrome (USS) is a congenital bleeding disorder characterized by repeated episodes of thrombocytopenia and\\u000a microangiopathic hemolytic anemia that respond to infusions of fresh frozen plasma. Inheritance of USS has been thought to\\u000a be autosomal recessive, because 2 siblings in the same family are often affected but their parents are asymptomatic. Recently,\\u000a chronic relapsing thrombotic thrombocytopenic purpura (CR-TTP), reported almost

S. Kinoshita; A. Yoshioka; Y. D. Park; H. Ishizashi; M. Konno; M. Funato; T. Matsui; K. Titani; H. Yagi; M. Matsumoto; Y. Fujimura

2001-01-01

27

Successful treatment with rituximab of refractory idiopathic thrombocytopenic purpura in a patient with Kabuki syndrome  

Microsoft Academic Search

Kabuki syndrome (KS) is often associated with autoimmune abnormalities, such as idiopathic thrombocytopenic purpura (ITP),\\u000a autoimmune hemolytic anemia, leukoplakia and thyroiditis, as well as congenital anomalies. We herein present a KS patient\\u000a with refractory ITP who achieved durable and complete remission in response to a total of four once-monthly infusions of rituximab.\\u000a KS patients are often more susceptible to infection,

Yuka Torii; Hiroshi Yagasaki; Hidenori Tanaka; Seiji Mizuno; Nobuhiro Nishio; Hideki Muramatsu; Asahito Hama; Yoshiyuki Takahashi; Seiji Kojima

2009-01-01

28

Stroke in thrombotic thrombocytopenic purpura induced by thyrotoxicosis: a case report.  

PubMed

Thrombotic thrombocytopenic purpura (TTP) is a hematologic disease involving the platelet aggregation and resulting in hemolytic anemia, thrombocytopenia, and microvascular occlusion. Although frequent neurologic features are headache and confusion, focal deficit is described in 30% of the cases. There are a lot of causes inducing thrombotic thrombocytopenic, but reports are lacking when associated with Grave disease. We describe the case of a 51-year-old Caucasian woman presenting a 24-hour story of sudden onset of dysarthria and left superior limb palsy. Four months before, she developed severe hyperthyroidism associated with petechiae, hemolytic anemia, thrombocytopenia, and schistocytes at blood film examination. Relapse of TTP in association with Grave disease was diagnosed. There are few reports describing association between Grave disease and TTP with only mild neurologic involvement. We described, to our knowledge, the first case of acute ischemic stroke secondary to thrombotic thrombocytopenic induced by thyrotoxicosis. PMID:24674955

Bellante, Flavio; Redondo Saez, Patricia; Springael, Cecile; Dethy, Sophie

2014-07-01

29

Expression of a structurally constrained von Willebrand factor variant triggers acute thrombotic thrombocytopenic purpura in mice.  

PubMed

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease that presents with thrombocytopenia, disseminated thrombosis, hemolytic anemia, and organ dysfunction. The etiology of TTP has revealed that patients share a deficiency in plasma protease a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), the enzyme responsible for cleaving ultra-large von Willebrand factor (VWF) multimers into nonthrombogenic fragments. Therefore, existing TTP mouse models were developed by targeted disruption of the ADAMTS13 gene. ADAMTS13(-/-) mice are mostly asymptomatic in the absence of a trigger, as redundant proteases appear to take on VWF processing. As an alternative approach to creating one such model, we devised a strategy based on the expression of a cleavage-resistant VWF mutant in mice. The creation of a disulfide bond within the A2 domain of VWF was found to render VWF multimers resistant to proteolysis by plasma proteases under flow. Furthermore, mice expressing the murine VWF/p.S1494C-p.A1534C mutant present with symptoms characteristics of acute TTP such as thrombocytopenia, red cell shredding, accumulation of VWF-rich thrombi in the microvasculature, and advanced TTP symptoms such as renal dysfunction and splenomegaly. Because this model appears to faithfully emulate the pathophysiology of TTP, it should prove most useful in the study of microangiopathic diseases and their treatment. PMID:24713928

Morioka, Yoko; Casari, Caterina; Wohner, Nikolett; Cho, Sungyun; Kurata, Sachiko; Kitano, Ayumi; Christophe, Olivier D; Lenting, Peter J; Li, Renhao; Denis, Cécile V; Prévost, Nicolas

2014-05-22

30

Immune thrombocytopenic purpura in ulcerative colitis: a case report and systematic review  

PubMed Central

Over 100 extraintestinal manifestations are reported in ulcerative colitis (UC). A commonly reported hematological manifestation is autoimmune hemolytic anemia. On rare occasions, immune thrombocytopenic purpura (ITP) has been reported with UC. The presence of thrombocytopenia can complicate the clinical scenario as the number of bloody bowel movements is an important indicator of disease activity in UC. A proposed theory for this association is antigenic mimicry between a platelet surface antigen and bacterial glycoprotein. We are reporting a case of UC and associated ITP managed successfully with anti-TNF therapy. We also performed a systemic review of case reports and a case series reporting this association. PMID:24765254

Chandra, Subhash; Finn, Sarah; Obah, Eugene

2014-01-01

31

Management of myocardial infarction in immune thrombocytopenic purpura with anti-phospholipid antibodies.  

PubMed

Sometimes it is difficult to distinguish anti-phospholipid syndrome (APS) from immune thrombocytopenic purpura (ITP). Here we present successful management of ITP with anti-phospholipid antibodies, complicated by acute coronary syndrome (ACS), using CT coronary angiography (CTCA). The therapy for ITP may be changed for APS if ACS was thromboembolic event. As coronary angiography is thought to be very dangerous for patients with severe thrombocytopenia, noninvasive CTCA was desirable for our patient. Since no occlusion or narrowing was observed in CTCA, she has been safely treated as ITP with immunosuppressive agents throughout the course without antiplatelet or antithrombin therapy. PMID:22733282

Tabata, Rie; Tabata, Chiharu; Kita, Yoshio

2013-01-01

32

Slow infusions of vinblastine in the treatment of adult idiopathic thrombocytopenic purpura: A report on 43 cases  

Microsoft Academic Search

Summary Forty-three adult patients with idiopathic thrombocytopenic purpura (ITP) were treated by slow intravenous infusions of vinblastine. Nineteen had ITP of recent onset (i.e. of less than 6 months duration) and had contraindication to steroids (3 patients), refractoriness to steroids (6 patients) or to steroids and high dose intravenous immunoglobulins (IVIg, 10 patients). Of the 19 patients, 10 achieved complete

P. Fenaux; Isabelle Quiquandon; M. T. Caulier; M. Simon; M. P. Walter; F. Bauters

1990-01-01

33

Thrombotic thrombocytopenic purpura and pregnancy: presentation, management, and subsequent pregnancy outcomes.  

PubMed

Pregnancy can precipitate thrombotic thrombocytopenic purpura (TTP). We present a prospective study of TTP cases from the United Kingdom Thrombotic Thrombocytopenic Purpura (UK TTP) Registry with clinical and laboratory data from the largest cohort of pregnancy-associated TTP and describe management through pregnancy, averting fetal loss and maternal complications. Thirty-five women presented with a first TTP episode during pregnancy: 23/47 with their first congenital TTP (cTTP) episode and 12/47 with acute acquired TTP in pregnancy. TTP presented primarily in the third trimester/postpartum, but fetal loss was highest in the second trimester. Fetal loss occurred in 16/38 pregnancies before cTTP was diagnosed, but in none of the 15 subsequent managed pregnancies. Seventeen of 23 congenital cases had a missense mutation, C3178T, within exon 24 (R1060W). There were 8 novel mutations. In acquired TTP presentations, fetal loss occurred in 5/18 pregnancies and 2 terminations because of disease. We also present data on 12 women with a history of nonpregnancy-associated TTP: 18 subsequent pregnancies have been successfully managed, guided by ADAMTS13 levels. cTTP presents more frequently than acquired TTP during pregnancy and must be differentiated by ADAMTS13 analysis. Careful diagnosis, monitoring, and treatment in congenital and acquired TTP have assisted in excellent pregnancy outcomes. PMID:24859360

Scully, Marie; Thomas, Mari; Underwood, Mary; Watson, Henry; Langley, Katherine; Camilleri, Raymond S; Clark, Amanda; Creagh, Desmond; Rayment, Rachel; Mcdonald, Vickie; Roy, Ashok; Evans, Gillian; McGuckin, Siobhan; Ni Ainle, Fionnuala; Maclean, Rhona; Lester, William; Nash, Michael; Scott, Rosemary; O Brien, Patrick

2014-07-10

34

Refractory thrombocytopenia. A myelodysplastic syndrome that may mimic immune thrombocytopenic purpura.  

PubMed

The French-American-British classification scheme of myelodysplastic syndromes includes a category of refractory cytopenia that includes refractory thrombocytopenia (RTC). Because dysmegakaryopoiesis manifesting as an isolated cytopenia can be difficult to identify morphologically and because it may be accompanied by megakaryocytic hyperplasia, RTC may be confused with idiopathic thrombocytopenic purpura. A review of 1,220 cases of myelodysplastic syndromes at Mayo Clinic Jacksonville and Mayo Clinic Rochester from 1979 to 1990 yielded 9 cases (0.7%) of isolated thrombocytopenia (RTC) associated with clonal chromosome abnormalities. Review of 319 marrow chromosome analyses performed at the cytogenetics laboratory at Mayo Clinic Rochester from 1979 to 1990 for patients with low platelet count yielded two additional cases of RTC (0.6%). Of the 11 RTC cases, 3 previously had been misdiagnosed as idiopathic thrombocytopenic purpura. All patients had oval macrocytes in peripheral blood smears and abnormal megakaryocyte morphology in bone marrow aspirates, lacked antiplatelet antibodies, and did not have splenomegaly on clinical examination. The most common clonal chromosome abnormalities involved chromosomes 3, 5, 8, or 20. Steroid therapy was ineffective. Clinical and laboratory findings can establish the diagnosis of RTC and allow the physician to avoid recommending inappropriate therapy (steroids or splenectomy) for these patients. PMID:1485603

Menke, D M; Colon-Otero, G; Cockerill, K J; Jenkins, R B; Noel, P; Pierre, R V

1992-11-01

35

Bilateral serous retinal detachment as a complication of acquired peripartum thrombotic thrombocytopenic purpura bout.  

PubMed

We report a case of a 26-year-old primigravid woman, believed to have HELLP (Hemolysis, Elevated Liver enzymes, Low Platelet count) syndrome, which turned out to be a thrombotic thrombocytopenic purpura (TTP) bout. At the 40th gestational week, based on the clinical picture of HELLP syndrome, a cesarean section was performed and a dysmature male newborn was delivered. Afterwards, clinical symptoms and laboratory abnormalities persisted. Severe ADAMTS13 deficiency with the presence of inhibitory anti-ADAMTS13 antibodies revealed acquired thrombotic thrombocytopenic purpura bout, which was complicated with bilateral vision decrease due to bilateral retinal detachment. At the first ophthalmological examination, ultrasonography and binocular indirect ophthalmoscopy confirmed the diagnosis of the serous retinal detachment. After the diagnosis of acquired TTP bout, the patient was treated with multiple plasmapheresis and intravenous immunoglobulin with rapid improvement of the clinical and laboratory parameters. The ophthalmologic complications disappeared later without sequelae. At the 18-month examination, substantial visual acuity improvement without serous retinal detachment and full best corrected visual acuity were observed. PMID:21599805

Kovács, Eszter Márta; Molvarec, Attila; Rigó, János; Szabó, Antal

2011-10-01

36

The blood counts and lactate dehydrogenase levels in thrombotic thrombocytopenic purpura (TTP).  

PubMed

The blood counts and lactic dehydrogenase values of eight patients with thrombotic thrombocytopenic purpura (TTP) were reviewed in relation to the clinical course. Three of the eight patients died. In these patients, the hemoglobin was significantly lower and the LDH higher at the time of presentation than that of the patients responding to treatment. The height of the absolute reticulocyte count and platelet count did not correlate as well with outcome as did the degree of anemia and LDH elevation. Microangiopathic changes were noted in all eight patients. A differential count showed that the total microangiopathic changes varied from 0.8 to 54%. The more severe microangiopathic changes occurred in the fatal cases. The observations indicate that the degree of anemia, elevation of LDH, and severity of microangiopathic changes at the time of presentation correlate with the outcome in TTP and provide useful parameters in the assessment of response to therapy. PMID:6685430

Crowley, J P; Metzger, J B; L'Europa, R A

1983-11-01

37

Immune thrombocytopenic purpura induced by intestinal tuberculosis in a liver transplant recipient  

PubMed Central

A variety of clinical manifestations are associated directly or indirectly with tuberculosis. Among them, haematological abnormalities can be found in both the pulmonary and extrapulmonary forms of the disease. We report a case of immune thrombocytopenic purpura (ITP) associated with intestinal tuberculosis in a liver transplant recipient. The initial management of thrombocytopenia, with steroids and intravenous immunoglobulin, was not successful, and the lack of tuberculosis symptoms hampered a proper diagnostic evaluation. After the diagnosis of intestinal tuberculosis and the initiation of specific treatment, a progressive increase in the platelet count was observed. The mechanism of ITP associated with tuberculosis has not yet been well elucidated, but this condition should be considered in cases of ITP that are unresponsive to steroids and intravenous immunoglobulin, especially in immunocompromised patients and those from endemic areas. PMID:25009408

Lugao, Renata dos Santos; Motta, Marina Pamponet; de Azevedo, Matheus Freitas Cardoso; de Lima, Roque Gabriel Rezende; Abrantes, Flavia de Azevedo; Abdala, Edson; Carrilho, Flair Jose; Mazo, Daniel Ferraz de Campos

2014-01-01

38

Immune thrombocytopenic purpura induced by intestinal tuberculosis in a liver transplant recipient.  

PubMed

A variety of clinical manifestations are associated directly or indirectly with tuberculosis. Among them, haematological abnormalities can be found in both the pulmonary and extrapulmonary forms of the disease. We report a case of immune thrombocytopenic purpura (ITP) associated with intestinal tuberculosis in a liver transplant recipient. The initial management of thrombocytopenia, with steroids and intravenous immunoglobulin, was not successful, and the lack of tuberculosis symptoms hampered a proper diagnostic evaluation. After the diagnosis of intestinal tuberculosis and the initiation of specific treatment, a progressive increase in the platelet count was observed. The mechanism of ITP associated with tuberculosis has not yet been well elucidated, but this condition should be considered in cases of ITP that are unresponsive to steroids and intravenous immunoglobulin, especially in immunocompromised patients and those from endemic areas. PMID:25009408

Lugao, Renata dos Santos; Motta, Marina Pamponet; de Azevedo, Matheus Freitas Cardoso; de Lima, Roque Gabriel Rezende; Abrantes, Flávia de Azevedo; Abdala, Edson; Carrilho, Flair José; Mazo, Daniel Ferraz de Campos

2014-07-01

39

High-dose intravenous therapy with immune globulin before delivery for idiopathic thrombocytopenic purpura.  

PubMed Central

A 15-year-old girl with a 9-year history of idiopathic thrombocytopenic purpura resistant to high-dose steroid therapy and to splenectomy was admitted to hospital at 35 weeks' gestation with a platelet count of 10 X 10(9)/L. The bleeding time was normal, and measures of platelet aggregation were nearly so. Treatment with high intravenous doses of polyvalent immune globulin led to a rise in the platelet count to more than 110 X 10(9)/L within 5 days. An elective cesarean section was performed through the lower uterine segment with good hemostasis. After delivery the platelet count fell to its former level, but no postpartum bleeding occurred. There was a brief episode of thrombocytopenia in the infant, with some petechiae but no other hemorrhagic manifestations. No untoward effects of the immune globulin infusion were observed in either mother or daughter. PMID:6423252

Adderley, R. J.; Rogers, P. C.; Shaw, D.; Wadsworth, L. D.

1984-01-01

40

Active pulmonary tuberculosis manifesting with idiopathic thrombocytopenic purpura: a rare presentation.  

PubMed

A 17-year-old girl presented with a 3-day history of epistaxis, vaginal bleeding and petechiae over the lower extremities. The patient had been feeling unwell with productive cough, fever, chills, poor appetite and weight loss for 2 months. Laboratory findings revealed anemia and thrombocytopenia, whereas bone marrow examination was unremarkable. She was diagnosed as having idiopathic thrombocytopenic purpura (ITP) in association with active tuberculosis (TB). The patient was treated with intravenous immunoglobulin (IVIg) and corticosteroid along with anti-TB drugs. During the follow-up period there was no recurrence of thrombocytopenia or TB. It is important to consider TB in the differential diagnosis of ITP, particularly in high TB-burden areas. PMID:21340308

Tabarsi, Payam; Merza, Muayad Aghali; Marjani, Majid

2010-01-01

41

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

PubMed Central

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.

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

2014-01-01

42

ST-segment elevation myocardial infarction treated with thrombolytic therapy in a patient with thrombotic thrombocytopenic purpura.  

PubMed

Acute myocardial infarction is a common complication of thrombotic thrombocytopenic purpura (TTP), but rarely the presenting manifestation. Anti-thrombotic therapy for myocardial infarction is rarely utilized in the setting of TTP because of elevated bleeding risk. We report a case of TTP presenting with ST-segment elevation myocardial infarction and treated with thrombolytic therapy. The resultant cardiac and neurological complications highlight the challenges of using evidence-based therapy for myocardial infarction in the setting of TTP. PMID:24189934

Doll, Jacob A; Kelly, Jacob P

2014-07-01

43

Effect of Helicobacter pylori Eradication in Patients with Chronic Idiopathic Thrombocytopenic Purpura—A Randomized Controlled Trial  

Microsoft Academic Search

OBJECTIVE:Eradication of Helicobacter pylori was reported to increase the platelet counts in some H. pylori-positive patients with chronic idiopathic thrombocytopenic purpura (cITP). However, the efficacy of the eradication was quite different according to the previous reports. To determine whether H. pylori infection can contribute to cITP, we performed a randomized controlled trial for the first time. In addition, to investigate

Takayoshi Suzuki; Masashi Matsushima; Aya Masui; Ken-ichi Watanabe; Atsushi Takagi; Yoshiaki Ogawa; Takayuki Shirai; Tetsuya Mine

2005-01-01

44

Sunitinib Induced Thrombotic Thrombocytopenic Purpura in addition to Severe Hypothyroidism: A Case Report and Review of the Literature.  

PubMed

Introduction. Sunitinib malate is an oral multitargeting tyrosine kinase inhibitor approved for the first line treatment of metastatic renal cell carcinoma. Sunitinib administration is associated with several adverse events including fatigue, diarrhea, skin toxicity, hypothyroidism, and cytopenia. Herein, we present a case of thrombotic thrombocytopenic purpura and clinical hypothyroidism presenting within 4 weeks of starting sunitinib therapy. Case Presentation. A 72-year-old woman with metastatic renal cell carcinoma presented with generalized fatigue 28 days after starting sunitinib 50?mg daily. She was found to have severe hypothyroidism, in addition to significant thrombocytopenia and anemia. The latter were explained by a clinical and laboratory diagnosis of thrombotic thrombocytopenic purpura. Sunitinib was stopped and she recovered completely after plasmapheresis. Conclusion. To our knowledge, this is the fourth case report of thrombotic thrombocytopenic purpura secondary to sunitinib. Oncologists should be aware of this rare but potentially fatal adverse event. We highly suggest to routinely test for platelet count and thyroid stimulating hormone level as early as two weeks after initiating sunitinib. PMID:25349620

El Dika, Imane; Mukherji, Deborah; Temraz, Sally; Assi, Rita; Shamseddine, Ali

2014-01-01

45

Sunitinib Induced Thrombotic Thrombocytopenic Purpura in addition to Severe Hypothyroidism: A Case Report and Review of the Literature  

PubMed Central

Introduction. Sunitinib malate is an oral multitargeting tyrosine kinase inhibitor approved for the first line treatment of metastatic renal cell carcinoma. Sunitinib administration is associated with several adverse events including fatigue, diarrhea, skin toxicity, hypothyroidism, and cytopenia. Herein, we present a case of thrombotic thrombocytopenic purpura and clinical hypothyroidism presenting within 4 weeks of starting sunitinib therapy. Case Presentation. A 72-year-old woman with metastatic renal cell carcinoma presented with generalized fatigue 28 days after starting sunitinib 50?mg daily. She was found to have severe hypothyroidism, in addition to significant thrombocytopenia and anemia. The latter were explained by a clinical and laboratory diagnosis of thrombotic thrombocytopenic purpura. Sunitinib was stopped and she recovered completely after plasmapheresis. Conclusion. To our knowledge, this is the fourth case report of thrombotic thrombocytopenic purpura secondary to sunitinib. Oncologists should be aware of this rare but potentially fatal adverse event. We highly suggest to routinely test for platelet count and thyroid stimulating hormone level as early as two weeks after initiating sunitinib. PMID:25349620

El Dika, Imane; Temraz, Sally

2014-01-01

46

Platelet destruction in autoimmune thrombocytopenic purpura: kinetics and clearance of indium-111-labeled autologous platelets  

SciTech Connect

Using autologous /sup 111/In-labeled platelets, platelet kinetics and the sites of platelet destruction were assessed in 16 normal subjects (13 with and three without spleens), in 17 studies of patients with primary autoimmune thrombocytopenic purpura (AITP), in six studies of patients with secondary AITP, in ten studies of patients with AITP following splenectomy, and in five thrombocytopenic patients with myelodysplastic syndromes. In normal subjects, the spleen accounted for 24 +/- 4% of platelet destruction and the liver for 15 +/- 2%. Untreated patients with primary AITP had increased splenic destruction (40 +/- 14%, p less than 0.001) but not hepatic destruction (13 +/- 5%). Compared with untreated patients, prednisone treated patients did not have significantly different spleen and liver platelet sequestration. Patients with secondary AITP had similar platelet counts, platelet survivals, and increases in splenic destruction of platelets as did patients with primary AITP. In contrast, patients with myelodysplastic syndromes had a normal pattern of platelet destruction. In AITP patients following splenectomy, the five nonresponders all had a marked increase (greater than 45%) in liver destruction compared to five responders (all less than 40%). Among all patients with primary or secondary AITP, there was an inverse relationship between the percent of platelets destroyed in the liver plus spleen and both the platelet count (r = 0.75, p less than 0.001) and the platelet survival (r = 0.86, p less than 0.001). In a stepwise multiple linear regression analysis, total liver plus spleen platelet destruction, the platelet survival and the platelet turnover were all significant independent predictors of the platelet count. Thus platelet destruction is shifted to the spleen in primary and secondary AITP. Failure of splenectomy is associated with a marked elevation in liver destruction.

Stratton, J.R.; Ballem, P.J.; Gernsheimer, T.; Cerqueira, M.; Slichter, S.J.

1989-05-01

47

[A case of sarcoidosis and idiopathic thrombocytopenic purpura accompanied with invasive pulmonary aspergillosis].  

PubMed

A 54-year-old woman with a 21-year history of sarcoidosis was admitted to our hospital with dyspnea on exertion, weight loss, and the appearance of consolidation in chest radiographs. The serum level of soluble IL-2 receptor was high, and CT findings demonstrated mediastinal, hilar and abdominal lymphadenopathy. The histological findings of subpleural consolidation in a transbronchial lung biopsy of the left lung showed giant cells; and those of a CT-assisted biopsy of a retroperitoneal lymph node revealed non-caseous epithelioid cell granulomas. After the biopsy, severe thrombocytopenia (6,000/microliter) developed. With prednisolone treatment, the platelet count rose to normal and the subpleural consolidation on chest radiography was improved. Five weeks later, the had a productive cough with fever, rapidly progressive cavitary lesions and consolidation on chest radiography. Aspergillus fumigatus was detected in the sputum by PCR, and Aspergillus antigen was detected in the serum. She died of progressive respiratory failure, in spite of therapy with amphotericin B and itraconazole. We report a rare case of sarcoidosis and idiopathic thrombocytopenic purpura accompanied with invasive pulmonary aspergillosis. PMID:12692945

Nakano, Takako; Fukuyama, Satoru; Inoue, Koji; Inoue, Hiromasa; Hagimoto, Naoki; Fujita, Masaki; Kuwano, Kazuyoshi; Hara, Nobuyuki

2002-12-01

48

Acquired Idiopathic ADAMTS13 Activity Deficient Thrombotic Thrombocytopenic Purpura in a Population from Japan  

PubMed Central

Thrombotic thrombocytopenic purpura (TTP) is a type of thrombotic microangiopathy (TMA). Studies report that the majority of TTP patients present with a deficiency of ADAMTS13 activity. In a database of TMA patients in Japan identified between 1998 and 2008, 186 patients with first onset of acquired idiopathic (ai) ADAMTS13-deficient TTP (ADAMTS13 activity <5%) were diagnosed. The median age of onset of TTP in this group of patients was 54 years, 54.8% were female, 75.8% had renal involvement, 79.0% had neurologic symptoms, and 97.8% had detectable inhibitors to ADAMTS13 activity. Younger patients were less likely to present with renal or neurologic dysfunction (p<0.01), while older patients were more likely to die during the TTP hospitalization (p<0.05). Findings from this cohort in Japan differ from those reported previously from the United States, Europe, and Korea with respect to age at onset (two decades younger in the other cohort) and gender composition (60% to 100% female in the other cohort). We conclude that in one of the largest cohorts of ai-TTP with severe deficiency of ADAMTS13 activity reported to date, demographic characteristics differ in Japanese patients relative to those reported from a large Caucasian registry from Western societies. Additional studies exploring these findings are needed. PMID:22427934

Matsumoto, Masanori; Bennett, Charles L.; Isonishi, Ayami; Qureshi, Zaina; Hori, Yuji; Hayakawa, Masaki; Yoshida, Yoko; Yagi, Hideo; Fujimura, Yoshihiro

2012-01-01

49

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

PubMed

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

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

2013-05-01

50

Favorable Response of Chronic Refractory Immune Thrombocytopenic Purpura to Mesenchymal Stem Cells  

PubMed Central

Seven patients with chronic refractory immune thrombocytopenic purpura (ITP) received adipose tissue-derived mesenchymal stem cells (AMSC) from haplo-identical family donors. The AMSC dose was 2.0×106/kg. No side effects were noted after the AMSC infusions. Overall responses were reached in all patients and sustained response rate was 57.1% (4/7). The serum levels of transforming growth factor ?1 (TGF-?1), interleukin (IL)-4, and IL-10 were significantly elevated, whereas those of interferon-? (IFN-?) and IL-2 were significantly decreased after AMSC administration, compared with those in the patients with active ITP. During follow-up, the cytokine profiles in patients maintaining sustained response remained stable compared with the post-treatment level, but IFN-? and IL-2 levels were significantly increased, and those of TGF-?1, IL-4, and IL-10 were significantly reduced again in relapsed patients. AMSC therapy seems to represent reasonable salvage treatment in severe, chronic refractory ITP by causing a shift in the Th1/Th2 cytokine balance to the same levels as normal controls. PMID:21711157

Fang, Baijun; Mai, Ling; Li, Ning

2012-01-01

51

Favorable response of chronic refractory immune thrombocytopenic purpura to mesenchymal stem cells.  

PubMed

Seven patients with chronic refractory immune thrombocytopenic purpura (ITP) received adipose tissue-derived mesenchymal stem cells (AMSC) from haplo-identical family donors. The AMSC dose was 2.0×10(6)/kg. No side effects were noted after the AMSC infusions. Overall responses were reached in all patients and sustained response rate was 57.1% (4/7). The serum levels of transforming growth factor ?1 (TGF-?1), interleukin (IL)-4, and IL-10 were significantly elevated, whereas those of interferon-? (IFN-?) and IL-2 were significantly decreased after AMSC administration, compared with those in the patients with active ITP. During follow-up, the cytokine profiles in patients maintaining sustained response remained stable compared with the post-treatment level, but IFN-? and IL-2 levels were significantly increased, and those of TGF-?1, IL-4, and IL-10 were significantly reduced again in relapsed patients. AMSC therapy seems to represent reasonable salvage treatment in severe, chronic refractory ITP by causing a shift in the Th1/Th2 cytokine balance to the same levels as normal controls. PMID:21711157

Fang, Baijun; Mai, Ling; Li, Ning; Song, Yongping

2012-02-10

52

[Treatment of immune thrombocytopenic purpura in Pediatrics. Therapeutic efficacy of a regional intravenous immunoglobulin G].  

PubMed

Immune thrombocytopenic purpura (ITP) is a bleeding disorder characterized by accelerated splenic removal of platelets opsonized with autoantibodies. Several different treatments have been tried in acute ITP patients, including intravenous immunoglobulin (IVIG) therapy. The aim of this paper was to assess the therapeutic efficacy, clinical tolerance and viral safety of Inmunoglobulina G Endovenosa-UNC, manufactured by Laboratorio de Hemoderivados, Cordoba National University, in the treatment of acute ITP patients. A prospective longitudinal study was carried out on 8 children, who were admitted to the Hospital de Niños de Córdoba, from July 1998 to June 1999. A dose of 1 g/Kg/day of Inmunoglobulina G Endovenosa-UNC was administered to those children whose platelet values remained < or = 20,000/mm3, 21 days after the first IVIG cycle. The observed results led us to conclude that Inmunoglobulina G Endovenosa-UNC is well tolerated and therapeutically effective in the treatment of acute ITP in children, with platelet values recovery, similar to those obtained with other IVIG. Moreover, it proved to be virally safe since the 8 patients were non reactive for viral markers of hepatitis B, hepatitis C and human immunodeficiency, 12 months after ending the treatment. PMID:11721317

Buteler, C; Colombo, H; Gabosi, G; Manfredi, M J; Montero, S; Pasquali, M A; Rougier, C; Sisti, A M

2001-01-01

53

Treatment of thrombotic thrombocytopenic purpura. Evaluation of plasma exchange and review of the literature.  

PubMed

This report examines the results of treatment in 21 patients with thrombotic thrombocytopenic purpura (TTP) diagnosed over a 4-year time period (1976-1980) with a review of the possible role of each form of therapy in relationship to the various proposed pathogenic mechanisms. There was a 76.2% (16/21) overall survival with no significant difference in initial hematologic values in patients not surviving. Patients not surviving did not achieve a sustained platelet count greater than 150,000/microliters at any time during their clinical course. 16 patients received steroids, antiplatelet agents and plasma exchange, with a total volume exchanged ranging from 20.8 to 1,455 ml/kg, as part of their treatment protocol. In this group of patients there was an 81.2% (13/16) survival, with 4 patients receiving additional therapy including splenectomy and/or vincristine. There was no correlation between the intensity of plasma exchange and the time to hematologic recovery. It is apparent that controlled clinical trials are necessary to better define the effectiveness of the present forms of therapy. PMID:6684834

Pisciotto, P; Rosen, D; Silver, H; Genco, P; Blumberg, N; Katz, A J; Morse, E E

1983-01-01

54

Evaluation of humoral immune function in patients with chronic idiopathic thrombocytopenic purpura.  

PubMed

Coincidence of autoimmune diseases such as immune thrombocytopenic purpura (ITP) with immunodeficiencies has been reported previously in patients who suffered from primary antibody deficiency (PAD). But there is no original study on immunological profiles of ITP patients to find out their probable immune deficiency. In this case-control study, ITP patients' humoral immunity was investigated for diagnosis of PAD in comparison with normal population. To evaluate the humoral immune system against polysaccharide antigens, patients' serum immunoglobulin levels were measured and a 23-valent pneumococcal capsular polysaccharide vaccine (PPV23) was administrated to evaluate the antibody response to vaccination. In this study, 14 out of 36 patients (39%) were diagnosed with antibody mediated immune deficiency including 2 patients (5.5%) with immunoglobulin class deficiency and 4 (11%) with IgG subclass deficiency. The remaining patients suffered from specific antibody deficiency. The most frequent deficiency in ITP patients was specific antibody deficiency.Therefore, immunological survey on ITP patients may be important especially for those who have undergone splenectomy. PMID:23454778

Rahiminejad, Mohammad Saeid; Mirmohammad Sadeghi, Mehrdad; Mohammadinejad, Payam; Sadeghi, Bamdad; Abolhassani, Hassan; Dehghani Firoozabadi, Mohammad Mehdi; Fathi, Seyed Mohammad; Rezvani, Hamid; Bahoush, Gholamreza; Ehsani, Mohammad Ali; Faranoush, Mohammad; Mehrvar, Azim; Torabi Sagvand, Babak; Ghadiani, Mojtaba; Rezaei, Nima; Aghamohammadi, Asghar

2013-03-01

55

Long-term results of laparoscopic splenectomy in pediatric chronic immune thrombocytopenic purpura  

PubMed Central

Purpose Laparoscopic splenectomy (LS) for pediatric chronic immune thrombocytopenic purpura (ITP) patients has recently become widespread. However, its long-term result is rarely reported in children. Methods We retrospectively analyzed the patients who underwent LS for pediatric chronic ITP from June 1998 to April 2007. Results There were 18 patients (14 male and 4 female) with mean age 9.5 ± 3.8 years. 14 complete response, 3 partial response, and 1 no response were occurred. During the 82-month median follow-up period, 9 patients maintained in a remission state without any additional treatment, and 9 patients relapsed. In a comparative analysis of the relapse group and no relapse group, hospital stays were longer in the relapse group and the preoperative platelet counts and platelet counts at 1 month post were lower in relapse group. A relapse-free survival among 17 patients who achieved partial or complete responses following LS showed 76.5%, 61.8%, and 33.0% at 1-, 5-, and 10-year following LS, respectively. Conclusion Although LS in pediatric chronic ITP patients had excellent results immediately after surgery, careful follow up is needed due to late relapse even when a complete response has been noted for several years. PMID:24949323

Kim, Dong Jin

2014-01-01

56

Decreased plasma cytokines associate with low platelet counts in aplastic anemia and immune thrombocytopenic purpura  

PubMed Central

Summary Background We previously found plasma levels of CD40 ligand (CD40L), chemokine (C-X-C motif) ligand 5 (CXCL5), chemokine (C-C motif) ligand 5 (CCL5), and epidermal growth factor (EGF) to be low in aplastic anemia (AA) patients and to be correlated with the platelet count. Objectives To study the association of CD40L, CXCL5, CCL5, and EGF with platelets. Patients/Methods We measured cytokines in the plasma of immune thrombocytopenic purpura (ITP) and AA patients using the Luminex assay and confirmed the results in a mouse model and in vitro experiments. Results Both ITP and AA showed similarly low levels of CD40L, CXCL5, CCL5, and EGF, compared with healthy controls. In ITP, levels of these proteins were significantly greater in patients with higher platelet counts than in those with lower platelet counts. In a murine thrombocytopenia model, levels of CD40L, CXCL5, CCL5, and EGF decreased with platelet count after immune-mediated destruction, while the cytokine levels increased when the platelet count recovered. In vitro, concentrations of these cytokines in the supernatants of platelet suspensions were proportional to platelet numbers, and levels in sera prepared by simple blood coagulation were equivalent to those in platelet-rich plasma-converted sera. mRNA expression for CXCL5, CCL5, and EGF was higher in platelets than in megakaryocytes, peripheral blood mononuclear cells, granulocytes, and non-megakaryocytic bone marrow cells. Conclusions Plasma CD40L, CXCL5, CCL5, and EGF are mainly platelet-derived, suggesting a role of platelets in immune responses and inflammation. Measurement of CD40L, CXCL5, CCL5, and EGF in human blood allowed testable inferences concerning physiology and pathophysiology in quantitative platelet disorders. PMID:22537155

Feng, Xingmin; Scheinberg, Phillip; Samsel, Leigh; Rios, Olga; Chen, Jichun; McCoy, J. Philip; Ghanima, Waleed; Bussel, James B.; Young, Neal S.

2012-01-01

57

Alterations in immune cell subsets and their cytokine secretion profile in childhood idiopathic thrombocytopenic purpura (ITP).  

PubMed

Immune thrombocytopenic purpura (ITP) is acquired autoimmune disease in children characterized by the breakdown of immune tolerance. This work is designed to explore the contribution of different lymphocyte subsets in acute and chronic ITP children. Imbalance in the T helper type 1 (Th1)/Th2 cytokine secretion profile was investigated. The frequency of T (CD3(+), CD4(+), CD8(+)) and B (CD19(+)) lymphocytes, natural killer (NK) (CD16(+) 56(+)) and regulatory T (T(reg)) [CD4(+) CD25(+high) forkhead box protein 3 (FoxP3)(+) ] cells was investigated by flow cytometry in 35 ITP children (15 acute and 20 chronic) and 10 healthy controls. Plasma levels of Th1 cytokines [interferon (IFN-?) and tumour necrosis factor (TNF-?)] and Th2 [interleukin (IL)-4, IL-6 and IL-10)] cytokines were measured using enzyme-linked immunosorbent assay (ELISA). The percentage of Treg (P?

Talaat, R M; Elmaghraby, A M; Barakat, S S; El-Shahat, M

2014-05-01

58

Platelet Count Response to Helicobacter pylori Eradication in Iranian Patients with Idiopathic Thrombocytopenic Purpura  

PubMed Central

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune hematological disorder characterized by auto antibody-mediated platelet destruction. Although the main cause of ITP remains unclear, but its relationship with some infection was demonstrated. In recent years, many studies have demonstrated improvement of platelet counts in ITP patients after treating Helicobacter pylori infection. The aim of this study was to investigate the effects of H. pylori eradication on platelet count response in Iranian ITP patients. A total of 26 patients diagnosed with both ITP and H. pylori infection. ITP were diagnosed whose platelet counts were less than 100×103/?L. These patients were tested for H. pylori infection by Urea Breath Test and serum H. pylori antibody. All patients received triple therapy for 7 or 14 days to eradicate H. pylori infection. These patients followed for six months. Prevalence of H. pylori was 67.3%. H. pylori eradication achieved in 89.5% (26/29). Of the 26 patients, 15 (57.7%) exhibited a complete response (CR) and 11 (42.3%) were unresponsive. We did not find partial responders. There was a significant difference in the baseline platelet count of responders and non-responders patients (p<0.001). All responders had platelet count ?50×103/?L and all non-responders had platelet count <50×103/?L. Results of this study revealed that eradication therapy of H. pylori infection can improve platelet counts in ITP patients especially with mild thrombocytopenia and support routine detection and treatment of H. pylori infection in ITP patients in populations with a high prevalence of this infection. PMID:22973500

Payandeh, Mehrdad; Sohrabi, Nasrollah; Zare, Mohammad Erfan; Kansestani, Atefeh Nasir; Hashemian, Amir Hossein

2012-01-01

59

Randomized Trial of Anti-D Immunoglobulin versus Low-Dose Intravenous Immunoglobulin in the Treatment of Childhood Chronic Idiopathic Thrombocytopenic Purpura  

Microsoft Academic Search

Background: Chronic idiopathic (immune) thrombocytopenic purpura (ITP) develops in approximately 20% of children with acute ITP. Six years ago, low-dose intravenous immunoglobulin (IVIG) treatment of childhood ITP was started at the Pediatric Hematology Unit, Ain Shams University, while intravenous anti-D has been introduced in Egypt in 2001. Objectives: To assess the efficacy and safety of intravenous anti-D compared to low-dose

Mohsen S. El Alfy; Galila M. Mokhtar; Mohamed A. M. El-Laboudy; Ahmed Samy Khalifa

2006-01-01

60

Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura  

Microsoft Academic Search

The role of rituximab, a chimeric monoclo- nal antibody directed against the CD20 antigen, in the treatment of patients with chronic idiopathic thrombocytopenic pur- pura (ITP) has not been determined. The effectiveness and side effects of this therapeutic modality were investigated in a cohort of 25 individuals with chronic ITP. All patients had ITP that had been resistant to between

Roberto Stasi; Adalberto Pagano; Elisa Stipa; Sergio Amadori

61

Evaluation of efficacy and safety of the anti-VWF Nanobody ALX-0681 in a preclinical baboon model of acquired thrombotic thrombocytopenic purpura.  

PubMed

ALX-0681 is a therapeutic Nanobody targeting the A1-domain of VWF. It inhibits the interaction between ultra-large VWF and platelet GpIb-IX-V, which plays a crucial role in the pathogenesis of thrombotic thrombocytopenic purpura (TTP). In the present study, we report the efficacy and safety profile of ALX-0681 in a baboon model of acquired TTP. In this model, acute episodes of TTP are induced by administration of an ADAMTS13-inhibiting mAb. ALX-0681 completely prevented the rapid onset of severe thrombocytopenia and schistocytic hemolytic anemia. After induction of TTP, platelet counts also rapidly recovered on administration of ALX-0681. This effect was corroborated by the full neutralization of VWF activity. The schistocytic hemolytic anemia was also halted and partially reversed by ALX-0681 treatment. Brain CT scans and post mortem analysis did not reveal any sign of bleeding, suggesting that complete neutralization of VWF by ALX-0681 under conditions of thrombocytopenia was not linked with an excessive bleeding risk. The results obtained in this study demonstrate that ALX-0681 can successfully treat and prevent the most important hallmarks of acquired TTP without evidence of a severe bleeding risk. Therefore, ALX-0681 offers an attractive new therapeutic option for acquired TTP in the clinical setting. PMID:22948047

Callewaert, Filip; Roodt, Jan; Ulrichts, Hans; Stohr, Thomas; van Rensburg, Walter Janse; Lamprecht, Seb; Rossenu, Stefaan; Priem, Sofie; Willems, Wouter; Holz, Josefin-Beate

2012-10-25

62

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

PubMed

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

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

2014-11-27

63

Thrombotic thrombocytopenic purpura: 2012 American Society for Apheresis (ASFA) consensus conference on classification, diagnosis, management, and future research.  

PubMed

The American Society for Apheresis (ASFA) conducted a 1 day consensus conference on Thrombotic Thrombocytopenic Purpura (TTP) during its annual meeting in Atlanta, GA, on April 10, 2012. The authors of this article, a subcommittee of ASFA's Clinical Applications Committee, developed several questions with regard to definitions, classification, pathophysiology, diagnosis, management, and future research in TTP. These questions were provided to the seven invited speakers who are the experts in the field of TTP. Two moderators conducted the proceedings of the conference which was attended by more than 100 participants. After each presentation, there was an open discussion that included moderator-selected written questions submitted by the audience. A medical writer-generated transcript of the proceedings as well as each presentation was made available to the authors. Each summary was reviewed and approved by the respective speaker before submission of this article. The subcommittee also developed seven key questions for blinded, electronic polling conducted by the moderators to generate a consensus amongst the speakers. This article includes these presentation summaries as well as results of the electronic poll. PMID:24136342

Sarode, Ravi; Bandarenko, Nick; Brecher, Mark E; Kiss, Joseph E; Marques, Marisa B; Szczepiorkowski, Zbigniew M; Winters, Jeffrey L

2014-06-01

64

Cocaine-induced microangiopathic hemolytic anemia mimicking idiopathic thrombotic thrombocytopenic purpura: A case report and review of the literature.  

PubMed

Our understanding of the pathogenesis of idiopathic thrombotic thrombocytopenic purpura (TTP) has increased, but remains incomplete, particularly with respect to cases of suspected TTP that are either unresponsive to therapeutic plasma exchange (TPE) or have normal ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13) activity. A 53-year-old woman presented with severe anemia (hemoglobin 1.8 g/dL) and clinical and laboratory findings consistent with TTP in conjunction with acute cocaine use. The patient was treated with TPE until the pre-treatment ADAMTS13 activity was reported as normal without evidence of an inhibitor. TPE was stopped and the patient continued to improve without treatment. This patient's microangiopathic hemolytic anemia (MAHA) appeared to be secondary to cocaine use. The proposed pathogenesis is likely a combination of cocaine-induced vasoconstriction, vascular damage, platelet activation, and procoagulation. This is the fifth published report of cocaine-induced MAHA and to our knowledge the first with ADAMTS13 testing. J. Clin. Apheresis 29:284-289, 2014. © 2014 Wiley Periodicals, Inc. PMID:24753113

Odronic, Shelley; Quraishy, NurJehan; Manroa, Pooja; Kier, Yelena; Koo, Anna; Figueroa, Priscilla; Hamilton, Aaron

2014-10-01

65

Diagnosis and follow-up of thrombotic thrombocytopenic purpura by means of von Willebrand factor collagen binding assay.  

PubMed

Thrombotic thrombocytopenic purpura (TTP) is characterized by intravascular thrombosis leading to consumption of large or unusually large von Willebrand factor (VWF) multimers. The usefulness of VWF collagen binding (VWF:CB) assay was assessed in detecting the decrease/absence of large VWF multimers or the presence of abnormally large forms in patients with TTP. Nine patients with TTP were studied during the acute phase of the disorder and the absence of large VWF multimers was demonstrated by means of the VWF:CB assay. These findings were confirmed by VWF multimer pattern analysis; VWF:CB deficiency appeared to correlate with abnormalities in large VWF multimers. The diagnostic potency of VWF:CB was especially evident when the values were expressed as VWF:CB/VWF:Ag ratio. VWF:CB was also used during the follow-up of the disorder to document improvement or restoration of large VWF multimers. VWF:CB was able to detect the absence or decrease of large VWF multimers better than VWF ristocetin cofactor (VWF:RCo); in fact, VWF:CB was defective when large VWF multimers persisted to be decreased, in contrast with what observed with VWF:RCo. In conclusion, VWF:CB is a simple test that appears to be useful, together with clinical symptoms and reduced platelet count, for the diagnosis and follow-up of TTP. PMID:16959682

Casonato, A; Fabris, F; Pontara, E; Cattini, M G; Zocca, N; Gallinaro, L; Girolami, A; Pagnan, A

2006-07-01

66

Mechanisms of smooth muscle antibody production: a clinical study in children with infections, haemolytic syndromes, and idiopathic thrombocytopenic purpura.  

PubMed Central

Sera from 530 children suffering from various diseases and from 64 controls were tested for smooth muscle autoantibodies (SMA) by indirect immunofluorescence. A high incidence of SMA (51-86%) was found in patients with viral and bacterial infections (viral hepatitis, infectious mononucleosis, measles, mumps, chickenpox, typhoid fever, and brucellosis), independently of liver invovlvement, and in patients with acute haemolytic anaemia due to G-6-PD deficiency (48%). By contrast, the incidence of SMA from patients with beta-thalassaemia major and idiopathic thrombocytopenic purpura was no higher than in the controls. The discrepancy in incidence in haemolytic anaemias due to different causes may reflect the effect of endogenous and extrinsic agents. In the viral infections, SMA were mainly of the IgM class and gave an 'SMA-V' staining pattern. In bacterial infections (typhoid fever and brucellosis), SMA were either IgG only or IgM and IgG, and the staining pattern was also mainly 'SMA-V'. In infections which affect or may affect the liver (viral hepatitis, infectious mononucleosis, typhoid fever, and brucellosis), SMA was present at high titres (1:80-1:320), whereas in infections not affecting the liver (measles, mumps, and chickenpox) the titres were lower (less than or equal to 1:80). In most patients SMA occurred transiently and without apparent pathogenetic significance. The antigen against which infection-induced SMA is directed is not actin; its nature has yet to be identified. PMID:575362

Kanakoudi-Tsakalidis, F; Cassimos, C; Papastavrou-Mavroudi, T; Akoglu, T; Toh, B H; Yildiz, A; Osung, O; Holborow, E J; Sotelo, J

1979-01-01

67

R1933X mutation in the MYH9 gene in May-Hegglin anomaly mimicking idiopathic thrombocytopenic purpura.  

PubMed

May-Hegglin anomaly (MHA) is a rare autosomal dominant disorder characterized by the triad of thrombocytopenia, giant platelets, and inclusion bodies in leukocytes. Recent evidence links MHA to mutations in the MYH9 gene. MHA has not been reported in Taiwan before. We report a 25-year-old Taiwanese man who presented with prolonged bleeding after dental extraction. Examination of peripheral blood smear revealed thrombocytopenia (platelet = 35,000/?L), giant platelets, and Döhle-like cytoplasmic inclusions in neutrophils. A strong family history of thrombocytopenia favored hereditary macrothrombocytopenia over idiopathic thrombocytopenic purpura (ITP). Electron microscopy revealed a spindle shape and parallel order of filaments in the inclusions, consistent with the diagnosis of MHA. We performed mutational analysis using polymerase chain reaction followed by direct sequence of the MYH9 gene for the patient, his maternal uncle and cousin, and all showed the same heterozygous R1933X mutation in exon 40. MHA should be considered when a young patient has thrombocytopenia, frequently misdiagnosed as ITP. Morphological examination of peripheral blood smear, family history tracing and genetic studies are required to make an accurate diagnosis and avoid unnecessary and even harmful therapies such as corticosteroids and splenectomy. PMID:23759689

Sung, Chih-Chien; Lin, Shih-Hua; Chao, Tai-Kuang; Chen, Yeu-Chin

2014-01-01

68

The disulfide-rich region of platelet glycoprotein (GP) IIIa contains hydrophilic peptide sequences that bind anti-GPIIIa autoantibodies from patients with immune thrombocytopenic purpura (ITP).  

PubMed

Immune thrombocytopenic purpura (ITP) is an autoimmune blood disease caused by autoantibody-mediated destruction of blood platelets. Platelet glycoprotein (GP) IIb/IIIa is a common target for antiplatelet autoantibodies. The present studies were undertaken (1). to confirm whether the disulfide rich repeat region of GPIIIa contains target epitopes for antiplatelet antibodies in patients with ITP; (2). to determine whether these antigens were defined by peptide sequences in the absence of post-translational modification; and (3). to correlate observed immunologic reactivity with the recently solved X-ray crystallographic structure of an analogous integrin complex, the vitronectin receptor, alpha(V)beta(3). Recombinant fusion proteins of four GPIIIa extracellular sequences were prepared and purified. Immunoblotting results with purified recombinant peptides showed potent reactivity of 16 of 24 ITP patient serum anti-GPIIb/IIIa antibodies with the fusion protein containing the GPIIIa sequence of residues from 468 to 691. These results are consistent with a report by Kekomaki et al. that a 50 kDa chymotryptic digestion product of GPIIIa isolated from blood platelets contains target epitopes for serum antiplatelet antibodies in 16 of 33 ITP patients. Smaller peptides including residues 446-501 and residues 593-691 each reacted with only 5 of the 24 patient sera; furthermore all but 3 of these interactions were very weak. Visualization of the conformation of the extracellular portion of alpha(V)beta(3) reveals the location of the 222-residue antigenic GPIIIa (beta(3)) peptide 'B' at the immediately extracellular region of the protein that includes a beta-tail domain and several integrin-EGF domains. In summary, predictions of hydrophilicity, surface accessibility and antigenicity and the three dimensional structure of the beta(3) integrin correlate with autoantibody binding to a recombinant GPIIIa peptide 'B' containing residues 468-691. PMID:14499914

Beardsley, D J S; Tang, C; Chen, B-G; Lamborn, C; Gomes, E; Srimatkandada, V

2003-09-01

69

Rituximab therapy for thrombotic thrombocytopenic purpura: A proposed study of the Transfusion Medicine\\/Hemostasis Clinical Trials Network with a systematic review of rituximab therapy for immune-mediated disorders  

Microsoft Academic Search

The rationale for immunosuppressive therapy of thrombotic thrombocytopenic purpura (TTP) was estab- lished by observations that TTP may be caused by autoantibodies to ADAMTS13. Patients with high-titer autoantibodies to ADAMTS13 may have a higher mortality, and survivors may require prolonged plasma exchange therapy in spite of adjunctive glucocorticoid treatment. More intensive immunosuppressive therapy with rituximab may provide benefit for many

James N. George; Robert D. Woodson; Joseph E. Kiss; Kiarash Kojouri; Sara K. Vesely

2006-01-01

70

Expression of the 60 kDa and 71 kDa heat shock proteins and presence of antibodies against the 71 kDa heat shock protein in pediatric patients with immune thrombocytopenic purpura  

Microsoft Academic Search

BACKGROUND: Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by platelet destruction resulting from autoantibodies against platelet proteins, particularly platelet glycoprotein IIb\\/IIIa. Heat shock proteins (Hsp) have been shown to be major antigenic determinants in some autoimmune diseases. Antibodies to Hsps have also been reported to be associated with a number of pathological states. METHODS: Using western blot, we

Chengfeng Xiao; Sheng Chen; Mingchun Yuan; Fuyue Ding; Dongliang Yang; Ruibo Wang; Jianxin Li; Robert M Tanguay; Tangchun Wu

2004-01-01

71

Expression patterns of Th1 and Th2 cytokine genes in childhood idiopathic thrombocytopenic purpura (ITP) at presentation and their modulation by intravenous immunoglobulin G (IVIg) treatment: their role in prognosis  

Microsoft Academic Search

Childhood idiopathic thrombocytopenic purpura (ITP) resolves usually after the first episode, although it may recur, and in 10% to 20% of patients develops into a chronic disorder. Evidence of the immuno- regulatory role of Th1\\/Th2 responses in autoimmune diseases prompted us to perform a prospective study of Th1\\/Th2 gene expression profiles and transform- ing growth factor (TGF-) plasma levels in

Athanasia Mouzaki; Maria Theodoropoulou; Ioannis Gianakopoulos; Vassiliki Vlaha; Maria-Christina Kyrtsonis; Alice Maniatis

2002-01-01

72

Thrombotic thrombocytopenic purpura  

MedlinePLUS

Plasma exchange (plasmapheresis plus infusion of donor plasma) is used to remove the antibodies that are affecting clotting from the blood. It also replace the missing enzyme. First, you will have ...

73

Idiopathic thrombocytopenic purpura (ITP)  

MedlinePLUS

... your blood clot by clumping together to plug small holes in damaged blood vessels. The antibodies attach to the platelets. The spleen destroys the platelets that carry the antibodies. In children, the disease sometimes follows a viral infection. In adults, it ...

74

Impact of chronic Immune Thrombocytopenic Purpura (ITP) on health-related quality of life: a conceptual model starting with the patient perspective  

PubMed Central

Background Immune thrombocytopenic purpura (ITP), a condition characterized by autoimmune-mediated platelet destruction and suboptimal platelet production, is associated with symptoms such as bruising, epistaxis, menorrhagia, mucosal bleeding from the gastrointestinal and urinary tracts and, rarely central nervous system bleeding. The aim of this research is to develop a conceptual model to describe the impact of ITP and its treatment on patients' health-related quality of life (HRQoL). Methods A literature search and focus groups with adult ITP patients were conducted to identify areas of HRQoL affected by ITP. Published literature was reviewed to identify key HRQoL issues and existing questionnaires used to assess HRQoL. Focus group transcripts were reviewed, and common themes were extracted by grouping conceptual categories that described the impact on HRQoL. Results The literature synthesis and themes from the focus group data suggest that decreased platelet counts, disease symptoms, and treatment side effects influence multiple domains of HRQoL for ITP patients. Key areas affected by ITP and its treatments include emotional and functional health, work life, social and leisure activities, and reproductive health. Conclusion ITP affects various areas of HRQoL. This conceptual model will help inform the evaluation of therapeutic strategies for ITP. PMID:18261217

Mathias, Susan D; Gao, Sue K; Miller, Kimberly L; Cella, David; Snyder, Claire; Turner, Ralph; Wu, Albert; Bussel, James B; George, James N; McMillan, Robert; Wysocki, Diane Kholos; Nichol, Janet L

2008-01-01

75

[Thrombopoietin receptor agonists administration for acute exacerbation of chronic idiopathic thrombocytopenic purpura and subsequent anticoagulant therapy for accompanying deep venous thrombosis of the lower limbs].  

PubMed

We report two patients (70- and 49-year-old Japanese men) with acute exacerbation of chronic idiopathic thrombocytopenic purpura (ITP) and deep venous thrombosis of the lower extremities. Both were successfully managed with thrombopoietin receptor agonist (TPO-RA) administration. Both had ITP refractory to steroid treatment. Their immature platelet fraction (absolute-IPF) counts were increased and paralleled the platelet recoveries after TPO-RA (eltrombopag and romiplostim, respectively) without progression of thrombosis. Although ITP has recently been evaluated as a thrombophilic disorder, reports on acute exacerbation of ITP with newly diagnosed thrombosis are limited, and the pathophysiology and association between ITP and thrombosis remain to be elucidated. Moreover, the influences of TPO-RA on thrombosis are still controversial. To our knowledge, this is the first case report describing patients with exacerbation of ITP who developed thrombosis and were treated with TPO-RA. The outcomes of our cases underscore the importance of monitoring thrombosis and not delaying the initiation of anticoagulation treatment during the use of TPO-RA. PMID:24975340

Kawano, Hiroki; Suzuki, Tomohide; Ishii, Shinichi; Wakahashi, Kanako; Kawano, Yuko; Sada, Akiko; Minagawa, Kentaro; Takaya, Tomofumi; Yamashita, Tomoya; Hirata, Ken-Ichi; Koriyama, Kenji; Nagamatsu, Yuichi; Matsui, Toshimitsu; Katayama, Yoshio

2014-06-01

76

Ticlopidine-, Clopidogrel-, and Prasugrel-Associated Thrombotic Thrombocytopenic Purpura: A 20-Year Review from the Southern Network on Adverse Reactions (SONAR)  

PubMed Central

Thienopyridine-derivatives (ticlopidine, clopidogrel, and prasugrel) are the primary antiplatelet agents. Thrombotic thrombocytopenic purpura (TTP) is a rare drug-associated syndrome, with the thienopyridines being the most common drugs implicated in this syndrome. We reviewed 20 years of information on clinical, epidemiologic, and laboratory findings for thienopyridine-associated TTP. Four, 11, and 11 cases of thienopyridine-associated TTP were reported in the first year of marketing of ticlopidine (1989), clopidogrel (1998), and prasugrel (2010), respectively. As of 2011, the FDA received reports of 97 ticlopidine-, 197 clopidogrel-, and 14 prasugrel-associated TTP cases. Severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was present in 80% and antibodies to 100% of these TTP patients on ticlopidine, 0% of the patients with clopidogrel-associated TTP (p < 0.05), and an unknown percentage of patients with prasugrel-associated TTP. TTP is associated with use of each of the three thienopyridines, although the mechanistic pathways may differ. PMID:23111862

Jacob, Sony; Dunn, Brianne L.; Qureshi, Zaina P.; Bandarenko, Nicholas; Kwaan, Hau C.; Pandey, Dilip K.; McKoy, June M.; Barnato, Sara E.; Winters, Jeffrey L.; Cursio, John F.; Weiss, Ivy; Raife, Thomas J.; Carey, Patricia M.; Sarode, Ravindra; Kiss, Joseph E.; Danielson, Constance; Ortel, Thomas L.; Clark, William F.; Rock, Gail; Matsumoto, Masanori; Fujimura, Yoshihiro; Zheng, X. Long; Chen, Hao; Chen, Fei; Armstrong, John M.; Raisch, Dennis W.; Bennett, Charles L.

2013-01-01

77

Inhibition of von Willebrand factor-platelet glycoprotein Ib interaction prevents and reverses symptoms of acute acquired thrombotic thrombocytopenic purpura in baboons.  

PubMed

The pathophysiology of thrombotic thrombocytopenic purpura (TTP) can be explained by the absence of active ADAMTS13, leading to ultra-large von Willebrand factor (UL-VWF) multimers spontaneously interacting with platelets. Preventing the formation of UL-VWF-platelet aggregates therefore is an attractive new treatment strategy. Here, we demonstrate that simultaneous administration of the inhibitory anti-VWF monoclonal antibody GBR600 and the inhibitory anti-ADAMTS13 antibody 3H9 to baboons (prevention group) precluded TTP onset as severe thrombocytopenia and hemolytic anemia were absent in these animals. In addition, partial VWF inhibition was not enough to prevent thrombocytopenia, demonstrating the specificity of this therapeutic strategy. GBR600 treatment of baboons during acute TTP (treatment group) resulted in a rapid recovery of severe thrombocytopenia similar to the platelet count increases observed in TTP patients treated by plasma exchange. Baboons in the control group only injected with 3H9 developed early stages of TTP as previously described. Hence, inhibiting VWF-GPIb interactions is an effective way to prevent and treat the early symptoms of acquired TTP in baboons. PMID:22855603

Feys, Hendrik B; Roodt, Jan; Vandeputte, Nele; Pareyn, Inge; Mottl, Harald; Hou, Sam; Lamprecht, Seb; Van Rensburg, Walter J; Deckmyn, Hans; Vanhoorelbeke, Karen

2012-10-25

78

Dieulafoy Lesion in the Ascending Colon Presenting with Gastrointestinal Bleeding and Severe Anemia Complicated by a Coexisting Severe Resistant Chronic Idiopathic Thrombocytopenic Purpura  

PubMed Central

Background. GI (gastrointestinal) bleeding can be due to a variety of etiologies ranging from being common like bleeding peptic ulcer disease or esophageal varices. One of the rarely documented causes is the Dieulafoy lesion which is known as an abnormally large ectatic artery that penetrates the gut wall, occasionally eroding through the mucosa causing massive bleeding. In addition to that, we refer to the uncommon presentation of Dieulafoy lesion itself as it is well known to be found in the stomach, esophagus, duodenum, and jejunum but not the ascending colon as in our case. The patient had a coexisting ITP (idiopathic thrombocytopenic purpura) that was resistant to different therapies. Case Report. We report a case of a 48-year-old Egyptian female known for chronic ITP resistant to treatment. The patient presented with bright red bleeding per rectum and severe life threatening anemia. Endoscopic study showed a Dieulafoy lesion. Endoscopic clipping was successful in controlling the bleeding. Conclusion. Dieulafoy lesion is a rare reason for GI bleeding and can present in common or unexpected places. Also extreme caution should be used in patients with bleeding tendency due to different reasons, like ITP in our case.

Eltawansy, Sherif Ali; Thyagarajan, Brag; Baig, Nadeem

2014-01-01

79

Ticlopidine-, clopidogrel-, and prasugrel-associated thrombotic thrombocytopenic purpura: a 20-year review from the Southern Network on Adverse Reactions (SONAR).  

PubMed

Thienopyridine-derivatives (ticlopidine, clopidogrel, and prasugrel) are the primary antiplatelet agents. Thrombotic thrombocytopenic purpura (TTP) is a rare drug-associated syndrome, with the thienopyridines being the most common drugs implicated in this syndrome. We reviewed 20 years of information on clinical, epidemiologic, and laboratory findings for thienopyridine-associated TTP. Four, 11, and 11 cases of thienopyridine-associated TTP were reported in the first year of marketing of ticlopidine (1989), clopidogrel (1998), and prasugrel (2010), respectively. As of 2011, the FDA received reports of 97 ticlopidine-, 197 clopidogrel-, and 14 prasugrel-associated TTP cases. Severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was present in 80% and antibodies to 100% of these TTP patients on ticlopidine, 0% of the patients with clopidogrel-associated TTP (p < 0.05), and an unknown percentage of patients with prasugrel-associated TTP. TTP is associated with use of each of the three thienopyridines, although the mechanistic pathways may differ. PMID:23111862

Jacob, Sony; Dunn, Brianne L; Qureshi, Zaina P; Bandarenko, Nicholas; Kwaan, Hau C; Pandey, Dilip K; McKoy, June M; Barnato, Sara E; Winters, Jeffrey L; Cursio, John F; Weiss, Ivy; Raife, Thomas J; Carey, Patricia M; Sarode, Ravindra; Kiss, Joseph E; Danielson, Constance; Ortel, Thomas L; Clark, William F; Rock, Gail; Matsumoto, Masanori; Fujimura, Yoshihiro; Zheng, X Long; Chen, Hao; Chen, Fei; Armstrong, John M; Raisch, Dennis W; Bennett, Charles L

2012-11-01

80

Disseminated intravascular coagulation associated with acute hemoglobinemia or hemoglobinuria following Rh(0)(D) immune globulin intravenous administration for immune thrombocytopenic purpura.  

PubMed

The Food and Drug Administration (FDA) licensed Rh(o)(D) immune globulin intravenous (anti-D IGIV) on March 24, 1995, for treatment of immune thrombocytopenic purpura (ITP). A previous review described data on 15 patients who experienced acute hemoglobinemia or hemoglobinuria following anti-D IGIV administration for ITP or secondary thrombocytopenia. Eleven of those patients also experienced clinically compromising anemia, transfusion with packed red blood cells, renal insufficiency, dialysis, or death. That review suggested that patients receiving anti-D IGIV be monitored for those and other potential complications of hemoglobinemia, particularly disseminated intravascular coagulation (DIC). Through November 30, 2004, the FDA received 6 reports of DIC associated with "acute hemolysis" (or similar terms), 5 of which involved fatalities. The attending or consulting physicians assessed that acute hemolysis or DIC caused or contributed to each death. This review presents the first case series of DIC associated with acute hemoglobinemia or hemoglobinuria following anti-D IGIV administration for ITP. The purpose of this review is to increase awareness among physicians and other health care professionals that DIC may be a rare but potentially severe complication of anti-D IGIV treatment. Increased awareness of DIC as a diagnostic possibility may enable prompt recognition and medical intervention in affected patients. PMID:15878975

Gaines, Ann Reed

2005-09-01

81

DNA methyltransferase 3B (DNMT3B -579G>T) promotor polymorphism and the susceptibility to pediatric immune thrombocytopenic purpura in Egypt.  

PubMed

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by increased platelet destruction. Although the etiology of ITP remains unclear, it is accepted that both environmental and genetic factors play an important role in the development of the disease. The present study aimed at exploring a novel molecular determinant that may influence the susceptibility and course of ITP in Egyptian children. To achieve our aim, genotyping of DNMT3B -579G>T promotor polymorphism by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. The current study was conducted on 140 ITP patients and 150 age and gender matched healthy controls. The results obtained revealed that DNMT3B -579 TT homotype was significantly higher in ITP patients and conferred almost three fold increased risk of ITP (OR=3.16, 95%CI=1.73-5.79). There was no statistically significant difference between ITP patients with wild or mutant genotypes as regards their clinical or laboratory data. Furthermore, there was no statistical difference in the distribution of DNMT3B -579G>T genotypes between acute and chronic ITP patients. In conclusion, DNMT3B -579G>T promotor polymorphism represents a novel genetic risk factor for ITP but not a predictor for tendency to chronicity in pediatric ITP in Egypt. PMID:23000068

Khorshied, Mervat Mamdooh; El-Ghamrawy, Mona Kamal

2012-12-10

82

Efficacy and Safety Profile of Solvent/Detergent Plasma in the Treatment of Acute Thrombotic Thrombocytopenic Purpura: A Single-Center Experience.  

PubMed

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare clinical disorder which was associated with poor prognosis for a long time. The outcome has been improved by the consistent introduction of thera-peutic plasma exchange (TPE) as standard treatment of TTP. PATIENTS AND METHODS: We describe our experience in the use of solvent/detergent-treated plasma (SDP) for TPE in TTP. We retrospectively analyzed acute TTP epi-sodes in 8 patients (mean age = 27 years, range 18-44 years) treated with TPE using SDP with regard to tolerability and efficacy. RESULTS: All 8 patients were positive for anti-ADAMTS-13 antibody. Seven out of 8 had a se-vere ADAMTS-13 deficiency. All patients responded rapidly to SDP TPE with an increase in platelet count to above 150 x 10(9)/l. Hemolytic anemia disappeared over the treatment period. Approximately 2,000 l SDP were used for more than 500 treatments. Treatment with SDP was well tolerated; none of the patients experienced an adverse drug reaction after exposure to SDP. No major complications occurred even after multiple TPE. CONCLUSION: Our investigations suggest that TPE using SDP as replacement fluid is an effective treatment for TTP. The data described also indicate that SDP might offer the benefit of reducing adverse drug reactions. PMID:20737012

Edel, Elvira; Al-Ali, Haifa Kathrin; Seeger, Susanne; Kauschat, Dörte; Matthes, Gert

2010-02-01

83

Low-dose autologous in vitro opsonized erythrocytes. Radioimmune method and autologous opsonized erythrocytes for refractory autoimmune thrombocytopenic purpura in adults  

SciTech Connect

Adult patients with chronic autoimmune thrombocytopenic purpura (ATP), which proved refractory to various treatments, received a single dose of autologous in vitro opsonized erythrocytes with 100 micrograms of anti-D IgG. In 1983, 30 of these patients were treated with autologous erythrocytes that had been opsonized and labeled with 25 mCi (740 MBq) of technetium Tc 99m; this treatment was designated as the radioimmune method. Favorable responses were noted in 36% of patients so treated. In 1985, another group of 16 patients with refractory ATP received therapy with autologous opsonized erythrocytes (AOPE) and 55% of these patients showed favorable responses. Five (17%) of the patients treated using the radioimmune method attained a complete, long-term (greater than 35 months) remission of their ATP, and five (31%) of the patients treated using AOPE remained in complete remission over 270 days after cessation of therapy. Major complications were not seen. We concluded that the interaction of macrophages with low-dose AOPE is a successful therapeutic approach in ATP refractory to standard treatment.

Ambriz, R.; Munoz, R.; Pizzuto, J.; Quintanar, E.; Morales, M.; Aviles, A.

1987-01-01

84

Recurrent Thrombotic Thrombocytopenic Purpura-Like Syndrome as a Paraneoplastic Phenomenon in Malignant Peritoneal Mesothelioma: A Case Report and Review of the Literature  

PubMed Central

We report the case of an African American male with no significant past medical history presenting with recurrent, rapidly relapsing episodes of thrombotic thrombocytopenic purpura (TTP) despite aggressive treatment with several lines of treatment. Incidentally, these episodes were associated with severe abdominal pain which eventually developed into acute abdomen and prompted exploratory laparotomy, revealing diffuse carcinomatosis with a tumor located on the left pelvis that was encasing the distal sigmoid colon. Pathology made a final diagnosis of peritoneal mesothelioma. TTP-like syndrome (TTP-LS) has been described as a paraneoplastic phenomenon in several malignancies but never before in the setting of malignant mesothelioma. Paraneoplastic TTP-like syndrome has historically been associated with a dismal prognosis and particular clinical and laboratory abnormalities described in this paper. It is of utmost importance to make a prompt determination whether TTP is idiopathic or secondary to an underlying condition because of significant differences in their prognosis, treatment, and response. This paper also reviews the current literature regarding this challenging condition. PMID:23082261

Socola, Francisco; Loaiza-Bonilla, Arturo; Bustinza-Linares, Ernesto; Correa, Ricardo; Rosenblatt, Joseph D.

2012-01-01

85

Intravenous Anti-D Treatment of Immune Thrombocytopenic Purpura: Analysis of Efficacy, Toxicity, and Mechanism of Effect  

Microsoft Academic Search

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 under- gone splenectomy and in three already splenectomized pa- tients. The mean platelet increase for the 43 nonsplenecto- mized patients was 95,OOO\\/pL (median 43,OOO\\/pL). Children had greater acute platelet responses than did adults. Human immunodeficiency

James B. Bussel; Joseph N. Graziano; Robert P. Kimberly; Savita Pahwa; Louis M. Aledort

1991-01-01

86

Acute onset hemoglobinemia and/or hemoglobinuria and sequelae following Rh(o)(D) immune globulin intravenous administration in immune thrombocytopenic purpura patients.  

PubMed

Rh(o)(D) immune globulin intravenous (anti-D IGIV) was licensed by the United States Food and Drug Administration (FDA) in March 1995 to treat patients with immune thrombocytopenic purpura (ITP). Anti-D IGIV induces extravascular hemolysis, an expected adverse reaction that is consistent with the presumed mechanism of action. Between licensure and April 1999, the FDA received 15 reports of hemoglobinemia and/or hemoglobinuria following anti-D IGIV administration that met the case definition for this review. The mechanism responsible for hemoglobinemia and/or hemoglobinuria is unexplained. Review of these reports was prompted by the seriousness and the unexpectedness of treatment-associated sequelae experienced by 11 patients. Of these patients, 7 developed sufficient onset or exacerbation of anemia that orders were written for packed red blood cell transfusions, although only 6 patients were transfused. Eight patients experienced the onset or exacerbation of renal insufficiency, and 2 patients underwent dialysis. One patient died due to complications of exacerbated anemia. Six patients experienced 2 to 3 sequelae. Absent validated incidence data, a 1.5% estimated incidence rate from published clinical trial data and a 0.1% estimated reporting rate from FDA and drug utilization data were calculated for reported cases of hemoglobinemia and/or hemoglobinuria. This review presents the first case series of anti-D-IGIV-associated hemoglobinemia and/or hemoglobinuria and provides pretreatment and posttreatment clinical and laboratory findings of the case series patients. The primary purpose of this review is to increase awareness of this potentially serious occurrence among physicians and health care professionals who manage ITP patients treated with anti-D IGIV, thereby enabling prompt recognition and treatment of sequelae. (Blood. 2000;95:2523-2529) PMID:10753830

Gaines, A R

2000-04-15

87

[Metastatic prostate cancer complicated with chronic disseminated intravascular coagulopathy causing acute renal failure, mimicking thrombotic thrombocytopenic purpura and hemolytic uremic syndrome: pathomechanism, differential diagnosis and therapy related to a case].  

PubMed

Disseminated intravascular coagulopathy (DIC) is characterized as activation of the clotting system resulting in fibrin thrombi, gradually diminishing levels of clotting factors with increased risk of bleeding. Basically two types of DIC are distinguished: (1) chronic (compensated) - with alteration of laboratory values and (2) acute (non-compensated) - with severe clinical manifestations: bleeding, shock, acute renal failure (ARF), transient focal neurologic deficit, delirium or coma. Chronic DIC related to metastatic neoplasia is caused by pancreatic, gastric or prostatic carcinoma in most of the cases. Incidence rate of DIC is 13-30% in prostate cancer, among those only 0.4-1.65% of patients had clinical signs and symptoms of DIC. In other words, chronic DIC is developed in one of eight patients with prostate cancer. DIC is considered as a poor prognostic factor in prostatic carcinoma. The similar clinical and laboratory findings of TTP-HUS (thrombotic thrombocytopenic purpura - hemolytic uremic syndrome) and DIC makes it difficult to differentiate between them. A 71 years old male patient with known chronic obstructive pulmonary disease, benign prostatic hyperplasia, significant carotid artery stenosis, gastric ulcer and alcoholic liver disease was admitted to another hospital with melena. Gastroscopy revealed intact gastric mucosa and actually non-bleeding duodenal ulcer covered by clots. Laboratory results showed hyperkalemia, elevated kidney function tests, indirect hyperbilirubinemia, increased liver function tests, leukocytosis, anemia, thrombocytopenia and elevated international normalized ratio (INR). He was treated with saline infusions, four units of red blood cells and one unit of fresh frozen plasma transfusions. Four days later he was transported to our Institution with ARF. Physical examination revealed dyspnoe, petechiae, hemoptoe, oliguria, chest-wall pain and aggressive behavior. Thrombocytopenia, signs of MAHA (fragmentocytes and helmet cells in the peripheral blood), normal INR, elevated lactate dehydrogenase (LDH) and ARF suggested TTP-HUS. Hemodialysis and six plasmaferesis (PF) were carried out. After the fifth PF, skin manifestations of thrombotic microangiopathy occurred on the feet. Clotting analysis revealed elevated D-dimer (>5 ?g/mL), normal fibrinogen (3.2 g/L), a slightly raised INR (1.36) and activated partial prothrombin time (APTT) (45.8 sec), normal reticulocyte (57 G/L) and a slightly low platelet count (123 G/L), which proved to be chronic DIC. Therapeutic dose of low-molecular-weight heparin (LMWH) was started. Elevated prostate-specific antigen (PSA) (109.6 ng/mL) suggested prostatic carcinoma. Prostate biopsy revealed adenocarcinoma (Gleason: 4+4 for left lobe and 3+3 for right lobe). Elevated alkaline phosphatase suggested metastases in the bone, which were confirmed by bone scintigraphy. Combined androgen blockade (CAB) was started. After three months follow-up our patient's status is satisfactory. PSA is in the normal range (4.6 ng/mL). Thrombocytopenia of uncertain origin with normal or raised INR, APTT, elevated D-dimer, normal fibrinogen and reticulocyte count prove the diagnosis of chronic DIC. This process warrants searching for metastatic neoplasia. Due to the relatively low serum levels of circulating procoagulant factors (e.g. tissue factor), therapeutic dose of LMWH can be used with good efficiency in chronic DIC with low risk of bleeding. Severe DIC as a complication of metastatic prostate cancer can be treated by androgen deprivation therapy (ADT) or CAB in combination with ketokonazole and concomitant use of supportive treatment. Deme D, Ragán M, Kovács L, Kalmár K, Varga E, Varga T, Rakonczai E. Metastatic prostate cancer complicated with chronic disseminated intravascular coagulopathy causing acute renal failure mimicking thrombotic thrombocytopenic purpura and hemolytic uremic syndrome: pathomechanism, differential diagnosis and therapy related to a case. PMID:21163766

Deme, Dániel; Ragán, Márton; Kalmár, Katalin; Kovács, Lajos; Varga, Erzsébet; Varga, Tünde; Rakonczai, Ervin

2010-12-01

88

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

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

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

2012-01-01

89

How Is Thrombotic Thrombocytopenic Purpura Treated?  

MedlinePLUS

... and surgery. Treatments are done in a hospital. Plasma Therapy Plasma is the liquid part of your blood. It ... nutrients to your body. TTP is treated with plasma therapy. This includes: Fresh frozen plasma for people ...

90

Progressive pigmentary purpura.  

PubMed

A 58-year-old man presented for evaluation and treatment of non-tender, non-pruritic, annular patches on the right temple and frontal aspect of the scalp that reddened with exercise. A biopsy specimen showed a purpuric dermatitis with features of lymphocytic vasculitis; a diagnosis of exercise-induced progressive pigmentary purpura was made. Whereas progressive pigmentary purpura is purported to be caused by exercise, other similar appearing entities are associated with exercise, namely exercise-induced vasculitis (EIV). EIV may be considered as an acute microcirculatory deficiency and thermoregulation decompensation that occurs after episodes of exhaustive major muscular activity or after unusual or excessive exercise. The combination of age greater than 50 years, heat, and prolonged exercise are the most potent contributing factors. This is the first report of exercise-induced progressive pigmentary purpura. PMID:22031640

Brauer, Jeremy A; Mundi, Jyoti; Chu, Julie; Patel, Rishi; Meehan, Shane; Greenspan, Alan H; Stein, Jennifer

2011-01-01

91

Purpura Fulminans following Thermal Injury  

PubMed Central

Purpura fulminans is a rare syndrome of intravascular thrombosis and hemorrhagic infarction of the skin, which is an unusual cutaneous manifestation of disseminated intravascular coagulation. It often occurs in small children and babies due to infection and/or sepsis, rarely in adults in clinic. We report the first case of deadly purpura fulminans following thermal injury in a 64-year-old Chinese woman. The purpura developed sharply and aggravated multiple organ dysfunction. The patient died of purpura fulminans, disseminated intravascular coagulation, and multiple organ dysfunction syndrome. PMID:23762660

Hu, Jiongyu; Jiang, Xupin; Luo, Qizhi

2013-01-01

92

A case of palpable purpura and nephropathy: Occam's Razor or Hickam's Dictum.  

PubMed

Vasculitis causing palpable purpura, nephropathy, and hematologic abnormalities is a well-known entity. However, sometimes, vasculitis may not be the primary cause but is part of a systemic disease. Literature suggests that infections like HIV can induce nephropathy and antineutrophilic cytoplasmic antibody-positive vasculitis, which is different from the well-known entity of "antineutrophilic cytoplasmic antibody-associated vasculitis." We present a 46-year-old female patient with a history of intravenous drug abuse who reported with a rash, swelling, and palpable purpura of the lower extremities. Peripheral smear showed no evidence of disseminated intravascular coagulation or thrombotic thrombocytopenic purpura; metabolic profile showed acute kidney injury. She was found to be HIV- and hepatitis C-positive. Immunologic workup was positive for both MPO and PR3 antineutrophilic cytoplasmic antibodies and negative for cryoglobulins; complement levels were low. Skin biopsy showed leukocytoclastic vasculitis but kidney biopsy was negative for any immunologic involvement; it showed only glomerulosclerosis. Thus, it was thought that nephropathy and vasculitis, in this case, are two distinct pathologic processes, both induced by infection (HIV and/or hepatitis C). The patient responded to low-dose steroid therapy. She was later started on the definitive therapy, the highly active antiretroviral therapy regimen. This case illustrates the fact that low-dose steroids can still be a good alternative in acute situations in patients at risk from immunosuppression. PMID:21248615

Mandhadi, Ranadeep; Kodumuri, Vamsi; Arora, Rohit; Puneet Singh, Param; Adigopula, Shashi; Chua, Serafin

2013-01-01

93

Purpura-associated congenital lymphedema.  

PubMed

An 8-year-old girl referred to our Department for a two-month worsening of congenital primary lymphedema of the lower limb and for the appearance of several purpuric lesions on the right thigh and knee. We diagnosed a lichenoid pigmented purpura of Gougerot and Blum in a patient with Milroy disease, complicated by an insufficiency of anterior saphena. We treated the patient with topical steroids and compression stockings, until surgical intervention of phlebectomy. We report this case for the rarity of the disease, for the even more rare association with lichenoid pigmented purpura and for cutaneous immunopathological findings. PMID:19620038

Berti, Samantha; Pieri, Alessandro; Lotti, Torello; Duranti, Alberto; Panelos, John; De Martino, Maurizio; Moretti, Silvia

2009-01-01

94

Accessory spleens: Clinical significance with particular reference to the recurrence of idiopathic thrombocytopenic purpura  

Microsoft Academic Search

One of the important stages during splenectomy is the search for accessory spleens. The average frequency of accessory spleens is an estimated 11%. In our own material in 611 patients who had splenectomy in hematological disorders, accessory spleens were found in 110 patients (18%). The surgical anatomy, embryology, and clinical significance of the accessory spleens, with particular reference to the

Witold J. Rudowski

1985-01-01

95

Resolution of Refractory Chronic Autoimmune Thrombocytopenic Purpura Following Mesenchymal Stem Cell Transplantation: A Case Report  

Microsoft Academic Search

Herein we have reported the case of a man with chronic autoimmune thrombocytopenia (AITP) refractory to conventional therapy who underwent T-cell-depleted autologous peripheral blood stem cell (PBSC) transplantation. A complete, steroid-independent, platelet remission was obtained, but unfortunately he subsequently relapsed after 3 months. Finally, we administered human adipose tissue-derived mesenchymal stem cells (AMSC) with resolution to the AITP.

B. Fang; Y. P. Song; N. Li; J. Li; Q. Han; R. C. Zhao

2009-01-01

96

Resolution of refractory chronic autoimmune thrombocytopenic purpura following mesenchymal stem cell transplantation: a case report.  

PubMed

Herein we have reported the case of a man with chronic autoimmune thrombocytopenia (AITP) refractory to conventional therapy who underwent T-cell-depleted autologous peripheral blood stem cell (PBSC) transplantation. A complete, steroid-independent, platelet remission was obtained, but unfortunately he subsequently relapsed after 3 months. Finally, we administered human adipose tissue-derived mesenchymal stem cells (AMSC) with resolution to the AITP. PMID:19545737

Fang, B; Song, Y P; Li, N; Li, J; Han, Q; Zhao, R C

2009-06-01

97

Indian tick typhus presenting as Purpura fulminans.  

PubMed

Seriously ill patients presenting with purpura fulminans, sepsis and multi-organ failure often require extensive diagnostic workup for proper diagnosis and management. Host of common infections prevalent in the tropics, e.g. malaria, dengue; other septicemic infections e.g. meningococcemia, typhoid, leptospirosis, toxic shock syndrome, scarlet fever, viral exanthems like measles, infectious mononucleosis, collagen vascular diseases (Kawasaki disease, other vasculitis) diseases, and adverse drug reactions are often kept in mind, and the index of suspicion for rickettsial illness is quite low. We present a case of Indian tick typhus presenting with purpura fulminans (retiform purpura all over the body), sepsis and multiorgan failure without lymphadenopathy and eschar, successfully treated with doxycycline and discharged home. Hence, a high index clinical suspicion and prompt administration of a simple therapy has led to successful recovery of the patient. PMID:25097365

Tirumala, Suhasini; Behera, Bijayini; Jawalkar, Srikanth; Mishra, Pradeep Kumar; Patalay, Pavithra Vani; Ayyagari, Sudha; Nimmala, Pavani

2014-07-01

98

Purpura haemorrhagica in 53 horses.  

PubMed

The medical records of 53 horses with purpura haemorrhagica were reviewed. Seventeen of them had been exposed to or infected with Streptococcus equi, nine had been infected with Corynebacterium pseudotuberculosis, five had been vaccinated with S. equi M protein, five had had a respiratory infection of unknown aetiology, and two had open wounds; the other 15 cases had no history of recent viral or bacterial infection. The horses were between six months and 19 years of age (mean 8.4 years). The predominant clinical signs were well demarcated subcutaneous oedema of all four limbs and haemorrhages on the visible mucous membranes; other signs included depression, anorexia, fever, tachycardia, tachypnoea, reluctance to move, drainage from lymph nodes, exudation of serum from the skin, colic, epistaxis and weight loss. Haematological and biochemical abnormalities commonly detected were anaemia, neutrophilia, hyperproteinaemia, hyperfibrinogenaemia, hyperglobulinaemia and high activities of muscle enzymes. All of the horses were treated with corticosteroids; 42 also received non-steroidal anti-inflammatory drugs and 26 received antimicrobial drugs. Selected cases received special nursing care, including hydrotherapy and bandaging of the limbs. Most of the horses were treated for more than seven days and none of them relapsed. Forty-nine of the horses survived, one died and three were euthanased, either because their severe clinical disease failed to respond to treatment or because they developed secondary complications. Two of the four non-survivors had been vaccinated against S. equi with a product containing the M protein, one had a S. equi infection and the other had a respiratory infection of undetermined aetiology. PMID:12918829

Pusterla, N; Watson, J L; Affolter, V K; Magdesian, K G; Wilson, W D; Carlson, G P

2003-07-26

99

President's Address: Purpura of the Urinary Tract.  

PubMed

Twenty-four cases of purpura of the urinary tract are discussed and analysed.Purpura of the kidney may be a cause of painless haematuria. In some cases nephrectomy may be necessary to check the bleeding.Purpura of the bladder is a cause of painful haematuria. In such cases the diagnosis can be made with the cytoscope.A number of the cases appear to be caused by a streptococcal infection of throat, teeth or bowel.The exhibition of horse serum by the mouth usually has an immediate effect in checking the bleeding tendencySplenectomy should be considered in severe chronic recurrent cases.Purpura is a symptom and not a disease. It can attack the kidney or bladder in any type of case. The attacks may be simple, recurrent or fulminating. In many cases no cause can be discovered, in others it is associated with acute rheumatism. In a number of cases a proximate cause can be discovered, in the nature of a bacterial infection, a chemical poison, a thrombocytopenia, splenomegaly, or the deprivation of some vitamin. PMID:19986473

Kidd, F

1928-04-01

100

Anti-human immunodeficiency virus type 1 antibody complexes on platelets of seropositive thrombocytopenic homosexuals and narcotic addicts.  

PubMed Central

Patients with human immunodeficiency virus type 1 (HIV-1) infection develop an immunologic thrombocytopenic purpura associated with markedly elevated platelet IgG, IgM, and C3C4 as well as serum immune complexes determined by the polyethylene glycol (PEG) method. Analysis of their serum PEG-precipitable immune complexes as well as platelet acid eluates revealed the presence of anti-HIV-1 antibody existing as a complex that eluted in the void volume of a Sephadex G-200 gel-filtration column. The complex binds to washed normal platelets, whereas affinity-purified anti-HIV-1 (gp120) antibody does not. HIV-1 antigen or proviral DNA was not detectable in the immune complexes or platelet extracts. However, anti-antibodies directed against anti-HIV-1 antibody were detectable in the immune complexes as well as platelet eluates. Approximately 50% of eluted platelet IgG contained anti-HIV-1 antibody. Thus the markedly elevated platelet immunoglobulin is partly due to the presence of anti-HIV-1 antibody complexes. This may be responsible for the enhanced platelet clearance and thrombocytopenia in patients with acquired immunodeficiency syndrome-related immunologic thrombocytopenia. Images PMID:3200854

Karpatkin, S; Nardi, M; Lennette, E T; Byrne, B; Poiesz, B

1988-01-01

101

Atypical pigmentary purpura: A clinical, histopathologic, and genotypic study  

Microsoft Academic Search

Background: The pigmentary purpuras (PPs) are a heterogeneous group of dermatoses defined by specific clinicopathologic features but sharing, at the light microscopic level, superficially disposed dermal lymphocytic infiltrates and hemorrhage. The term atypical pigmentary purpura (APP) is used by the authors in reference to cases of PP in which individual lesions, although clinically presenting as PP, show morphological features typically

A. Neil Crowson; Cynthia M Magro; Robert Zahorchak

1999-01-01

102

Mechanisms of thrombocytopenia in chronic autoimmune thrombocytopenic purpura. Evidence of both impaired platelet production and increased platelet clearance.  

PubMed Central

Mechanisms of thrombocytopenia were studied in 38 patients with mild to moderately severe chronic autoimmune thrombocytopenia (AITP). 51Cr and 111In-labeled autologous platelet turnover studies and in vitro analysis of committed megakaryocyte progenitors (CFU-Meg) were used as independent measures of platelet production. Autologous 111In-labeled platelet localization studies were performed to assess platelet clearance. Although there was no increase in the frequency of marrow CFU-Meg, a specific increase in the CFU-Meg [3H]TdR suicide rate was seen which was inversely correlated with the platelet count (P less than 0.001). Platelet turnover studies showed significant numbers of patients had inappropriate thrombopoietic responses to their reduced platelet counts. Platelet-associated antibody levels correlated inversely with platelet turnover suggesting that antiplatelet antibody impairs platelet production. The circulating platelet count was best predicted by an index relating platelet production (i.e., turnover) to the spleen-liver platelet clearance that correlated directly with platelet survival (P less than 0.001). In summary, both depressed platelet production and increased platelet clearance by the liver and spleen contribute to the thrombocytopenia of AITP. PMID:3597777

Ballem, P J; Segal, G M; Stratton, J R; Gernsheimer, T; Adamson, J W; Slichter, S J

1987-01-01

103

Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial  

Microsoft Academic Search

Methods In two parallel trials, 63 splenectomised and 62 non-splenectomised patients with ITP and a mean of three platelet counts 30×10?\\/L or less were randomly assigned 2:1 to subcutaneous injections of romiplostim (n=42 in splenectomised study and n=41 in non-splenectomised study) or placebo (n=21 in both studies) every week for 24 weeks. Doses of study drug were adjusted to maintain

David J Kuter; James B Bussel; Roger M Lyons; Vinod Pullarkat; Terry B Gernsheimer; Francis M Senecal; Louis M Aledort; James N George; Craig M Kessler; Miguel A Sanz; Howard A Liebman; Frank T Slovick; J Th M de Wolf; Emmanuelle Bourgeois; Troy H Guthrie; Adrian Newland; Jeffrey S Wasser; Solomon I Hamburg; Carlos Grande; François Lefrère; Alan Eli Lichtin; Michael D Tarantino; Howard R Terebelo; Jean-François Viallard; Francis J Cuevas; Ronald S Go; David H Henry; Robert L Redner; Lawrence Rice; Martin R Schipperus; D Matthew Guo; Janet L Nichol

2008-01-01

104

Efficacy and safety of a nanofiltered liquid intravenous immunoglobulin product in patients with primary immunodeficiency and idiopathic thrombocytopenic purpura  

Microsoft Academic Search

BACKGROUND AND OBJECTIVES: In the production process of a new 5% liquid intravenous immunoglobulin (IVIG-L) product (Nanogam((R)) ), a combined pepsin\\/pH 4.4 treatment\\/15-nm filtration (pH 4.4\\/15NF) step and a solvent-detergent (SD) treatment step were incorporated to improve the virus inactivating\\/reducing capacity of the manufacturing process. Two prospective uncontrolled multicentre studies were performed to evaluate the safety and efficacy of this

J. W. van der Meer; R. T. van Beem; T. Robak; A. Deptala; P. F. W. Strengers

2011-01-01

105

Acute infectious purpura fulminans due to probable spotted fever.  

PubMed

Purpura fulminans (PF) is associated with several infections, most notably with meningococcus, staphylococcus, and streptococcus infections. However, there are few reports of association of this entity with spotted fever from India. We report the case of a 55-year-old man who presented with fever, headache, and myalgia. On the seventh day of fever he developed nonblanching purple hemorrhagic purpura on the trunk and most prominently on the extremities consistent with purpura fulminans. Immunofluorescent assay confirmed the diagnosis of spotted fever. PF though common with rocky mountain spotted fever (RMSF) is rarely seen in association with Indian tick typhus, the usual cause of spotted fever in India. PMID:24823524

Kundavaram, A; Francis, N R; Jude, A P J; Varghese, G N

2014-01-01

106

Infarctive purpura hemorrhagica in five horses.  

PubMed

Five horses were examined because of signs of muscle stiffness, colic, or both. All 5 had been exposed to Streptococcus equi within 3 weeks prior to examination or had high serum titers of antibodies against the M protein of S equi. Horses had signs of unrelenting colic-like pain and focal areas of muscle swelling. Four horses were euthanatized. The fifth responded to treatment with penicillin and dexamethasone; after 3 weeks of treatment with dexamethasone, prednisolone was administered for an additional 10 weeks. Common hematologic and serum biochemical abnormalities included neutrophilia with a left shift and toxic changes, hyperproteinemia, hypoalbuminemia, and high serum creatine kinase and aspartate transferase activities. Necropsy revealed extensive infarction of the skeletal musculature, skin, gastrointestinal tract, pancreas, and lungs. Histologic lesions included leukocytoclastic vasculitis in numerous tissues and acute coagulative necrosis resembling infarction. These horses appeared to have a severe form of purpura hemorrhagica resembling Henoch-Schönlein purpura in humans and characterized by infarction of skeletal muscles. Early recognition of focal muscle swelling, abdominal discomfort, neutrophilia, hypoalbuminemia, and high serum creatine kinase activity combined with antimicrobial and corticosteroid treatment may enhance the likelihood of a successful outcome. PMID:15934258

Kaese, Heather J; Valberg, Stephanie J; Hayden, David W; Wilson, Julia H; Charlton, Patricia; Ames, Trevor R; Al-Ghamdi, Ghanem M

2005-06-01

107

Henoch-Schonlein purpura presenting sequentially as nodular rash, erythema nodosum, and palpable purpura  

PubMed Central

We describe a 26-year-old woman who presented with a nodular rash on the elbows following an insect bite. Two days later, she developed erythema nodosum. Both these lesions were treated symptomatically. One week later, she had purpura, abdominal pain, hematuria, and arthralgias, following which steroids were administered. Her investigations revealed only microscopic hematuria that disappeared with therapy. This pattern of sequential appearance of rash and a nodular morphology are both unique features not previously reported. PMID:24696039

Balamurugesan, Kandan; Viswanathan, Stalin

2014-01-01

108

Henoch-Schonlein purpura on an infant's legs (image)  

MedlinePLUS

... children than adults and often occurs after an upper respiratory infection. It causes skin rashes that bleed into the skin (petechiae and purpura). Bleeding may also occur from the gastrointestinal tract and kidneys.

109

Henoch-Schonlein purpura on the legs (image)  

MedlinePLUS

... children than adults and often occurs after an upper respiratory infection. It causes skin rashes that bleed into the skin (petechiae and purpura). Bleeding may also occur from the gastrointestinal tract and kidneys.

110

Henoch-Schonlein purpura on an infant's foot (image)  

MedlinePLUS

... children than adults and often occurs after an upper respiratory infection. It causes skin rashes that bleed into the skin (petechiae and purpura). Bleeding may also occur from the gastrointestinal tract and kidneys.

111

Identification of Differentially Expressed Serum Proteins in Infectious Purpura Fulminans  

PubMed Central

Purpura fulminans (PF) is a life-threatening hemorrhagic condition. Because of the rarity and randomness of the disease, no improvement in treatment has been made for a long time. In this study, we assessed the serum proteome response to PF by comparing serum proteins between healthy controls and PF patient. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) approach was used after depleting 6 abundant proteins of serum. In total, 262 proteins were confidently identified with 2 unique peptides, and 38 proteins were identified significantly up- (?2) or downregulated (?0.5) based on spectral counting ratios (SpCPF/N). In the 38 proteins with significant abundance changes, 11 proteins were previously known to be associated with burn or sepsis response, but 27 potentially novel proteins may be specifically associated with PF process. Two differentially expressed proteins, alpha-1-antitrypsin (SERPINA1) and alpha-2 antiplasmin (SERPINF2), were validated by Western blot. This is the first study where PF patient and healthy controls are compared in a proteomic study to elucidate proteins involved in the response to PF. This study provides an initial basis for future studies of PF, and the differentially expressed proteins might provide new therapeutic targets to decrease the mortality of PF. PMID:24659849

Hu, Jiong-yu; Han, Jian; Zhang, Dong-xia; Jiang, Xu-pin; Chen, Bing; Huang, Yue-sheng

2014-01-01

112

Bartonella seropositivity in children with Henoch-Schonlein purpura  

Microsoft Academic Search

BACKGROUND: An association between Henoch-Schonlein purpura (HSP) and seropositivity for Bartonella henselae (BH) has been described. The objective of this study was to see if such an association exists in northern Alberta. METHODS: Immunofluorescent antibody testing utilizing an antigen prepared from B. henselae was undertaken on sera from six children with current HSP, 22 children with remote HSP, and 28

Joan L Robinson; Donald W Spady; Errol Prasad; Dorothy McColl; Harvey Artsob

2005-01-01

113

Vasculitic purpura in vinyl chloride disease: a case report  

SciTech Connect

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.''

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

1986-05-01

114

Acquired amegakaryocytic thrombocytopenia purpura in a Rhesus macaque (Macaca mulatta).  

PubMed

A 10-y-old multiparous rhesus macaque presented for an annual routine physical examination. Clinically, the animal had pale mucous membranes, petechial and ecchymotic hemorrhages in multiple sites, and a laceration at the tail base. Severe pancytopenia was noted on hematologic evaluation. The monkey was seronegative for SIV, simian T-lymphotropic virus, simian retrovirus type D, and Macacine herpesvirus 1. Bone marrow evaluation revealed a paucity of megakaryocytic precursors in a hypercellular marrow with marked erythroid hyperplasia. In light of these findings, the diagnosis was acquired amegakaryocytic thrombocytopenia purpura. Due to the poor prognosis of the syndrome and clinical deterioration of the monkey, euthanasia was elected. A definitive cause of the thrombocytopenia was not identified; however, the syndrome may have developed secondary to a recent spontaneous abortion. To our knowledge, this case represents the first reported observation of acquired amegakaryocytic thrombocytopenia purpura in a rhesus monkey. PMID:22776057

Hanley, Patrick W; Baze, Wallace B; McArthur, Mark J; Bernacky, Bruce J; Wilkerson, Greg K; Barnhart, Kirstin F

2012-06-01

115

/sup 111/In-oxine platelet survivals in thrombocytopenic infants  

SciTech Connect

Thrombocytopenia is a common occurrence (20%) in sick neonates, but the causes have not been well studied. In this report we demonstrate that thrombocytopenia in the neonate is characterized by increased platelet destruction as shown by shortened homologous /sup 111/In-oxine-labeled platelet life spans. Thirty-one prospectively studied thrombocytopenic neonates were investigated by measuring the /sup 111/In-labeled platelet life span, platelet-associated IgG (PAIgG), and coagulation screening tests. In every infant, the thrombocytopenia was shown to have a destructive component since the mean platelet life span was significantly shortened to 65 +/- 6 (mean +/- SEM) hours with a range of one to 128 hours compared with adult values (212 +/- 8; range, 140 to 260; gamma function analysis). The platelet survival was directly related to the lowest platelet count and inversely related to both the highest mean platelet volume and duration of the thrombocytopenia. In 22 infants the percent recovery of the radiolabeled platelets was less than 50%, which suggested that increased sequestration also contributed to the thrombocytopenia. Infants with laboratory evidence of disseminated intravascular coagulation (n = 8) or immune platelet destruction evidenced by elevated levels of PAIgG (n = 13) had even shorter platelet survivals and a more severe thrombocytopenia compared with the ten infants in whom an underlying cause for the thrombocytopenia was not apparent. Full-body scintigraphic images obtained in 11 infants showed an increased uptake in the spleen and liver, with a spleen-to-liver ratio of 3:1. This study indicates that thrombocytopenia in sick neonates is primarily destructive, with a subgroup having evidence of increased platelet sequestration.

Castle, V.; Coates, G.; Kelton, J.G.; Andrew, M.

1987-09-01

116

A Case Report of Gemcitabine Treatment for Duodenal Cancer: The Good (A Sustained Response) and The Bad (Life Threatening Refractory Thrombotic Thrombocytopenic Purpura)  

Microsoft Academic Search

Introduction  Adenocarcinoma of the duodenum is a rare cancer and not submitted to the type of clinical trials that guide chemotherapy treatments\\u000a in other gastrointestinal malignancies.\\u000a \\u000a \\u000a \\u000a \\u000a Case Report  This case demonstrates the potential use for gemcitabine, a chemotherapy typically used in pancreas and biliary tract tumors,\\u000a in this difficult to treat disease as this patient had a partial response to single agent

Andrew Robinson; William F. Clark

2010-01-01

117

Organism-specific platelet response and factors affecting survival in thrombocytopenic very low birth weight babies with sepsis  

Microsoft Academic Search

Objective:To study organism-specific platelet response and factors affecting survival in thrombocytopenic very low birth weight (VLBW) babies with sepsis.Study Design:Very low birth weight babies (birth weight <1500 g) admitted to a single level-three intensive care unit from January 2000 to December 2005 were prospectively evaluated for sepsis by rapid screen test, blood counts and blood culture. In thrombocytopenic babies, organism-specific

M A Bhat; J I Bhat; M S Kawoosa; S M Ahmad; S W Ali

2009-01-01

118

Streptococcus pneumoniae-induced purpura fulminans in a woman with functional asplenia.  

PubMed

ABSTRACTPurpura fulminans is a rare complication of septic shock, often associated with Streptococcus pneumoniae. Patients with anatomic or functional asplenia are at increased risk for infection because of impairment of their ability to defend against encapsulated pathogens. We report the case of a previously healthy, unimmunized 33-year-old female with functional asplenia who presented in septic shock and purpura fulminans and died in spite of maximal resuscitative measures. The clinical presentation, diagnosis, and management of purpura fulminans are reviewed. Purpura fulminans is a rare condition that requires early diagnosis and aggressive management by emergency physicians. PMID:25060091

Wojtowicz, Jeremy M; Longden Jones, Graham

2014-07-01

119

Streptococcus pneumoniae-induced purpura fulminans in a woman with functional asplenia.  

PubMed

ABSTRACTPurpura fulminans is a rare complication of septic shock, often associated with Streptococcus pneumoniae. Patients with anatomic or functional asplenia are at increased risk for infection because of impairment of their ability to defend against encapsulated pathogens. We report the case of a previously healthy, unimmunized 33-year-old female with functional asplenia who presented in septic shock and purpura fulminans and died in spite of maximal resuscitative measures. The clinical presentation, diagnosis, and management of purpura fulminans are reviewed. Purpura fulminans is a rare condition that requires early diagnosis and aggressive management by emergency physicians. PMID:23870635

Wojtowicz, Jeremy M; Longden Jones, Graham

2013-01-01

120

Abnormalities of vascular prostaglandins in Henoch-Sch?nlein purpura.  

PubMed Central

The ability of plasma to support prostacyclin like activity from human umbilical arterial rings was studied in 17 patients with Henoch-Schönlein purpura and 17 controls matched for age and sex. Plasma from 13 of the 17 patients showed a diminished or absent ability to support prostacyclin like activity in vitro. Six patients whose plasma had a low or absent ability to support prostacyclin like activity showed evidence of inhibitory activity. Plasma from three of these patients also failed to preserve the effect of a stable prostacyclin like analogue (ZK36-374). The plasma concentration of prostacyclin metabolite and the serum concentration of thromboxane A2 metabolite, thromboxane B2, were measured simultaneously. The concentration of plasma prostacyclin metabolite in 10 of the 14 patients was decreased, and a positive correlation was found between the plasma prostacyclin metabolite values and the ability of the plasma to support prostacyclin like activity. There was no significant difference in the serum thromboxane A2 metabolite concentrations between the patients and controls. These data suggest that abnormalities of vascular prostaglandin metabolism are involved in the pathophysiology of Henoch-Schönlein purpura. PMID:2420289

Turi, S; Belch, J J; Beattie, T J; Forbes, C D

1986-01-01

121

Purpura fulminans associated with Streptococcus pneumoniae septicemia in an asplenic pediatric patient.  

PubMed

Purpura fulminans is a rapidly progressive syndrome of small-vessel thrombosis and hemorrhagic necrosis of the skin accompanied by disseminated intravascular coagulation. We describe a case of Streptococcus pneumoniae septicemia in an asplenic 5-year-old boy on oral tacrolimus, with a past medical history of multivisceral organ transplantation and subsequent development of purpura fulminans on his chest and distal extremities. The acute infectious form of purpura fulminans is usually caused by gram-negative bacteria. Cases secondary to gram-positive encapsulated bacteria usually occur when individuals are immuno-suppressed or have anatomic or functional asplenia. Our patient had both, which likely increased his susceptibility, and he responded well to antimicrobial therapy in addition to prophylactic coverage in the setting of his immunosuppression. We review the literature for similar cases due to S. pneumoniae in the pediatric population and discuss the etiology and treatment of purpura fulminans. PMID:23985086

Konda, S; Zell, D; Milikowski, C; Alonso-Llamazares, J

2013-09-01

122

Purpura fulminans caused by community-associated methicillin-resistant Staphylococcus aureus.  

PubMed

Sepsis-induced purpura fulminans is a rare but life-threatening condition characterized by rapidly progressive hemorrhagic infarction of the skin due to dermal vascular thrombosis resulting in tissue loss and severe scarring. Although most commonly related to meningococcal or invasive group A streptococcal disease, it may also be caused by several other bacterial or viral pathogens including Pneumococcus and Varicella. Purpura fulminans associated with Staphylococcus aureus sepsis is rare but has been reported in adults. However, the syndrome is very unusual in children, and to our knowledge, only 2 cases of staphylococcal purpura fulminans have been reported in children, both due to methicillin-susceptible S aureus in the United Kingdom. We report the first well-described case of purpura fulminans due to community-associated methicillin-resistant S aureus in a child. PMID:21641144

Fitzgerald, Casimir J; Pranikoff, Thomas V; Ross, Gregory A; Mou, Steven; Givner, Laurence B; Shetty, Avinash K

2012-07-01

123

Renal involvement in Henoch-Schönlein purpura: A multivariate analysis of prognostic factors  

Microsoft Academic Search

Renal involvement in Henoch-Schönlein purpura: A multivariate analysis of prognostic factors. This study is the first report in which the relationship between the progression of renal involvement in Henoch-Schönlein purpura (HSP) and various factors was evaluated using a multivariate analysis. Sixty-five (33.5%) of 194 patients with HSP developed renal involvement from three days to 17 months after the onset of

Yoshitsugu Kaku; Kaoru Nohara; Sunao Honda

1998-01-01

124

Renal manifestations of Henoch–Schönlein purpura in a 6-month prospective study of 223 children  

Microsoft Academic Search

ObjectiveTo assess the risk factors for developing Henoch–Schönlein purpura nephritis (HSN) and to determine the time period when renal involvement is unlikely after the initial disease onset.DesignA prospective study of 223 paediatric patients to examine renal manifestations of Henoch–Schönlein purpura (HSP). The patient's condition was monitored with five outpatient visits to the research centre and urine dipstick testing at home.ResultsHSN

Outi Jauhola; Jaana Ronkainen; Olli Koskimies; Marja Ala-Houhala; Pekka Arikoski; Tuula Hölttä; Timo Jahnukainen; Jukka Rajantie; Timo Örmälä; Juha Turtinen; Matti Nuutinen

2010-01-01

125

Long-term Outcome in Children After Henoch-Schönlein Purpura Nephritis  

Microsoft Academic Search

This study investigated predictors of renal survival in children with Henoch-Schönlein purpura glomerulonephritis. Records of patients with Henoch-Schönlein purpura glomerulonephritis evaluated at our center, from 1953-1990, were reviewed. Data were abstracted from records of patients seen within 5 years. Others were mailed a questionnaire or contacted by telephone. Primary outcome measures were renal survival and presence of urinary abnormalities or

Lavjay Butani; Bruce Z. Morgenstern

2007-01-01

126

Atypical presentation of purpura fulminans following sepsis in an adult  

PubMed Central

A 67-year-old morbidly obese female with a background of stage 4 chronic renal failure, ischaemic heart disease, congestive cardiac failure, atrial fibrillation and type 2 diabetes mellitus presented with sepsis and necrotic lesions of the proximal lower limbs. Initial histological findings were consistent with the clinical diagnosis of calciphylaxis and supportive treatment was commenced with addition of a phosphate binder and dietary restriction. Due to high anaesthetic risk, her wounds were managed with larva therapy in the first instance, however, ultimately surgical debridement was the required. Repeat histology from a further biopsy revealed necrosis secondary to numerous thrombi in the cutaneous vessels and a new diagnosis of purpura fulminans was made, likely secondary to her sepsis. Unfortunately, despite aggressive medical and surgical treatment measures, this patient died of multiple organ dysfunction following a prolonged admission. PMID:22675087

Lyon, Paul; Nambi, Rabi; Faruqi, Faisal

2011-01-01

127

Oxford classification of IgA nephropathy is applicable to predict long-term outcomes of Henoch-Schönlein purpura nephritis.  

PubMed

Abstract Henoch-Schönlein purpura nephritis and IgA nephropathy are currently considered to be different clinical presentations of the same disease. There is need for a reliable proven, morphologic classification that can help clinicians more accurately formulate treatment strategies for patients with Henoch-Schönlein purpura nephritis. Considering that Henoch-Schönlein purpura nephritis and IgA nephropathy have common characteristics of pathogenesis and histopathologic findings, we postulate that, the Oxford classification could also help predict long-term outcomes in Henoch-Schönlein purpura nephritis. Hence, we suggest to applicate the Oxford classification for patients with Henoch-Schönlein purpura nephritis. PMID:25148806

Nasri, Hamid

2014-12-01

128

Establishing hospital admission criteria of pediatric Henoch-Schonlein purpura.  

PubMed

The current study aimed to define evidence-based admission criteria of pediatric Henoch-Schonlein purpura (HSP). In addition, we aimed to better characterize epidemiological and clinical features of pediatric HSP in Israel. We performed a retrospective cohort study of all children with HSP admitted during a 15 years period to a single pediatric department. We strictly collected the clinical data of all HSP cases. Each case was categorized as either "necessary admission" or "unnecessary admission." We compared the two groups, using initially Chi square (? (2)) and student "t" tests, and thereafter, we employed logistic stepwise regression analysis. One hundred and sixty-three children with HSP were included. A set of six clinical criteria of which the presence of minimum one predicts the need for hospitalization were identified including: orchitis, moderate or severe abdominal pain, arthritis involving more than two joints, proteinuria, clear evidence of gastrointestinal bleeding, and inability to ambulate. In conclusion, we suggest a predictive model for the admission of pediatric patients with acute HSP. The implementation of this model can significantly reduce unnecessary admissions. PMID:24563020

Masarweh, Kamal; Horovitz, Yoseph; Avital, Avi; Spiegel, Ronen

2014-11-01

129

Central venous catheter infection-induced Henoch-Schönlein purpura in a patient on hemodialysis.  

PubMed

A 69-year-old man, who had been dialyzed using a permanent central venous catheter for 2 years, presented with Henoch-Schönlein purpura and positive perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA). He was diagnosed with catheter-related infection by Staphylococcus aureus. After administration of antibiotic and steroid therapy, purpura disappeared and p-ANCA gradually became negative. This case supports the conclusion that infection can be pathogenesis of the vasculitis, including ANCA-positive HSP. Additionally, impregnation of catheters with antibiotics can be an effective treatment for catheter infections. PMID:24845224

Gao, Jian Jun; Wei, Jia Mei; Gao, Yue Hua; Li, Shuang; Na, Yu

2014-08-01

130

Anaphylactoid purpura: Characteristics of 16 patients who progressed to renal failure  

Microsoft Academic Search

Renal insufficiency occurs in at least 1.5% of children with anaphylactoid purpura (AP). We reviewed the records of 16 children who developed end-stage renal disease (ESRD group) secondary to AP and matched them for age, era of onset, renal histology, and clinical severity at onset with 16 children who has AP but whose creatinine clearance returned to and remained normal

Timothy E. Bunchman; S. Michael Mauer; Richard K. Sibley; Robert L. Vernier

1988-01-01

131

Multiple small-intestine intussusceptions: a complication of purpura haemorrhagica in a horse.  

PubMed

A Belgian draft horse stallion presented with classical signs of purpura haemorrhagica: oedema of the distal limbs, ventral abdomen and head, ecchymotic haemorrhage of mucous membranes, epistaxis, fever, lethargy, reluctance to move, and anorexia. Serum chemistry revealed a highly elevated gamma-globulin fraction. Streptococcal lymphadenitis (strangles) had been present on a neighbouring farm in the past few months. After an initial positive response to therapy with benzylpenicillin, flunixin and dexamethasone, the horse's condition deteriorated suddenly on day 4 of hospitalization, with signs of severe endotoxaemia and small-intestine obstruction. The horse was euthanized because of its poor prognosis and because of economic considerations. On necropsy, large serosal haemorrhages in the small and large intestine and multiple jejunojejunal intussusceptions were found. Intussusception is a well-known complication in children with Henoch-Schonlein purpura, a human autoimmune disease resembling purpura haemorrhagica in horses. To the author's knowledge, this is the first report to describe intussusception as a complication of purpura haemorrhagica in a horse. PMID:21699093

Dujardin, C L L

2011-06-01

132

Effectiveness of early prednisone treatment in preventing the development of nephropathy in anaphylactoid purpura  

Microsoft Academic Search

A prospective study was performed to verify whether early administration of prednisone could be useful in preventing the development of nephropathy in anaphylactoid purpura. Only patients without signs of nephropathy upon initial presentation entered into the study. A total of 84 patients received delta-prednisone (1 mg\\/kg per day per os for 2 weeks), and 84 patients did not receive steroids.

F. Mollica; S. LiVolti; R. Garozzo; G. Russo

1992-01-01

133

Anti-?-galactosyl antibodies and immune complexes in children with Henoch–Schönlein purpura or IgA nephropathy  

Microsoft Academic Search

Anti-?-galactosyl antibodies and immune complexes in children with Henoch–Schönlein purpura or IgA nephropathy. Episodes of hematuria in IgA nephropathy or Henoch-Schönlein purpura are frequently associated with microbial infections. Some of those infectious agents bear ?-galactosyl residues on their cell surface. These observations prompted us to determine, by passive hemagglutination, the titers of natural anti-galactosyl antibodies in the serum of children

Michel Malaise; Jacqueline Foidart; Philippe Mahieu; J C Davin

1987-01-01

134

[Signs of hypercoagulation and activation of fibrinolysis in patients with Wegeners's granulomatosis and Schoenlein-Genoch's purpura].  

PubMed

The patients with Wegener's granulomatosis and Schoenlein-Genoch's purpura included in this study were examined in the E.A.M. Tareev Clinic during 2006-2008. They showed signs of hypercoagulation and activation of fibrinolysis, viz. enhanced SFMC, D-dimer and antiphospholipid antibody levels, platelet aggregation. Hypercoagulation correlated with the activity of both Wegeners's granulematosis and Schoenlein-Genoch's purpura. PMID:22993951

Strizhakov, L A; Chegaeva, E P; Krivosheev, O G; Semenkova, E N; Ba?muradova, S M

2012-01-01

135

Unusual patterns of serum antibodies to Streptococcus equi in two horses with purpura hemorrhagica.  

PubMed

An enzyme-linked immunosorbent assay (ELISA) was developed for use in horses to determine serum titers of antibodies of the immunoglobulin classes IgA, IgG, and IgM to Streptococcus equi M-like protein and culture supernatant protein antigens. Serum antibodies were determined in 28 adult horses, including 9 horses with recent S. equi infections, 17 horses without known exposure to S. equi, but without a history of respiratory disease in the preceding 4 months, and 2 horses with clinical purpura hemorrhagica. Serum IgA titers to culture supernatant protein antigen were highest in recently infected horses (P less than 0.001). Serial determinations of antibody titers in the horses with purpura showed that IgG antibodies to both S. equi M-like protein and culture supernatant protein antigens were undetectable initially, but later rose coincidental with clinical recovery from the disease. Possible mechanisms for these findings are discussed. PMID:1748978

Heath, S E; Geor, R J; Tabel, H; McIntosh, K

1991-01-01

136

Combined diagnostic imaging of intestinal involvement in Henoch-Schönlein purpura.  

PubMed

The case of a 39-year-old male patient with symptoms of persistent abdominal pain and melena, affected by Henoch-Schönlein purpura, is reported. Abdominal CT was requested. The examination was justified by the fact that symptoms could be correlated with other pathological conditions (volvulus, neoplasms, Chron's disease, etc.) which had to be excluded. For optimum study of the abdominal wall, correct preparation and the use of oral contrast agents were required. From the analysis of CT findings, in particular loop thickening with stratified density, the increased density of mesenteric fat and the presence of fluid among loops led to the radiological diagnosis of intestinal involvement in Henoch-Schönlein purpura. Other imaging procedures (double contrast enema, sonography, Doppler US, MRI) now used in the study of intestinal loops, are examined. PMID:14509190

Maggi, Fabio; Minordi, Laura Maria; Macis, Giuseppe; Vecchioli, Amorino

2003-01-01

137

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

PubMed

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

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

2007-10-01

138

Palpable purpura and uveitis precipitated by splenectomy in an atypical case of Cogan's syndrome.  

PubMed

A patient with a baffling multisystem illness developed uveitis and palpable purpura shortly after a splenectomy, leading to the diagnosis of vasculitis. Clearance by the mononuclear phagocyte system is a key factor determining the pathogenicity of circulating immune complexes, which are known to be the cause of some forms of vasculitis. The sudden appearance of uveitis and cutaneous vasculitis in an illness of many years' duration was probably a direct result of removal of the spleen. PMID:1920316

Wohlgethan, J R; Stilmant, M M; Smith, H R

1991-07-01

139

Henoch–Schönlein purpura nephritis complicated by reversible posterior leukoencephalopathy syndrome  

Microsoft Academic Search

We report a young female patient with Henoch–Schönlein purpura (HSP) nephritis complicated by reversible posterior leukoencephalopathy\\u000a syndrome (RPLS). The patient suddenly showed generalized seizures and cortical blindness with severe hypertension due to renal\\u000a insufficiency approximately 1 year after cessation of corticosteroid treatment for HSP nephritis. Magnetic resonance imaging\\u000a (MRI) demonstrated bilateral abnormal signals mainly in the cerebellum and white matter of

Daimei Sasayama; Yasuhiro Shimojima; Takahisa Gono; Kazuma Kaneko; Masayuki Matsuda; Shu-ichi Ikeda

2007-01-01

140

Low serum C3, leukopenia, and thrombocytopenia: unusual features of Henoch-Schonlein purpura  

Microsoft Academic Search

Henoch-Schonlein purpura (HSP) affects predominantly the skin, joints, gastrointestinal tract and kidney. Although the pathogenesis\\u000a is probably of immune origin and complement activation is thought to play a role, laboratory findings including the serum\\u000a level of the complement components are usually normal. We present a patient with a severe form of HSP nephritis who had unusual\\u000a laboratory findings of a

I. Krause; B. Z. Garty; M. Davidovits; R. Cleper; H. Tamary; E. Rosenmann; B. Eisenstein

1999-01-01

141

Petechiae and purpura: the ominous and the not-so-obvious?  

PubMed

Petechiae and purpura are among the most alarming findings a pediatrician will commonly observe in the office. Severity of illness can range from a temper tantrum, to common viral infections, to the most deadly infections and diseases. To avoid many of the pitfalls in diagnosis, practitioners will need to be thorough in history taking, assessing fever and immunization status, and physical examination. In addition, a few simple laboratory tests will usually be needed and possibly a manual differential. PMID:25102482

Block, Stan L

2014-08-01

142

Goodpasture syndrome during the course of a Schönlein-Henoch purpura  

Microsoft Academic Search

Two months after surgical resection of a bronchogenic carcinoma, a 69-year-old patient presented with Schönlein-Henoch purpura with kidney involvement followed by pulmonary hemorrhage. The presence of an IgA linear pattern on the kidney biopsy specimen and circulating anti-glomerular basement membrane (GBM) IgA antibodies led to the diagnosis of Goodpasture syndrome, which implies the possibility that the well-known pulmonary involvement during

Luis Carreras; Rafael Poveda; Jordi Bas; Mariona Mestre; Inés Rama; Marta Carrera

2002-01-01

143

Effects of Increased Von Willebrand Factor Levels on Primary Hemostasis in Thrombocytopenic Patients with Liver Cirrhosis  

PubMed Central

In patients with liver cirrhosis procoagulant and anticoagulant changes occur simultaneously. During primary hemostasis, platelets adhere to subendothelial structures, via von Willebrand factor (vWF). We aimed to investigate the influence of vWF on primary hemostasis in patients with liver cirrhosis. Therefore we assessed in-vitro bleeding time as marker of primary hemostasis in cirrhotic patients, measuring the Platelet Function Analyzer (PFA-100) closure times with collagen and epinephrine (Col-Epi, upper limit of normal ?165 s) or collagen and ADP (Col-ADP, upper limit of normal ?118 s). If Col-Epi and Col-ADP were prolonged, the PFA-100 was considered to be pathological. Effects of vWF on primary hemostasis in thrombocytopenic patients were analyzed and plasma vWF levels were modified by adding recombinant vWF or anti-vWF antibody. Of the 72 included cirrhotic patients, 32 (44.4%) showed a pathological result for the PFA-100. They had mean closure times (± SD) of 180±62 s with Col-Epi and 160±70 s with Col-ADP. Multivariate analysis revealed that hematocrit (P?=?0.027) and vWF-antigen levels (P?=?0.010) are the predictors of a pathological PFA-100 test in cirrhotic patients. In 21.4% of cirrhotic patients with platelet count ?150/nL and hematocrit ?27.0%, pathological PFA-100 results were found. In thrombocytopenic (<150/nL) patients with cirrhosis, normal PFA-100 results were associated with higher vWF-antigen levels (462.3±235.9% vs. 338.7±151.6%, P?=?0.021). These results were confirmed by multivariate analysis in these patients as well as by adding recombinant vWF or polyclonal anti-vWF antibody that significantly shortened or prolonged closure times, respectively. In conclusion, primary hemostasis is impaired in cirrhotic patients. The effect of reduced platelet count in cirrhotic patients can at least be partly compensated by increased vWF levels. Recombinant vWF could be an alternative to platelet transfusions in the future. PMID:25397410

Wannhoff, Andreas; Müller, Oliver J.; Friedrich, Kilian; Rupp, Christian; Klöters-Plachky, Petra; Leopold, Yvonne; Brune, Maik; Senner, Mirja; Weiss, Karl-Heinz; Stremmel, Wolfgang; Schemmer, Peter; Katus, Hugo A.; Gotthardt, Daniel N.

2014-01-01

144

What Are the Signs and Symptoms of Thrombocytopenia?  

MedlinePLUS

... Signs & Symptoms Diagnosis Treatments Prevention Living With Clinical Trials Links Related Topics Aplastic Anemia Immune Thrombocytopenia Thrombotic Thrombocytopenic Purpura Disseminated Intravascular Coagulation Blood ...

145

How Is Thrombocytopenia Treated?  

MedlinePLUS

... Signs & Symptoms Diagnosis Treatments Prevention Living With Clinical Trials Links Related Topics Aplastic Anemia Immune Thrombocytopenia Thrombotic Thrombocytopenic Purpura Disseminated Intravascular Coagulation Blood ...

146

Thrombocytopenia  

MedlinePLUS

... Signs & Symptoms Diagnosis Treatments Prevention Living With Clinical Trials Links Related Topics Aplastic Anemia Immune Thrombocytopenia Thrombotic Thrombocytopenic Purpura Disseminated Intravascular Coagulation Blood ...

147

How Is Thrombocytopenia Diagnosed?  

MedlinePLUS

... Signs & Symptoms Diagnosis Treatments Prevention Living With Clinical Trials Links Related Topics Aplastic Anemia Immune Thrombocytopenia Thrombotic Thrombocytopenic Purpura Disseminated Intravascular Coagulation Blood ...

148

Sirolimus for Autoimmune Disease of Blood Cells  

ClinicalTrials.gov

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

2014-02-03

149

Two cases of meningococcal purpura fulminans: the 'less is more' approach.  

PubMed

This study presents a case series of patients with meningococcal purpura fulminans who were treated at a tertiary referral centre within a few days of each other. Presenting with signs and symptoms of florid meningococcal sepsis, they were managed initially by physicians and intensivists, whereas the development of large purpuric areas and tissue necrosis was managed expectantly by plastic surgeons. When the patients were deemed to have recovered clinically and the necrosis delineated, surgical management was implemented with subsequent involvement of various rehabilitation services. This article highlights the cases of two patients, and their clinical presentation, management and rehabilitation together with a current literature review on this area. PMID:23323934

Ahmad, Zeeshan; Jordan, Robert; Das-Gupta, Rana; Srivastava, Shekhar

2014-12-01

150

A case of lupus-like glomerulonephritis in an HIV patient with nephrotic range proteinuria, purpura, and elevated IgA level  

PubMed Central

Human immunodeficiency virus (HIV) infection is growing medical concern worldwide. There are many types of glomerulonephritis which are associated with HIV infection. We report a case of a 53-year-old Korean man with an HIV infection, who was developed nephritic range proteinuria and purpura with elevated IgA level rasing a possibility of Henoch-Schölein Purpura (H-S purpura). However, renal biopsy showed “lupus-like feature” glomerulonephritis without clinical or serologic evidence of systemic lupus erythematosus. Although baseline renal function was maintained without further need for maintenance dialysis following anti-retroviral therapy (ART) and steroid, patient died from uncontrolled gastrointestinal bleeding. PMID:25120835

Yang, Jihyun; Seo, Min Young; Kim, Ki Tae; Lee, Jun Yong; Kim, Sun-Chul; Kim, Myung-gyu; Jo, Sang-Kyung; Cho, Won-Yong; Kim, Hyoung-Kyu; Won, Nam Hee; Cha, Ran-Hui; Cho, Eunjung

2014-01-01

151

Purpura Fulminans and Late Onset Group B Streptococcal Sepsis in a Premature Twin  

PubMed Central

Introduction:?Purpura fulminans (PF) is a skin manifestation due to hemorrhagic infarction caused by intravascular thrombosis secondary to bacterial infections or deficiency of anticoagulants such as protein C and protein S. Neonatal PF is a rare but potentially disabling disorder associated with a high mortality and severe long term morbidity in those who survive. Case description:?We report a case of a premature infant who developed extensive PF due to late onset group B streptococcus sepsis. Despite early identification and initiation of antibiotic therapy in our patient, PF progressed rapidly, leading to autoamputation of fingers and toes and severe brain injury. Conclusion:?In conclusion, our case highlights the severe sequelae of PF due to late onset GBS sepsis in a premature infant.

Elayappen, Avanikkha; Jain, Sunil K.; Loeffelholz, Michael J.; Patel, Janak

2014-01-01

152

An 11-year and 10-month-old girl with purpura and chest pain.  

PubMed

Mucosa-associated lymphoid tissue lymphoma (MALToma) is a type of B-cell lymphoma. Case reports of childhood thymic MALToma and its association with vasculitis are rarely found in the related literature. Herein, we present a report of an 11-year and 10-month-old girl who was initially diagnosed with cutaneous vasculitis characterized by nonthrombocytopenic palpable purpura, positive antinuclear antibody and anti-SSA (Ro) antibody. Eight months later, a thymic mediastinal mass was found. Surgical excision was performed and results of pathological analysis revealed an extranodal marginal zone CD20(+) B-cell MALToma. Benign response to the chemotherapeutic regimen of Berlin-Frankfurt-Münster group NHL-BFM 90 R2 without relapse was noted in 2 years of follow-up. For the first time, our case demonstrated some clinical evidence of the association between vasculitis and childhood MALToma. PMID:23006506

Chen, Pei-Hsuan; Chiang, Bor-Luen; Lu, Meng-Yao; Yang, Yao-Hsu

2014-10-01

153

Polyarteritis nodosa and Henoch–Schönlein purpura nephritis in a child with familial Mediterranean fever: a case report  

Microsoft Academic Search

Familial Mediterranean fever is an autosomal recessive disease characterized by recurrent self-limited attacks of fever accompanied\\u000a by peritonitis, pleuritis, and arthritis. Approximately 5% of individuals with familial Mediterranean fever have been reported\\u000a to have Henoch–Schonlein purpura and about 1% to have polyarteritis nodosa. A 7-year-old girl presenting with complaints of\\u000a purpuric rash, abdominal pain, arthritis, hematuria, and proteinuria and having

Ilknur Girisgen; Ferah Sonmez; Kutsi Koseoglu; Seda Erisen; Dilek Y?lmaz

154

Effective therapy for severe Henoch-Schonlein purpura nephritis with prednisone and azathioprine: A clinical and histopathologic study  

Microsoft Academic Search

Objectives: To validate a scoring system to assess the severity of renal lesions and to correlate histology with clinical findings. We also examined the efficacy of treatment with prednisone (1 to 2 mg\\/kg\\/d) and azathioprine (1 to 2 mg\\/kg\\/d) for severe Henoch-Schonlein purpura (HSP) nephritis. Methods: Twenty patients were evaluated retrospectively. All underwent biopsy before treatment, and 13 underwent biopsy

Bethany J Foster; Chantal Bernard; Keith N Drummond; Atul K Sharma

2000-01-01

155

Romiplostim treatment allows for platelet transfusion-free liver transplantation in pediatric thrombocytopenic patient with primary sclerosing cholangitis.  

PubMed

Thrombocytopenia is a major risk factor for cirrhotic liver disease. Patients with thrombocytopenia may have esophageal or gastric varices secondary to portal hypertension, leading to variceal bleeding which exposes the liver to further damage. Here, we present a female pediatric patient with PSC and CD, whose progressive thrombocytopenia was successfully controlled by romiplostim, a TPO receptor agonist. The patient developed bloody diarrhea at four yr of age, and was subsequently diagnosed with PSC and CD when seven yr old. While CD was well-controlled by immunomodulators, the patient's thrombocytopenia gradually progressed resulting in petechiae (platelet count of 11 × 10(9) /L) when she was 10 yr and four months old. She responded poorly to immunoglobulin and corticosteroids. Weekly subcutaneous injection of romiplostim was therefore initiated, and platelet counts were maintained over at 50 × 10(9) /L. She was able to undergo successful LDLT without platelet transfusion seven months after the initiation of romiplostim. Romiplostim was not required after LDLT with improved platelet counts. This case report suggests that romiplostim may be effective in the treatment of thrombocytopenic children with liver cirrhosis and portal hypertension, and in eliminating the need for platelet transfusion during the peri-transplant period. PMID:25041553

Minowa, Kei; Arai, Katsuhiro; Kasahara, Mureo; Sakamoto, Seisuke; Shimizu, Hirotaka; Nakano, Natsuko; Ito, Reiko; Obayashi, Naho; Nakazawa, Atsuko; Ishiguro, Akira

2014-09-01

156

Self-organizing phenomena induced by LLLT in Henoch-Schoenlein purpura  

NASA Astrophysics Data System (ADS)

Henoch-Schoenlein purpura is characterized by vasculitis of small vessels, particularly those of the skin, gastrointestinal tract, and kidney. Patients have characteristic purpuric skin rash plus all or some of the following: migratory polyarthralgias or polyarthritis, colicky abdominal pain, nephritis. Because until now there is no satisfactory treatment, we applied low level laser therapy (LLLT) in order to compare it with the classical therapy. Twenty-three children (2-15 years of age) have been treated at debut of the disease. They were randomly divided: group A (11 children) received LLLT; group B (12 children) was administrated classical therapy. Two GaAlAs diode lasers (670 nm and 830 nm) were used. The density of energy (4-8 J/cm2), irradiating frequency (2.4 Hz) was applied one session daily, using scanning technique under a special treatment protocol on cutaneous purpuric areas (20 sessions). The best results were obtained in laser group. Despite the complex medication, some patients from group B fell back into the former state after apparent improvement, and two children developed nephritis. The results could be explained by self-organization. LLLT is acting as a trigger factor causing certain systemic effects through circulating blood and a response of the entire immune system, by way of synergetic mechanisms.

Ailioaie, Laura; Ailioaie, C.

2001-06-01

157

Corticosteroids May Improve Clinical Outcomes During Hospitalization for Henoch-Sch?nlein Purpura  

PubMed Central

OBJECTIVE To characterize the effect of corticosteroid exposure on clinical outcomes in children hospitalized with new-onset Henoch-Schönlein purpura (HSP). PATIENTS AND METHODS We conducted a retrospective cohort study of children discharged with an International Classification of Diseases, Clinical Modification code of HSP between 2000 and 2007 by using inpatient administrative data from 36 tertiary care children’s hospitals. We used stratified Cox proportional hazards regression models to estimate the relative effect of time-varying corticosteroid exposure on the risks of clinical outcomes that occur during hospitalization for acute HSP. RESULTS During the 8-year study period, there were 1895 hospitalizations for new-onset HSP. After multivariable regression modeling adjustment, early corticosteroid exposure significantly reduced the hazard ratios for abdominal surgery (0.39 [95% confidence interval (CI): 0.17– 0.91]), endoscopy (0.27 [95% CI: 0.13– 0.55]), and abdominal imaging (0.50 [95% CI: 0.29 – 0.88]) during hospitalization. CONCLUSIONS In the hospital setting, early corticosteroid exposure was associated with benefits for several clinically relevant HSP outcomes, specifically those related to the gastrointestinal manifestations of the disease. PMID:20855386

Weiss, Pamela F.; Klink, Andrew J.; Localio, Russell; Hall, Matt; Hexem, Kari; Burnham, Jon M.; Keren, Ron; Feudtner, Chris

2012-01-01

158

Variation in inpatient therapy and diagnostic evaluation of children with Henoch Sch?nlein purpura  

PubMed Central

Objective To describe variation regarding inpatient therapy and evaluation of children with Henoch Schönlein purpura (HSP) admitted to children’s hospitals across the United States. Study design We conducted a retrospective cohort study of children discharged with a diagnosis of HSP between 2000 and 2007 using inpatient administrative data from 36 children’s hospitals. We examined variation among hospitals in the use of medications, diagnostic tests, and intensive care services using multivariate mixed effects logistic regression models. Results During the initial HSP hospitalization (N=1,988), corticosteroids were the most common medication (56% of cases), followed by opioids (36%), NSAIDs (35%), and anti-hypertensives (11%). After adjustment for patient characteristics, hospitals varied significantly in their use of corticosteroids, opioids, and NSAIDs; the use of diagnostic abdominal imaging, endoscopy, laboratory testing, and renal biopsy; and the utilization of intensive care services. By contrast, hospitals did not differ significantly regarding administration of anti-hypertensives or performance of skin biopsy. Conclusions The significant variation identified may contribute to varying HSP clinical outcomes between hospitals, warrants further investigation, and represents a potentially important opportunity to improve quality of care. PMID:19643437

Weiss, Pamela F.; Klink, Andrew J.; Hexem, Kari; Burnham, Jon M.; Leonard, Mary B.; Keren, Ron; Localio, Russell; Feudtner, Chris

2009-01-01

159

[A case of disseminated nontuberculous mycobacteriosis during purpura associated with hypergammaglobulinemia and hepatitis type C].  

PubMed

A 74-year-old woman with hepatitis due to hepatitis C virus followed up using oral predonisolone (3 mg/day) for two years because of hypergammaglobulinemia-associated purpura reported fever and lumbago in February 2005. Upon admission in June, she was found in chest-computed tomography to have atelectasia in the right middle lung lobe and a nodule with a cavity in the right lower lobe. She tested positive for tuberculous glycolipid antibody. Gallium scintigraphy showed an abnormal accumulation in the lower lumbar vertebra. Magnetic resonance imaging showed abnormal enhancement at L4, L5, and their intervertebral disc. Mycobacterium intracellulare (M. intracellulare) was detected in blood culture, bronchoalveolar lavage, and a biopsy specimen from the intervertebral disc, yielding a diagnosis of disseminated nontuberculous mycobacteriosis (NTM) due to M. intracellulare. She was treated with clarithromycin (CAM), ethambutol (EB), and rifampicin (RFP), but EB and RFP were discontinued due to of the fever they induced. She was then treated with a combination of CAM, levofloxacin, and streptomycin and followed up as an out patient. Based on case reports of disseminated NTM infection in Japan, the prognosis is poor and a protocol must be established for its treatment. PMID:19086421

Ueno, Shiro; Miyauchi, Shunichi; Umekita, Kunihiko; Kusumoto, Norio; Takajo, Ichiro; Kuroki, Masayuki; Kai, Yasufumi; Nagatomo, Yasuhiro; Okayama, Akihiko

2008-11-01

160

A Case of Henoch-Sch?nlein Purpura with P369S Mutation in MEFV Gene  

PubMed Central

Background Henoch-Schönlein purpura (HSP) is the most common vasculitis of childhood. HSP can affect multiple organs presenting with a characteristic rash in most of the patients. Familial Mediterranean Fever (FMF) is an inherited inflammatory disease common in mediterranean populations. HSP is the most common vasculitis seen in children with FMF. Case Presentation A 16 year old boy was referred with history of abdominal pain lasting for 20 days. He was hospitalized and had appendectomy. Due to the persistence of his abdominal pain after surgery he was admitted to our hospital. His physical examination showed palpable purpuric rashes symmetrically distributed on lower extremities. Abdominal examination revealed periumbilical tenderness. Laboratory tests showed elevated erythrocyte sedimentation rate, Creactive protein and fibrinogen. Urinalysis revealed microscopic hematuria and severe proteinuria. The fecal occult blood testing was positive. Based on these clinic findings, the patient was diagnosed as HSP with renal, gastrointestinal tract and skin involvement. We performed DNA analysis in our patient because he had diagnosis of vasculitis with severe symptoms and found that he was carrying heterozygote P369S mutation. Conclusion Our case is noteworthy as it indicates that it may be important not to overlook presence of FMF mutations in patients with a diagnosis of severe vasculitis. PMID:23056796

Ertan, Pelin; Tekin, Gokhan; Sahin, Gulseren Evirgen; Kas?rga, Erhun; Taneli, Fatma; Kandioglu, Ali Riza; Sozeri, Betul

2011-01-01

161

Henoch-Sch?nlein purpura associated with a neuroblastoma: Report of one case and a review of the literature  

PubMed Central

Summary Malignancies such as solid tumors and hematologic malignancies can often induce or be associated with Henoch-Schönlein purpura (HSP) in older males but not in children. Described here is the case of a 5-year-old boy who clinically presented with HSP. An imaging study of the abdomen revealed a right retroperitoneal neoplasm that histopathology postoperatively confirmed to be a neuroblastoma. Malignancies are sometimes associated with HSP mostly in older males, though children are affected, albeit rarely. Thus, all patients with HSP must be carefully examined to identify or exclude an underlying disease.

Dong, Qiaoli; Cao, Shanshan; Zhang, Hongwen; Geng, Hui

2012-01-01

162

The incidence and severity of Henoch-Schönlein purpura nephritis over a 22-year period in Fukushima Prefecture, Japan  

Microsoft Academic Search

Background  Recently, there have been a few reports on the decrease in the incidence of severe Henoch-Schönlein purpura nephritis (HSPN)\\u000a in Japan. To evaluate the incidence and the severity of HSPN, we examined the epidemiology and clinical manifestations of\\u000a HSPN in Fukushima Prefecture over a 22-year period.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  We enrolled 61 patients (Group 1) diagnosed with HSPN between 1987 and 1997 and

Yukihiko Kawasaki; Kazuhide Suyama; Eichi Yugeta; Masahiko Katayose; Shigeo Suzuki; Hiroko Sakuma; Kenji Nemoto; Akira Tsukagoshi; Katsutoshi Nagasawa; Mitsuaki Hosoya

2010-01-01

163

Acral purpura as leading clinical manifestation of dermatitis herpetiformis: report of two adult cases with a review of the literature.  

PubMed

Dermatitis herpetiformis (DH) is an autoimmune disease that clinically manifests as pruritic vesicles and papules. The diagnosis of DH is often challenging because of its wide spectrum of clinical presentations. We here report 2 patients with DH in whom finger petechiae represented the initial and leading manifestation of the disease, and the confirmed diagnosis critically relied on immunopathological studies. Therefore, besides the classic causes, clinicians should also consider DH in the differential diagnosis of acral purpura, even in patients only presenting with discrete acral petechial lesions. We also review the recent literature regarding the rare cases of petechiae in adult DH patients. PMID:23970137

Tu, Honggang; Parmentier, Laurent; Stieger, Marco; Spanou, Zoe; Horn, Michael; Beltraminelli, Helmut; Borradori, Luca

2013-01-01

164

Posttransfusion purpura associated with an autoantibody directed against a previously undefined platelet antigen.  

PubMed

Although alloantibody against the PLA1 platelet antigen is usually found in patients with posttransfusion purpura (PTP), the mechanism of destruction of the patient's own PLA1-negative platelets is unexplained. We used a sensitive immunoblot technique to detect antiplatelet antibodies in a patient with classic PTP. The patient's acute-phase serum contained antibodies against three proteins present in control (PLA1-positive) platelets: an antibody that bound to a previously unrecognized platelet protein of mol wt 120,000 [glycoprotein (GP) 120], antibodies that bound to PLA1 (mol wt 90,000), and an epitope of GP IIb (mol wt 140,000). The antibodies against PLA1 and GP IIb did not react with the patient's own PLA1-negative platelets, control PLA1-negative platelets, or thrombasthenic platelets. In contrast, the antibody against GP 120 recognized this protein in all three platelet preparations, but not in Bernard-Soulier or Leka (Baka)-negative platelets. Antibody against GP 120 was not detected in the patient's recovery serum, although the antibodies against PLA1 and GP IIb persisted. F(ab)2 prepared from the patient's acute-phase serum also bound to GP 120. These results suggest that in PTP, transient autoantibody production may be responsible for autologous (PLA1-negative) platelet destruction. In addition, alloantibodies against more than one platelet alloantigen may be found in this disease. The nature of the GP 120 autoantigen and the GP IIb-related alloantigen defined by our patient's serum remains to be determined. PMID:3567361

Stricker, R B; Lewis, B H; Corash, L; Shuman, M A

1987-05-01

165

[Determination of trace elements in Mongolian medicine Zidianling curing allergic purpura disease by ICP-AES].  

PubMed

During the study of the Mongolian medicine Zidianling, the authors found that the Mongolian medicine Zidianling contains great amount of trace elements in which human-body-needed trace elements are fairly much but the heavy metals are very little. A method using ICP-AES with microwave digestion was studied for the determination of 15 elements including Ca, Mg, Sr, Fe, Mn, Zn, Cu, Pb, etc. in Mongolian medicine-Zidianling. The major function of this medicine is clearing away heat and removing toxic substances, and cooling blood to stop bleeding. To explain the Zidianling's clinical effects, the authors chose 260 allergic purpura patients with 140 male and 120 female. The youngest was 6 years old, the oldest was 62 years old. Most of patients were between 6 and 16, accounting for nearly 90%. The results of clinical effects show that 234 patients were cured, roughly 90% of the total number Thirteen patients showed obvious effects (5% of the total number) and 11 had effective cures of illnesses (4.23% of the total number). Two patients had no cures of illnesses (0.77% of the total number). And the integrated effective rate may reach 99.23%. The results show that Mongolian medicine Zidianling has great amount of trace elements and its Sr content is different from other Mongolian medicines and is especially high. The recoveries of standard addition are in the range of 94.63%-106.40%. The relative standard deviation RSD< or = 3.17%, and the detection limit is in the range of < or = 0.009 microg x mL(-1). PMID:19271517

Er-Deng-Sang, E; Hang, Gai-Ba-Te-Re; Ba, Tu

2008-11-01

166

Experience of buffy coat pooling of platelets as a supportive care in thrombocytopenic dengue patients: A prospective study  

PubMed Central

Random donor platelet (RDP) is not sufficient to improve the platelet count in most thrombocytopenic patients. Single donor platelet (SDP) or buffy coat pooled platelet (BCPP) are the two choices to provide a full therapeutic dose of platelets. However, there are constraints in the preparation of SDP due to stringent donor selection procedure, time required for procedure, and need of special expensive equipments and kits. BCPP is widely practiced, especially in the European countries, since 1995. In India, we decided to adopt the procedure of buffy coat pooling of platelets, especially for economically backward patients and for emergencies. This study was prospectively conducted from September 2009 to September 2010. A total of 129 units of BCPP [tested prior for viral markers by enzyme-linked immunosorbent assay (ELISA) and individual donor nucleic acid amplification test (ID-NAT)] were issued to 129 patients suffering from dengue and were included in this study. For comparison between efficacy of SDP and BCCP, patients were divided into two groups of 50 each. The post-transfusion platelet counts of the patients were noted after 2 hours of transfusion for each type of component. The platelet yield varied from 2.5 to 4.4 ? 1011 in BCPP samples. The samples analyzed were sterile without any contamination. The different biochemical parameters were analyzed in detail. The observed post-transfusion platelet recovery and corrected count increment (CCI) at 1 hour and 24 hours after BCPP transfusion were similar to that after SDP transfusion. Hence, we concluded that BCPP can be a low cost alternative to SDP in the times of emergencies like dengue and non-affordability by the patient for SDP. PMID:25161345

Chatterjee, Kabita; Coshic, Poonam; Borgohain, Mayuri; Agarwal, Nitin

2014-01-01

167

IgA-containing circulating immune complexes in dermatitis herpetiformis, Henoch-Sch?nlein purpura, systemic lupus erythematosus and other diseases.  

PubMed Central

The sera of patients with dermatitis herpetiformis, Henoch-Schönlein purpura and systemic lupus erythematosus were examined for IgA-containing immune complexes using a newly described radioimmunoassay. The IgG Raji cell radioimmunoassay and the 125I-C1q binding assay were also used to detect IgG- and IgM- containing soluble immune complexes. IgA-containing immune complexes were found in the sera of twelve of forty-nine (24%) patients with dermatitis herpetiformis, four of six (67%) patients with Henoch-Schönlein purpura, and seven of ten (70%) patients with systemic lupus erythematosus. IgG- or IgM- containing immune complexes were also found in six of forty-seven patients with dermatitis herpetiformis, in one of six patients with Henoch-Schönlein purpura, and in nine of ten patients with systemic lupus erythematosus, by either the 125I-Clq binding assay or the IgG Raji cell assay. The finding of soluble IgA immune complexes in a high percentage of patients with systemic lupus erythematosus and Henoch-Schönlein purpura suggests that they may play an important role in the pathogenesis of these diseases. In contrast, their low prevalence in patients with dermatitis herpetiformis suggests that IgA-containing immune complexes may not play a major role in the pathogenesis of dermatitis herpetiformis. PMID:7418261

Hall, R P; Lawley, T J; Heck, J A; Katz, S I

1980-01-01

168

Hemostatic Function and Transfusion Efficacy of Apheresis Platelet Concentrates Treated with Gamma Irradiation in Use for Thrombocytopenic Patients  

PubMed Central

Summary Background During the transfusion of blood components, the transfer of allogeneic donor white blood cells (WBCs) can mediate transfusion-associated graft-versus-host disease (TA-GVHD). To minimize the reaction, exposure of blood products to gamma irradiation is currently the standard of care. The aim of our study was to evaluate and compare hemostatic function, transfusion efficacy, and safety of gamma-irradiated single-donor apheresis platelet concentrates (PCs) and of conventional non-irradiated PCs in patients with chemotherapy-induced thrombocytopenia. Methods 20 double-dose single-donor leukoreduced PCs were split in two identical units; one was gamma-irradiated with 25 Gy (study arm A) and the other remains non-irradiated (study arm B). Both units were stored under equal conditions. Hematologic patients were randomly assigned to receive gamma-irradiated or conventional non-irradiated PCs. Hemostatic function was evaluated by thrombelastography (TEG). TEG measurements were taken pre transfusion and 1 and 24 h post transfusion. TEG profiles were measured, noting the time to initiate clotting (R), the angle of clot formation (?), and the maximum amplitude (clot strength (MA)). Whole blood samples were collected from these thrombocytopenic patients at 1 and 24 h for PLT count increments (CIs) and corrected count increments (CCIs) with assessments of transfusion efficacy. Time to next PLT transfusion, transfusion requirement of RBCs, active bleeding, and adverse events (AEs), were analyzed. Results No differences could be found in hemostatic function parameters (MA, R, and ?) between study arms A and B (all p values > 0.096) pre transfusion as well as 1 and 24 h post transfusion. No differences between study arms A and B were observed for mean (± standard deviation (SD)) 1-hour CCI (12.83 ± 6.33 vs. 11.59 ± 5.97) and 24-hour CCI (6.56 ± 4.10 vs. 5.76 ± 4.05). Mean 1-hour CI and 24-hour CI were not significantly different in both study arms (p = 0.254 and p = 0.242 respectively). Median time to the next PC transfusion after study PC was not significantly different between groups: (2.4 vs. 2.2 days, p = 0.767). No differences could be found in transfusion requirement of red blood cells (p = 0.744) between both study arms. There were also no regarding bleeding, adverse events, and acute transfusion reaction(s). Conclusions This study confirms safety of gamma-irradiated PCs for treatment thrombocytopenia. Hemostatic function, transfusion efficacy, bleeding, and safety of single-donor apheresis PCs treated with gamma irradiation versus untreated control PCs are comparable. PMID:25053932

Zhu, Mei; Xu, Wei; Wang, Bao-Long; Su, Hong

2014-01-01

169

Microcirculatory Disturbances and Human Myocardial Infarction.  

National Technical Information Service (NTIS)

Thirty-nine cases of thrombotic thrombocytopenic purpura (Moschcowitz's disease) were examined, and the severe, obstructive involvement of the intramyocardial arterial branches was compared to the myocardial condition. In only 4 cases (10.2 per cent) was ...

G. Baroldi, W. C. Manion

1966-01-01

170

Are there specific haemostatic abnormalities in children surviving septic shock with purpura and having skin necrosis or limb ischaemia that need skin grafts or limb amputations?  

Microsoft Academic Search

More than 10% of children surviving septic shock with purpura have skin necrosis or limb ischaemia (SNLI.). Among 44 children\\u000a consecutively admitted to our pediatric intensive care unit, 35 (80%) survived, 6 of them (17%) developed SNLI (defined as\\u000a the need of a surgical procedure). Two timed haemostasis measurements included the determination of coagulation factors, protein\\u000a C (PC), protein S

R. Cremer; F. Leclerc; B. Jude; A. Sadik; S. Leteurtre; C. Fourier; A. Martinot; J. F. Diependaele

1999-01-01

171

Cocaine-associated retiform purpura: a C5b-9-mediated microangiopathy syndrome associated with enhanced apoptosis and high levels of intercellular adhesion molecule-1 expression.  

PubMed

Cocaine-associated retiform purpura is a recently described entity characterized by striking hemorrhagic necrosis involving areas of skin associated with administration of cocaine. Levamisole, an adulterant in cocaine, has been suggested as the main culprit pathogenetically. Four cases of cocaine-associated retiform purpura were encountered in the dermatopathology practice of C. M. Magro. The light microscopic findings were correlated with immunohistochemical and immunofluorescence studies. All 4 cases showed a very striking thrombotic diathesis associated with intravascular macrophage accumulation. Necrotizing vasculitis was noted in 1 case. Striking intercellular adhesion molecule-1 (ICAM-1)/CD54 expression in vessel wall along with endothelial expression of caspase 3 and extensive vascular C5b-9 deposition was observed in all biopsies examined. Cocaine-induced retiform purpura is a C5b-9-mediated microvascular injury associated with enhanced apoptosis and prominent vascular expression of ICAM-1, all of which have been shown in prior in vitro and in vivo murine models to be a direct effect of cocaine metabolic products. Antineutrophilic cytoplasmic antibody and antiphospholipid antibodies are likely the direct sequelae of the proapoptotic microenvironment. The inflammatory vasculitic lesion could reflect the downstream end point reflective of enhanced ICAM-1 expression and the development of antineutrophilic cytoplasmic antibody. Levamisole likely works synergistically with cocaine in the propagation of this syndromic complex. PMID:23392134

Magro, Cynthia M; Wang, Xuan

2013-10-01

172

MASKER MASKER TARGET TARGET TARGET  

E-print Network

from a large speech database (Ives et al,2005). The original speech is from one speaker Probabilitycorrect -6 dB 0 dB Listeners were presented with two phrases of concurrent speech syllables. The masker syllables coincided with the second and third target syllables. The speech syllables were taken

Ives, D. Timothy

173

Novel thrombopoietic agents: a new era for management of patients with thrombocytopenia  

Microsoft Academic Search

fter many decades of an orphan existence, immune thrombocytopenic purpura (ITP) is a central focus for the clinical development of mul- tiple, novel thrombopoietic agents. These agents have the potential to transform the management of ITP and possibly other thrombocytopenic disorders. Now, with the approval of the first agents for clinical use, their role in patient care will become established

James N. George; Deirdra R. Terrell

2008-01-01

174

Adhesion of Neisseria meningitidis to Dermal Vessels Leads to Local Vascular Damage and Purpura in a Humanized Mouse Model  

PubMed Central

Septic shock caused by Neisseria meningitidis is typically rapidly evolving and often fatal despite antibiotic therapy. Further understanding of the mechanisms underlying the disease is necessary to reduce fatality rates. Postmortem samples from the characteristic purpuric rashes of the infection show bacterial aggregates in close association with microvessel endothelium but the species specificity of N. meningitidis has previously hindered the development of an in vivo model to study the role of adhesion on disease progression. Here we introduced human dermal microvessels into SCID/Beige mice by xenografting human skin. Bacteria injected intravenously exclusively associated with the human vessel endothelium in the skin graft. Infection was accompanied by a potent inflammatory response with the secretion of human inflammatory cytokines and recruitment of inflammatory cells. Importantly, infection also led to local vascular damage with hemostasis, thrombosis, vascular leakage and finally purpura in the grafted skin, replicating the clinical presentation for the first time in an animal model. The adhesive properties of the type IV pili of N. meningitidis were found to be the main mediator of association with the dermal microvessels in vivo. Bacterial mutants with altered type IV pili function also did not trigger inflammation or lead to vascular damage. This work demonstrates that local type IV pili mediated adhesion of N. meningitidis to the vascular wall, as opposed to circulating bacteria, determines vascular dysfunction in meningococcemia. PMID:23359320

Melican, Keira; Michea Veloso, Paula; Martin, Tiffany; Bruneval, Patrick; Dumenil, Guillaume

2013-01-01

175

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

ClinicalTrials.gov

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

2005-06-23

176

[Management of complex thrombocytopenia with thrombelastometry : a case of simultaneous posttransfusion purpura and heparin-induced thrombocytopenia].  

PubMed

The case presented describes the combined onset of heparin-induced thrombocytopenia II (HIT) and post-transfusion purpura (PTP) 5-10 days following exposure to heparin and blood transfusion during aortic dissection repair. On day 4 the platelet count decreased by 40% and D-dimers started to increase again. Despite a low clinical probability for HIT-II at this time (4T score of 3) serological testing was done the next day and yielded a negative test result. Following a transient rise after platelet transfusion another 40% decrease in platelet count occurred on day 8. To increase precision of the 4T score, screening ultrasonography was performed and identified a clinically unapparent jugular vein thrombosis. As this increased the 4T score to 6 points, serological testing was repeated and now showed the presence of HIT-II antibodies. Despite switching from heparin to argatroban the platelet count continued to decrease to <5×10(3)/µl. Conventional clotting tests showed a prolonged prothrombin time and severe hypofibrinogenemia. Because of the female sex, age >50 years, history of pregnancy and transfusion 8 days before, PTP was suspected. The alteration of the plasmatic coagulation, however, could not be explained by PTP. Therefore, disseminated intravascular coagulation (DIC) and interference of argatroban with conventional clotting tests were considered as alternative diagnoses. In order to differentiate between the two alternatives rotational thrombelastometry (ROTEM®) was performed and revealed an increased functional fibrinogen level without signs of hyperfibrinolysis. This argued for an interference of argatroban with the Clauss method of fibrinogen measurement and rendered DIC unlikely. Under suspicion of PTP, treatment with immunoglobulin was initiated and blood transfusions were avoided. Detection of PTP antibodies 1 day later confirmed the combined presence of PTP and HIT-II. As hyperfibrinogenemia compensated for the effects of thrombocytopenia on clot firmness in ROTEM®, anticoagulation with lepirudin was started at 9×10(3) platelets/µl only. The next day the platelet count increased to 32×10(3)/µl and clot firmness returned to normal. No thromboembolic complications and no relevant bleeding were observed. In summary, this case shows for the first time that HIT-II and PTP can occur in parallel in patients with simultaneous exposure to heparin and blood transfusions. Confounding effects of argatroban on conventional clotting tests may mimic DIC under these circumstances and make diagnosis difficult. Careful evaluation of the time-related magnitude in platelet decrease, patient history, course of D-dimers, screening ultrasonography and ROTEM® seem to be helpful to initiate early appropriate therapy before serological test results become available. In contrast to the Clauss method of fibrinogen measurement, assessment of clot firmness in ROTEM® is not influenced by argatroban. Moreover, ROTEM® reveals the compensatory effects of increased functional fibrinogen on clot firmness during severe thrombocytopenia as an important variable for anticoagulation therapy during thrombocytopenia with increased thromboembolic risk. PMID:20922353

Haeberle, H A; Menzel, D; Unertl, K; Nohé, B

2011-12-01

177

Henoch-Schönlein Purpura  

MedlinePLUS

... container in a health care provider’s office or commercial facility and can be tested in the same ... Government does not endorse or favor any specific commercial product or company. Trade, proprietary, or company names ...

178

Sputter target  

DOEpatents

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.

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

1980-01-01

179

ISAC targets  

NASA Astrophysics Data System (ADS)

The TRIUMF-ISAC radioactive ion beam facility was designed and constructed to allow irradiation of thick targets with up to 100 A proton beam intensities. Since beginning operation in 1998, beam intensities on ISAC targets have progressively increased toward the 100 A design limit. Routine operation with p + intensities up to 75 A is currently possible for both refractory metal target materials and for composite metal carbide materials; full 99 A p + intensity has been achieved for Nb foil target material. Consideration must be given to the beam power deposition, the power dissipation and the limiting temperature criteria of each target material. Increased beam power dissipation has been achieved by modifying target materials and target containers. Increasing irradiation currents have produced benefits, drawbacks and unexpected results for ISOL operations.

Dombsky, M.; Kunz, P.

2014-01-01

180

Human protein C concentrate in the treatment of purpura fulminans: a retrospective analysis of safety and outcome in 94 pediatric patients  

PubMed Central

Introduction Purpura fulminans (PF) is a devastating complication of uncontrolled systemic inflammation, associated with high incidence of amputations, skin grafts and death. In this study, we aimed to clarify the clinical profile of pediatric patients with PF who improved with protein C (PC) treatment, explore treatment effects and safety, and to refine the prognostic significance of protein C plasma levels. Methods In Germany, patients receiving protein C concentrate (Ceprotin®, Baxter AG, Vienna, Austria) are registered. The database was used to locate all pediatric patients with PF treated with PC from 2002 to 2005 for this national, retrospective, multi-centered study. Results Complete datasets were acquired in 94 patients, treated in 46 centers with human, non-activated protein C concentrate for purpura fulminans. PC was given for 2 days (median, range 1-24 days) with a median daily dose of 100 IU/kg. Plasma protein C levels increased from a median of 27% to a median of 71% under treatment. 22.3% of patients died, 77.7% survived to discharge. Skin grafts were required in 9.6%, amputations in 5.3%. PF recovered or improved in 79.8%, remained unchanged in 13.8% and deteriorated in 6.4%. Four adverse events occurred in 3 patients, none classified as severe. Non-survivors had lower protein C plasma levels (P < 0.05) and higher prevalence of coagulopathy at admission (P < 0.01). Time between admission and start of PC substitution was longer in patients who died compared to survivors (P = 0.03). Conclusions This retrospective dataset shows that, compared to historic controls, only few pediatric patients with PF under PC substitution needed dermatoplasty and/or amputations. Apart from epistaxis, no bleeding was observed. Although the data comes from a retrospective study, the evidence we present suggests that PC had a beneficial impact on the need for dermatoplasty and amputations, pointing to the potential value of carrying out a prospective randomised controlled trial. PMID:20723255

2010-01-01

181

Targeted Metabolomics  

PubMed Central

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 in 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 the procedures for extracting nitrogenous metabolites, including the amino acids, lipids, and intermediary metabolites, including the TCA cycle oxoacids, from blood plasma. Specifically, protocols for the analysis of these metabolites using liquid chromatography-mass spectrometry-based targeted metabolomics experiments is discussed. PMID:22470063

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

2012-01-01

182

Targeting Subgroups.  

ERIC Educational Resources Information Center

By requiring limited-English-proficient students and students with disabilities to meet the same targets at the same times as all other students, the NCLB imposes a one-size-fits-all approach that ignores the individual child. Challenges school leaders to take care not to blame the students and still hold themselves accountable for continual…

Schwartzbeck, Terri Duggan

2003-01-01

183

Target assembly  

DOEpatents

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.

Lewis, Richard A. (Falls Church, VA)

1980-01-01

184

[Syk inhibitors].  

PubMed

Non-receptor type of protein-tyrosine kinase Syk (spleen tyrosine kinase) was isolated in the University of Fukui in 1991. Syk is known to be essential for the various physiological functions, especially in hematopoietic lineage cells. Moreover, ectopic expression of Syk by epigenetic changes is reported to cause retinoblastoma. Recently, novel Syk inhibitors were developed and its usefulness has been evaluated in the treatment of allergic rhinitis, rheumatoid arthritis, and idiopathic thrombocytopenic purpura. In this review, we will summarize the history, structure, and function of Syk, and then describe the novel Syk inhibitors and their current status. Furthermore, we will introduce our findings of the adaptor protein 3BP2 (c-Abl SH3 domain-binding protein-2), as a novel target of Syk. PMID:23961675

Kimura, Yukihiro; Chihara, Kazuyasu; Takeuchi, Kenji; Sada, Kiyonao

2013-07-01

185

Accelerator target  

SciTech Connect

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.

Schlyer, David J. (Bellport, NY); Ferrieri, Richard A. (Patchogue, NY); Koehler, Conrad (Miller Place, NY)

1999-01-01

186

Accelerator target  

DOEpatents

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.

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

1999-06-29

187

Acute Renal Failure, Translocational Hyponatremia and Hyperkalemia following Intravenous Immunoglobulin Therapy  

Microsoft Academic Search

Background\\/Aims: Intravenous immunoglobulin (IVIG) therapy has been associated with renal adverse effects and electrolyte disturbances. Methods: We retrospectively evaluated a cohort of 66 unselected patients with idiopathic thrombocytopenic purpura, who received 140 courses of IVIG therapy. Acute renal failure (ARF), hyponatremia and hyperkalemia, as potential complications of IVIG therapy, were assessed from 100 IVIG courses with sufficient data for analysis.

Eugene Daphnis; Kostas Stylianou; Michael Alexandrakis; Irene Xylouri; Eleftheria Vardaki; Spyros Stratigis; John Kyriazis

2007-01-01

188

Mechanism of action of IVIG and anti-D in ITP  

Microsoft Academic Search

Infusion of large amounts of intravenous immunoglobulin (IVIG) or polyclonal anti-D can reverse thrombocytopenia in patients with idiopathic thrombocytopenic purpura within hours of the administration of these products. It has been suggested that the effects of IVIG appear to far outlast several half-lives of the product. Several mechanisms have been proposed to explain both the acute and long term effects

Alan H. Lazarus; Andrew R. Crow

2003-01-01

189

ANTICARDIOLIPIN ANTIBODY-RELATED THROMBOCYTOPENIA: PERSISTENT REMISSION AFTER SPLENECTOMY  

Microsoft Academic Search

The lupus anticoagulant (LAC) and anticardiolipin antibody (ACA) syndromes require particular therapeutic approaches: thrombotic accidents are an indication for oral anticoagulant therapy (OAT), whereas severe thrombocytopenia may require the special treatments used for immunologic thrombocytopenic purpura (ITP). We describe the case of a 21-year-old male who presented with axillary vein thrombosis associated with LAC and ACA at high titers in

Giorgio Ballerini; Donato Gemmati; Stefano Moratelli; Paola Morelli; Maria Luisa Serino

190

Hematologic complications of primary immune deficiencies  

Microsoft Academic Search

Primary immune deficiencies have an estimated overall incidence of 1 in 10,000 individuals. These disorders are diverse, depending on the specific immune functions involved, and lead to chronic or recurrent infections, inflammatory conditions, and a variety of autoimmune diseases. The most common autoimmune disorder is immune thrombocytopenic purpura (ITP), followed by autoimmune hemolytic anemia (AHA). While cytopenias are common in

C. Cunningham-Rundles

2002-01-01

191

HumanWildlife Conflicts 1(1):6877, Spring 2007 Two members of the family Enterobacteriacea,  

E-print Network

(fragmented red blood cells), and thrombotic thrombocytopenic purpura (a blood disorder characterized by low platelets, low red blood cell count, abnormalities in kidney and neurological functions (Lewis 1997). The epidemiology of outbreaks of STEC in humans is linked to the consumption of contaminated bovine products

192

Laparoscopic splenectomy in children  

Microsoft Academic Search

To determine the safety and efficiacy of laparoscopic splenectomy (LS) in children, a retrospective review of our preliminary experience using LS was compared to results in patients who previously underwent open splenectomy (OS). From July 1993 to January 1995, we performed eight LS procedures in six children with hereditary spherocytosis (HS) and two with immune thrombocytopenic purpura (ITP). Laparoscopic cholecystectomy

K. Yoshida; Y. Yamazaki; R. Mizuno; H. Yamadera; A. Hara; J. Yoshizawa; M. Kanai

1995-01-01

193

Target: Terror  

NSDL National Science Digital Library

This week's In the News investigates the US military strike against targets linked to international terrorism. The eight resources discussed provide analysis, commentary, and recent news. On August 7, simultaneous bombings of US embassies in Nairobi, Kenya and Dar es Salaam, Tanzania, injured thousands of civilians and killed more than 250, including a dozen Americans. In a reprisal on August 20, based on "compelling evidence" from US intelligence agencies, President Clinton ordered a Tomahawk cruise missile attack on several sites suspected of being connected to the terrorist network responsible for the embassy bombings. The targets of the assault included six sites within the distributed Zhawar Kili al-Badr guerrilla camp near Khost, Afghanistan, and the El Shifa Pharmaceutical Plant near Khartoum, Sudan--assumed to be a manufacturing center for chemical weapons. Both locations are believed to be supported by Osama Bin Muhammad Bin Laden, who is, according to the Pentagon, linked to the embassy bombings and considered the "world's leading individual sponsor of terrorism against Americans." The transnational missile attack marks the most powerful military offensive against a private sponsor of confederate terrorist groups. The US called the assault a pre-emptive measure against terrorism and justified its use of force under Article 51 of the UN charter, which authorizes nations to act in self-defense if they anticipate aggression. US Defense Secretary William Cohen acknowledged that the military retaliation "will not eliminate the problem" of terrorism, but he believes the disruption and destruction of terrorist sanctuaries sends a clear message that the US will be steadfast in defense of its citizens "against these cowardly attacks."

Osmond, Andrew.

194

Target vehicle developments  

NASA Astrophysics Data System (ADS)

To effectively test Ballistic Missile Defense systems, realistic targets are needed for demonstration and validation, which would effectively balance the contradictory requirements of cost effectiveness and precise targeting. This paper describes a family of target vehicles developed for that purpose, which provides a high degree of hardware and procedural commonality, while covering a broad range of performance requirements. The target vehicles can be readily adapted to a variety of Theater Missile Defense sensors and interceptor test requirements. The target vehicles can also be used for phenomenology experiments. The paper describes the target vehicle design, the target vehicle motors, the payload module bus modular subsystems, the mission unique subsystems, and launch operations.

Schoneman, Scott R.; Knoblach, Gerald

1993-06-01

195

Experience with IPNS targets  

SciTech Connect

Three targets have operated in the IPNS Neutron Scattering Facility. The first, a depleted Uranium target, served from 1981 until it was replaced in 1988 by the Enriched Uranium Booster Target. The Booster Target had operated for nearly three years when it suffered a cladding leak and was replaced with the retired depleted Uranium target. That target reached its end-of-life after less than one year`s further operation, and was replaced with an identical one newly assembled from spare components, which is still operating satisfactorily. This paper reviews the operating history of the IPNS targets and the findings reached during analysis of the failures. Similarities with ISIS target experience, preliminary conclusions and plans for providing spares and improved targets are discussed. We present some preliminary results from the hot cell examination of the failed depleted Uranium target.

Carpenter, J.M.; Hins, A.G.

1993-12-31

196

Magnetized Target Fusion: Improving the plasma target  

NASA Astrophysics Data System (ADS)

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.

Intrator, T.

2011-11-01

197

Human target acquisition performance  

NASA Astrophysics Data System (ADS)

The battlefield has shifted from armored vehicles to armed insurgents. Target acquisition (identification, recognition, and detection) range performance involving humans as targets is vital for modern warfare. The acquisition and neutralization of armed insurgents while at the same time minimizing fratricide and civilian casualties is a mounting concern. U.S. Army RDECOM CERDEC NVESD has conducted many experiments involving human targets for infrared and reflective band sensors. The target sets include human activities, hand-held objects, uniforms & armament, and other tactically relevant targets. This paper will define a set of standard task difficulty values for identification and recognition associated with human target acquisition performance.

Teaney, Brian P.; Du Bosq, Todd W.; Reynolds, Joseph P.; Thompson, Roger; Aghera, Sameer; Moyer, Steven K.; Flug, Eric; Espinola, Richard; Hixson, Jonathan

2012-06-01

198

Magnetically attached sputter targets  

DOEpatents

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.

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

1994-02-15

199

Magnetically attached sputter targets  

DOEpatents

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.

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

1994-01-01

200

Quick response targeting program  

NASA Technical Reports Server (NTRS)

Computer program generates and verifies operational launch vehicle targeting presettings for lunar free-return missions and lunar landing missions. Program is applicable in astronomy and nuclear physics, and in areas where improved targeting techniques are valuable.

Bosley, J. T.

1971-01-01

201

Targets for Precision Measurements  

NASA Astrophysics Data System (ADS)

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.

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

202

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.

203

Measles vaccine adverse events reported in the mass vaccination campaign of Sichuan province, China from 2007 to 2008.  

PubMed

The aim of this study was to characterize the adverse events of attenuated measles vaccine in mainland China. We carried out prospective follow-up of adverse events after mass measles immunization practices, categorizing them into two groups: allergic reactions and serious adverse events. The incidence of anaphylaxis reaction was estimated to be 6.5 per million for attenuated measles vaccine. Among 14.3 million vaccination practices, 1 case each of acute disseminated encephalomyelitis (ADEM) and idiopathic thrombocytopenic purpura (ITP) and 28 cases of Henoch-Schonlein purpura (HSP) were reported. The total incidence of serious adverse events after vaccination was 2.14 per million doses. PMID:19909830

Shu, Min; Liu, Qinglian; Wang, Jin; Ao, Rui; Yang, Chaomei; Fang, Gang; Wan, Chaomin; Guo, Wenjun

2011-04-18

204

Bar coded retroreflective target  

DOEpatents

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.

Vann, Charles S. (Fremont, CA)

2000-01-01

205

Effective neutron targets  

SciTech Connect

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.

Gao, H.

1997-07-01

206

TARGET SPECIES Table 1. Terrestrial target species.  

E-print Network

American Pika CFLS Black Tern CFLS Northern Goshawk Big Brown Bat CFLS Black-backed Woodpecker Northern descriptions of each of the target species and general and specific links with more detailed information Canada Goose Black-bellied Plover Moose Mute Swan Semipalmated Plover American Dipper Trumpeter Swan

207

Inertial Confinement fusion targets  

NASA Technical Reports Server (NTRS)

Inertial confinement fusion (ICF) targets are made as simple flat discs, as hollow shells or as complicated multilayer structures. Many techniques were devised for producing the targets. Glass and metal shells are made by using drop and bubble techniques. Solid hydrogen shells are also produced by adapting old methods to the solution of modern problems. Some of these techniques, problems, and solutions are discussed. In addition, the applications of many of the techniques to fabrication of ICF targets is presented.

Hendricks, C. D.

1982-01-01

208

Targeted Radionuclide Therapy  

PubMed Central

Targeted radiotherapy is an evolving and promising modality of cancer treatment. The killing of cancer cells is achieved with the use of biological vectors and appropriate radionuclides. Among the many advantages of this approach are its selectiveness in delivering the radiation to the target, relatively less severe and infrequent side effects, and the possibility of assessing the uptake by the tumor prior to the therapy. Several different radiopharmaceuticals are currently being used by various administration routes and targeting mechanisms. This article aims to briefly review the current status of targeted radiotherapy as well as to outline the advantages and disadvantages of radionuclides used for this purpose. PMID:24213114

Ersahin, Devrim; Doddamane, Indukala; Cheng, David

2011-01-01

209

Targeting the tumor microenvironment  

SciTech Connect

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.

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

2006-11-07

210

GWAS and drug targets  

PubMed Central

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

2014-01-01

211

Targeted anti bacterial therapy.  

PubMed

The increasing development of bacterial resistance to traditional antibiotics has reached alarming levels, thus necessitating a strong need to develop new antimicrobial agents. These new antimicrobials should possess novel modes of action and/or different cellular targets compared with the existing antibiotics. As a result, new classes of compounds designed to avoid defined resistance mechanisms are undergoing pre clinical and clinical evaluation. Microbial and phage genomic sequencing are now being used to find previously unidentified genes and their corresponding proteins. In both traditional and newly developed antibiotics, the target selectivity lies in the drug itself, in its ability to affect a mechanism that is unique to prokaryotes. As a result, a vast number of potent agents that, due to low selectivity, in addition to the pathogen also affect the eukaryote host have been excluded from use as therapeutics. Such compounds could be re-considered for clinical use if applied as part of a targeted delivery platform where the drug selectivity is replaced by target-selectivity borne by the targeting moiety. With a large number of antibodies and antibody-drug conjugates already approved or near approval as cancer therapeutics, targeted therapy is becoming increasingly attractive and additional potential targeting moieties that are non-antibody based, such as peptides, non-antibody ligand-binding proteins and even carbohydrates are receiving increasing attention. Still, targeted therapy is mostly focused on cancer, with targeted anti bacterial therapies being suggested only very recently. This review will focus in the various methods of antimicrobial targeting, by systemic and local application of targeted antimicrobial substances. PMID:17897058

Yacoby, Iftach; Benhar, Itai

2007-09-01

212

Precision Medicine and Targeted Therapy  

Cancer.gov

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

213

Knowing Your Learning Target  

ERIC Educational Resources Information Center

No matter what we decide students need to learn, not much will happen until students understand what they are supposed to learn during a lesson and set their sights on learning it. Crafting learning targets for each lesson and deliberately sharing them with students is one way to give students the direction they need. Targets that tell students…

Moss, Connie M.; Brookhart, Susan M.; Long, Beverly A.

2011-01-01

214

Cellular Targets of Gefitinib  

Microsoft Academic Search

Targeted inhibition of protein kinases with small molecule drugs has evolved into a viable approach for anticancer therapy. However, the true selectivity of these therapeutic agents has remained unclear. Here, we used a proteomic method to profile the cellular targets of the clinical epidermal growth factor receptor kinase inhibitor gefitinib. Our data suggest alternative cellular modes of action for gefitinib

Dirk Brehmer; Klaus Godl; Stephanie Blencke; Alexander Kurtenbach; Martina Weber; Stefan Muller; Bert Klebl; Matt Cotten; Gyorgy Keri; Josef Wissing; Henrik Daub

2005-01-01

215

Recruitment of T cells into bone marrow of ITP patients possibly due to elevated expression of VLA4 and CX3CR1  

Microsoft Academic Search

In idiopathic thrombocytopenic purpura (ITP), platelets are destroyed in the spleen, liver, and bone marrow (BM) by autoanti- bodies and cytotoxic T cells. In a DNA microarray screen of peripheral blood T cells, we found that VLA-4, CX3CR1, and CXCR4, involved in T-cell homing, had increased expression in ITP patients compared with controls. However, we only found increased protein expression

Bob Olsson; Borje Ridell; Lena Carlsson; Stefan Jacobsson; Hans Wadenvik

2008-01-01

216

Amino acid regions 572-579 and 657-666 of the spacer domain of ADAMTS 13 provide a common antigenic core required for binding of antibodies in patients with acquired TTP  

Microsoft Academic Search

Antibodies directed against ADAMTS13 have been detected in the majority of patients with acquired thrombotic thrombocytopenic purpura (TTP). We have previously localized a major antigenic determinant within the spacer domain of ADAMTS13. To identify the amino acid residues of the spacer domain that are involved in binding of anti-ADAMTS13 antibodies, we constructed a series of fifteen hybrids (designated A-O) in

Brenda M. Luken; Ellen A. M. Turenhout; Paul H. P. Kaijen; Mascha J. Greuter; Wouter Pos; Mourik van J. A; Rob Fijnheer; Jan Voorberg

2006-01-01

217

Anti-Factor H Autoantibodies Associated with Atypical Hemolytic Uremic Syndrome  

Microsoft Academic Search

Several studies have demonstrated genetic predisposition in non-shigatoxin-associated hemolytic uremic syndrome (HUS), involving regulatory proteins of the complement alternative pathway: Factor H (FH) and membrane co-factor protein (CD46). Regarding the observations of thrombotic thrombocytopenic purpura patients, in whom a von Willebrand factor protease (ADAMST-13) deficiency may be inherited or acquired secondary to IgG antibodies, it was speculated that HUS might

Marie-Agnes Dragon-Durey; Chantal Loirat; Sylvie Cloarec; Marie-Alice Macher; Jacques Blouin; Hubert Nivet; Laurence Weiss; Wolf Herman Fridman; Veronique Fremeaux-Bacchi

2005-01-01

218

A new method for active surveillance of adverse events from diphtheria\\/tetanus\\/pertussis and measles\\/mumps\\/rubella vaccines  

Microsoft Academic Search

We describe a new method for active post-marketing surveillance of vaccine safety based on patient records. We studied the association between diphtheria\\/ tetanus\\/pertussis (DTP) vaccination and febrile convulsion, and between measles\\/mumps\\/rubella (MMR) vaccination and febrile convulsion and idiopathic thrombocytopenic purpura (ITP) in five district health authorities in England by linking vaccination records with computerised hospital admission records. We found an

P Farrington; M Rush; E Miller; S Pugh; A Colville; A Flower; J Nash; P Morgan-Capner

1995-01-01

219

Hospital-Acquired Pneumonia and Bacteremia Caused by Legionella pneumophila in an Immunocompromised Patient  

Microsoft Academic Search

\\u000a Abstract\\u000a   The Legionella species is an important cause of communityand hospital-acquired pneumonia. Bacteremic pneumonia caused by L. pneumophila is rarely reported. We describe the first reported case of hospital-acquired pneumonia and bacteremia caused by L. pneumophila from Taiwan in a patient with idiopathic thrombocytopenic purpura who received steroid treatment. The patient was successfully\\u000a treated with ceftazidime and clindamycin initially, followed

C.-C. Lai; C.-K. Tan; C.-H. Chou; H.-L. Hsu; Y.-T. Huang; C.-H. Liao; P.-R. Hsueh

2010-01-01

220

Increased Plasma Tissue-Type Plasminogen Activator Levels in Patients with Chronic Thrombocytopenia  

Microsoft Academic Search

Plasma fibrinolytic factors were measured in 14 patients with chronic idiopathic thrombocytopenic purpura (ITP), in 5 patients with chronic central thrombocytopenia and in 16 healthy volunteers. The von Willebrand factor (vWF), tissue-type plasminogen activator (t-PA) and D-dimer (DD) antigens were found to be significantly higher in both patient groups than in the control group. No difference appeared in euglobulin fibrinolytic

M. Hanss; D. Ville; M. Dechavanne

1990-01-01

221

Therapeutic targets for neuroblastomas  

PubMed Central

Introduction Neuroblastoma (NB) is the most common and deadly solid tumor in children. Despite recent improvements, the long-term outlook for high-risk NB is still < 50%. Further, there is considerable short- and long-term toxicity. More effective, less toxic therapy is needed, and the development of targeted therapies offers great promise. Areas covered Relevant literature was reviewed to identify current and future therapeutic targets that are critical to malignant transformation and progression of NB. The potential or actual NB therapeutic targets are classified into four categories: i) genes activated by amplification, mutation, translocation or autocrine overexpression; ii) genes inactivated by deletion, mutation or epigenetic silencing; iii) membrane-associated genes expressed on most NBs but few other tissues; or iv) common target genes relevant to NB as well as other tumors. Expert opinion Therapeutic approaches have been developed to some of these targets, but many remain untargeted at the present time. It is unlikely that single targeted agents will be sufficient for long-term cure, at least for high-risk NBs. The challenge will be how to integrate targeted agents with each other and with conventional therapy to enhance their efficacy, while simultaneously reducing systemic toxicity. PMID:24387342

Brodeur, Garrett M; lIyer, Radhika; Croucher, Jamie L; Zhuang, Tiangang; Higashi, Mayumi; Kolla, Venkatadri

2014-01-01

222

Immunogenicity of targeted lentivectors.  

PubMed

To increase the safety and possibly efficacy of HIV-1 derived lentivectors (LVs) as an anti-cancer vaccine, we recently developed the Nanobody (Nb) display technology to target LVs to antigen presenting cells (APCs). In this study, we extend these data with exclusive targeting of LVs to conventional dendritic cells (DCs), which are believed to be the main cross-presenting APCs for the induction of a TH1-conducted antitumor immune response. The immunogenicity of these DC-subtype targeted LVs was compared to that of broad tropism, general APC-targeted and non-infectious LVs. Intranodal immunization with ovalbumin encoding LVs induced proliferation of antigen specific CD4+ T cells, irrespective of the LVs' targeting ability. However, the cytokine secretion profile of the restimulated CD4+ T cells demonstrated that general APC targeting induced a similar TH1-profile as the broad tropism LVs while transduction of conventional DCs alone induced a similar and less potent TH1 profile as the non-infectious LVs. This observation contradicts the hypothesis that conventional DCs are the most important APCs and suggests that the activation of other APCs is also meaningful. Despite these differences, all targeted LVs were able to stimulate cytotoxic T lymphocytes, be it to a lesser extent than broad tropism LVs. Furthermore this induction was shown to be dependent on type I interferon for the targeted and non-infectious LVs, but not for broad tropism LVs. Finally we demonstrated that the APC-targeted LVs were as potent in therapy as broad tropism LVs and as such deliver on their promise as safer and efficacious LV-based vaccines. PMID:24519916

Goyvaerts, Cleo; Kurt, De Groeve; Van Lint, Sandra; Heirman, Carlo; Van Ginderachter, Jo A; De Baetselier, Patrick; Raes, Geert; Thielemans, Kris; Breckpot, Karine

2014-02-15

223

Rapid Target Locator  

NASA Astrophysics Data System (ADS)

Like beauty, "real time" is in the eye of the beholder. Airborne electro-optical (EO) reconnaissance systems can transmit an image in real time to a display in an imagery interpreter's (II) console, but it then takes around 15 min for the II to issue his report. Thus, while the II sees real-time imagery, the officer in the field who requested the coverage sees a report that is not real time and that may be rapidly losing its value. The greatest delay in issuing the report comes from having to determine where the target is. This is currently done on the Analytical Photogrammetric Positioning System (APPS) that uses stereophotomaps to determine the x, y, z coordinates of a point on the ground; it takes many minutes to measure the position of each target. Our goal is to reduce that portion of the recce cycle that uses Itek technology--from time over target to issuance of a report--to less than 2 min. A still shorter time would be desirable in the face of rapidly moving targets,, but there is little point in making the time negligible compared to that required for Oil to evaluate the report and issue orders, plus the time required to respond to the orders. It is clear that we can achieve this 2-min goal only if we can greatly reduce the time it now takes to determine the location of a target. The accuracy with which a target is located should not suffer while the time is reduced. There is a tradeoff to be made between timeliness and accuracy when the target is moving: neither short time with poor accuracy nor high accuracy with long time is desirable. We have arbitrarily adopted goals in which a target can be located to about 100 ft in less than half a minute. The experiments reported here investigated one concept, called Rapid Target Locator (RATL), for achieving this performance.

Bisbee, John

1985-12-01

224

USGS aerial resolution targets.  

USGS Publications Warehouse

It is necessary to measure the achievable resolution of any airborne sensor that is to be used for metric purposes. Laboratory calibration facilities may be inadequate or inappropriate for determining the resolution of non-photographic sensors such as optical-mechanical scanners, television imaging tubes, and linear arrays. However, large target arrays imaged in the field can be used in testing such systems. The USGS has constructed an array of resolution targets in order to permit field testing of a variety of airborne sensing systems. The target array permits any interested organization with an airborne sensing system to accurately determine the operational resolution of its system. -from Author

Salamonowicz, P. H.

1982-01-01

225

Internal polarized targets  

SciTech Connect

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.

Kinney, E.R.; Coulter, K.; Gilman, R.; Holt, R.J.; Kowalczyk, R.S.; Napolitano, J.; Potterveld, D.H.; Young, L. (Argonne National Lab., IL (USA)); Mishnev, S.I.; Nikolenko, D.M.; Popov, S.G.; Rachek, I.A.; Temnykh, A.B.; Toporkov, D.K.; Tsentalovich, E.P.; Wojtsekhowski, B.B. (AN SSSR, Novosibirsk (USSR). Inst. Yadernoj Fiziki)

1989-01-01

226

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

227

Target Heart Rate Calculator  

MedlinePLUS

... My Saved Articles » My ACS » + - Text Size Target Heart Rate Calculator Compute your best workout Enter your age ... is your age? years. How to Check Your Heart Rate Right after you stop exercising, take your pulse: ...

228

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

229

Combining Targeted Therapies  

Microsoft Academic Search

Many new agents have emerged in the drug development pipeline that target the mechanisms driving the development and progression\\u000a of specific cancers. Ultimately, the goal is to create personalized treatment plans for each patient’s tumor(s). Despite promising\\u000a early preclinical data, only a handful of the targeted molecules developed thus far have shown benefit when used as single\\u000a agents. The need

David Hong; Lakshmi Chintala

230

Drug—target network  

Microsoft Academic Search

The global set of relationships between protein targets of all drugs and all disease-gene products in the human protein–protein interaction or 'interactome' network remains uncharacterized. We built a bipartite graph composed of US Food and Drug Administration–approved drugs and proteins linked by drug–target binary associations. The resulting network connects most drugs into a highly interlinked giant component, with strong local

Muhammed A Y?ld?r?m; Kwang-Il Goh; Michael E Cusick; Albert-László Barabási; Marc Vidal

2007-01-01

231

Targeted therapy in lymphoma  

Microsoft Academic Search

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)

Patrick B Johnston; RuiRong Yuan; Franco Cavalli; Thomas E Witzig

2010-01-01

232

High pressure gas target  

NASA Astrophysics Data System (ADS)

Compact, high pressure, high current gas target features all metal construction and semi-automatic window assembly change. The unique aspect of this target is the domed-shaped window. The Havar alloy window is electron beam welded to a metal ring, thus forming one, interchangeable assembly. The window assembly is sealed by knife-edges locked by a pneumatic toggle allowing a quick, in situ window change.

Gelbart, W.; Johnson, R. R.; Abeysekera, B.

2012-12-01

233

Target activated frame capture  

NASA Astrophysics Data System (ADS)

Over the past decade, technological advances have enabled the use of increasingly intelligent systems for battlefield surveillance. These systems are triggered by a combination of external devices including acoustic and seismic sensors. Such products are mainly used to detect vehicles and personnel. These systems often use infra-red imagery to record environmental information, but Textron Defense Systems' Terrain Commander is one of a small number of systems which analyze these images for the presence of targets. The Terrain Commander combines acoustic, infrared, magnetic, seismic, and visible spectrum sensors to detect nearby targets in military scenarios. When targets are detected by these sensors, the cameras are triggered and images are captured in the infrared and visible spectrum. In this paper we discuss a method through which such systems can perform target tracking in order to record and transmit only the most pertinent surveillance images. This saves bandwidth which is crucial because these systems often use communication systems with throughputs below 2400bps. This method is expected to be executable on low-power processors at frame rates exceeding 10HZ. We accomplish this by applying target activated frame capture algorithms to infra-red video data. The target activated frame capture algorithms combine edge detection and motion detection to determine the best frames to be transmitted to the end user. This keeps power consumption and bandwidth requirements low. Finally, the results of the algorithm are analyzed.

Roberts, G. Marlon; Fitzgerald, James; McCormack, Michael; Steadman, Robert

2008-04-01

234

Quantum state targeting  

E-print Network

We introduce a new primitive for quantum communication that we term "state targeting" wherein the goal is to pass a test for a target state even though the system upon which the test is performed is submitted prior to learning the target state's identity. Success in state targeting can be described as having some control over the outcome of the test. We show that increasing one's control above a minimum amount implies an unavoidable increase in the probability of failing the test. This is analogous to the unavoidable disturbance to a quantum state that results from gaining information about its identity, and can be shown to be a purely quantum effect. We provide some applications of the results to the security analysis of cryptographic tasks implemented between remote antagonistic parties. Although we focus on weak coin flipping, the results are significant for other two-party protocols, such as strong coin flipping, partially binding and concealing bit commitment, and bit escrow. Furthermore, the results have significance not only for the traditional notion of security in cryptography, that of restricting a cheater's ability to bias the outcome of the protocol, but also on a novel notion of security that arises only in the quantum context, that of cheat-sensitivity. Finally, our analysis of state targeting leads to some interesting secondary results, for instance, a generalization of Uhlmann's theorem and an operational interpretation of the fidelity between two mixed states.

Terry Rudolph; Robert W. Spekkens

2003-10-09

235

High power density targets  

NASA Astrophysics Data System (ADS)

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.

Pellemoine, Frederique

2013-12-01

236

Penetration of concrete targets  

SciTech Connect

We developed penetration equations for ogive-nosed projectiles that penetrated concrete targets after normal impact. Our penetration equations predict axial force on the projectile nose, rigid-body motion, and final penetration depth. For target constitutive models, we conducted triaxial material experiments to confining pressures of 600 MPa and curve-fit these data with a linear pressure-volumetric strain relation and with a linear Mohr-Coulomb, shear strength-pressure relation. To verify our penetration equations, we conducted eleven penetration experiments with 0.90 kg, 26.9-mm-diameter, ogive-nosed projectiles into 1.37-m-diameter concrete targets with unconfined compressive strengths between 32-40 MPa. Predictions from our penetration equation are compared with final penetration depth measurements for striking velocities between 280--800 m/s.

Forrestal, M.J. [Sandia National Labs., Albuquerque, NM (United States); Cargile, J.D. [Corps of Engineers, Vicksburg, MS (United States). Waterways Experiment Station; Tzou, R.D.Y. [New Mexico Univ., Albuquerque, NM (United States). Dept. of Mechanical Engineering

1993-08-01

237

Phoenix Color Targets  

NASA Technical Reports Server (NTRS)

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.

2008-01-01

238

Integrin Targeted Therapeutics  

PubMed Central

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

Millard, Melissa; Odde, Srinivas; Neamati, Nouri

2011-01-01

239

Target fragmentation in radiobiology  

NASA Technical Reports Server (NTRS)

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.

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

1993-01-01

240

Tungsten Helium cooled Target  

E-print Network

shock and low stress level Flexible target material (choice, arrangement, geometry...) #12;Page 6Cyril and after heat Less frequent maintenance and handling of radioactive material Solid waste Upgradeable cladding >Advantages: Known technology Low activity in the cooling fluid Leak tightness >Drawbacks

McDonald, Kirk

241

Antibody-targeted vaccines.  

PubMed

The specificity and high affinity binding of antibodies provides these molecules with ideal properties for delivering a payload to target cells. This concept has been commercialized for cancer therapies using toxin- or radionucleotide-conjugated antibodies that are designed to selectively deliver cytotoxic molecules to cancer cells. Exploiting the same effective characteristics of antibodies, antibody-targeted vaccines (ATV) are designed to deliver disease-specific antigens to professional antigen-presenting cells (APCs), thus enabling the host's immune system to recognize and eliminate malignant or infected cells through adaptive immunity. The concept of ATVs has been in development for many years, and recently has entered clinical trials. Early studies with ATVs focused on the ability to induce humoral immunity in the absence of adjuvants. More recently, ATVs targeted to C-type lectin receptors have been exploited for induction of potent helper and cytolytic T-cell responses. To maximize their stimulatory capacity, the ATVs are being evaluated with a variety of adjuvants or other immunostimulatory agents. In the absence of co-administered immunostimulatory signals, APC-targeting can induce antigen-specific tolerance and, thus, may also be exploited in developing specific treatments for autoimmune and allergic diseases, or for preventing transplant rejection. The successful clinical application of this new class of antibody-based products will clearly depend on using appropriate combinations with other strategies that influence the immune system. PMID:17530028

Keler, T; He, L; Ramakrishna, V; Champion, B

2007-05-28

242

Neutrino Factory Target Cryostat  

E-print Network

SC-2 SC-3 SC-4 SC-5 Window Nozzle Tube Mercury Drains Proton Beam Mercury Pool Water-cooled Tungsten Target Cryostat Review 10 Aug 2010 #12;Some Questions as Design Progresses · Can system perform without for nozzle &Removal simplifies remote maintenance, provides more space for nozzle & beam dump. · What does

McDonald, Kirk

243

Target-Rich Environment  

ERIC Educational Resources Information Center

Target marketing is defining school enrollment goals and then developing a strategic plan to accomplish those goals through the use of specific communication vehicles and community focus. It is critical to reach the right audience, with the right message, at the right time, for the right cost. In this brief article, the author describes several…

Perna, Mark C.

2005-01-01

244

Targeted headache history.  

PubMed

Armed with information obtained from the targeted headache history, clinicians can almost always make an accurate diagnosis or at least determine sick from well. Through using the information obtained, clinicians can craft a safe and cost-effective treatment plan that has a high likelihood of success. PMID:23419620

Waldman, Steven D

2013-03-01

245

Infrared target recognition  

NASA Astrophysics Data System (ADS)

In this thesis, three approaches were used for Automatic Target Recognition (ATR). These approaches were shape, moment and Fourier generated features, Karhunen-Loeve Transform (KLT) generated features and Discrete Cosine Transform (DCT) generated features. The KLT approach was modelled after the face recognition research by Suarez, AFIT, and Turk and Pentland, MIT. A KLT is taken of a reduced covariance matrix, composed all three classes of targets, and the resulting eigenimages are used to reconstruct the original images. The reconstruction coefficients for each original image are found by taking the dot product of the original image with each eigenimage. These reconstruction coefficients were implemented as features into a three layer backprop with momentum network. Using the hold one-cut-out technique of testing data, the net could correctly differentiate the targets 100 percent of the time. Using standard features, the correct classification rate was 99.33 percent. The DCT was also taken of each image, and 16 low frequency Fourier components were kept as features. These recognition rates were compared to FFT results where each set contained the top five feature, as determined by a saliency test. The results proved that the DCT and the FFT were equivalent concerning classification of targets.

Singstock, Brian D.

1991-12-01

246

Targeting the RAS oncogene  

PubMed Central

Introduction The Ras proteins (K-Ras, N-Ras, H-Ras) are GTPases that function as molecular switches for a variety of critical cellular activities and their function is tightly and temporally regulated in normal cells. Oncogenic mutations in the RAS genes, which create constitutively-active Ras proteins, can result in uncontrolled proliferation or survival in tumor cells. Areas covered The paper discusses three therapeutic approaches targeting the Ras pathway in cancer: 1) Ras itself, 2) Ras downstream pathways, and 3) synthetic lethality. The most adopted approach is targeting Ras downstream signaling, and specifically the PI3K-AKT-mTOR and Raf-MEK pathways, as they are frequently major oncogenic drivers in cancers with high Ras signaling. Although direct targeting of Ras has not been successful clinically, newer approaches being investigated in preclinical studies, such as RNA interference-based and synthetic lethal approaches, promise great potential for clinical application. Expert opinion The challenges of current and emerging therapeutics include the lack of “tumor specificity” and their limitation to those cancers which are “dependent” upon aberrant Ras signaling for survival. While the newer approaches have the potential to overcome these limitations, they also highlight the importance of robust preclinical studies and bidirectional translational research for successful clinical development of Ras-related targeted therapies. PMID:23360111

Takashima, Asami

2013-01-01

247

Genomic Targets in Saliva  

PubMed Central

Saliva, the most accessible and noninvasive biofluid of our body, harbors a wide spectrum of biological analytes informative for clinical diagnostic applications. While proteomic constituents are a logical first choice as salivary diagnostic analytes, genomic targets have emerged as highly informative and discriminatory. This awareness, coupled with the ability to harness genomic information by high-throughput technology platforms such as genome-wide microarrays, ideally positions salivary genomic targets for exploring the value of saliva for detection of specific disease states and augmenting the diagnostic and discriminatory value of the saliva proteome for clinical applications. Buccal cells and saliva have been used as sources of genomic DNA for a variety of clinical and forensic applications. For discovery of disease targets in saliva, the recent realization that there is a transcriptome in saliva presented an additional target for oral diagnostics. All healthy subjects evaluated have approximately 3,000 different mRNA molecules in their saliva. Almost 200 of these salivary mRNAs are present in all subjects. Exploration of the clinical utility of the salivary transcriptome in oral cancer subjects shows that four salivary mRNAs (OAZ, SAT, IL8, and IL1b) collectively have a discriminatory power of 91% sensitivity and specificity for oral cancer detection. Data are also now in place to validate the presence of unique diagnostic panels of salivary mRNAs in subjects with Sjöogren's disease. PMID:17435127

ZIMMERMANN, BERNHARD G.; PARK, NOH JIN; WONG, DAVID T.

2010-01-01

248

Cellular Targeting in Autoimmunity  

PubMed Central

Many biologic agents that were first approved for the treatment of malignancies are now being actively investigated and used in a variety of autoimmune diseases such as rheumatoid arthritis (RA), antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, systemic lupus erythematosus (SLE), and Sjogren’s syndrome. The relatively recent advance of selective immune targeting has significantly changed the management of autoimmune disorders, and in part, can be attributed to the progress made in understanding effector cell function and their signaling pathways. In this review, we will discuss the recent FDA approved biologic therapies that directly target immune cells as well as the most promising investigational drugs affecting immune cell function and signaling for the treatment of autoimmune disease. PMID:23054625

Rogers, Jennifer L.; Serafin, Donald S.; Timoshchenko, Roman G.; Tarrant, Teresa K.

2012-01-01

249

Phoenix on Target  

NASA Technical Reports Server (NTRS)

This topography map illustrates where NASA's Phoenix Mars Lander is targeted to land on May 25, 2008, based on expectations as of noon pacific time (3 p.m. eastern time), May 24, 2008.

Phoenix is most likely to land at the cross-shaped target at the center of the red ellipse and least likely to land at the ellipse's edges. The ellipse is positioned over the northern arctic plains of Mars, and is approximately 70 kilometers (44 miles) long.

The topography data was taken by NASA's Mars Global Surveyor. It shows exaggerated differences in the height of the terrain.

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.

2008-01-01

250

Children: a soft target.  

PubMed

The inability to resist the ease with which they can be enticed and the absence of possible pregnancy complications make children easy targets for sexual assaults in India. According to the Indian crime statistics, 25% of the 10,000 reported rape cases in 1990 involve children under 16 years old. During a public hearing on minor rape conducted by the India Democratic Women's Association, several incidents of child rape came into the open as parents recalled the incidents before the jury and the public. Commenting on the common trends observed on the revealed cases, the district secretary, Sarasam Jayaraj, noted that the rapist was invariably a familiar person and that the defenseless daily wage earners were the common targets. Considering the seriousness of this problem, the issue has to be a priority in welfare and women's organizations in their national campaigns. This crime also demands an urgent response from the government and sociopolitical systems. PMID:12179546

Sivaraman, M

1998-02-01

251

Foucault on targets.  

PubMed

This paper seeks to gain an insight into the behavior of a large NHS trust, in its attempt to meet a 90 percent patient access target, in a week long national audit in March 2003. Why did individuals act in dramatically different ways to their norm over this period. The work of Michel Foucault is used to explore these issues. The discourses of power, knowledge, discipline and governmentality are identified as key foucaudian themes that offer an alternative interpretation of how individuals behave in their place of work. The importance of the historical context of discourse within the NHS cannot be underestimated in shaping the behavior of individuals and groups today. Power and knowledge permeate NHS organizations through disciplinary practices and dressage. Governmentality seeks to maintain the status quo through disciplinary processes such as national healthcare targets. The natural response of NHS organizations is therefore, to seek order and conformity rather than disorder and conflict. PMID:15366279

Lynch, John

2004-01-01

252

Complement-targeted therapeutics  

PubMed Central

The complement system is a central component of innate immunity and bridges the innate to the adaptive immune response. However, it can also turn its destructive capabilities against host cells and is involved in numerous diseases and pathological conditions. Modulation of the complement system has been recognized as a promising strategy in drug discovery, and a large number of therapeutic modalities have been developed. However, successful marketing of complement-targeted drugs has proved to be more difficult than initially expected, and many strategies have been discontinued. The US Food and Drug Administration’s approval of the first complement-specific drug, an antibody against complement component C5 (eculizumab; Soliris), in March 2007, was a long-awaited breakthrough in the field. Approval of eculizumab validates the complement system as therapeutic target and might facilitate clinical development of other promising drug candidates. PMID:17989689

Ricklin, Daniel; Lambris, John D

2010-01-01

253

Biological and Targeted Therapies  

Microsoft Academic Search

\\u000a Biotherapy and molecular targeted therapies are innovative methods of treatment for cancer and have recently become standard\\u000a modalities for pediatric oncology, both alone and as adjuvants to other modalities such as surgery, radiation, and chemotherapy.\\u000a Bio-therapy uses the body's immune system, either directly or indirectly, to attack malignant cells or to minimize the side\\u000a effects caused by traditional cancer treatments.

Lindsay Gainer

254

Genetic targeting of microglia.  

PubMed

Genetic targeting of microglia and other myeloid cells in the central nervous system (CNS) is highly desirable as they are critical effectors and regulators of changes in CNS homeostasis during development as well as in health and disease. Therefore, genetic reprogramming of microglia could constitute a central approach for potentially reducing disease burden. Previous attempts to target only microglia in vivo failed because of the similarities to their hematopoietic relatives in the circulation. However, this concept has been challenged by recent results of developmental and gene expression profiling studies which used novel molecular biological tools to unravel the origin of microglia and to define their role as specialized tissue macrophages clearly distinct from monocytes or monocyte-derived macrophages. The aim of this review is to recapitulate the history of microglia targeting approaches and finally highlight recent achievements in the field. We will discuss the pros and cons of the newly available genetic tools, their potential for future microglia research and genetic strategies. GLIA 2015;63:1-22. PMID:25132502

Wieghofer, Peter; Knobeloch, Klaus-Peter; Prinz, Marco

2015-01-01

255

CDTI target selection criteria  

NASA Technical Reports Server (NTRS)

A Cockpit Display of Traffic Information (CDTI) is a cockpit instrument which provides information to the aircrew on the relative location of aircraft traffic in the vicinity of their aircraft (township). In addition, the CDTI may provide information to assist in navigation and in aircraft control. It is usually anticipated that the CDTI will be integrated with a horizontal situation indicator used for navigational purposes and/or with a weather radar display. In this study, several sets of aircraft traffic data are analyzed to determine statistics on the number of targets that will be displayed on a CDTI using various target selection criteria. Traffic data were obtained from an Atlanta Terminal Area Simulation and from radar tapes recorded at the Atlanta and Miami terminal areas. Results are given in the form of plots showing the average percentage of time (or probability) that an aircraft equipped with a CDTI would observe from 0 to 10 other aircraft on the display for range settings on the CDTI up to 30 n. mi. and using various target discrimination techniques.

Britt, C. L.; Davis, C. M.; Jackson, C. B.; Mcclellan, V. A.

1984-01-01

256

Novel diuretic targets  

PubMed Central

As the molecular revolution continues to inform a deeper understanding of disease mechanisms and pathways, there exist unprecedented opportunities for translating discoveries at the bench into novel therapies for improving human health. Despite the availability of several different classes of antihypertensive medications, only about half of the 67 million Americans with hypertension manage their blood pressure appropriately. A broader selection of structurally diverse antihypertensive drugs acting through different mechanisms would provide clinicians with greater flexibility in developing effective treatment regimens for an increasingly diverse and aging patient population. An emerging body of physiological, genetic, and pharmacological evidence has implicated several renal ion-transport proteins, or regulators thereof, as novel, yet clinically unexploited, diuretic targets. These include the renal outer medullary potassium channel, ROMK (Kir1.1), Kir4.1/5.1 potassium channels, ClC-Ka/b chloride channels, UTA/B urea transporters, the chloride/bicarbonate exchanger pendrin, and the STE20/SPS1-related proline/alanine-rich kinase (SPAK). The molecular pharmacology of these putative targets is poorly developed or lacking altogether; however, recent efforts by a few academic and pharmaceutical laboratories have begun to lessen this critical barrier. Here, we review the evidence in support of the aforementioned proteins as novel diuretic targets and highlight examples where progress toward developing small-molecule pharmacology has been made. PMID:23863472

Pao, Alan C.; Maduke, Merritt

2013-01-01

257

Targeted Endoscopic Imaging  

PubMed Central

Summary Endoscopy has undergone explosive technological growth in over recent years, and with the emergence of targeted imaging, its truly transformative power and impact in medicine lies just over the horizon. Today, our ability to see inside the digestive tract with medical endoscopy is headed toward exciting crossroads. The existing paradigm of making diagnostic decisions based on observing structural changes and identifying anatomical landmarks may soon be replaced by visualizing functional properties and imaging molecular expression. In this novel approach, the presence of intracellular and cell surface targets unique to disease are identified and used to predict the likelihood of mucosal transformation and response to therapy. This strategy can result in the development of new methods for early cancer detection, personalized therapy, and chemoprevention. This targeted approach will require further development of molecular probes and endoscopic instruments, and will need support from the FDA for streamlined regulatory oversight. Overall, this molecular imaging modality promises to significantly broaden the capabilities of the gastroenterologist by providing a new approach to visualize the mucosa of the digestive tract in a manner that has never been seen before. PMID:19423025

Li, Meng; Wang, Thomas D

2011-01-01

258

Nanocrystal targeting in vivo  

NASA Astrophysics Data System (ADS)

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.

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

2002-10-01

259

Pathology Case Study: Fever, Purpura and Hypotension  

NSDL National Science Digital Library

The Department of Pathology at the University of Pittsburgh Medical Center has compiled a wide range of pathology case studies to aid students and instructors in the medical/health science field. In this case, a 20 year old male college student is admitted to the emergency room with "general malaise, low-grade fever, and purplish discoloration on his face. Using the information provided, which includes patient and social history, images and descriptions from his physical exam, the hospital course and microscopic images, students are encouraged to test their knowledge of pathology and diagnose the patient's medical condition. You can check your diagnosis against the official conclusions in the "Final Diagnosis" section. This is an excellent resource for providing students experience with patient history, lab results and diagnostics.

Anhalt, John P.; Aronica, Patricia; Pasculle, A. W.; Richert, Charles A.

2007-11-22

260

Target Asteroids! Observing Targets for 2014 October through December  

NASA Astrophysics Data System (ADS)

Asteroids to be observed by the Target Asteroids! program during the period of October to December 2014 are presented. In addition to asteroids on the original Target Asteroids! list of easily accessible spacecraft targets, an effort has been made to identify other asteroids that are 1) brighter and easier to observe for small telescope users and 2) analogous to (101955) Bennu, the target asteroid of the OSIRIS-REx sample return mission.

Hergenrother, Carl; Hill, Dolores

2014-10-01

261

Target Asteroids! Observing Targets for July through September 2013  

NASA Astrophysics Data System (ADS)

Asteroids to be observed by the Target Asteroids! program during the period of July to September 2013 are presented. In addition to asteroids on the original Target Asteroids! list of easily accessible spacecraft targets, an effort has been made to identify other asteroids that are 1) brighter and, hence, easier to observe for small telescope users and 2) analogous to (101955) Bennu, the target asteroid of the OSIRIS-REx sample return mission.

Hergenrother, Carl; Hill, Dolores

2013-07-01

262

Target Asteroids! Observing Targets for 2014 July through September  

NASA Astrophysics Data System (ADS)

Asteroids to be observed by the Target Asteroids! program during the period of July to September 2014 are presented. In addition to asteroids on the original Target Asteroids! list of easily accessible spacecraft targets, an effort has been made to identify other asteroids that are 1) brighter and easier to observe for small telescope users and 2) analogous to (101955) Bennu, the target asteroid of the OSIRIS-REx sample return mission.

Hergenrother, Carl; Hill, Dolores

2014-07-01

263

Target Asteroids! Observing Targets for 2014 April through June  

NASA Astrophysics Data System (ADS)

Asteroids to be observed by the Target Asteroids! program during the period of 2014 April through June are presented. In addition to asteroids on the original Target Asteroids! list of easily accessible spacecraft targets, an effort has been made to identify other asteroids that are 1) brighter and easier to observe for small telescope users and 2) analogous to 101955 Bennu, the target asteroid of the OSIRIS-REx sample return mission.

Hergenrother, Carl; Hill, Dolores

2014-04-01

264

Target Asteroids! Observing Targets for October through December 2013  

NASA Astrophysics Data System (ADS)

Asteroids to be observed by the Target Asteroids! program during the period of July to September 2013 are presented. In addition to asteroids on the original Target Asteroids! list of easily accessible spacecraft targets, an effort has been made to identify other asteroids that are 1) brighter and, hence, easier to observe for small telescope users and 2) analogous to (101955) Bennu, the target asteroid of the OSIRIS-REx sample return mission.

Hergenrother, Carl; Hill, Dolores

2013-10-01

265

Target Asteroids! Observing Targets for 2014 January through March  

NASA Astrophysics Data System (ADS)

Asteroids to be observed for the Target Asteroids! program during the period of 2014 January to March are presented. In addition to asteroids on the original Target Asteroids! list of easily accessible spacecraft targets, an effort has been made to identify other asteroids that are 1) brighter and easier to observe for small telescope users and 2) analogous to (101955) Bennu, the target asteroid of the OSIRIS-REx sample return mission.

Hergenrother, Carl; Hill, Dolores

2014-01-01

266

Targeting proteins for degradation  

PubMed Central

Protein degradation plays a central role in many cellular functions. Misfolded and damaged proteins are removed from the cell to avoid toxicity. The concentrations of regulatory proteins are adjusted by degradation at the appropriate time. Both foreign and native proteins are digested into small peptides as part of the adaptive immune response. In eukaryotic cells, an ATP-dependent protease called the proteasome is responsible for much of this proteolysis. Proteins are targeted for proteasomal degradation by a two-part degron, which consists of a proteasome binding signal and a degradation initiation site. Here we describe how both components contribute to the specificity of degradation. PMID:19841631

Schrader, Erin K; Harstad, Kristine G; Matouschek, Andreas

2014-01-01

267

TARGETing "When" and "Where"  

NSDL National Science Digital Library

In Drosophila, the cyclic adenosine monophosphate (cAMP) pathway has been shown to be crucial for learning and memory, but whether this represents a developmental or a specific effect has not been resolved. Research with a new targeting system that allows both spatial and temporal control of gene expression shows that expression of rutabaga-encoded adenylyl cyclase, a component of the cAMP signaling pathway, in the mushroom bodies of adult flies is necessary and sufficient to rescue the learning defect of rutabaga mutant. This demonstrates an acute role for Rutabaga in learning and memory.

Yalin Wang (Cold Spring Harbor Laboratory; REV); Yi Zhong (Cold Spring Harbor Laboratory; REV)

2004-02-17

268

Reference Target Correction Based on Point-Target SAR Simulation  

Microsoft Academic Search

The backscattering from man-made point targets like passive corner reflectors and active transponders is often used as a radiometric calibration standard for synthetic aperture radar (SAR) calibration. As new systems emerge and the demand for more accurate systems increases, it becomes necessary to better understand the effects of real or imperfect targets on the radiometric calibration results. Therefore, a point-target

Björn J. Doring; Philipp R. Looser; Matthias Jirousek; Marco Schwerdt

2012-01-01

269

Molecular and Cellular Targets  

PubMed Central

Carcinogenesis is a multistage process consisting of initiation, promotion and progression stages and each stage may be a possible target for chemopreventive agents. A significant outcome of these investigations on the elucidation of molecular and cellular mechanisms is the explication of signal transduction pathways induced by tumor promoters in cancer development. The current belief today is that cancer may be prevented or treated by targeting specific cancer genes, signaling proteins and transcription factors. The molecular mechanisms explaining how normal cells undergo neoplastic transformation induced by tumor promoters are rapidly being clarified. Accumulating research evidence suggests that many of dietary factors, including tea compounds, may be used alone or in combination with traditional chemotherapeutic agents to prevent or treat cancer. The potential advantage of many natural or dietary compounds seems to focus on their potent anticancer activity combined with low toxicity and very few adverse side effects. This review summarizes some of our recent work regarding the effects of the various tea components on signal transduction pathways involved in neoplastic cell transformation and carcinogenesis. PMID:16688728

Bode, Ann M.; Dong, Zigang

2008-01-01

270

Targeted therapy for sarcomas  

PubMed Central

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

Forscher, Charles; Mita, Monica; Figlin, Robert

2014-01-01

271

Targeting adipose tissue.  

PubMed

Two different types of adipose tissues can be found in humans enabling them to respond to starvation and cold: white adipose tissue (WAT) is generally known and stores excess energy in the form of triacylglycerol (TG), insulates against cold, and serves as a mechanical cushion. Brown adipose tissue (BAT) helps newborns to cope with cold. BAT has the capacity to uncouple the mitochondrial respiratory chain, thereby generating heat rather than adenosine triphosphate (ATP). The previously widely held view was that BAT disappears rapidly after birth and is no longer present in adult humans. Using positron emission tomography (PET), however, it was recently shown that metabolically active BAT occurs in defined regions and scattered in WAT of the adult and possibly has an influence on whole-body energy homeostasis. In obese individuals adipose tissue is at the center of metabolic syndrome. Targeting of WAT by thiazolidinediones (TZDs), activators of peroxisome proliferator-activated receptor ? (PPAR?) a 'master' regulator of fat cell biology, is a current therapy for the treatment of type 2 diabetes. Since its unique capacity to increase energy consumption of the body and to dissipate surplus energy as heat, BAT offers new perspectives as a therapeutic target for the treatment of obesity and associated diseases such as type 2 diabetes and metabolic syndrome. Recent discoveries of new signaling pathways of BAT development give rise to new therapeutic possibilities in order to influence BAT content and activity. PMID:23102228

Haas, Bodo; Schlinkert, Paul; Mayer, Peter; Eckstein, Niels

2012-01-01

272

Magnetized Target Fusion  

NASA Technical Reports Server (NTRS)

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.

Griffin, Steven T.

2002-01-01

273

A Note on Inflation Targeting.  

ERIC Educational Resources Information Center

Presents a pedagogical graphical exposition to illustrate the stabilizing effect of price target zones. Finds that authorities' commitment to defend a price target zone affects the public's inflation expectations and, in turn, reduces actual inflation. (RLH)

Lai, Ching-chong; Chang, Juin-jen

2001-01-01

274

Advances in Targeted Therapies Tutorial  

Cancer.gov

A tutorial for health professionals that gives an overview of targeted therapies, an emerging approach to cancer treatment. Includes examples of the main types of targeted therapies and describes their mechanisms of action.

275

Role of Siglec-7 in Apoptosis in Human Platelets  

PubMed Central

Background Platelets participate in tissue repair and innate immune responses. Sialic acid-binding immunoglobulin-like lectins (Siglecs) are well-characterized I-type lectins, which control apoptosis. Methodology/Principal Findings We characterized the expression of Siglec-7 in human platelets isolated from healthy volunteers using flow cytometry and confocal microscopy. Siglec-7 is primarily expressed on ? granular membranes and colocalized with CD62P. Siglec-7 expression was increased upon platelet activation and correlated closely with CD62P expression. Cross-linking Siglec-7 with its ligand, ganglioside, resulted in platelet apoptosis without any significant effects on activation, aggregation, cell morphology by electron microscopy analysis or secretion. We show that ganglioside triggered four key pathways leading to apoptosis in human platelets: (i) mitochondrial inner transmembrane potential (??m) depolarization; (ii) elevated expression of pro-apoptotic Bax and Bak proteins with reduced expression of anti-apoptotic Bcl-2 protein; (iii) phosphatidylserine exposure and (iv), microparticle formation. Inhibition of NAPDH oxidase, PI3K, or PKC rescued platelets from apoptosis induced by Siglec-7 recruitment, suggesting that the platelet receptors P2Y1 and GPIIbIIIa are essential for ganglioside-induced platelet apoptosis. Conclusions/Significance The present work characterizes the role of Siglec-7 and platelet receptors in regulating apoptosis and death. Because some platelet pathology involves apoptosis (idiopathic thrombocytopenic purpura and possibly storage lesions), Siglec-7 might be a molecular target for therapeutic intervention/prevention. PMID:25230315

Nguyen, Kim Anh; Hamzeh-Cognasse, Hind; Palle, Sabine; Anselme-Bertrand, Isabelle; Arthaud, Charles-Antoine; Chavarin, Patricia; Pozzetto, Bruno; Garraud, Olivier; Cognasse, Fabrice

2014-01-01

276

Abnormalities in the alternative pathway of complement in children with hematopoietic stem cell transplant-associated thrombotic microangiopathy  

PubMed Central

Hematopoietic stem cell transplant (HSCT)-associated thrombotic microangiopathy (TMA) is a complication that occurs in 25% to 35% of HSCT recipients and shares histomorphologic similarities with hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). The hallmark of all thrombotic microangiopathies is vascular endothelial cell injury of various origins, resulting in microangiopathic hemolytic anemia, platelet consumption, fibrin deposition in the microcirculation, and tissue damage. Although significant advances have been made in understanding the pathogenesis of other thrombotic microangiopathies, post-HSCT TMA remains poorly understood. We report an analysis of the complement alternative pathway, which has recently been linked to the pathogenesis of both the Shiga toxin mediated and the atypical forms of HUS, with a focus on genetic variations in the complement Factor H (CFH) gene cluster and CFH autoantibodies in six children with post-HSCT TMA. We identified a high prevalence of deletions in CFH-related genes 3 and 1 (delCFHR3-CFHR1) and CFH autoantibodies in these patients with HSCT-TMA. Conversely, CFH autoantibodies were not detected in 18 children undergoing HSCT who did not develop TMA. Our observations suggest that complement alternative pathway dysregulation may be involved in the pathogenesis of post-HSCT TMA. These findings shed light on a novel mechanism of endothelial injury in transplant-TMA and may therefore guide the development of targeted treatment interventions. PMID:23814021

Licht, Christoph; Goebel, Jens; Dixon, Bradley P.; Zhang, Kejian; Sivakumaran, Theru A.; Davies, Stella M.; Pluthero, Fred G.; Lu, Lily; Laskin, Benjamin L.

2013-01-01

277

Unintended events following immunization with MMR: a systematic review.  

PubMed

Public debate over the safety of the trivalent measles, mumps and rubella (MMR) vaccine and the drop in vaccination rates in several countries persists despite its almost universal use and accepted effectiveness. We carried out a systematic review to assess the evidence of unintended effects (beneficial or harmful) associated with MMR and the applicability of systematic reviewing methods to the field of safety evaluation. Eligible studies were comparative prospective or retrospective on healthy individuals up to 15 years of age, carried out or published by 2003. We identified 120 articles satisfying our inclusion criteria and included 22. MMR is associated with a lower incidence of upper respiratory tract infections, a higher incidence of irritability, similar incidence of other adverse effects compared to placebo and is likely to be associated with benign thrombocytopenic purpura (TP), parotitis, joint and limb complaints and aseptic meningitis (mumps Urabe strain-containing MMR). Exposure to MMR is unlikely to be associated with Crohn's disease, ulcerative colitis, autism or aseptic meningitis (mumps Jeryl-Lynn strain-containing MMR). The design and reporting of safety outcomes in MMR vaccine studies, both pre- and post-marketing, are largely inadequate. The evidence of adverse events following immunization with MMR cannot be separated from its role in preventing the target diseases. PMID:12922131

Jefferson, Tom; Price, Deirdre; Demicheli, Vittorio; Bianco, Elvira

2003-09-01

278

Open-Economy Inflation Targeting  

Microsoft Academic Search

The paper examines inflation targeting in a small open economy with forward-looking aggregate supply and demand with microfoundations, and with stylised realistic lags in the different monetary-policy transmission channels. The paper compares strict and flexible targeting of CPI and domestic inflation and inflation-targeting reaction functions and the Taylor rule. Flexible CPI-inflation targeting does not only limit the variability of CPI

Lars E. O. Svensson

1998-01-01

279

Open-economy inflation targeting  

Microsoft Academic Search

The paper examines inflation targeting in a small open economy with forward-looking aggregate supply and demand with microfoundations, and with stylized realistic lags in the different monetary-policy transmission channels. The paper compares strict and flexible targeting of CPI and domestic inflation, and inflation-targeting reaction functions and the Taylor rule. Flexible CPI-inflation targeting does not limit the variability of CPI inflation

Lars E. O. Svensson

2000-01-01

280

Rotating Target Development for SNS Second Target Station  

SciTech Connect

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

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

2010-01-01

281

Target preparation method and characterisation  

NASA Astrophysics Data System (ADS)

The activities in the target preparation laboratory (TPL) at Daresbury Laboratory, including the range of targets and the techniques used over the last two years are reported. The new and upgraded equipment used in the laboratory and how it is applied to monitor and improve the quality of the targets are described.

Morrall, P. S.

2010-02-01

282

Policy Rules for Inflation Targeting  

Microsoft Academic Search

Policy rules that are consistent with inflation targeting are examined in a small macroeconomic model of the US economy. We compare the properties and outcomes of explicit instrument rules' as well as targeting rules.' The latter, which imply implicit instrument rules, may be closer to actual operating procedures of inflation-targeting central banks. We find that inflation forecasts are central for

Glenn D. Rudebusch; Lars E. O. Svensson

1998-01-01

283

Stroke Neuroprotection: Targeting Mitochondria  

PubMed Central

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

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

2013-01-01

284

ORION laser target diagnostics  

SciTech Connect

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.

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. [Plasma Physics Department, Atomic Weapons Establishment, Aldermaston, Reading, Berkshire RG7 4PR (United Kingdom); and others

2012-10-15

285

Target detection portal  

DOEpatents

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.

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

2002-01-01

286

Mobile target ladar ATR system  

NASA Astrophysics Data System (ADS)

The Mobile Target Acquisition System (MTAS) is an automatic target recognition (ATR) system developed by the Naval Air Warfare Center Weapons Division, China Lake, CA, under funding by the Office of Naval Research (ONR) to detect and identify mobile target laser detection and ranging (LADAR) range signatures. The primary objective was to achieve high correct system identification rates for range signatures of relatively low numbers of pixels on target and, at the same time, maintain a low system identification false alarm rate. MTAS met this objective by stressing conservation and efficient exploitation of target information at all levels of processing. Adaptive noise cleaning conserves target information by filtering pixels only when the pixel and its neighbors satisfied the criteria for range dropouts. The MTAS detector holds false alarms to a low level by convolving synthetic templates with the gradient of the range image and fusing the resulting correlation surface with a blob size filter. Mobile target identification fuses 2-D silhouette shape with 3-D (21/2-D) volumetric shape where the mixture of 2- and 3-D shapes is controlled by a single parameter. The match between the measured LADAR range signature and the synthetic range template efficiently and effectively exploits scarce target information by including all target and template pixels in the Fuzzy Tanimoto Distance similarity measure. This system has successfully detected and identified measured mobile LADAR target signatures with 200 pixels on target and greater with a low confuser identification rate and no system clutter identification false alarms.

Hodge, Jesse L.; DeKruger, David H.; Park, Alden E.

2001-10-01

287

Therapeutic target database update 2014: a resource for targeted therapeutics  

PubMed Central

Here we describe an update of the Therapeutic Target Database (http://bidd.nus.edu.sg/group/ttd/ttd.asp) for better serving the bench-to-clinic communities and for enabling more convenient data access, processing and exchange. Extensive efforts from the research, industry, clinical, regulatory and management communities have been collectively directed at the discovery, investigation, application, monitoring and management of targeted therapeutics. Increasing efforts have been directed at the development of stratified and personalized medicines. These efforts may be facilitated by the knowledge of the efficacy targets and biomarkers of targeted therapeutics. Therefore, we added search tools for using the International Classification of Disease ICD-10-CM and ICD-9-CM codes to retrieve the target, biomarker and drug information (currently enabling the search of almost 900 targets, 1800 biomarkers and 6000 drugs related to 900 disease conditions). We added information of almost 1800 biomarkers for 300 disease conditions and 200 drug scaffolds for 700 drugs. We significantly expanded Therapeutic Target Database data contents to cover >2300 targets (388 successful and 461 clinical trial targets), 20 600 drugs (2003 approved and 3147 clinical trial drugs), 20 000 multitarget agents against almost 400 target-pairs and the activity data of 1400 agents against 300 cell lines. PMID:24265219

Qin, Chu; Zhang, Cheng; Zhu, Feng; Xu, Feng; Chen, Shang Ying; Zhang, Peng; Li, Ying Hong; Yang, Sheng Yong; Wei, Yu Quan; Tao, Lin; Chen, Yu Zong

2014-01-01

288

Target control of complex networks.  

PubMed

Controlling large natural and technological networks is an outstanding challenge. It is typically neither feasible nor necessary to control the entire network, prompting us to explore target control: the efficient control of a preselected subset of nodes. We show that the structural controllability approach used for full control overestimates the minimum number of driver nodes needed for target control. Here we develop an alternate 'k-walk' theory for directed tree networks, and we rigorously prove that one node can control a set of target nodes if the path length to each target node is unique. For more general cases, we develop a greedy algorithm to approximate the minimum set of driver nodes sufficient for target control. We find that degree heterogeneous networks are target controllable with higher efficiency than homogeneous networks and that the structure of many real-world networks are suitable for efficient target control. PMID:25388503

Gao, Jianxi; Liu, Yang-Yu; D'Souza, Raissa M; Barabási, Albert-László

2014-01-01

289

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

...Determination of target normal cost and funding target. 1.430(d)-1 Section...Determination of target normal cost and funding target. (a) In general —(1...determining a plan's target normal cost and funding target under sections...

2014-04-01

290

Using the Nova target chamber for high-yield targets  

SciTech Connect

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.

Pitts, J.H.

1987-09-28

291

[Target volume margins for lung cancer: internal target volume/clinical target volume].  

PubMed

The aim of this study was to carry out a review of margins that should be used for the delineation of target volumes in lung cancer, with a focus on margins from gross tumour volume (GTV) to clinical target volume (CTV) and internal target volume (ITV) delineation. Our review was based on a PubMed literature search with, as a cornerstone, the 2010 European Organisation for Research and Treatment of Cancer (EORTC) recommandations by De Ruysscher et al. The keywords used for the search were: radiotherapy, lung cancer, clinical target volume, internal target volume. The relevant information was categorized under the following headings: gross tumour volume definition (GTV), CTV-GTV margin (first tumoural CTV then nodal CTV definition), in field versus elective nodal irradiation, metabolic imaging role through the input of the PET scanner for tumour target volume and limitations of PET-CT imaging for nodal target volume definition, postoperative radiotherapy target volume definition, delineation of target volumes after induction chemotherapy; then the internal target volume is specified as well as tumoural mobility for lung cancer and respiratory gating techniques. Finally, a chapter is dedicated to planning target volume definition and another to small cell lung cancer. For each heading, the most relevant and recent clinical trials and publications are mentioned. PMID:23988437

Jouin, A; Pourel, N

2013-10-01

292

Immunotherapy Targets in Pediatric Cancer  

PubMed Central

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

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

2011-01-01

293

Guidance and targeting for the Strategic Target System  

NASA Astrophysics Data System (ADS)

Guidance algorithms and targeting procedures for the Strategic Target System (STARS) launch vehicle are described. The STARS vehicle is a three stage booster, based partly upon retired Polaris A3 missile assets, which is intended to support development and testing of the Strategic Defense Initiative by delivering target payloads to the vicinity of the Kwajalein Atoll. STARS will be launched from the Kauai Test Facility located on Kauai, Hawaii. The STARS guidance objective is to deliver payloads to a prescribed target location with maximum accuracy at intercontinental ballistic missile velocities. Mission objectives are achieved with a combination of guidance algorithms.

White, John E.

294

Drugs targeting parasite lysosomes.  

PubMed

Lysosomes were first described as vacuolar structures containing various hydrolytic enzymes at acidic pH. Subsequent studies revealed that the lysosome/vacuolar system is complex and composed of distinct membrane-enclosed vesicles including endosomes, primary and mature lysosomes, autophagic vesicles, residual bodies, multivesicular bodies, and digestive lysosomes. Lysosomes express a battery of hydrolytic enzymes including proteases, acid phosphatases, glycosidases, and lipases. Parasitic protozoa also possess complex intracellular lysosomes/endosomes/vesicles involved in digestion, transport and recycling of molecules similar to those of mammalian cells. Unique characteristics are ascribed to lysosomes of different parasites and may even differ between parasite stages. Transport of hydrolases and proteins to parasite lysosomes is directed either from the Golgi complex via endosomal vesicles or from endocytic vesicles originated in the cell surface. Inhibition of lysosomal proteases demonstrated that different proteolytic machineries catabolize distinct classes of proteins, and this selectivity may be exploited for the development of effective antiparasitic drugs. This review describes lysosomal molecules that are either validated or potential drug targets for Chagas' disease, sleeping sickness, leishmaniasis, toxoplasmosis, malaria, amebiasis, and giardiasis. PMID:18473838

Doyle, Patricia S; Sajid, Mohamed; O'Brien, Theresa; Dubois, Kelly; Engel, Juan C; Mackey, Zachary B; Reed, Sharon

2008-01-01

295

Contraceptive vaccines targeting sperm.  

PubMed

Overpopulation is a global problem of significant magnitude, with grave implications for the future. Development of new contraceptives is necessary, as existing forms of birth control are unavailable, impractical and/or too expensive for many individuals due to sociological, financial or educational limitations. Immunocontraception and, in particular, the targeting of antibodies to sperm-specific antigens implicated in sperm-egg binding and fertilisation offers an attractive approach to control fertility. Sperm-specific antibodies may impair fertility by inhibiting sperm motility, by reducing penetration of the cervical mucus by sperm, or by interfering in sperm capacitation or the acrosome reaction; alternatively, antisperm antibodies may invoke the complement cascade, resulting in sperm lysis. The antibodies raised against sperm-specific antigens have proved to be extremely effective at reducing sperm-egg interactions in vitro; fertility trials in subhuman primates will eventually be needed to prove the effectiveness of the sperm antigens in terms of contraceptive efficacy before trials in humans can be justified. In addition, existing and emerging strategies (such as sperm proteomics, the determination of molecular and structural details of sperm proteins, and the modelling of protein-ligand interactions using X-ray and/or NMR structures to name a few) are expected to provide the experimental foundation for the design of small molecule inhibitors with antifertility effects. The technology underpinning vaccine development is constantly being developed and the introduction of DNA/RNA vaccines is certain to impact upon the field of immunocontraception. PMID:15833075

Suri, Anil

2005-03-01

296

Targeting cancer metabolism.  

PubMed

The understanding that oncogenes can have profound effects on cellular metabolism and the discovery of mutations and alterations in several metabolism-related enzymes--isocitrate dehydrogenase 1 (IDH1), isocitrate dehydrogenase 2 (IDH2), succinate dehydrogenase (SDH), fumarate hydratase (FH), and pyruvate kinase M2 (PKM2)--has renewed interest in cancer metabolism and renewed hope of taking therapeutic advantage of cancer metabolism. Otto Warburg observed that aerobic glycolysis was a characteristic of cancer cells. More than 50 years later, we understand that aerobic glycolysis and uptake of glutamine and glycine allow cancer cells to produce energy (ATP) and the nucleotides, amino acids, and lipids required for proliferation. Expression of the MYC oncogene drives the increase in cellular biomass facilitating proliferation. PKM2 expression in cancer cells stimulates aerobic glycolysis. Among intermediary metabolism enzymes, mutations in SDH occur in gastointestinal stromal tumors and result in a pseudohypoxic metabolic milieu. FH mutations lead to a characteristic renal cell carcinoma. Isocitrate dehydrogenase (IDH1/2) mutations have been found in leukemias, gliomas, prostate cancer, colon cancer, thyroid cancer, and sarcomas. These recently recognized oncogenic metabolic lesions may be selective targets for new anticancer therapeutics. PMID:23071355

Teicher, Beverly A; Linehan, W Marston; Helman, Lee J

2012-10-15

297

The OLYMPUS Internal Hydrogen Target  

E-print Network

An internal hydrogen target system was developed for the OLYMPUS experiment at DESY, in Hamburg, Germany. The target consisted of a long, thin-walled, tubular cell within an aluminum scattering chamber. Hydrogen entered at the center of the cell and exited through the ends, where it was removed from the beamline by a multistage pumping system. A cryogenic coldhead cooled the target cell to counteract heating from the beam and increase the density of hydrogen in the target. A fixed collimator protected the cell from synchrotron radiation and the beam halo. A series of wakefield suppressors reduced heating from beam wakefields. The target system was installed within the DORIS storage ring and was successfully operated during the course of the OLYMPUS experiment in 2012. Information on the design, fabrication, and performance of the target system is reported.

J. C. Bernauer; V. Carassiti; G. Ciullo; B. S. Henderson; E. Ihloff; J. Kelsey; P. Lenisa; R. Milner; A. Schmidt; M. Statera

2014-04-02

298

The OLYMPUS internal hydrogen target  

NASA Astrophysics Data System (ADS)

An internal hydrogen target system was developed for the OLYMPUS experiment at DESY, in Hamburg, Germany. The target consisted of a long, thin-walled, tubular cell within an aluminum scattering chamber. Hydrogen entered at the center of the cell and exited through the ends, where it was removed from the beamline by a multistage pumping system. A cryogenic coldhead cooled the target cell to counteract heating from the beam and increase the density of hydrogen in the target. A fixed collimator protected the cell from synchrotron radiation and the beam halo. A series of wakefield suppressors reduced heating from beam wakefields. The target system was installed within the DORIS storage ring and was successfully operated during the course of the OLYMPUS experiment in 2012. Information on the design, fabrication, and performance of the target system is reported.

Bernauer, J. C.; Carassiti, V.; Ciullo, G.; Henderson, B. S.; Ihloff, E.; Kelsey, J.; Lenisa, P.; Milner, R.; Schmidt, A.; Statera, M.

2014-08-01

299

The OLYMPUS Internal Hydrogen Target  

E-print Network

An internal hydrogen target system was developed for the OLYMPUS experiment at DESY, in Hamburg, Germany. The target consisted of a long, thin-walled, tubular cell within an aluminum scattering chamber. Hydrogen entered at the center of the cell and exited through the ends, where it was removed from the beamline by a multistage pumping system. A cryogenic coldhead cooled the target cell to counteract heating from the beam and increase the density of hydrogen in the target. A fixed collimator protected the cell from synchrotron radiation and the beam halo. A series of wakefield suppressors reduced heating from beam wakefields. The target system was installed within the DORIS storage ring and was successfully operated during the course of the OLYMPUS experiment in 2012. Information on the design, fabrication, and performance of the target system is reported.

Bernauer, J C; Ciullo, G; Henderson, B S; Ihloff, E; Kelsey, J; Lenisa, P; Milner, R; Schmidt, A; Statera, M

2014-01-01

300

Targeting Translation Dependence in Cancer  

PubMed Central

A challenge in cancer therapy is to selectively target activities that are essential for survival of malignant cells while sparing normal cells. Translational control represents a potential anti-neoplastic target because it is exerted by major signaling pathways that are often usurped in cancers. Herein we describe approaches being developed that target eukaryotic initiation factor (eIF) 4F, a heterotrimeric complex that integrates multiple signaling inputs to the translation apparatus. PMID:21378410

Malina, Abba; Cencic, Regina; Pelletier, Jerry

2011-01-01

301

Targeted nanotechnology for cancer imaging.  

PubMed

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

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

2014-09-30

302

Targets and Secondary Beam Extraction  

NASA Astrophysics Data System (ADS)

Several applications make use of secondary beams of particles generated by the interaction of a primary beam of particles with a target. Spallation neutrons, bremsstrahlung photon-produced neutrons, radioactive ions and neutrinos are available to users at state-of-the-art facilities worldwide. Plans for even higher secondary beam intensities place severe constraints on the design of targets. This article reports on the main targetry challenges and highlights a variety of solutions for targetry and secondary beam extraction. Issues related to target station layout, instrumentation at the beam-target interface, safety and radioprotection are also discussed.

Noah, Etam

2014-02-01

303

Data Mining for Target Marketing  

NASA Astrophysics Data System (ADS)

Targeting is the core of marketing management. It is concerned with offering the right product/service to the customer at the right time and using the proper channel. In this chapter we discuss how Data Mining modeling and analysis can support targeting applications. We focus on three types of targeting models: continuous-choice models, discrete-choice models and in-market timing models, discussing alternative modeling for each application and decision making. We also discuss a range of pitfalls that one needs to be aware of in implementing a data mining solution for a targeting problem.

Levin, Nissan; Zahavi, Jacob

304

Vision-based Target Tracking with Adaptive Target State Estimator  

Microsoft Academic Search

This paper presents an approach to vision-based target tracking with a neural network (NN) augmented Kalman filter as the adaptive target state estimator. The vision sensor onboard the follower (tracker) aircraft is a single camera. Real-time image processing implemented in the onboard flight computer is used to derive measurements of relative bearing (azimuth and elevation angles) and the maximum angle

Ramachandra J. Sattigeri; Eric Johnson; Anthony J. Calise; Jincheol Ha

2007-01-01

305

Pharmacological treatment of alcohol dependence: Target symptoms and target mechanisms  

Microsoft Academic Search

Alcoholism is a major public health problem and resembles, in many ways, other chronic relapsing medical conditions. At least 2 separate dimensions of its symptomatology offer targetable pathophysiological mechanisms. Systems that mediate positive reinforcement by alcohol are likely important targets in early stages of the disease, particularly in genetically susceptible individuals. In contrast, long term neuroadaptive changes caused by chronic

Markus Heilig; Mark Egli

2006-01-01

306

Targeted chromosome elimination from ES-  

E-print Network

Targeted chromosome elimination from ES- somatic hybrid cells Hiroyuki Matsumura1,6, Masako Tada1 cell genome, we developed a technology for targeted elimination of chromosomes from mouse embryonic stem (ES)­somatic hybrid cells. Here we demonstrate the use of a universal chromosome elimination

Cai, Long

307

Dual targeting of peroxisomal proteins  

PubMed Central

Cellular compartmentalization into organelles serves to separate biological processes within the environment of a single cell. While some metabolic reactions are specific to a single organelle, others occur in more than one cellular compartment. Specific targeting of proteins to compartments inside of eukaryotic cells is mediated by defined sequence motifs. To achieve multiple targeting to different compartments cells use a variety of strategies. Here, we focus on mechanisms leading to dual targeting of peroxisomal proteins. In many instances, isoforms of peroxisomal proteins with distinct intracellular localization are encoded by separate genes. But also single genes can give rise to differentially localized proteins. Different isoforms can be generated by use of alternative transcriptional start sites, by differential splicing or ribosomal read-through of stop codons. In all these cases different peptide variants are produced, of which only one carries a peroxisomal targeting signal. Alternatively, peroxisomal proteins contain additional signals that compete for intracellular targeting. Dual localization of proteins residing in both the cytoplasm and in peroxisomes may also result from use of inefficient targeting signals. The recent observation that some bona fide cytoplasmic enzymes were also found in peroxisomes indicates that dual targeting of proteins to both the cytoplasm and the peroxisome might be more widespread. Although current knowledge of proteins exhibiting only partial peroxisomal targeting is far from being complete, we speculate that the metabolic capacity of peroxisomes might be larger than previously assumed. PMID:24151469

Ast, Julia; Stiebler, Alina C.; Freitag, Johannes; Bolker, Michael

2013-01-01

308

Targeted Marketing and Public Health  

Microsoft Academic Search

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

Sonya A. Grier; Shiriki Kumanyika

2010-01-01

309

Targetability of Human Disease Genes  

Microsoft Academic Search

The availability of complete genome sequences and the wealth of large-scale biological datasets provide an un- precedented opportunity to elucidate the genetic basis of human diseases. Therapeutically relevant targets should be both 'druggable' and 'disease modifying'. In this review we examine the application of computational biology towards the ex- ploration of druggability, targetability and evolutionary conservation of human disease genes.

Meena K. Sakharkar; Kishore R. Sakharkar

310

Recent progress in targeting cancer  

PubMed Central

In recent years, numerous new targets have been identified and new experimental therapeutics have been developed. Importantly, existing non-cancer drugs found novel use in cancer therapy. And even more importantly, new original therapeutic strategies to increase potency, selectivity and decrease detrimental side effects have been evaluated. Here we review some recent advances in targeting cancer. PMID:22228887

Demidenko, Zoya N.; McCubrey, James A.

2011-01-01

311

Molecular targets for cancer chemoprevention  

Microsoft Academic Search

Vaccines targeting infections with hepatitis B virus, a risk factor for hepatocellular cancer, and human papillomavirus, a risk factor for cervical cancer, are considered major clinical cancer chemoprevention successes. Molecularly targeted agents can prevent breast cancer (raloxifene and tamoxifen), colorectal adenomas (celecoxib), and prostate cancer (finasteride). Nevertheless, the broad translation of chemoprevention to the clinic is not yet a reality.

William N. William; John V. Heymach; Edward S. Kim; Scott M. Lippman

2009-01-01

312

Metabolomics in Drug Target Discovery  

PubMed Central

Most diseases result in metabolic changes. In many cases, these changes play a causative role in disease progression. By identifying pathological metabolic changes, metabolomics can point to potential new sites for therapeutic intervention. Particularly promising enzymatic targets are those that carry increased flux in the disease state. Definitive assessment of flux requires the use of isotope tracers. Here we present techniques for finding new drug targets using metabolomics and isotope tracers. The utility of these methods is exemplified in the study of three different viral pathogens. For influenza A and herpes simplex virus, metabolomic analysis of infected versus mock-infected cells revealed dramatic concentration changes around the current antiviral target enzymes. Similar analysis of human-cytomegalovirus-infected cells, however, found the greatest changes in a region of metabolism unrelated to the current antiviral target. Instead, it pointed to the tricarboxylic acid (TCA) cycle and its efflux to feed fatty acid biosynthesis as a potential preferred target. Isotope tracer studies revealed that cytomegalovirus greatly increases flux through the key fatty acid metabolic enzyme acetyl-coenzyme A carboxylase. Inhibition of this enzyme blocks human cytomegalovirus replication. Examples where metabolomics has contributed to identification of anticancer drug targets are also discussed. Eventual proof of the value of metabolomics as a drug target discovery strategy will be successful clinical development of therapeutics hitting these new targets. PMID:22114327

Rabinowitz, J.D.; Purdy, J.G.; Vastag, L.; Shenk, T.; Koyuncu, E.

2014-01-01

313

Radioisotope production targets and modules  

NASA Astrophysics Data System (ADS)

We have experienced the need to supply full radioisotope production systems that incorporate the accelerator, the beam lines, the targets and the radiochemistry in a unified package. The key component improvements are higher beam currents, more robust production targets, and efficient radiosynthesis modules. This note describes the progress we have made to produce efficient, high yield systems.

Johnson, R. R.; Erdman, K.; Gyles, W.; Burbee, J.; Manegoda, A.; Sabaiduc, V.; Kovac, B.; VanLier, E.; Wong, J.; Watt, R.; Wilson, J.; Zyuzin, A.

2005-12-01

314

Inflation Targeting in Latin America  

Microsoft Academic Search

This paper analyzes Latin America’s recent experience with the use of inflation targeting (IT) while the region has made substantial progress toward eradicating high inflation. The paper assesses the implementation and results of inflation targeting in Latin America from a broad perspective. It starts by reviewing the issues relevant for the choice of exchange-rate regimes and monetary frameworks, documenting the

Vittorio Corbo; Klaus Schmidt-Hebbel

2001-01-01

315

Inflation Targeting in Latin America  

Microsoft Academic Search

This paper analyzes Latin America’s recent experience with the use of inflation targeting (IT) while the region has made substantial progress toward eradicating high inflation. The paper assesses the implementation and results of inflation targeting in Latin America from a broad perspective. It starts by reviewing the issues relevant for the choice of exchange-rate regimes and monetary frameworks, documenting the

Vittorio Corbo; Klaus Schmidt-Hebbel

2002-01-01

316

Targeted marketing and public health.  

PubMed

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

Grier, Sonya A; Kumanyika, Shiriki

2010-01-01

317

Target identification with Bayesian networks  

NASA Astrophysics Data System (ADS)

Tracking algorithms can tell fairly reliable where target is heading. That is enough in civilian aviation, but in defence applications it might be not. Target's type and its hostility are at least as important. Normally, identification of type or friend or foe cannot be determined from target's kinematic information. To identify a target we also need other information. Every plane type has its own specialities e.g. we know that certain type has two engines which affects directly to heat of exhaust fumes. This kind of speciality is generally referred as an attribute information. Because attribute information is type depended, it must be modelled by an expert, who has beforehand knowledge of the target's causality relations. One of the best theories to get expert's knowledge into a tracking system is Bayesian networks. Bayesian networks is a model that describes relationships between attributes. In this paper we concentrate to identification problem. Question is how comprehension of the target's type changes with time when observations are corrupted by noise. We illustrate theory of Bayesian networks and explain its place in racking system. Finally we analyze performance of Bayesian networks in case where the problem is to identify targets from noisy data set.

Hautaniemi, Sampsa K.; Korpisaari, Petri T.; Saarinen, Jukka P. P.

2000-04-01

318

Auditory target detection in reverberation  

NASA Astrophysics Data System (ADS)

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.

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

2004-04-01

319

Behavioral Targeting—Consumer Tracking  

NASA Astrophysics Data System (ADS)

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.

Srimani, P. K.; Srinivas, A.

2011-12-01

320

Aided targeting system simulation evaluation  

NASA Technical Reports Server (NTRS)

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.

Demaio, Joe; Becker, Curtis

1994-01-01

321

Targeted Therapies for Lung Cancer  

PubMed Central

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

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

2012-01-01

322

Molecularly targeted therapies for recurrent glioblastoma: current and future targets.  

PubMed

Object Glioblastoma is the most aggressive and diffusely infiltrative primary brain tumor. Recurrence is expected and is extremely difficult to treat. Over the past decade, the accumulation of knowledge regarding the molecular and genetic profile of glioblastoma has led to numerous molecularly targeted therapies. This article aims to review the literature and highlight the mechanisms and efficacies of molecularly targeted therapies for recurrent glioblastoma. Methods A systematic search was performed with the phrase "(name of particular agent) and glioblastoma" as a search term in PubMed to identify all articles published up until 2014 that included this phrase in the title and/or abstract. The references of systematic reviews were also reviewed for additional sources. The review included clinical studies that comprised at least 20 patients and reported results for the treatment of recurrent glioblastoma with molecular targeted therapies. Results A total of 42 articles were included in this review. In the treatment of recurrent glioblastoma, various targeted therapies have been tested over the past 10-15 years. The targets of interest include epidermal growth factor receptor, vascular endothelial growth factor receptor, platelet-derived growth factor receptor, Ras pathway, protein kinase C, mammalian target of rapamycin, histone acetylation, and integrins. Unfortunately, the clinical responses to most available targeted therapies are modest at best. Radiographic responses generally range in the realm of 5%-20%. Progression-free survival at 6 months and overall survival were also modest with the majority of studies reporting a 10%-20% 6-month progression-free survival and 5- to 8-month overall survival. There have been several clinical trials evaluating the use of combination therapy for molecularly targeted treatments. In general, the outcomes for combination therapy tend to be superior to single-agent therapy, regardless of the specific agent studied. Conclusions Recurrent glioblastoma remains very difficult to treat, even with molecular targeted therapies and anticancer agents. The currently available targeted therapy regimens have poor to modest activity against recurrent glioblastoma. As newer agents are actively being developed, combination regimens have provided the most promising results for improving outcomes. Targeted therapies matched to molecular profiles of individual tumors are predicted to be a critical component necessary for improving efficacy in future trials. PMID:25434384

Lau, Darryl; Magill, Stephen T; Aghi, Manish K

2014-12-01

323

Integrated precision SAR targeting: a SAR targeting simulation  

Microsoft Academic Search

Operational deficiencies exist in the current ability to perform high resolution synthetic aperture radar (SAR) targeting for precision strike missions in difficult electronic countermeasure (ECM) and anti-aircraft environments. Increasingly sophisticated enemy defenses require that fire control information be derived from highly maneuverable aircraft trajectories rather than traditional straight-and-level flight. In addition, target area aspect information is needed to determine optimal

J. A. Toussaint; D. M. Martinsek

1999-01-01

324

Guidance and targeting for the strategic target system  

NASA Astrophysics Data System (ADS)

Guidance algorithms and targeting procedures for the Strategic Target System (STARS) launch vehicle are described. The STARS vehicle is a three stage booster, based partly upon retired Polaris A3 missile assets, which is intended to support development and testing of the Strategic Defense Initiative by delivering target payloads to the vicinity of the Kwajalein Atoll. STARS will be launched from the Kauai Test Facility located on Kauai, Hawaii. The STARS guidance objective is to deliver payloads to a prescribed target location with maximum accuracy at inter-continental ballistic missile velocities. The guidance problem is complicated by the fact that all three stages lack thrust termination or other velocity control mechanisms, and by range safety requirements for one or more out-of-plane turns. Mission objectives are achieved with a combination of guidance algorithms. The original Polaris guidance is used during the atmospheric ascent phase. The powered-explicit-guidance used by the Space Shuttle is later employed to execute an out-of-plane turn and to place the third stage as closely as possible into the desired coast trajectory. Third stage targeting is a modified Lambert procedure formulated to eliminate the target miss due to off-nominal ascent phase performance. Active guidance is also used during the third stage burn to maximize the delivery accuracy.

White, John E.

1989-11-01

325

Modeling techniques for target detection  

NASA Astrophysics Data System (ADS)

To better study hyperspectral imaging sensors and remote sensing system performance, different parts of the remote sensing system can be modeled. Here, a scientific overview of recent modeling techniques is presented to come up with an appropriate approach for modeling of a target detection system. In particular, this study focuses on the development in modeling of scene, sensors, and processing algorithms. Moreover, the parallelization of the detection methods is emphasized for which the process of target detection accelerates. In conclusion, an appropriate model to evaluate a target detection system can be a hybrid model in which hyperspectral sensors, radars, and local sensors have been modeled.

Attapattu, Jeevake; Sharifahmadian, Ershad; Latifi, Shahram

2014-06-01

326

Targeting the p53 Pathway  

PubMed Central

SYNOPSIS This review summarizes data on translational studies to target the p53 pathway in cancer. It describes the functions of the p53 and Mdm-2 signaling pathways and discusses current therapeutic approaches to target p53 pathways, including reactivation of p53. In addition, direct interaction and colocalization of the p53 and focal adhesion kinase (FAK) proteins in cancer cells have been demonstrated, and different approaches to target this interaction are reviewed. In summary, this is a broad review of p53 function as it relates to the diagnosis and treatment of a broad range of cancers. PMID:24012397

Golubovskaya, Vita M.; Cance, William G.

2013-01-01

327

Versatile cold atom target apparatus.  

PubMed

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. PMID:22852676

Götz, Simone; Höltkemeier, Bastian; Hofmann, Christoph S; Litsch, Dominic; DePaola, Brett D; Weidemüller, Matthias

2012-07-01

328

TRAINER CERTIFICATE PROGRAM Target Audience  

E-print Network

-end analysis * Systems approach to instructional design * Adult Learning Theory * Writing performance a needs assessment * Learn to apply adult learning principles. * A Trainer Certificate from the UniversityTRAINER CERTIFICATE PROGRAM Target Audience: * For emerging learning and development professionals

Azevedo, Ricardo

329

Targeting stroma to treat cancers  

PubMed Central

All cancers depend on stroma for support of growth. Leukemias, solid tumors, cancer cells causing effusions, metastases as well as micro-disseminated cancer cells release factors that stimulate stromal cells, which in turn produce ligands that stimulate cancer cells. Therefore, elimination of stromal support by destroying the stromal cells or by inhibiting feedback stimulation of cancer growth is in the focus of many evolving therapies. A stringent evaluation of the efficacy of stromal targeting requires testing in animal models. Most current studies emphasize the successes of stromal targeting rather than deciphering its limitations. Here we show that many of the stromal targeting approaches, while often reducing tumor growth rates, are rarely curative. Therefore, we will also discuss conditions where stromal targeting can eradicate large established tumors. Finally, we will examine still unanswered questions of this promising and exciting area of cancer research. PMID:22212863

Engels, Boris; Rowley, Donald A.; Schreiber, Hans

2012-01-01

330

Gene targeting with retroviral vectors  

SciTech Connect

The authors have designed and constructed integration-defective retroviral vectors to explore their potential for gene targeting in mammalian cells. Two nonoverlapping deletion mutants of the bacterial neomycin resistance (neo) gene were used to detect homologous recombination events between viral and chromosomal sequences. Stable neo gene correction events were selected at a frequency of approximately 1 G418/sup r/ cell per 3 x 10/sup 6/ infected cells. Analysis of the functional neo gene in independent targeted cell clones indicated that unintegrated retroviral linear DNA recombined with the target by gene conversion for variable distances into regions of nonhomology. In addition, transient neo gene correction events which were associated with the complete loss of the chromosomal target sequences were observed. These results demonstrated that retroviral vectors can recombine with homologous chromosomal sequences in rodent and human cells.

Ellis, J.; Bernstein, A. (Toronto Univ., ON (Canada))

1989-04-01

331

Target detection through quantum illumination  

E-print Network

Classical target detection can suffer large error probabilities in noisy and lossy environments when noise photons are mistaken for signal photons reflected from an object. It has been shown theoretically that the correlation ...

Mouradian, Sara L

2012-01-01

332

Nanoparticles for Targeted Drug Delivery  

E-print Network

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) ...

Chow, Gan-Moog

333

Target identification using laser imaging  

SciTech Connect

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.

Jennings, J.; Baker, M.; Barrett, J.; Ellis, B.N.; Kacerek, J.; Yee, J. [AlliedSignal Aerospace Co., Teterboro, NJ (United States)

1994-12-31

334

The JLab Frozen Spin Target  

SciTech Connect

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.

Keith, C. D. [Thomas Jefferson National Accelerator Facility, Newport News, VA 23606 (United States)

2009-08-04

335

Emerging Concepts in the Analysis of Transcriptional Targets of the MYC Oncoprotein: Are the Targets Targetable?  

PubMed

Activation of the MYC oncoprotein is among the most ubiquitous events in human cancer. MYC functions in part as a sequence-specific regulator of transcription. Although early searches for direct downstream target genes that explain MYC's potent biological activity were met with enthusiasm, the postgenomic decade has brought the realization that MYC regulates the transcription of not just a manageably small handful of target genes but instead up to 15% of all active loci. As the dust has begun to settle, two important concepts have emerged that reignite hope that understanding MYC's downstream targets might still prove valuable for defining critical nodes for therapeutic intervention in cancer patients. First, it is now clear that MYC target genes are not a random sampling of the cellular transcriptome but instead fall into specific, critical biochemical pathways such as metabolism, chromatin structure, and protein translation. In retrospect, we should not have been surprised to discover that MYC rewires cell physiology in a manner designed to provide the tumor cell with greater biosynthetic properties. However, the specific details that have emerged from these studies are likely to guide the development of new clinical tools and strategies. This raises the second concept that instills renewed optimism regarding MYC target genes. It is now clear that not all MYC target genes are of equal functional relevance. Thus, it may be possible to discern, from among the thousands of potential MYC target genes, those whose inhibition will truly debilitate the tumor cell. In short, targeting the targets may ultimately be a realistic approach after all. PMID:21533016

Van Dang, Chi; McMahon, Steven B

2010-06-01

336

Molecular Imaging and Targeted Therapies  

PubMed Central

Targeted therapeutic and imaging agents are becoming more prevalent, and are used to treat increasingly smaller segments of the patient population. This has lead to dramatic increases in the costs for clinical trials. Biomarkers have great potential to reduce the numbers of patients needed to test novel targeted agents by predicting or identifying non-response early-on and thus enriching the clinical trial population with patients more likely to respond. Biomarkers are characteristics that are objectively measured and evaluated as indicators of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. Biomarkers can be used to predict response to specific therapies, predict response regardless of therapy, or to monitor response once a therapy has begun. In terms of drug development, predictive biomarkers have the greatest impact, as they can be used as inclusion criteria for patient segmentation. Prognostic markers are used routinely in clinical practice but do not provide direction for the use of targeted therapies. Imaging biomarkers have distinct advantages over those that require a biopsy sample in that they are “non-invasive” and can be monitored longitudinally at multiple time points in the same patient. This review will examine the role of functional and molecular imaging in predicting response to specific therapies; will explore the advantages and disadvantages of targeting intracellular or extracellular markers; and will discuss the attributes of useful targets and methods for target identification and validation. PMID:20399197

Morse, David L.; Gillies, Robert J.

2010-01-01

337

The HERMES Polarized Hydrogen Internal Gas Target  

E-print Network

The HERMES Polarized Hydrogen Internal Gas Target J. Stewart for The HERMES Collaboration internal gas targets. The HERMES hydrogen target is an internal polarized gas target using the storage cell University of Liverpool, Liverpool L69 3BX, UK. Abstract. The HERMES polarized hydrogen target is an internal

338

Targets and methods for target preparation for radionuclide production  

DOEpatents

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.

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

2012-10-16

339

Targeted therapy for breast cancer.  

PubMed

Breast cancer is a heterogeneous group of diseases that are clinically subdivided as hormone receptor-positive, human epidermal growth factor receptor 2-positive (HER2(+)), and triple-negative breast cancer, to guide therapeutic interventions. Agents that target estrogen receptor (ER) and HER2 are among the most successful cancer therapeutics. However, de novo or acquired resistance is common, despite the development of newer agents against these pathways. As our understanding of tumor biology improves, novel targets are being identified. Notably, inhibitors against several pathways [including, among others, the phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR), cell-cycle regulation, heat shock protein, and epigenetic pathways] have demonstrated promising activity in clinical trials, and the mTOR-inhibitor everolimus has been approved for advanced or metastatic aromatase inhibitor-resistant ER(+) breast cancer. At present, there are no established targeted agents for triple-negative breast cancer (negative ER, progesterone receptor, and HER2). Although poly(ADP-ribose) polymerase inhibitors have shown promising activity in BRCA-related cancers, its value in the treatment of triple-negative breast cancers remains to be demonstrated. In this Review, we present a basic understanding of the major targeted agents in current practice and under development for the treatment of breast cancer in the context of the three clinical subgroups. PMID:23988612

Mohamed, Ali; Krajewski, Kenneth; Cakar, Burcu; Ma, Cynthia X

2013-10-01

340

Targeted Therapies for Malignant Glioma  

PubMed Central

Malignant gliomas represent one of the most aggressive forms of brain cancer. Recent advances in the understanding of the deregulated molecular pathways of gliomas have brought about targeted therapies that have the ability to increase therapeutic efficacy in tumors while decreasing toxicity. Multi-targeted kinase inhibitors, novel monoclonal antibodies, and new vaccines have been developed. Standard treatments and current development of new therapies for malignant gliomas are reviewed, focusing specifically on growth factors and their receptors (e.g. epidermal growth factor receptor, vascular endothelial growth factor receptor, and platelet-derived growth factor receptor), as well as the intracellular effector molecules that are downstream of these growth factors (e.g. Ras/Raf/mitogen-activated protein kinase, phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin, and protein kinase C). The efficacies of other novel targeted inhibitors such as deacetylase inhibitors and heat shock protein 90 inhibitors in the treatment of gliomas are also discussed, as well as new combination therapies. In order for new agents to increase treatment efficacy, new targets need to be developed, drug delivery efficiency needs to be improved, and new biomarkers need to be discovered. All of these goals can be accomplished with time through innovative experimental designs. PMID:19344189

Mercer, Ronald W.; Tyler, Matthew A.; Ulasov, Ilya V.; Lesniak, Maciej S.

2009-01-01

341

The Target Preparation Laboratory at Daresbury  

NASA Astrophysics Data System (ADS)

The Target Preparation Laboratory at Daresbury Laboratory is described. This laboratory provides targets for the UK Nuclear Physics community whose experimental programme is performed in several laboratories worldwide. Details are given of its present capabilities and range of targets produced.

Morrall, P. S.

2008-06-01

342

77 FR 30928 - Target Date Disclosure  

Federal Register 2010, 2011, 2012, 2013

...Administration 29 CFR Part 2550 RIN 1210-AB38 Target Date Disclosure AGENCY: Employee Benefits...relating to enhanced disclosure concerning target date or similar investments, originally...20210, Attention: RIN 1210-AB38; Target Date Disclosure. Comments received...

2012-05-24

343

40 CFR 35.9020 - Planning targets.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 2010-07-01 false Planning targets. 35.9020 Section 35.9020 ...Estuary Program § 35.9020 Planning targets. The EPA Assistant Administrator for Water develops planning targets each year to help each Management...

2010-07-01

344

Thermal Targets for Satellite Calibration  

SciTech Connect

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.

Villa-Aleman, E.

2001-01-10

345

Hybrid detectors for subpixel targets.  

PubMed

Subpixel detection is a challenging problem in hyperspectral imagery analysis. Since the target size is smaller than the size of a pixel, detection algorithms must rely solely on spectral information. A number of different algorithms have been developed over the years to accomplish this task, but most detectors have taken either a purely statistical or a physics-based approach to the problem. We present two new hybrid detectors that take advantage of these approaches by modeling the background using both physics and statistics. Results demonstrate improved performance over the well known AMSD and ACE subpixel algorithms in experiments that include multiple targets, images, and area types--especially when dealing with weak targets in complex backgrounds. PMID:17848772

Broadwater, Joshua; Chellappa, Rama

2007-11-01

346

A cryogenic infrared calibration target  

NASA Astrophysics Data System (ADS)

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.

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

2014-04-01

347

3-Bromopyruvate: targets and outcomes.  

PubMed

The pyruvate mimetic 3-bromopyruvate (3-BP) is generally presented as an inhibitor of glycolysis and has shown remarkable efficacy in not only preventing tumor growth, but even eradicating existant tumors in animal studies. We here review reported molecular targets of 3-BP and suggest that the very range of possible targets, which pertain to the altered energy metabolism of tumor cells, contributes both to the efficacy and the tumor specificity of the drug. Its in vivo efficacy is suggested to be due to a combination of glycolytic and mitochondrial targets, as well as to secondary effects affecting the tumor microenvironment. The cytotoxicity of 3-BP is less due to pyruvate mimicry than to alkylation of, e.g., key thiols. Alkylation of DNA/RNA has not been reported. More research is warranted to better understand the pharmacokinetics of 3-BP, and its potential toxic effects to normal cells, in particular those that are highly ATP-/mitochondrion-dependent. PMID:22298255

Shoshan, Maria C

2012-02-01

348

Targeting cancer using cholesterol conjugates  

PubMed Central

Conjugation of cholesterol moiety to active compounds for either cancer treatment or diagnosis is an attractive approach. Cholesterol derivatives are widely studied as cancer diagnostic agents and as anticancer derivatives either in vitro or in vivo using animal models. In largely growing studies, anticancer agents have been chemically conjugated to cholesterol molecules, to enhance their pharmacokinetic behavior, cellular uptake, target specificity, and safety. To efficiently deliver anticancer agents to the target cells and tissues, many different cholesterol–anticancer conjugates were synthesized and characterized, and their anticancer efficiencies were tested in vitro and in vivo. PMID:24493968

Radwan, Awwad A.; Alanazi, Fares K.

2013-01-01

349

[Bone targeted therapies: new agents].  

PubMed

The development of bisphosphonates and anti-RANK/RANKL agents was associated with a better understanding of physiological and pathological processes of bone remodeling. New agents are now developed in this context targeting factors associated with osteoclastogenesis (TGF?, PTHrP), with signaling pathways activated during bone remodeling (Src, Cathepsin K) or with tumor cells homing into bone (chemokines). This review aims to present the underlying rationale for these developments as well as the clinical results. The emergence of new bone targeting therapies is discussed. PMID:24158596

Barth, Claire; Massard, Christophe; Vignot, Stéphane

2013-11-01

350

Transmission Line MTF: Magnetized Target Fusion  

E-print Network

Transmission Line MTF: Magnetized Target Fusion Initial target: preheated & magnetized Subsequent for the FRC. Abstract Block Diagram theta coil transmission line Bias cap. bank maincapacitor inductor PI cap

351

Exploitation of target shadows in synthetic aperture radar imagery for automatic target recognition  

Microsoft Academic Search

The utility of target shadows for automatic target recognition (ATR) in synthetic aperture radar (SAR) imagery is investigated. Although target shadow, when available, is not a powerful target discriminating feature, it can effectively increase the overall accuracy of the target classification when it is combined with other target discriminating features such as peaks, edges, and corners. A second and more

John A. Saghri; Andrew DeKelaita

2006-01-01

352

26 CFR 1.338-1 - General principles; status of old target and new target.  

Code of Federal Regulations, 2012 CFR

... false General principles; status of old target and new target. 1.338-1 ...338-1 General principles; status of old target and new target. (a) In general...made, then two separate corporations, old target and new target, generally are...

2012-04-01

353

26 CFR 1.338-1 - General principles; status of old target and new target.  

Code of Federal Regulations, 2013 CFR

... false General principles; status of old target and new target. 1.338-1 ...338-1 General principles; status of old target and new target. (a) In general...made, then two separate corporations, old target and new target, generally are...

2013-04-01

354

Automatic target recognition of time critical moving targets using 1D high range resolution (HRR) radar  

Microsoft Academic Search

Synthetic Aperture Radar (SAR) imaging and Automatic Target Recognition (ATR) of moving targets pose a significant challenge due to the inherent difficulty of focusing moving targets. As a result, ATR of moving targets has recently received increased interest. High Range Resolution (HRR) radar mode offers an approach for recognizing moving targets by forming focused HRR profiles with significantly enhanced target-to-(clutter+noise)

R. Williams; J. Westerkamp; D. Gross; A. Palomino

2000-01-01

355

An unusual case of rapidly progressive hyperbilirubinemia.  

PubMed

We present an unusual case of hyperbilirubinemia with rapid early progression leading to bilirubin encephalopathy in a term neonate. Despite early recognition and intervention, the total serum bilirubin reached a maximum level of 39?mg/dL at 32 hours of life. Prior to an emergent exchange transfusion, the patient's diagnostic evaluation was significant for Coombs-negative microangiopathic hemolytic anemia and thrombocytopenia. Further testing revealed a deficiency of ADAMTS13 protein, or von Willebrand factor-cleaving protease, a finding diagnostic of congenital thrombotic thrombocytopenic purpura, or Upshaw-Schulman syndrome. This rare disease is often misdiagnosed, especially in the newborn period. PMID:24288641

Thornton, Kimberly M; Nyp, Michael F; Music Aplenc, Lejla; Jones, Gary L; Carpenter, Shannon L; Guest, Erin M; Shapiro, Steven M; Manimtim, Winston M

2013-01-01

356

Single-access transumbilical laparoscopic splenectomy using curved reusable instruments  

Microsoft Academic Search

Background  The authors report a single-access transumbilical laparoscopic splenectomy (SATLS) performed with curved reusable instruments.\\u000a \\u000a \\u000a \\u000a Methods  A 23-year-old female consulted for steroid-resistant idiopathic thrombocytopenic purpura and clinical evidence of secondary\\u000a Cushing syndrome. Preoperative workup showed a normal-sized spleen and thrombocytopenia. The umbilicus was incised and a purse-string\\u000a suture was applied. A reusable 11-mm trocar was inserted for a 10-mm, 30° angled scope.

Giovanni Dapri; Dominique Bron; Jacques Himpens; Lorenzo Casali; Pietro Carnevali; Pavlos Koustas; Guy-Bernard Cadière

357

Breast cancer presenting as paraneoplastic erythroderma: an extremely rare case.  

PubMed

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

Protopsaltis, Ioannis; Drossou, Aspasia; Katsantonis, Ioannis; Roussos, Nikolaos; Manoludaki, Kassiani; Arvanitis, Miltiadis; Papazafiropoulou, Athanasia; Antonopoulos, Stavros

2014-01-01

358

Breast Cancer Presenting as Paraneoplastic Erythroderma: An Extremely Rare Case  

PubMed Central

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

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

2014-01-01

359

Automated targeting data fusion (ATDF)  

Microsoft Academic Search

Automated all source data fusion primarily fuses analyst generated messages. The Automated Targeting Data Fusion (ATDF) effort created an application that rapidly associated very diverse information sources automatically. In recent military conflict situations, enormous amounts of multi-source data have been made available to war-fighters. These data include imagery, signals intelligence, acoustic information, input from human analysts, and other sources. The

Randy K. Young; Peter S. Wyckoff; James H. Wise

2003-01-01

360

Right on Target: Catapult Game  

NSDL National Science Digital Library

Students experience the engineering design process as they design and build accurate and precise catapults using common materials. They use their catapults to participate in a game in which they launch Ping-Pong balls to attempt to hit various targets.

Integrated Teaching And Learning Program

361

Biological Control not on Target  

Microsoft Academic Search

Non-target effects of exotic biological control agents, parasitoids and predators, released worldwide to control insect pests, are becoming more apparent. This paper summarizes previously recorded information on the diet breadth of natural enemies released to control insect pests worldwide. It also summarizes the diet breadth of native parasitic hymenoptera in North America to determine whether the diet breadths of native

Peter Stiling

2004-01-01

362

Target Proposal Feb. 15, 2000  

E-print Network

engineering. . Consider geometry options which aid cooling & minimize radiation dose -- Example: Rotating band is that cooling requirement is much reduced -- At 1 ­ 1.5 MW beam, radiative cooling appears feasible (J. Haines or stranded fibers ~ golf club shaft) . Radiation damage -- Plan facility to replace target at ~ 5 dpa

McDonald, Kirk

363

Keeping Your Head On Target  

PubMed Central

The mechanisms by which the human brain controls eye movements are reasonably well understood, but those for the head less so. Here, we show that the mechanisms for keeping the head aimed at a stationary target follow strategies similar to those for holding the eyes steady on stationary targets. Specifically, we applied the neural integrator hypothesis that originally was developed for holding the eyes still in eccentric gaze positions to describe how the head is held still when turned toward an eccentric target. We found that normal humans make head movements consistent with the neural integrator hypothesis, except that additional sensory feedback is needed, from proprioceptors in the neck, to keep the head on target. We also show that the complicated patterns of head movements in patients with cervical dystonia can be predicted by deficits in a neural integrator for head motor control. These results support ideas originally developed from animal studies that suggest fundamental similarities between oculomotor and cephalomotor control, as well as a conceptual framework for cervical dystonia that departs considerably from current clinical views. PMID:23825431

Wong, Aaron L.; Zee, David S.; Jinnah, H. A.

2013-01-01

364

Targeting Resources for Local Growth.  

ERIC Educational Resources Information Center

Focusing state and federal dollars on targeted areas, the Kentucky Appalachian Community Development Initiative helps communities in eastern Kentucky fund their own strategies for economic growth. In Hindman, the project focuses on creating the Kentucky School of Crafts, to train master artisans; supporting the Kentucky Appalachian Artisan Center;…

Casto, James E.

2001-01-01

365

Foam shell cryogenic ICF target  

DOEpatents

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.

Darling, Dale H. (Pleasanton, CA)

1987-01-01

366

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...

367

Hypoxia-mediated tumour targeting  

Microsoft Academic Search

Hypoxia is a common physiological feature of tumours. It activates a signalling cascade that culminates in the stabilization of the HIF-1 transcription factor and activation of genes that possess a hypoxia response element (HRE). We have used an optimized hypoxia responsive promoter (OBHRE) to investigate hypoxia-targeted gene expression in vivo in the context of an adenovirus vector. The OBHRE promoter

K Binley; Z Askham; L Martin; H Spearman; D Day; S Kingsman; S Naylor

2003-01-01

368

Polarimetric imaging of underwater targets  

NASA Astrophysics Data System (ADS)

Underwater imaging is challenging because of the significant attenuation of light due to absorption and scattering of light in water. Using polarization properties of light is one of the options for improving image quality. We present results of imaging of a polarized target in open ocean (Curacao) and coastal (NY Bight) waters. The target in the shape of a square is divided into several smaller squares, each of which is covered with a polarizing film with different polarization orientations or transmission coefficients was placed on a mirror and imaged under water by a green-band full-Stokes polarimetric video camera at the full range of azimuth angles against the Sun. The values of the Stokes vector components from the images are compared with the modeled image of the target using radiative transfer code for the atmosphere-ocean system combined with the simple imaging model. It is shown that even in clear water the impact of the water body on the polarized underwater image is very significant and retrieval of target polarization characteristics from the image is extremely challenging.

Gilerson, Alex; Carrizo, Carlos; Tonizzo, Alberto; Ibrahim, Amir; El-Habashi, Ahmed; Foster, Robert; Ahmed, Samir

2013-06-01

369

RESEARCH COMMUNICATION Targeting genes for  

E-print Network

in turn used to generate chimeric mice. In these chimeras, somatic cells derived from the ES cells embryo-derived stem (ES) cell. Cells containing the modification are placed in an embryonic environmentRESEARCH COMMUNICATION Targeting genes for self-excision in the germ line Michaeline Bunting,1

Capecchi, Mario R.

370

Target Audience: Health care professionals  

E-print Network

(palliative care, chronic ill- ness), child welfare, and do- mestic violence. Valerie is an AssistantTarget 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

Haykin, Simon

371

Inflation Targeting in Dollarized Economies  

Microsoft Academic Search

The shift to inflation targeting has contributed to the relatively low inflation observed in some emerging market economies although, as noted by many economists, the preconditions required for a successful implementation were not in place. The existence of managed exchange rate regimes, a narrow base of domestic nominal financial assets, the lack of market instruments to hedge exchange rate risks,

Leonardo Leiderman; Rodolfo Maino; Eric Parrado

2006-01-01

372

Therapeutic targets for premature ejaculation.  

PubMed

Premature ejaculation (PE) is the most common male sexual complaint, and may exert a profound negative impact on the man's life and partnership. Using currently available treatment alternatives (e.g., selective serotonin uptake inhibitor, agents acting locally on the penis), PE can be treated in most, but not all patients. However, since long term success rates have been disappointing, and the only approved treatment so far is the short-acting selective serotonin re-uptake inhibitor dapoxetine, there is currently an intensive search for new treatment modalities. Selection of the most promising therapeutic targets from a host of current and potential candidates depends heavily on their roles in the pathophysiology of PE. Possible central nervous targets that will be discussed are serotonin transporters, and CNS receptors for 5-HT(IA) and 5-HT(1B), dopamine, oxytocin, opioids, neurokinin-1, and glutamate. Putative peripheral targets include ?(1)-adrenoceptors, phosphodiestrase enzymes, Rho kinases, purinergic (P2X) receptors, and penile sensory nerves. It is clear that exploiting the full therapeutic potential of these targets will require additional basic and clinical research. PMID:21816550

Andersson, Karl-Erik; Abdel-Hamid, Ibrahim A

2011-09-01

373

Polarized Sources, Targets and Polarimetry  

NASA Astrophysics Data System (ADS)

Remarks on the history of workshops on "spin tools" / E. Steffens -- Polarized proton beams in RHIC / A. Zelenski -- The COSY/Julich polarized H[symbol] and D[symbol] ion source / O. Felden -- The new source of polarized ions for the JINR accelerator complex / V. V. Fimushkin -- Resonance effects in nuclear dichroism - an inexpensive source of tensor-polarized deuterons / H. Seyfarth -- Polarized electrons and positrons at the MESA accelerator / K. Aulenbacher -- Status report of the Darmstadt polarized electron injector / Y. Poltoratska -- The Mott polarimeter at MAMI / V. Tioukine -- Proton polarimetry at the relativistic heavy ion collider / Y. Makdisi -- Polarisation and polarimetry at HERA / B. Sobloher -- Polarisation measurement at the ILC with a Compton polarimeter / C. Bartels -- Time evolution of ground motion-dependent depolarisation at linear colliders / A. Hartin -- Electron beam polarimetry at low energies and its applications / R. Barday -- Polarized solid targets: recent progress and future prospects / C. D. Keith -- HD gas distillation and analysis for HD frozen spin targets / A. D'Angelo -- Electron spin resonance study of hydrogen and alkyl free radicals trapped in solid hydrogen aimed for dynamic nuclear polarization of solid HD / T. Kumada -- Change of ultrafast nuclear-spin polarization upon photoionization by a short laser pulse / T. Nakajima -- Radiation damage and recovery in polarized [symbol]NH[symbol] ammonia targets at Jefferson lab / J. D. Maxwell.Polarized solid proton target in low magnetic field and at high temperature / T. Uesaka -- Pulse structure dependence of the proton spin polarization rate / T. Kawahara -- Proton NMR in the large COMPASS [symbol]NH[symbol] target / J. Koivuniemi -- DNP with TEMPO and trityl radicals in deuterated polystyrene / L. Wang -- The CLIC electron and positron polarized sources / L. Rinolfi -- Status of high intensity polarized electron gun at MIT-Bates / E. Tsentalovich -- Target section for spin filtering studies at COSY and CERN/AD / C. Barschel -- First experiments with the polarized internal gas target at ANKE/COSY / M. Mikirtychyants -- Extra physics with an ABS and a Lamb-shift polarimeter / R. Engels -- Systematic studies for the development of high-intensity ABS / L. Barion -- Upgrade of the 50 keV GaAs source of polarized electrons at ELSA / D. Heiliger -- Lifetime measurements of DBR and nonDBR photocathodes at high laser intensities / E. Riehn -- Polarized electron source based on FZD SRF gun / R. Xiang -- Major advances in SEOP of [symbol]He targets / P. Dolph -- A study of polarized metastable [symbol]He beam production / Yu. A. Plis -- Polarized [symbol]He targets for real and virtual photons / J. Krimmer -- Spin-filtering studies at COSY and AD / F. Rathmann -- Experimental setup for spin-filtering studies at COSY and AD / A. Nass -- Polarizing a stored proton beam by spin-flip? - A reanalysis / D. Oellers -- Tracking studies of spin coherence in COSY in view of EDM polarization measurements / A. U. Luccio -- Summary of the XIII international workshop on polarized sources, targets and polarimetry / F. Rathmann.

Ciullo, Guiseppe; Contalbrigo, Marco; Lenisa, P.

2011-01-01

374

Targeted multi-pinhole SPECT  

PubMed Central

Purpose Small-animal single photon emission computed tomography (SPECT) with focused multi-pinhole collimation geometries allows scanning modes in which large amounts of photons can be collected from specific volumes of interest. Here we present new tools that improve targeted imaging of specific organs and tumours, and validate the effects of improved targeting of the pinhole focus. Methods A SPECT system with 75 pinholes and stationary detectors was used (U-SPECT-II). An XYZ stage automatically translates the animal bed with a specific sequence in order to scan a selected volume of interest. Prior to stepping the animal through the collimator, integrated webcams acquire images of the animal. Using sliders, the user designates the desired volume to be scanned (e.g. a xenograft or specific organ) on these optical images. Optionally projections of an atlas are overlaid semiautomatically to locate specific organs. In order to assess the effects of more targeted imaging, scans of a resolution phantom and a mouse myocardial phantom, as well as in vivo mouse cardiac and tumour scans, were acquired with increased levels of targeting. Differences were evaluated in terms of count yield, hot rod visibility and contrast-to-noise ratio. Results By restricting focused SPECT scans to a 1.13-ml resolution phantom, count yield was increased by a factor 3.6, and visibility of small structures was significantly enhanced. At equal noise levels, the small-lesion contrast measured in the myocardial phantom was increased by 42%. Noise in in vivo images of a tumour and the mouse heart was significantly reduced. Conclusion Targeted pinhole SPECT improves images and can be used to shorten scan times. Scan planning with optical cameras provides an effective tool to exploit this principle without the necessity for additional X-ray CT imaging. PMID:21063706

Vastenhouw, Brendan; van der Have, Frans; Blezer, Erwin L. A.; Bleeker, Wim K.; Beekman, Freek J.

2010-01-01

375

Simultaneous identification and tracking of moving targets  

Microsoft Academic Search

This paper describes a framework for simultaneous identification and tracking of moving targets in random media. Video and IR thermal sensors are used to obtain the target signature. Classical Kalman filtering methods are implemented on targets with unknown trajectories. Computer vision methodologies are proposed to design a smart interceptor which identifies the targets based on shape and thermal signatures. The

Ahmed Shalaby; Asem Ali; Aly Farag

2011-01-01

376

Possible Target Options Michael A. Green  

E-print Network

Possible Target Options Michael A. Green WATER COOLED SOLID TARGETS For high energy drivers a high melting point material. Low Z targets will have much less proton energy deposited within them per for the target, such as carbon, the proton beam energy should be reduced. At 2 to 4 GeV, carbon will produce more

McDonald, Kirk

377

Targeting an efficient target-to-target interval for P300 speller brain-computer interfaces.  

PubMed

Longer target-to-target intervals (TTI) produce greater P300 event-related potential amplitude, which can increase brain-computer interface (BCI) classification accuracy and decrease the number of flashes needed for accurate character classification. However, longer TTIs requires more time for each trial, which will decrease the information transfer rate of BCI. In this paper, a P300 BCI using a 7 × 12 matrix explored new flash patterns (16-, 18- and 21-flash pattern) with different TTIs to assess the effects of TTI on P300 BCI performance. The new flash patterns were designed to minimize TTI, decrease repetition blindness, and examine the temporal relationship between each flash of a given stimulus by placing a minimum of one (16-flash pattern), two (18-flash pattern), or three (21-flash pattern) non-target flashes between each target flashes. Online results showed that the 16-flash pattern yielded the lowest classification accuracy among the three patterns. The results also showed that the 18-flash pattern provides a significantly higher information transfer rate (ITR) than the 21-flash pattern; both patterns provide high ITR and high accuracy for all subjects. PMID:22350331

Jin, Jing; Sellers, Eric W; Wang, Xingyu

2012-03-01

378

Targeting Wnt Pathways in Disease  

PubMed Central

Wnt-mediated signal transduction pathways have long been recognized for their roles in regulating embryonic development, and have more recently been linked to cancer, neurologic diseases, inflammatory diseases, and disorders of endocrine function and bone metabolism in adults. Although therapies targeting Wnt signaling are attractive in theory, in practice it has been difficult to obtain specific therapeutics because many components of Wnt signaling pathways are also involved in other cellular processes, thereby reducing the specificity of candidate therapeutics. New technologies, and advances in understanding the mechanisms of Wnt signaling, have improved our understanding of the nuances of Wnt signaling and are leading to promising new strategies to target Wnt signaling pathways. PMID:23001988

Zimmerman, Zachary F.; Moon, Randall T.

2012-01-01

379

Targeting molecular addictions in cancer.  

PubMed

Cancer cells depend on a finite number of critical signals for their survival. Oncogene addiction, that is, the acquired dependence of a cancer cell on the activity of a single oncogenic gene product, has been the basis for the targeted therapy paradigm, and operationally defines such signals. Additionally, cancer cells have altered metabolic requirements that create addictions to specific nutrients such as glucose and glutamine. In this review, I will discuss the therapeutic opportunities that these two types of molecular addictions offer, focusing on lessons learned from targeting members of the epidermal growth factor receptor family of kinases, and components of MAPK pathway. I will also discuss the challenges in simultaneously harnessing two types of molecular addictions for therapeutic benefit, and the importance of understanding not only the effects of oncogenic signal transduction on metabolism, but also the impact of metabolic states on signal transduction. PMID:25268375

Vivanco, I

2014-11-25

380

Remote moving target indication assessment  

SciTech Connect

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.

Canavan, G.H.

1996-10-01

381

Targeting glutamate synapses in schizophrenia  

PubMed Central

Although early clinical observations implicated dopamine dysfunction in the neuropathology of schizophrenia, accumulating evidence suggests that multiple neurotransmitter pathways are dysregulated. The psychotomimetic actions of NMDA receptor antagonists point to an imbalance of glutamatergic signaling. Encouragingly, numerous preclinical and clinical studies have elucidated several potential targets for increasing NMDA receptor function and equilibrating glutamatergic tone, including the metabotropic glutamate receptors 2, 3 and 5, the muscarinic acetylcholine receptors M1 and M4, and the glycine transporter GlyT1. Highly specific allosteric and orthosteric ligands have been developed that modify the activity of these novel target proteins, and in this review we summarize both the glutamatergic mechanisms and the novel compounds that are increasing promise for a multifaceted pharmacological approach to treat schizophrenia. PMID:21955406

Field, Julie R.; Walker, Adam G.; Conn, P. Jeffrey

2011-01-01

382

Jet Perturbation by HE target  

SciTech Connect

We have previously reported the degree of attenuation and perturbation by a Cu jet passing through Comp B explosive. Similar tests have now been performed with high explosive (HE) targets having CJ pressures higher than and lower than the CJ pressure of Comp B. The explosives were LX-14 and TNT, respectively. We found that the measured exit velocity of the jet where it transitions from perturbed to solid did not vary significantly as a function of HE type for each HE thickness. The radial momentum imparted to the perturbed jet segment did vary as a function of HE type, however, and we report the radial spreading of the jet and the penetration of a downstream target as a function of HE type and thickness.

Poulsen, P; Kuklo, R M

2001-03-01

383

Targeting caspases in cancer therapeutics  

PubMed Central

The identification of the fundamental role of apoptosis in the growth balance and normal homeostasis against cell proliferation led to the recognition of its loss contributing to tumorigenesis. The mechanistic significance of reinstating apoptosis signaling towards selective targeting of malignant cells heavily exploits the caspase family of death-inducing molecules as a powerful therapeutic platform for the development of potent anticancer strategies. Some apoptosis inhibitors induce caspase expression and activity in preclinical models and clinical trials by targeting both the intrinsic and extrinsic apoptotic pathways and restoring the apoptotic capacity in human tumors. Furthermore, up-regulation of caspases emerges as a sensitizing mechanism for tumors exhibiting therapeutic resistance to radiation and adjuvant chemotherapy. This review provides a comprehensive discussion of the functional involvement of caspases in apoptosis control and the current understanding of reactivating caspase-mediated apoptosis signaling towards effective therapeutic modalities in cancer treatment. PMID:23509217

Hensley, Patrick; Mishra, Murli; Kyprianou, Natasha

2013-01-01

384

Phase I dose-escalation study of SGN-75 in patients with CD70-positive relapsed/refractory non-Hodgkin lymphoma or metastatic renal cell carcinoma.  

PubMed

Purpose This first-in-human study evaluated the CD70-targeted antibody-drug conjugate SGN-75 in patients with relapsed or refractory CD70-positive non-Hodgkin lymphoma (NHL) or metastatic renal cell carcinoma (RCC). Methods SGN-75 was administered intravenously to 58 patients (39 RCC, 19 NHL) every 3 weeks (Q3Wk; doses escalated from 0.3 to 4.5 mg/kg) or on Days 1, 8, and 15 of 28-day cycles (weekly; doses of 0.3 or 0.6 mg/kg). Dose-limiting toxicities were evaluated during Cycle 1; treatment response was monitored every 2 cycles. Results The maximum tolerated dose of SGN-75 in RCC patients was 3 mg/kg Q3Wk. Due to toxicity concerns (idiopathic thrombocytopenic purpura in 2 NHL patients treated weekly), dose escalation in the weekly schedule was terminated; no regimen was recommended for NHL patients. The most common adverse events reported in patients treated Q3Wk (N?=?47) were fatigue (40 %), dry eye (32 %), nausea (30 %), and thrombocytopenia (26 %). The nadir for thrombocytopenia typically occurred during Cycle 1. Ocular adverse events (e.g., corneal epitheliopathy, dry eye) were reported for 57 % of patients treated Q3Wk and were generally reversible. Antitumor activity in patients treated Q3Wk included 1 complete response, 2 partial responses, and 20 stable disease. SGN-75 exposures were approximately dose proportional, with a mean terminal half-life of 10 days. Substantial depletions of CD70-positive peripheral blood lymphocytes were observed after SGN-75 treatment. Conclusions Modest single-agent activity and generally manageable adverse events were observed in heavily pretreated RCC and NHL patients. Administration Q3Wk was better tolerated than weekly dosing. Targeted ablation of CD70-positive lymphocytes was demonstrated. PMID:25142258

Tannir, Nizar M; Forero-Torres, Andres; Ramchandren, Radhakrishnan; Pal, Sumanta K; Ansell, Stephen M; Infante, Jeffrey R; de Vos, Sven; Hamlin, Paul A; Kim, Stella K; Whiting, Nancy C; Gartner, Elaina M; Zhao, Baiteng; Thompson, John A

2014-12-01

385

Fixed target flammable gas upgrades  

SciTech Connect

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.

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

1996-12-01

386

Nanowire target support and method  

US Patent & Trademark Office Database

The invention provides an apparatus that produces analyte ions for detection by a detector. The apparatus includes a matrix based ion source having a nanowire target substrate for producing analyte ions, an ion transport system adjacent to the matrix based ion source for transporting analyte ions from the matrix based ion source; and an ion detector downstream from the ion transport system for detecting the analyte ions. The invention also provides a method for producing and detecting the analyte ions.

2006-07-18

387

Preparation of thick molybdenum targets  

NASA Technical Reports Server (NTRS)

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.

Singh, J. J.

1974-01-01

388

Coherent Communications, Imaging and Targeting  

SciTech Connect

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.

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

2003-10-03

389

Effects of target typicality on categorical search  

PubMed Central

The role of target typicality in a categorical visual search task was investigated by cueing observers with a target name, followed by a five-item target present/absent search array in which the target images were rated in a pretest to be high, medium, or low in typicality with respect to the basic-level target cue. Contrary to previous work, we found that search guidance was better for high-typicality targets compared to low-typicality targets, as measured by both the proportion of immediate target fixations and the time to fixate the target. Consistent with previous work, we also found an effect of typicality on target verification times, the time between target fixation and the search judgment; as target typicality decreased, verification times increased. To model these typicality effects, we trained Support Vector Machine (SVM) classifiers on the target categories, and tested these on the corresponding specific targets used in the search task. This analysis revealed significant differences in classifier confidence between the high-, medium-, and low-typicality groups, paralleling the behavioral results. Collectively, these findings suggest that target typicality broadly affects both search guidance and verification, and that differences in typicality can be predicted by distance from an SVM classification boundary.

Maxfield, Justin T.; Stalder, Westri D.; Zelinsky, Gregory J.

2014-01-01

390

Targeting calpain in synaptic plasticity  

PubMed Central

Introduction Calpains represent a family of neutral, calcium-dependent proteases, which modify the function of their target proteins by partial truncation. These proteases have been implicated in numerous cell functions, including cell division, proliferation, migration, and death. In the CNS, where ?-calpain and m-calpain are the main calpain isoforms, their activation has been linked to synaptic plasticity as well as to neurodegeneration. This review will focus on the role of calpains in synaptic plasticity and discuss the possibility of developing methods to manipulate calpain activity for therapeutic purposes. Areas covered This review covers the literature showing how calpains are implicated in synaptic plasticity and in a number of conditions associated with learning impairment. The possibility of developing new drugs targeting these enzymes for treating these conditions is discussed. Expert opinion As evidence accumulates that calpain activation participates in neurodegeneration and cancer, there is interest in developing therapeutic approaches using direct or indirect calpain inhibition. In particular, a peptide derived from the calpain truncation site of mGluR1? was shown to decrease neurodegeneration following neonatal hypoxia/ischemia. More selective approaches need to be developed to target calpain or some of its substrates for therapeutic indications associated with deregulation of synaptic plasticity. PMID:23379852

Baudry, Michel; Chou, Maggie M; Bi, Xiaoning

2014-01-01

391

Thomson scattering on inhomogeneous targets  

SciTech Connect

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.

Thiele, R.; Sperling, P.; Bornath, Th.; Kraeft, W.-D.; Redmer, R. [Institut fuer Physik, Universitaet Rostock, D-18051 Rostock (Germany); Chen, M. [Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS 71-259, Berkeley, California 94720 (United States); Institut fuer Theoretische Physik I, Heinrich-Heine-Universitaet Duesseldorf, D-40225 Duesseldorf (Germany); Faeustlin, R. R.; Toleikis, S. [DESY, Notkestrasse 85, D-22607 Hamburg (Germany); Fortmann, C. [Department of Physics and Astronomy, University of California-Los Angeles, Los Angeles, California 90095 (United States); Lawrence Livermore National Laboratory, P.O. Box 808, L-399, Livermore, California 94551 (United States); Glenzer, S. H. [Lawrence Livermore National Laboratory, P.O. Box 808, L-399, Livermore, California 94551 (United States); Pukhov, A. [Institut fuer Theoretische Physik I, Heinrich-Heine-Universitaet Duesseldorf, D-40225 Duesseldorf (Germany); Tschentscher, Th. [European XFEL GmbH, Albert-Einstein-Ring 19, D-22761 Hamburg (Germany)

2010-11-15

392

A Cryogenic Infrared Calibration Target  

E-print Network

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...

Wollack, Edward J; Rinehart, Stephan A

2014-01-01

393

The npdgamma liquid parahydrogen target  

NASA Astrophysics Data System (ADS)

The NPDGamma Experiment is measuring the parity-violating correlation Agamma between neutron spin and gamma momentum in the radiative capture of a polarized cold neutron beam on a cryogenic liquid parahydrogen target. This measurement is expected to give insight into theories that incorporate the weak interaction into what is primarily a strongly interacting system. This dissertation discusses the operation and characterization of the liquid hydrogen target, including the calibration of the instrumentation that monitors the state of the hydrogen. An important consideration is the fact that for safety reasons the instrumentation in direct contact with the hydrogen is limited, and so a detailed understanding of the target design and of the properties of hydrogen is required in order to interpret the state of the system. For this experiment, it is essential that the hydrogen be kept mostly in the para state in order to prevent the beam from being significantly depolarized before capture. Since the uncatalyzed conversion rate is slow, an ortho-para conversion loop is used to promote conversion from the room temperature orthohydrogen fraction to the fraction associated with the temperatures of the cryogenic vessel. In addition to the calibration and characterization studies, a method is introduced for placing an empirical limit on the deviation of the orthohydrogen fraction inside the vessel from the desired level associated with the temperature of the ortho-para conversion catalyst and vessel. This method, which does not require precise knowledge of the parahydrogen cross section, involves observing the transmission of the beam through the target while the rate of flow of hydrogen through the ortho-para conversion loop is changed. In addition to the studies of the hydrogen target, this dissertation discusses a calibration of some 3He ion chambers that monitor the flux of the neutron beam and that are used to perform beam transmission measurements. This calibration, which involves a study of the noise inherent in the signal due to neutron capture, does not involve comparison to a separate calibrated detector.

Gillis, Robert Chat

394

Practical issues in target tracking  

NASA Astrophysics Data System (ADS)

This dissertation is on three topics in target tracking: the effect of radar/sonar waveforms on tracking performance, a modified probabilistic data association filter (PDAF) based on a Bayes detector and sufficient conditions for the matrix Cramer-Rao lower bound (CRLB) scaling due to measurements of uncertain origin. In the first part (chapter 2), the effect of radar/sonar waveforms on tracking performance is investigated. The traditional approach for tracking system design is to treat the detection and tracking subsystems as independent units. However, the two subsystems can be designed jointly to obtain better tracking performance. Different waveforms, sidelobe-reduction techniques and measurement-extraction schemes are explored from the detection-tracking system point of view via the hybrid conditional averaging (HYCA) technique. The second part (chapter 3) is on a modified PDAF based on a Bayes detector. Existing detection systems generally operate using a fixed threshold, optimized to the Neyman-Pearson criterion. An alternative is Bayes detection, in which the threshold varies according to the ratio of prior probabilities. In a recursive target tracker such as the PDAF such priors are available in the form of a predicted location and associated covariance. A new PDAF with a Bayes detector is developed. The third part (chapter 4) deals with the matrix CRLB scaling due to measurements of uncertain origin. In many target tracking situations measurements are of uncertain origin. That is, at each scan a number of measurements are obtained, and it is not known which, if any, of these is target-originated. In several earlier papers the surprising observation was made that the CRLB for the estimation of a fixed parameter vector that characterizes the target motion, for the special case of measurements in the presence of additive white Gaussian noise, is simply a multiple of that for the case with no uncertainty. This is particularly useful as it allows comparison in terms of a scalar. This result is explored to determine how wide the class of such problems is. It includes many non-Gaussian situations.

Niu, Ruixin

395

Pharmacological treatment of alcohol dependence: target symptoms and target mechanisms.  

PubMed

Alcoholism is a major public health problem and resembles, in many ways, other chronic relapsing medical conditions. At least 2 separate dimensions of its symptomatology offer targetable pathophysiological mechanisms. Systems that mediate positive reinforcement by alcohol are likely important targets in early stages of the disease, particularly in genetically susceptible individuals. In contrast, long term neuroadaptive changes caused by chronic alcohol use primarily appear to affect systems mediating negative affective states, and gain importance following a prolonged history of dependence. Feasibility of pharmacological treatment in alcoholism has been demonstrated by a first wave of drugs which consists of 3 currently approved medications, the aldehyde dehydrogenase blocker disulfiram, the opioid antagonist naltrexone (NTX) and the functional glutamate antagonist acamprosate (ACM). The treatment toolkit is likely to be expanded in the near future. This will improve overall efficacy and allow individualized treatment, ultimately taking in account the patient's genetic makeup. In a second wave, early human efficacy data are available for the 5HT3 antagonist ondansetron, the GABA-B agonist baclofen and the anticonvulsant topiramate. The third wave is comprised of compounds predicted to be effective based on a battery of animal models. Using such models, a short list of additional targets has accumulated sufficient preclinical validation to merit clinical development. These include the cannabinoid CB1 receptor, receptors modulating glutamatergic transmission (mGluR2, 3 and 5), and receptors for stress-related neuropeptides corticotropin releasing factor (CRF), neuropeptide Y (NPY) and nociceptin. Once novel treatments are developed, the field faces a major challenge to assure their delivery to patients. PMID:16545872

Heilig, Markus; Egli, Mark

2006-09-01

396

Targeting Cancer with Antisense Oligomers  

SciTech Connect

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

DJ Hnatowich

2008-10-28

397

Targeting inhibitory neurotransmission in tinnitus  

PubMed Central

Tinnitus perception depends on the presence of its neural correlates within the auditory neuraxis and associated structures. Targeting specific circuits and receptors within the central nervous system in an effort to relieve the perception of tinnitus and its impact on one’s emotional and mental state has become a focus of tinnitus research. One approach is to upregulate endogenous inhibitory neurotransmitter levels (e.g. glycine and GABA) and selectively target inhibitory receptors in key circuits to normalize tinnitus pathophysiology. Thus, the basic functional and molecular properties of two major ligand-gated inhibitory receptor systems, the GABAA receptor (GABAAR) and glycine receptor (GlyR) are described. Also reviewed is the rationale for targeting inhibition which stems from reported tinnitus-related homeostatic plasticity of inhibitory neurotransmitter systems and associated enhanced neuronal excitability throughout most central auditory structures. However, the putative role of the medial geniculate body (MGB) in tinnitus has not been previously addressed, specifically in terms of its inhibitory afferents from inferior colliculus and thalamic reticular nucleus and its GABAAR functional heterogeneity. This heterogeneous population of GABAARs, which may be altered in tinnitus pathology, and its key anatomical position in the auditory CNS make the MGB a compelling structure for tinnitus research. Finally, some selective compounds, which enhance tonic inhibition, have successfully ameliorated tinnitus in animal studies, suggesting that the MGB and, to a lesser degree, the auditory cortex may be their primary locus of action. These pharmacological interventions are examined, in terms of their mechanism of action and why these agents, may be effective in tinnitus treatment. PMID:22405692

Richardson, Ben D.; Brozoski, Thomas J.; Ling, Lynne L.; Caspary, Donald M.

2012-01-01

398

Envisaging bacteria as phage targets  

PubMed Central

It can be difficult to appreciate just how small bacteria and phages are or how large, in comparison, the volumes that they occupy. A single milliliter, for example, can represent to a phage what would be, with proper scaling, an “ocean” to you and me. Here I illustrate, using more easily visualized macroscopic examples, the difficulties that a phage, as a randomly diffusing particle, can have in locating bacteria to infect. I conclude by restating the truism that the rate of phage adsorption to a given target bacterium is a function of phage density, that is, titer, in combination with the degree of bacterial susceptibility to adsorption by an encountering phage. PMID:23616932

Abedon, Stephen T.

2011-01-01

399

Electromagnetic Scattering from Realistic Targets  

NASA Technical Reports Server (NTRS)

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.

Lee, Shung- Wu; Jin, Jian-Ming

1997-01-01

400

Cascaded target normal sheath acceleration  

SciTech Connect

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.

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. [State Key Laboratory of High Field Laser Physics, Shanghai Institute of Optics and Fine Mechanics, Chinese Academy of Sciences, Shanghai 201800 (China)] [State Key Laboratory of High Field Laser Physics, Shanghai Institute of Optics and Fine Mechanics, Chinese Academy of Sciences, Shanghai 201800 (China)

2013-11-15

401

Approaching Rock Target No. 1  

NASA Technical Reports Server (NTRS)

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.

2004-01-01

402

Properties and identification of antibiotic drug targets  

PubMed Central

Background We analysed 48 non-redundant antibiotic target proteins from all bacteria, 22 antibiotic target proteins from E. coli only and 4243 non-drug targets from E. coli to identify differences in their properties and to predict new potential drug targets. Results When compared to non-targets, bacterial antibiotic targets tend to be long, have high ?-sheet and low ?-helix contents, are polar, are found in the cytoplasm rather than in membranes, and are usually enzymes, with ligases particularly favoured. Sequence features were used to build a support vector machine model for E. coli proteins, allowing the assignment of any sequence to the drug target or non-target classes, with an accuracy in the training set of 94%. We identified 319 proteins (7%) in the non-target set that have target-like properties, many of which have unknown function. 63 of these proteins have significant and undesirable similarity to a human protein, leaving 256 target like proteins that are not present in humans. Conclusions We suggest that antibiotic discovery programs would be more likely to succeed if new targets are chosen from this set of target like proteins or their homologues. In particular, 64 are essential genes where the cell is not able to recover from a random insertion disruption. PMID:20406434

2010-01-01

403

Bioengineering Strategies for Designing Targeted Cancer Therapies  

PubMed Central

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

Wen, Xuejun

2014-01-01

404

Automatic target recognition of time critical moving targets using 1D high range resolution (HRR) radar  

Microsoft Academic Search

Synthetic aperture radar (SAR) imaging and automatic target recognition (ATR) of moving targets pose a significant challenge due to the inherent difficulty of focusing moving targets. As a result, ATR of moving targets has received increased interest. High range resolution (HRR) radar mode offers an approach for recognizing moving targets by forming focused HRR profiles with significantly enhanced target-to-(clutter+noise) (T\\/(C+N))

R. Williams; J. Westerkamp; D. Gross; A. Palomion; T. Fister

1999-01-01

405

Seismoelectric imaging of shallow targets  

USGS Publications Warehouse

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.

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

2007-01-01

406

Multifunction sensor for target recognition  

NASA Astrophysics Data System (ADS)

The U.S. Army has a critical need for the capability provided by a multifunction sensor. This is (in effect) a smart sensor system that can adapt to environmental conditions and adjust its mode of operation to effectively counter any threat it meets. It will have an intelligent signal processor which has all of the system's sensor signals to choose from. The processor chooses the appropriate signal information to rapidly detect, acquire, track, and automatically identify all targets in the vicinity of the sensor under a wide variety of battlefield scenarios and environmental conditions. The multiphenomenology signal information provides the flexibility to overcome the adverse effects of clutter, countermeasures (both active and passive), illumination, obscurants, target orientation, and weather. It should be noted, however, that the types of sensory information required is dependent on the mission and the operating environment. For instance, a strategic defense sensor operating in space can use (and will need) different types of sensor data than the multifunction sensor employed on an attack helicopter. In fact, the sensor configuration on a helicopter operating in Saudi Arabia may be quite different from one that is deployed to Vietnam. For the purpose of this paper we generalize about the technologies desired for an adaptable, `smart' sensor system. We do not specify a particular mission nor define a specific threat. However, in any case, we can assume the need to fuse sensor signal information in an intelligent processor to provide robust performance in the battlefield environment. 12

James, William M.; Lindberg, Perry C.

1993-09-01

407

Aptamer-targeted Antigen Delivery  

PubMed Central

Effective therapeutic vaccines often require activation of T cell-mediated immunity. Robust T cell activation, including CD8 T cell responses, can be achieved using antibodies or antibody fragments to direct antigens of interest to professional antigen presenting cells. This approach represents an important advance in enhancing vaccine efficacy. Nucleic acid aptamers present a promising alternative to protein-based targeting approaches. We have selected aptamers that specifically bind the murine receptor, DEC205, a C-type lectin expressed predominantly on the surface of CD8?+ dendritic cells (DCs) that has been shown to be efficient at facilitating antigen crosspresentation and subsequent CD8+ T cell activation. Using a minimized aptamer conjugated to the model antigen ovalbumin (OVA), DEC205-targeted antigen crosspresentation was verified in vitro and in vivo by proliferation and cytokine production by primary murine CD8+ T cells expressing a T cell receptor specific for the major histocompatibility complex (MHC) I-restricted OVA257–264 peptide SIINFEKL. Compared with a nonspecific ribonucleic acid (RNA) of similar length, DEC205 aptamer-OVA-mediated antigen delivery stimulated strong proliferation and production of interferon (IFN)-? and interleukin (IL)-2. The immune responses elicited by aptamer-OVA conjugates were sufficient to inhibit the growth of established OVA-expressing B16 tumor cells. Our results demonstrate a new application of aptamer technology for the development of effective T cell-mediated vaccines. PMID:24682172

Wengerter, Brian C; Katakowski, Joseph A; Rosenberg, Jacob M; Park, Chae Gyu; Almo, Steven C; Palliser, Deborah; Levy, Matthew

2014-01-01

408

String theory in target space  

E-print Network

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.

Rutger H. Boels; Tobias Hansen

2014-02-25

409

Nanoparticles for targeting the infarcted heart  

E-print Network

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 ...

Dvir, Tal

410

28 CFR 55.17 - Targeting.  

Code of Federal Regulations, 2010 CFR

...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...

2010-07-01

411

28 CFR 55.17 - Targeting.  

Code of Federal Regulations, 2011 CFR

...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...

2011-07-01

412

Review of the Renewable Energy Target  

E-print Network

Review of the Renewable Energy Target Response to Expert Panel's Call for Submissions Paper #12;NSW Government Submission to the Review of the Renewable Energy Target, May 2014 2/20 Contents EXECUTIVE SUMMARY........................................................................................................................... 3 RENEWABLE ENERGY IN NSW

Peters, Richard

413

Combining Targeted Therapies for Metastatic Colorectal Cancer  

Cancer.gov

In this trial, researchers are combining the targeted monoclonal antibody cetuximab (Erbitux) with another targeted drug called sorafenib (Nexavar) to treat patients with metastatic colorectal cancer whose tumors show epidermal growth factor receptor (EGFR) activity.

414

Encapsulated Target for Isotope Production Cyclotrons  

NASA Astrophysics Data System (ADS)

The current solid isotope production targets at TRIUMF can only be used to irradiate metallic materials with high melting point. In order to irradiate liquids, powders, and materials with low melting point, a new encapsulated target is being developed specifically for use on isotope production cyclotrons. This concentrically water-cooled target must withstand a 240 microA @ 30 MeV proton beam. The target is a round container with a pocket to hold the target material; the target material is encapsulated using a thin foil which is electron-beam welded on the target. The cooling and the heat-induced stresses of the target are being analyzed using finite element methods. The results will then be compared with actual measurements obtained using surface embedded thermocouples. The paper discusses the results and the current status of the project.

Bakhtiari, Shervin; Gelbart, William Z.; Ho, Wendy; Stevenson, Nigel R.

1997-05-01

415

47 CFR 10.450 - Geographic targeting.  

Code of Federal Regulations, 2010 CFR

...COMMUNICATIONS COMMISSION GENERAL COMMERCIAL MOBILE ALERT SYSTEM Alert Message Requirements § 10.450 Geographic targeting...establishes minimum requirements for the geographic targeting of Alert Messages. A Participating CMS Provider will...

2010-10-01

416

47 CFR 10.450 - Geographic targeting.  

Code of Federal Regulations, 2011 CFR

...COMMUNICATIONS COMMISSION GENERAL COMMERCIAL MOBILE ALERT SYSTEM Alert Message Requirements § 10.450 Geographic targeting...establishes minimum requirements for the geographic targeting of Alert Messages. A Participating CMS Provider will...

2011-10-01

417

47 CFR 10.450 - Geographic targeting.  

Code of Federal Regulations, 2013 CFR

...COMMUNICATIONS COMMISSION GENERAL WIRELESS EMERGENCY ALERTS Alert Message Requirements § 10.450 Geographic targeting...establishes minimum requirements for the geographic targeting of Alert Messages. A Participating CMS Provider will...

2013-10-01

418

47 CFR 10.450 - Geographic targeting.  

Code of Federal Regulations, 2012 CFR

...COMMUNICATIONS COMMISSION GENERAL COMMERCIAL MOBILE ALERT SYSTEM Alert Message Requirements § 10.450 Geographic targeting...establishes minimum requirements for the geographic targeting of Alert Messages. A Participating CMS Provider will...

2012-10-01

419

Machine Intelligence Technology for Automatic Target Recognition.  

National Technical Information Service (NTIS)

Automatic target recognition (ATR)-the use of computer processing to detect and identify targets (such as tanks, howitzers, and armored personnel carriers) automatically-is becoming critically important in several military applications. ATR systems can re...

J. G. Verly, R. L. Delanoy, D. E. Dudgeon

1989-01-01

420

TargetRNA2: identifying targets of small regulatory RNAs in bacteria  

PubMed Central

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

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

2014-01-01

421

Direct drive fuel target optimization in HIF  

NASA Astrophysics Data System (ADS)

This study investigates a target for heavy ion fusion (HIF) using light target materials. In this study, the target structure, the heavy ion beam (HIB) input pulse shape and the HIB input pulse energy are optimized for the maximal fusion energy output. We performed two-dimensional fluid implosion simulations to obtain a high pellet gain. The optimized target shows a high yield of a gain 223. The input Pb beam energy is 1.8 MJ.

Koseki, S.; Kawata, S.; Hisatomi, Y.; Kurosaki, T.; Barada, D.; Ogoyski, A. I.

2013-11-01

422

Nanoparticle and targeted systems for cancer therapy  

Microsoft Academic Search

This review explores recent work directed towards more targeted treatment of cancer, whether through more specific anti-cancer agents or through methods of delivery. These areas include delivery by avoiding the reticuloendothelial system, utilizing the enhanced permeability and retention effect and tumor-specific targeting. Treatment opportunities using antibody-targeted therapies are summarized. The ability to treat cancer by targeting delivery through angiogenesis is

Lisa Brannon-Peppas; James O. Blanchette

2004-01-01

423

Algorithm research of infrared target recognition  

Microsoft Academic Search

Target recognition is an important content of computer intelligent vision surveillance system. A method of joint transform recognition is proposed for identifying and tracking the target from the infrared thermal image, which based on wavelet packet, Laplace operator and Fourier transform. The experimental result shows that the algorithm has a good performance in real-time, moreover, it can recognize the target

Wenzhe Liu; Wensheng Wang; Yongli Ma

2010-01-01

424

Categorically Defined Targets Trigger Spatiotemporal Visual Attention  

ERIC Educational Resources Information Center

Transient attention to a visually salient cue enhances processing of a subsequent target in the same spatial location between 50 to 150 ms after cue onset (K. Nakayama & M. Mackeben, 1989). Do stimuli from a categorically defined target set, such as letters or digits, also generate transient attention? Participants reported digit targets among…

Wyble, Brad; Bowman, Howard; Potter, Mary C.

2009-01-01

425

Species of Redundancy in Visual Target Detection  

ERIC Educational Resources Information Center

We report a series of investigations into the effects of common names, physical identity, and physical similarity on visual detection time. The effect of these factors on the capacity of the system processing the signals was also examined. We used a redundant targets design with separate testing of the target-distractor (single target),…

Ben-David, Boaz M.; Algom, Daniel

2009-01-01

426

Eye and head movements to auditory targets  

Microsoft Academic Search

Three adult female monkeys were trained to direct their gaze toward auditory targets. When the animals were free to move their heads about the vertical axis, this was accomplished with shortlatency, coordinated eye-head movements reminiscent of responses to visual targets. The similarity of response to auditory and visual targets suggests a common motor program elicited by stimuli of different modalities.

D. A. Whittington; M.-C. Hepp-Reymond; W. Flood

1981-01-01

427

Characterization of COROT seismology targets Claude Catala  

E-print Network

Characterization of COROT seismology targets Claude Catala Observatoire Midi­Pyrâ??enâ??ees, Toulouse, France ABSTRACT We have started to build preliminary entry catalogues of potential targets for the COROT/H], v sin i, etc...) of the 1,100 potential targets of the COROT central and exploratory

Demoulin, Pascal

428

Predicting new molecular targets for known drugs  

E-print Network

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

Kaski, Samuel

429

Alternative Splicing: Therapeutic Target and Tool  

Microsoft Academic Search

Alternative splicing swells the coding capacity of the human genome, expanding the pharmacoproteome, the proteome that provides targets for ther- apy. Splicing, both constitutive and regulated forms, can itself be targeted by conventional and molecular therapies. This review focuses on splicing as a therapeutic target with a particular emphasis on molecular approaches. The review looks at the use of antisense

Mariano A. Garcia-Blanco

430

Electromagnetic Scattering From Foliage Camouflaged Complex Targets  

Microsoft Academic Search

In this paper, a hybrid target-foliage model based on existing electromagnetic techniques is developed to investigate the scattering behavior of hard targets embedded inside a forest canopy at high frequencies. The proposed model is composed of two basic scattering models, one for foliage and the other for the hard targets. The connection between these two models, which accounts for the

Mojtaba Dehmollaian; Kamal Sarabandi

2006-01-01

431

Automatic target identification using neural networks  

Microsoft Academic Search

Neural network theories are applied to attain human-like performance in areas such as speech recognition, statistical mapping, and target recognition or identification. In target identification, one of the difficult tasks has been the extraction of features to be used to train the neural network which is subsequently used for the target's identification. The purpose of this paper is to describe

Mahmoud A. Abdallah; Tayib I. Samu; William A. Grissom

1995-01-01

432

Proprioceptive information about target location suppresses autokinesis  

NASA Technical Reports Server (NTRS)

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.

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

1977-01-01

433

Gene targeting in adult rhesus macaque fibroblasts  

Microsoft Academic Search

BACKGROUND: Gene targeting in nonhuman primates has the potential to produce critical animal models for translational studies related to human diseases. Successful gene targeting in fibroblasts followed by somatic cell nuclear transfer (SCNT) has been achieved in several species of large mammals but not yet in primates. Our goal was to establish the protocols necessary to achieve gene targeting in

Daniel T Meehan; Mary Ann Zink; Melissa Mahlen; Marilu Nelson; Warren G Sanger; Shoukhrat M Mitalipov; Don P Wolf; Michel M Ouellette; Robert B Norgren Jr

2008-01-01

434

Dynamic nuclear polarization of irradiated targets  

Microsoft Academic Search

We have irradiated and studied dynamic nuclear polarization in ammonia, deuterated ammonia, butanol, borane ammonia, methylamine, ethane and lithium borohydride in order to test these substances for potential use as polarized target materials. These studies were conducted using a polarized target system operating at a temperature of 1K and a magnetic field of 5T. The target system was set up

M. L. Seely; A. Amittay; M. R. Bergstrom; S. K. Dhawan; V. W. Hughes; R. F. Oppenheim; K. P. Schueler; P. A. Souder; K. Kondo; S. Miyashita; K. Morimoto; S. J. St. Lorant; Y.-N. Guo; A. Winnacker

1983-01-01

435

Gene Therapy Targeting HIV Entry  

PubMed Central

Despite the unquestionable success of antiretroviral therapy (ART) in the treatment of HIV infection, the cost, need for daily adherence, and HIV-associated morbidities that persist despite ART all underscore the need to develop a cure for HIV. The cure achieved following an allogeneic hematopoietic stem cell transplant (HSCT) using HIV-resistant cells, and more recently, the report of short-term but sustained, ART-free control of HIV replication following allogeneic HSCT, using HIV susceptible cells, have served to both reignite interest in HIV cure research, and suggest potential mechanisms for a cure. In this review, we highlight some of the obstacles facing HIV cure research today, and explore the roles of gene therapy targeting HIV entry, and allogeneic stem cell transplantation in the development of strategies to cure HIV infection. PMID:24662607

Didigu, Chuka; Doms, Robert

2014-01-01

436

Tensor Target Polarization at TRIUMF  

NASA Astrophysics Data System (ADS)

The first measurements of tensor observables in ?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 ?vec d elastic scattering were measured: T20, T21, and T22. The vector analyzing power iT11 was also measured. These results led to a better understanding of the three-body theory used to describe this reaction. 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°cm in the ?vec d ? 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.

Smith, G.

2014-10-01

437

Fabrication of boron sputter targets  

DOEpatents

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.

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

1995-01-01

438

Fabrication of boron sputter targets  

DOEpatents

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.

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

1995-02-28

439

Synchronous identification of friendly targets  

DOEpatents

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.

Telle, John M. (126 Shady Oak Cir., Tijeras, NM 87059); Roger, Stutz A. (5 Kiowa La., Los Alamos, NM 87544)

1998-01-01

440

Targeting Pili in Enterococcal Pathogenesis  

PubMed Central

Passive protection, the administration of antibodies to prevent infection, has garnered significant interest in recent years as a potential prophylactic countermeasure to decrease the prevalence of hospital-acquired infections. Pili, polymerized protein structures covalently anchored to the peptidoglycan wall of many Gram-positive pathogens, are ideal targets for antibody intervention, given their importance in establishing infection and their accessibility to antibody interactions. In this work, we demonstrated that a monoclonal antibody to the major component of Enterococcus faecalis pili, EbpC, labels polymerized pilus structures, diminishes biofilm formation, and significantly prevents the establishment of a rat endocarditis infection. The effectiveness of this anti-EbpC monoclonal provides strong evidence in support of its potential as a preventative. In addition, after radiolabeling, this monoclonal identified the site of enterococcal infection, providing a rare example of molecularly specific imaging of an established bacterial infection and demonstrating the versatility of this agent for use in future diagnostic and therapeutic applications. PMID:24452680

Pinkston, Kenneth L.; Singh, Kavindra V.; Gao, Peng; Wilganowski, Nathaniel; Robinson, Holly; Ghosh, Sukhen; Azhdarinia, Ali; Sevick-Muraca, Eva M.; Murray, Barbara E.

2014-01-01

441

Apoptosis: Targets in Pancreatic Cancer  

PubMed Central

Pancreatic adenocarcinoma is characterized by poor prognosis, because of late diagnosis and lack of response to chemo- and/or radiation therapies. Resistance to apoptosis mainly causes this insensitivity to conventional therapies. Apoptosis or programmed cell death is a central regulator of tissue homeostasis. Certain genetic disturbances of apoptotic signaling pathways have been found in carcinomas leading to tumor development and progression. In the past few years, the knowledge about the complex pathways of apoptosis has strongly increased and new therapeutic approaches based on this knowledge are being developed. This review will focus on the role of apoptotic proteins contributing to pancreatic cancer development and progression and will demonstrate possible targets to influence this deadly disease. PMID:12605713

Westphal, Sabine; Kalthoff, Holger

2003-01-01

442

Dendritic Cell-Targeted Vaccines  

PubMed Central

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

Cohn, Lillian; Delamarre, Lelia

2014-01-01

443

Terahertz-based target typing.  

SciTech Connect

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.

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

2008-09-01

444

Genomic targeting with purified Cre recombinase.  

PubMed Central

Purified Cre recombinase protein introduced directly into cultured mammalian cells by lipofection catalyzes both site-specific chromosomal integration of a co-transfected lox targeting vector and precise excision of genomic DNA flanked by directly repeated lox sites. This procedure eliminates the need to transfect cre expression plasmids to activate recombination at lox sites. We used this simplified procedure to investigate the effect on targeting efficiency of both lox vector design and chromosomal position of the lox target. We show that such chromosomal position effects can exert at least a 50-fold per lox target difference in targeting efficiency in a human osteosarcoma cell line. Images PMID:8502542

Baubonis, W; Sauer, B

1993-01-01

445

Design considerations for targeted optical contrast agents  

PubMed Central

Optical fluorescence imaging with the right combination of imaging modality and targeted contrast agents offers tremendous improvement in intraoperative imaging and clinical output (i.e., image-guided cancer surgery). Therefore, it is of paramount importance to gain an in-depth knowledge in the design of targeted contrast agents to meet clinical requirements. Currently, there are several clinically approved contrast agents available; however, none perform optimally in vivo by providing optimum sensitivity, stability, specificity, and safety for target imaging, diagnosis, and therapy. In this review, we discuss basic design considerations for targeted contrast agents in terms of optical and physicochemical properties, biological and physiological interactions, and biodistribution and targeting. PMID:23289086

Lee, Jeong Heon; Park, Gwangli; Hong, Gloria H.; Choi, Jungmun

2012-01-01

446

Ignition of deuterium-tritium fuel targets  

DOEpatents

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.

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

1991-08-27

447

Ignition of deuterium-trtium fuel targets  

DOEpatents

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.

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

1991-01-01

448

Molecular targeting to treat gastric cancer  

PubMed Central

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.

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

2014-01-01

449

Liquid Hydrogen Target Experience at SLAC  

SciTech Connect

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.

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

2005-08-29

450

Confidence-driven infrared target detection  

NASA Astrophysics Data System (ADS)

The confidence of target detection can be used to evaluate the reliability and risk level of the detected targets and can effective help to exclude the false alarms, but very little investigation was involved in the past. In this letter, a confidence-driven infrared target detection method is proposed. We develop three confidence evaluating methods: (1) the median classification confidence of the cascade classifier; (2) the context confidence based on the number and the confidence of the merged detection rectangles around the detected target; and (3) the contrast confidence based on the difference between the detected target distribution and the around background distribution. The three confidences are combined to form the final confidence of the detected targets. We then use the confidence to refine the localization of the targets. The evaluation using real infrared images demonstrates the good performance of the proposed confidence-driven infrared detection algorithm on both undetected error and false alarm.

Zhang, Zhiguo; Liu, Liman; Tao, Wenbing; Tang, Yuanyan

2014-09-01

451

The target implant method for predicting target difficulty and detector performance in hyperspectral imagery  

Microsoft Academic Search

The utility of a hyperspectral image for target detection can be measured by synthetically implanting target spectra in the image and applying detection algorithms.1 In this paper we apply this method, called the target implant method, for the purpose of determining the top performing algorithms for a given image and given target and for determining the relative difficulty for detection

William F. Basener; Eric Nance; John Kerekes

2011-01-01

452