Scintigraphic appearances of Gaucher's disease

International Nuclear Information System (INIS)

Okada, Junichi; Uchiyama, Guio; Hayakawa, Kazushige; Araki, Tsutomu; Hayashi, Sanshin; Yamada, Kayoko; Seto, Kazuhiko

1985-01-01

Gaucher's disease is an inborn error of metabolism in which glucocerebroside accumlates within reticuloendotherial cells of spleen, liver and bone marrow. The scintigraphic appearances are described in a 19-year-old man with Gaucher's disease. The colloid scan showed increased uptake in the lung and bone marrow of legs where the reticuloendotherial system was activated. The bone scan demonstrated increased activity in the metaphyseal and diaphyseal region infiltrated by Gaucher's cell. Ga-67 was thought to be accumlated in the progressive focus of the disease. (author)

Timing of initiation of enzyme replacement therapy after diagnosis of type 1 Gaucher disease: effect on incidence of avascular necrosis

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Mistry, Pramod K; Deegan, Patrick; Vellodi, Ashok; Cole, J Alexander; Yeh, Michael; Weinreb, Neal J

2009-01-01

Data from the International Collaborative Gaucher Group Gaucher Registry were analysed to assess the relationship between enzyme replacement therapy with imiglucerase (ERT) and incidence of avascular necrosis (AVN) in type 1 Gaucher disease (GD1), and to determine whether the time interval between diagnosis and initiation of ERT influences the incidence rate of AVN. All patients with GD1 enrolled in the Gaucher Registry who received ERT and did not report AVN prior to starting therapy (n = 2700) were included. The incidence rate of AVN following initiation of ERT was determined. An incidence rate of AVN of 13·8 per 1000 person-years was observed in patients receiving ERT. Patients who initiated ERT within 2 years of diagnosis had an incidence rate of 8·1 per 1000 person-years; patients who started ERT ≥2 years after diagnosis had an incidence rate of 16·6 per 1000 person-years. The adjusted incidence rate ratio was 0·59 [95% confidence interval (CI) 0·36–0·96, P = 0·0343]. Splenectomy was an independent risk factor for AVN (adjusted incidence rate ratio 2·23, 95% CI 1·61–3·08, P < 0·0001). In conclusion, the risk of AVN was reduced among patients who initiated ERT within 2 years of diagnosis, compared to initiating treatment ≥2 years after diagnosis. A higher risk of AVN was observed among patients who had previously undergone splenectomy. PMID:19732054

[Type 3 Gaucher disease, also an adult disease?

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Leurs, A; Chepy, A; Detonellaere, C; Pascal, L; Gallois, P; Tran, T-A-C; Caillaud, C; Hatron, P-Y; Rose, C

2018-03-30

Gaucher disease is a genetic lysosomal storage disorder due to a glucocerebrosidase deficiency. Type 3, including neurological impairment, may have a specific phenotype in the context of the D409H mutation. We report the case of a 22-year-old woman who presented with Gaucher disease. Enzyme replacement therapy by imiglucerase was followed by rapid clinical and biological improvement. However, communication difficulties, which were initially attributed to the language barrier, revealed neurological impairment. After complementary assessment, the diagnosis of type 3 Gaucher disease was suspected. Gene analysis of the glucocerebrosidase showed a homozygous D409H mutation. This mutation results in calcified heart valves, corneal opacities, alteration of oculomotricity and hydrocephalus. The mild manifestation at onset and the late neurological involvement in the medical history make the diagnosis more difficult. This particular clinical phenotype deserves to be known in adult medicine departments. Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Perinatal-lethal Gaucher disease presenting as hydrops fetalis.

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BenHamida, Emira; Ayadi, Imene; Ouertani, Ines; Chammem, Maroua; Bezzine, Ahlem; BenTmime, Riadh; Attia, Leila; Mrad, Ridha; Marrakchi, Zahra

2015-01-01

Perinatal-lethal Gaucher disease is very rare and is considered a variant of type 2 Gaucher disease that occurs in the neonatal period. The most distinct features of perinatal-lethal Gaucher disease are non-immune hydrops fetalis. Less common signs of the disease are hepatosplenomegaly, ichthyosis and arthrogryposis. We report a case of Gaucher's disease (type 2) diagnosed in a newborn who presented with Hydrops Fetalis.

Gaucher disease: a model disorder for biomarker discovery

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Boot, Rolf G; van Breemen, Mariëlle J; Wegdam, Wouter

2009-01-01

Gaucher disease is an inherited lysosomal storage disorder, characterized by massive accumulation of glucosylceramide-laden macrophages in the spleen, liver and bone marrow as a consequence of deficient activity of glucocerebrosidase. Gaucher disease has been the playground to develop new therape...... in clinical management of Gaucher patients are discussed. Moreover, the use of several modern proteomic technologies for the identification of Gaucher biomarkers is reviewed....

A familial concurrence of schizophrenia and Gaucher's disease

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Siomos Konstantinos E

2007-12-01

Full Text Available Abstract Background Gaucher's disease (GD is the most frequently encountered lysosomal storage disease. Here, we describe and discuss the observed concurrence of schizophrenia and Gaucher's disease in two siblings. Methods Presentation of a family with two siblings with Gaucher's disease. Results In a six-member family, the first son suffers from schizophrenia, while the third and fourth sons suffer from the Gaucher's disease (type 1 non-neuronopathic. The parents and the second son do not suffer from either illness. Conclusion The concurrence of schizophrenia and Gaucher's disease in the same family is an unusual phenomenon. The literature regarding this coincidence is limited, despite the fact that patients with Gaucher's disease have one or two mutated alleles, considered to be a risk factor leading to conditions such as Dementia, Parkinson's disease and schizophrenia.

Hemorrhagic Aspects of Gaucher Disease

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Hanna Rsenbaum

2014-10-01

Full Text Available Gaucher disease (GD is an inherited lysosomal disorder, originating from deficient activity of the lysosomal enzyme glucocerebrosidase (GCase. Normally, GCase hydrolyzes glucocerebroside (GC to glucose and ceramide; however, impaired activity of this enzyme leads to the accumulation of GC in macrophages, termed “Gaucher cells.” Gaucher disease is associated with hepatosplenomegaly, cytopenias, skeletal complications and in some forms involves the central nervous system. Coagulation abnormalities are common among GD patients due to impaired production and chronic consumption of coagulation factors. Bleeding phenomena are variable (as are other symptoms of GD and include mucosal and surgical hemorrhages. Four main etiological factors account for the hemostatic defect in GD: thrombocytopenia, abnormal platelet function, reduced production of coagulation factors, and activation of fibrinolysis. Thrombocytopenia relates not only to hypersplenism and decreased megakaryopoiesis by the infiltrated bone marrow but also to immune thrombocytopenia. Autoimmunity, especially the induction of platelet antibody production, might cause persistent thrombocytopenia. Enzyme replacement therapy reverses only part of the impaired coagulation system in Gaucher disease. Other therapeutic and supportive measures should be considered to prevent and/or treat bleeding in GD. Gaucher patients should be evaluated routinely for coagulation abnormalities especially prior to surgery and dental and obstetric procedures.

Gaucher disease with jawbone involvement: a case report.

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Ahmadieh, Azadeh; Farnad, Fariborz; Sedghizadeh, Parish P

2014-11-05

Gaucher disease is an autosomal recessive systemic condition, and the most common of the lysosomal storage disorders. It is characterized by lipid accumulation in certain cells and organs, particularly macrophages, which appear on light microscopy as 'Gaucher cells' or vacuolated lipid-laden reticuloendothelial cells. Long bone involvement is common in Gaucher disease, whereas craniofacial bone involvement is extremely rare. Reports confirming the diagnoses of Gaucher disease involving craniofacial bones by histopathologic evidence are even rarer. A 46-year-old Caucasian Ashkenazi Jewish woman with Gaucher disease presented with jawbone pain and lytic radiographic lesions of her mandible. Surgical biopsy of a mandibular lesion revealed Gaucher cells infiltrating the mandible, which correlated with radiographic and clinical findings, supporting a diagnosis of Gaucher disease with jawbone involvement. Lysosomal storage diseases can have head and neck manifestations, and bone involvement in Gaucher disease is common. Therefore, careful consideration of signs and symptoms and medical history, with a thorough review of systems, is important when evaluating patients with lysosomal storage disorders to rule out head and neck involvement of disease. Biopsy may be warranted in some cases for more definitive diagnosis of painful jawbone lesions and to rule out other odontogenic and non-odontogenic conditions in the differential diagnosis.

Thalassaemia Trait with Gaucher Disease: A Diagnostic Dilemma.

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Kini, Jyoti Ramnath; Sreeram, Saraswathy; Hegde, Anupama; Kamath, Sowmini; Pai, Radha Ramachandra

2017-09-01

Gaucher Disease is an autosomal recessive disease caused by the accumulation of glucocerebrosidase due to deficiency in lysosomal glucocerebrosidase. Thalassaemia trait is asymptomatic and is usually an incidental diagnosis. Both thalassaemia and Gaucher disease can have similar haematologic manifestations and hence, their coexistence causes diagnostic dilemma. Our patient presented at one-and-a-half years with weakness, pallor, failure to thrive and massive hepatosplenomegaly. Clinical examination and history pointed to a lipid storage disease. Peripheral smear revealed microcytic hypochromic cells and nucleated red cells with haemolytic blood picture. Thalassaemia trait was indicated on haemoglobin variant analysis using High Performance Liquid Chromatography. Liver biopsy, bone marrow aspirate and therapeutic splenectomy revealed Gaucher-like cells. Type 1 Gaucher disease can be clinically asymptomatic as well as present with massive liver and spleen enlargement and involvement of bone marrow. Anaemia, splenomegaly and thrombocytopenia are the usual presentations at diagnosis, similar to the haemoglobinopathies. Gaucher-like cells with normal beta-glucocerebrosidase (pseudo-Gaucher cells) are seen in thalassaemia, leukaemia, mycobacterial infections and myeloma. Gaucher disease coexisting with thalassaemia trait is uncommon. We report the occurrence of thalassaemia trait and Gaucher disease in a child, which resulted in confusion regarding the haematological diagnosis. This report highlights the necessity of independent establishment of the diagnosis in every patient so that appropriate management decisions are taken.

Morbus gaucher: A report of two cases

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Đokić Milomir

2006-01-01

Full Text Available Backround. Clinical features of inherited glucocerebrosidase deficiency were first described by Phillippe Charles Ernest Gaucher, French physician (1854-1918. Deficiency of glucocerebrosidase leads to the accumulation of the lipid glucocerebroside within the lysosomes of the monocyte macrophage system. Lipid-laden cells, known as Gaucher cells, lead to hepatosplenomegaly, multiorgan dysfunction and sceletal deterioration. Case report. We reported a 36- year-old male and a 42-year-old female admitted for the clinical examination due to hepatosplenomegaly. The Clinical diagnosis was provided by a bone marrow examination and demonstration of the characteristic Gaucher cells. Both of the patients had type I Gaucher's disease (a mild form of the disease, which is distinguished by the lack of central nervous system involvement and striking phenotypic variation. We had not a possibility of testing β-glucocerebrosidase activity in peripheral leukocytes (a definitive diagnosis of Gaucher's disease. Also, enzyme replacement therapy had not been available in our country. Conclusion. Althoungh rare, Gaucher's disease is also present in our country. Both molecular genetic, and the enzyme β-glucocerebrosidase activity testing in peripheral leukocytes are needed for the definitive diagnosis of this disease.

Mandibular and Dental Manifestations of Gaucher Disease

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Saranjam, Hamid R.; Sidransky, Ellen; Levine, William Z.; Zimran, Ari; Elstein, Deborah

2012-01-01

Gaucher disease is a systemic lysosomal storage disorder with a high prevalence among Ashkenazi Jews. It is caused by an inherited deficiency of the lysosomal enzyme glucocerebrosidase. Common signs and symptoms include hepatosplenomegaly, anemia, thrombocytopenia, and skeletal involvement. Oral and dental manifestations are less commonly seen. These manifestations are often asymptomatic, although they may be detected by routine dental x-rays. There are several case reports and a few larger series published describing patients with Gaucher disease who have mandibulo-maxillofacial involvement. This review aims to examine the oral manifestations observed in Gaucher disease and to suggest practical guidelines for dealing with these often worrisome signs. Among the critical issues are the benign nature of Gaucher cell infiltration of the mandible and the critical importance of being prepared for post-procedure bleeding and/or infections. Therefore, it is essential that dental practitioners be aware of the possible oral and dental complications of Gaucher disease, as well as the available treatment modalities. PMID:22251146

Renal involvement in Gaucher's disease.

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Siegal, A.; Gutman, A.; Shapiro, M. S.; Griffel, B.

1981-01-01

A patient with chronic Gaucher's disease is described who developed glomerulopathy 24 years after splenectomy terminating in renal failure. The pathological changes of this very rare complication of Gaucher's disease are described. The few similar cases reported in the literature are reviewed and the possible pathogenetic pathways discussed. Images Fig. 1 Fig. 2 Fig. 3 PMID:7301691

Liver involvement in Gaucher disease - Review and clinical approach.

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Adar, Tomer; Ilan, Yaron; Elstein, Deborah; Zimran, Ari

2018-02-01

Gaucher disease (GD), one of the most prevalent lysosomal storage diseases, is associated with glucocerebroside accumulation in cells of the monocyte-macrophage system in various organs, including the liver. Evaluating and managing liver disease in patients with Gaucher disease may be challenging. While hepatic involvement is common in Gaucher disease, its severity, and clinical significance span a wide spectrum, ranging from sub-clinical involvement to liver cirrhosis with its associated complications including portal hypertension. Apart from liver involvement in Gaucher disease, patients with may also suffer from other comorbidities involving the liver. That Gaucher disease itself can mimic hepatic lesions, affect laboratory tests used to characterize liver disease, and may be associated with non-cirrhotic portal hypertension, complicates the diagnostic approach even more. Better understanding of liver involvement in Gaucher disease can spare patients unnecessary invasive testing, and assist physicians in decision making when evaluating patients with Gaucher disease suspected for significant liver disease. This review describes the various clinical manifestations, laboratory and imaging abnormalities that may be encountered when following patients with Gaucher disease for liver involvement. The mechanism for liver disease are discussed, as well as the possible hepato-protective effect of glucocerebroside, and the a diagnostic and treatment approaches. Copyright © 2016 Elsevier Inc. All rights reserved.

Gaucher disease and the synucleinopathies: refining the relationship

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Campbell Tessa N

2012-01-01

Full Text Available Abstract Gaucher disease (OMIM 230800, 230900, 231000, the most common lysosomal storage disorder, is due to a deficiency in the enzyme glucocerebrosidase. Gaucher patients display a wide spectrum of clinical presentation, with hepatosplenomegaly, haematological changes, and orthopaedic complications being the predominant symptoms. Gaucher disease is classified into three broad phenotypes based upon the presence or absence of neurological involvement: Type 1 (non-neuronopathic, Type 2 (acute neuronopathic, and Type 3 (subacute neuronopathic. Nearly 300 mutations have been identified in Gaucher patients, with the majority being missense mutations. Though studies of genotype-to-phenotype correlations have revealed significant heterogeneity, some consistent patterns have emerged to inform prognostic and therapeutic decisions. Recent research has highlighted a potential role for Gaucher disease in other comorbidities such as cancer and Parkinson's Disease. In this review, we will examine the potential relationship between Gaucher disease and the synucleinopathies, a group of neurodegenerative disorders characterized by the development of intracellular aggregates of α-synuclein. Possible mechanisms of interaction will be discussed.

Unexpected macrophage-independent dyserythropoiesis in Gaucher disease.

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Reihani, Nelly; Arlet, Jean-Benoit; Dussiot, Michael; de Villemeur, Thierry Billette; Belmatoug, Nadia; Rose, Christian; Colin-Aronovicz, Yves; Hermine, Olivier; Le Van Kim, Caroline; Franco, Melanie

2016-12-01

Gaucher disease is a rare inherited disease caused by a deficiency in glucocerebrosidase leading to lipid accumulation in cells of mononuclear-macrophage lineage known as Gaucher cells. Visceral enlargement, bone involvement, mild anemia and thrombocytopenia are the major manifestations of Gaucher disease. We have previously demonstrated that the red blood cells from patients exhibit abnormal properties, which indicates a new role in Gaucher disease pathophysiology. To investigate whether erythroid progenitors are affected, we examined the in vitro erythropoiesis from the peripheral CD34 + cells of patients and controls. CD34- cells were differentiated into macrophages and co-cultivated with erythroblasts. We showed an accelerated differentiation of erythroid progenitors without maturation arrest from patients compared to controls. This abnormal differentiation persisted in the patients when the same experiments were performed without macrophages, which strongly suggested that dyserythropoiesis in Gaucher disease is secondary to an inherent defect in the erythroid progenitors. The accelerated differentiation was associated with reduced cell proliferation. As a result, less mature erythroid cells were generated in vitro in the Gaucher disease cultures compared to the control. We then compared the biological characteristics of untreated patients according to their anemic status. Compared to the non-anemic group, the anemic patients exhibit higher plasma levels of growth differentiation factor-15, a marker of ineffective erythropoiesis, but they had no indicators of hemolysis and similar reticulocyte counts. Taken together, these results demonstrated an unsuspected dyserythropoiesis that was independent of the macrophages and could participate, at least in part, to the basis of anemia in Gaucher disease. Copyright© Ferrata Storti Foundation.

Efferocytosis is impaired in Gaucher macrophages.

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Aflaki, Elma; Borger, Daniel K; Grey, Richard J; Kirby, Martha; Anderson, Stacie; Lopez, Grisel; Sidransky, Ellen

2017-04-01

Gaucher disease, the inherited deficiency of lysosomal glucocerebrosidase, is characterized by the presence of glucosylceramide-laden macrophages resulting from impaired digestion of aged erythrocytes or apoptotic leukocytes. Studies of macrophages from patients with type 1 Gaucher disease with genotypes N370S/N370S, N370S/L444P or N370S/c.84dupG revealed that Gaucher macrophages have impaired efferocytosis resulting from reduced levels of p67 phox and Rab7. The decreased Rab7 expression leads to impaired fusion of phagosomes with lysosomes. Moreover, there is defective translocation of p67 phox to phagosomes, resulting in reduced intracellular production of reactive oxygen species. These factors contribute to defective deposition and clearance of apoptotic cells in phagolysosomes, which may have an impact on the inflammatory response and contribute to the organomegaly and inflammation seen in patients with Gaucher disease. Copyright© Ferrata Storti Foundation.

Twenty years of treatment for Gaucher disease: emerging challenges

NARCIS (Netherlands)

van Dussen, L.

2014-01-01

Gaucher disease is an autosomal recessively inherited lysosomal storage disorder (LSD). Type I Gaucher disease, the so-called non-neuronopathic variant, is mainly characterised by cytopenia, hepatosplenomegaly and bone complications. Gaucher disease was the first LSD for which enzyme replacement

Dental profile of patients with Gaucher disease

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Fischman, Stuart L; Elstein, Deborah; Sgan-Cohen, Harold; Mann, Jonathan; Zimran, Ari

2003-01-01

Background This study was conducted to determine whether patients with Gaucher disease had significant dental pathology because of abnormal bone structure, pancytopenia, and coagulation abnormalities. Methods Each patient received a complete oral and periodontal examination in addition to a routine hematological evaluation. Results Gaucher patients had significantly fewer carious lesions than otherwise healthy carriers. Despite prevalence of anemia, there was no increase in gingival disease; despite the high incidence of thrombocytopenia, gingival bleeding was not noted; and despite radiological evidence of bone involvement, there was no greater incidence loss of teeth or clinical tooth mobility. Conclusions These data represent the first survey of the oral health of a large cohort of patients with Gaucher disease. It is a pilot study of a unique population and the results of the investigation are indications for further research. Based on our findings, we recommend regular oral examinations with appropriate dental treatment for patients with Gaucher disease as for other individuals. Consultation between the dentist and physician, preferably one with experience with Gaucher disease, should be considered when surgical procedures are planned. PMID:12875661

Radiological aspects of Gaucher disease

International Nuclear Information System (INIS)

Katz, Robert; Booth, Tom; Hargunani, Rikin; Wylie, Peter; Holloway, Brian

2011-01-01

Advances in imaging and the development of commercially available enzyme therapy have significantly altered the traditional radiology of Gaucher disease. The cost of treatment and need for monitoring response to therapy have magnified the importance of imaging. There are no recent comprehensive reviews of the radiology of this relatively common lysosomal storage disease. This article describes the modern imaging, techniques and radiological manifestations of Gaucher disease. (orig.)

Radiological aspects of Gaucher disease

Energy Technology Data Exchange (ETDEWEB)

Katz, Robert; Booth, Tom; Hargunani, Rikin; Wylie, Peter; Holloway, Brian [Royal Free Hospital, Radiology Department, London (United Kingdom)

2011-12-15

Advances in imaging and the development of commercially available enzyme therapy have significantly altered the traditional radiology of Gaucher disease. The cost of treatment and need for monitoring response to therapy have magnified the importance of imaging. There are no recent comprehensive reviews of the radiology of this relatively common lysosomal storage disease. This article describes the modern imaging, techniques and radiological manifestations of Gaucher disease. (orig.)

Extraosseous manifestation of Gaucher's disease type I: MR and histological appearance

International Nuclear Information System (INIS)

Poll, L.W.; Koch, J.A.; Moedder, U.

2000-01-01

Gaucher's disease type I is the most prevalent lysosomal storage disorder caused by an autosomal-recessive inherited deficiency of glucocerebrosidase activity with secondary accumulation of glucocerebrosides within the lysosomes of macrophages. The storage disorder produces a multisystem disease characterized by progressive visceral enlargement and gradual replacement of bone marrow with lipid-laden macrophages. Skeletal disease is a major source of disability in Gaucher's disease. Extraosseous extension of Gaucher cells is an extremely rare manifestation of skeletal Gaucher's disease. This is a report on the MRI and histopathological findings of an extraosseous Gaucher-cell extension into the midface in a patient with Gaucher's disease. (orig.)

Gauchers sygdom

DEFF Research Database (Denmark)

Leth, Peter Mygind; Knudsen, Ida Mølgård

1987-01-01

Gaucher's disease is an autosomal recessive disease due to deficiency of the enzyme glucocerebrosidase with subsequent accumulation of glucocerebroside in the reticuloendothelial system. The disease is subdivided into Types 1, 2 and 3. Type 1 is associated with hepatosplenomegaly and lesions...

Tc-99m-sestamibi scintigraphy in gaucher disease, type 1

International Nuclear Information System (INIS)

Park, Chan H.; Pai, Moon S.; Ha, Man J.; Yoon, S. N.; Kim, S.; Whang, K. H.; Kim, Hyun J.

1999-01-01

Gaucher disease is an autosomal recessive disorder characterized by lysosomal glycolipid storage in reticuloendothelial cells due to the deficiency of lysosomal enzyme, acid-glucosidase. Type 1 is one of the three subtypes of Gaucher disease and is manifested by a chronic and progressive involvement of the spleen, liver, bone marrow and other visceral organs. This study was done to see imaging feasibility of bone marrow involvement of Gaucher cells using sestamibi. Five patients with Gaucher disease, type I (M:F=4:1, age range: 9-25) underwent a simultaneous anterior and posterior whole body scan as well as spot views of the lower extremities as needed in 10-20 min following the IV administration of 0.2 mCi/kg of Tc-99m-sestamibi. Control group consisted of 10 patients with osteosarcoma, simple bone cyst, nonossifying fibroma, osteoid osteoma, exostosis and neuroblastoma ( M: F=9:1, age range: 2-20, mean : 12.1) and sestamibi images of the group were obtained as in Gaucher cases. For in vitro evaluation, Gaucher cells were isolated from the splenectomy specimen. The cells were incubated in media containing sestamibi for 10, 29, 30 min. After washing the cells twice with saline, cell labeling was checked by external counting. Control group depicted no appreciable sestamibi uptake in the lower extremities while 5 patients with Gaucher disease, type I revealed variable degrees of sestamibi uptake. It was difficult to assess vertebral activities due to hepatosplenomegaly. Ioslated Gaucher cells took up sestamibi supported by an increasing external counting in proportion to incubation time. There was sestamibi uptake in the lower extremities involved by Gaucher disease, type I, which was distinctly different from the control group. Also in vitro study revealed sestamibi uptake in Gaucher cells. On the basis of these results, we believe, it may be possible to evaluate enzyme replacement therapy in Gaucher disease, type I, utilizing sestamibi scintiscan

Tc-99m-sestamibi scintigraphy in gaucher disease, type 1

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Park, Chan H.; Pai, Moon S.; Ha, Man J.; Yoon, S. N.; Kim, S.; Whang, K. H.; Kim, Hyun J. [College of Medicine, Ajou Univ., Suwon (Korea, Republic of)

1999-07-01

Gaucher disease is an autosomal recessive disorder characterized by lysosomal glycolipid storage in reticuloendothelial cells due to the deficiency of lysosomal enzyme, acid-glucosidase. Type 1 is one of the three subtypes of Gaucher disease and is manifested by a chronic and progressive involvement of the spleen, liver, bone marrow and other visceral organs. This study was done to see imaging feasibility of bone marrow involvement of Gaucher cells using sestamibi. Five patients with Gaucher disease, type I (M:F=4:1, age range: 9-25) underwent a simultaneous anterior and posterior whole body scan as well as spot views of the lower extremities as needed in 10-20 min following the IV administration of 0.2 mCi/kg of Tc-99m-sestamibi. Control group consisted of 10 patients with osteosarcoma, simple bone cyst, nonossifying fibroma, osteoid osteoma, exostosis and neuroblastoma ( M: F=9:1, age range: 2-20, mean : 12.1) and sestamibi images of the group were obtained as in Gaucher cases. For in vitro evaluation, Gaucher cells were isolated from the splenectomy specimen. The cells were incubated in media containing sestamibi for 10, 29, 30 min. After washing the cells twice with saline, cell labeling was checked by external counting. Control group depicted no appreciable sestamibi uptake in the lower extremities while 5 patients with Gaucher disease, type I revealed variable degrees of sestamibi uptake. It was difficult to assess vertebral activities due to hepatosplenomegaly. Ioslated Gaucher cells took up sestamibi supported by an increasing external counting in proportion to incubation time. There was sestamibi uptake in the lower extremities involved by Gaucher disease, type I, which was distinctly different from the control group. Also in vitro study revealed sestamibi uptake in Gaucher cells. On the basis of these results, we believe, it may be possible to evaluate enzyme replacement therapy in Gaucher disease, type I, utilizing sestamibi scintiscan.

Gaucher disease. Unusual presentation and mini-review.

Science.gov (United States)

Rizk, Tamer M; Ariganjoye, Rafiu O; Alsaeed, Gihad I

2015-07-01

We aim to describe an 8-year-old boy with an unusual clinical presentation of Gaucher disease (GD). Gaucher disease is a progressive lysosomal storage disorder due to deficiency of the specific enzyme glucocerebrosidase with varying clinical features, but often involving the monocytes-macrophages systems. This child ran a progressive course with a devastating outcome. Three distinct GD subtypes have been described with varying clinical features based on the presence or absence of neurologic involvement. Gaucher disease diagnosis is obtained via: enzyme activity assay, gene mutation study, bone marrow aspiration in addition to multiple other tests that have been successfully used in diagnosis of cases of GD. Treatment modalities include enzyme replacement treatment, substrate reduction therapy, bone marrow transplantation, blood transfusion, and surgery are available management modalities for GD. Gaucher disease is a chronic disease requiring a multidisciplinary team approach with regular follow up with multiple subspecialties.

Growth and final height of children with Gaucher disease: A 15-year follow-up at an Israeli Gaucher center.

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Mendelsohn, Espen; Meir, Amos; Abrahamov, Aya; Elstein, Deborah; Zimran, Ari; Levy-Khademi, Floris

2018-02-01

It is held that enzyme replacement therapy (ERT) accelerates the growth rate in children with Gaucher disease, but its effect on final height has not been established with certainty. This study presents final heights of Gaucher patients followed up for 15years. The study included 41 adults with non-neuronopathic Gaucher disease. The final height of the patients and age at puberty was compared to their mid-parental target height and to their siblings' heights. Mean final height standard deviation score (HSDS) in the patients was -0.22, but none of the patients was abnormally short (HSDS of less than -2.2). Mean age at menarche of the female patients (14.7years) was significantly delayed compared to that of their mothers (P=0.0005), and mean age at first shaving in the boys was 16years. Our study showed that the mean final height of Gaucher patients fell below the mean of the 2000 CDC growth charts, but the patients were not of short stature (height less than the 3rd percentile). ERT treatment did not significantly impact the mean final HSDS. The onset of puberty, as indicated by the age at menarche, was delayed in girls with Gaucher disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Therapeutic goals in the treatment of Gaucher disease

NARCIS (Netherlands)

Pastores, Gregory M.; Weinreb, Neal J.; Aerts, Hans; Andria, Generoso; Cox, Timothy M.; Giralt, Manuel; Grabowski, Gregory A.; Mistry, Pramod K.; Tylki-Szymańska, Anna

2004-01-01

Gaucher disease, the most common lysosomal storage disorder, is a heterogeneous multisystem condition. Patients with non-neuronopathic (type 1) Gaucher disease may suffer from hepatomegaly, splenomegaly, thrombocytopenia, bleeding tendencies, anemia, hypermetabolism, skeletal pathology, growth

[An adult form of type-I. Gaucher's disease].

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Múzes, G; Pitlik, E; Gohér, A; Somogyi, A; Tulassay, Z

2000-03-26

A young woman with no previous history of any diseases was admitted for further evaluation of a mild thrombocytopenia she has had for some months. No signs of bleeding have so far occurred. Physical examination was normal except for a moderately enlarged spleen. Routine investigations showed lower platelet count. There was no laboratory evidence of disease conditions with autoimmune/inflammatory or hematologic origin. Bone marrow aspirate indicated Gaucher's-like cells raising the suspicion of Gaucher's disease. This was further supported by electron microscopic demonstration of Gaucher's bodies (with the characteristic tubular structures) in crista biopsy specimens. However, definitive diagnosis was obtained by verifying deficient lysosomal glucosylceramide-beta-D-glucosidase activity in peripheral blood leukocytes. Upon the absence of neurologic involvement the patient was typical for the adult form or type-1 Gaucher's disease.

Prevalence of autoantibodies in the course of Gaucher disease type 1: A multicenter study comparing Gaucher disease patients to healthy subjects.

Science.gov (United States)

Serratrice, Christine; Bensalah, Nesma; Penaranda, Guillaume; Bardin, Nathalie; Belmatoug, Nadia; Masseau, Agathe; Rose, Christian; Lidove, Olivier; Camou, Fabrice; Maillot, François; Leguy, Vanessa; Magy-Bertrand, Nadine; Marie, Isabelle; Cherin, Patrick; Bengherbia, Monia; Carballo, Sebastian; Boucraut, José; Serratrice, Jacques; Berger, Marc; Verrot, Denis

2018-01-01

Type 1 Gaucher disease may be related to the presence of autoantibodies. Their clinical significance is questioned. Primary endpoint was to compare the prevalence of autoantibodies in type 1 Gaucher disease patients with healthy subjects, seeking correlations with autoimmune characteristics. Secondary endpoints were to determine whether patients with autoantibodies reported autoimmunity-related symptoms and if genotype, splenectomy or treatment influenced autoantibodies presence. Type 1 Gaucher disease patients and healthy volunteers were included in this national multicenter exploratory study. Autoantibodies presence was compared in both groups and assessed regarding to genotype, splenectomy, Gaucher disease treatment and autoimmunity-related symptoms. Twenty healthy subjects and 40 type 1 Gaucher disease patients were included. Of the studied group: 15 patients undergone splenectomy, 37 were treated either with enzyme replacement therapy (34) or with substrate reduction therapy (3), 25 were homozygous/heterozygous for the N370S mutation. In type 1 Gaucher disease group (studied group), 52% had positive autoantibodies versus 26% in control group. Antiphospholipid antibodies were more frequent in the studied group (30% vs. 5%), but without correlation to thrombosis, osteonecrosis or bone infarcts. In the studied group, antinuclear antibodies were more frequent (25% vs. 16%). None of the patients with autoantibodies had clinical manifestations of autoimmune diseases. Autoantibodies were not correlated with treatment, genotype, or splenectomy, except for anticardiolipid, more frequent in splenectomized patients. In type 1 Gaucher disease, autoantibodies were more frequent compared to a healthy population. However, they were not associated with an increased prevalence of clinical active autoimmune diseases. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Long-term clinical outcomes in type 1 Gaucher disease following 10 years of imiglucerase treatment.

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Weinreb, Neal J; Goldblatt, Jack; Villalobos, Jacobo; Charrow, Joel; Cole, J Alexander; Kerstenetzky, Marcelo; vom Dahl, Stephan; Hollak, Carla

2013-05-01

We studied the effect of long-term alglucerase/imiglucerase (Ceredase®/Cerezyme®, Genzyme, a Sanofi company, Cambridge, MA, USA) treatment on hematological, visceral, and bone manifestations of Gaucher disease type 1 (GD1). The International Collaborative Gaucher Group (ICGG) Gaucher Registry identified GD1 patients treated with alglucerase/imiglucerase who had dose and clinical data at first infusion and after 10 years of follow-up. Data for hemoglobin, platelet count, organ volumes, bone pain, and bone crisis were analyzed. Tests of the null hypothesis (no change from first infusion to 10 years) were performed using t tests for within-patient absolute change in continuous measurements and McNemar/chi-square tests for change in distributions using categorical values. An alpha level of 0.05 designated statistical significance. As of October 2011, 557 nonsplenectomized and 200 splenectomized patients met the inclusion criteria. The majority of GD1 patients had at least one N370S allele. Compared with nonsplenectomized patients at first infusion, splenectomized patients had lower percentages of anemia (26.0 % vs. 42.8 %) and thrombocytopenia (14.2 % vs. 76.3 %), similar percentages of moderate or severe hepatomegaly (81.2 % vs. 80.0 %), and higher percentages of bone pain (88.9 % vs. 52.4 %) and bone crises (38.3 % vs. 16.0 %). After 10 years, both groups showed significant (p < 0.05) improvements in mean hemoglobin levels, platelet count, liver, and spleen (nonsplenectomized) volumes, and bone crises. Initial dosing in both groups ranged from <15 U/kg to ≤90 U/kg every 2 weeks. After 10 years, the majority was receiving 15 to ≤45 U/kg every 2 weeks. Ten years of imiglucerase treatment results in sustainable improvements in all GD1 parameters.

Consensus Conference: A reappraisal of Gaucher disease - diagnosis and disease management algorithms

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Mistry, Pramod K.; Cappellini, Maria Domenica; Lukina, Elena; Özsan, Hayri; Pascual, Sara Mach; Rosenbaum, Hanna; Solano, Maria Helena; Spigelman, Zachary; Villarrubia, Jesús; Watman, Nora Patricia; Massenkeil, Gero

2010-01-01

Type 1 (non neuronopathic) Gaucher disease was the first lysosomal storage disorder for which an effective enzyme replacement therapy was developed and it has become a prototype for treatments for related orphan diseases. There are currently four treatment options available to patients with Gaucher disease, nevertheless, almost 25% of type 1 Gaucher patients do not gain timely access to therapy because of delays in diagnosis after the onset of symptoms. Diagnosis of Gaucher disease by enzyme testing is unequivocal, but the rarity of the disease and non-specific and heterogeneous nature of Gaucher disease symptoms may impede consideration of this disease in the differential diagnosis. To help promote timely diagnosis and optimal management of the protean presentations of Gaucher disease, a consensus meeting was convened to develop algorithms for diagnosis and disease management for Gaucher disease. PMID:21080341

Thromboelastography as a Surrogate Marker of Perisurgical Hemostasis in Gaucher Disease.

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Ioscovich, Alexander; Fadeev, Dmitri; Kenet, Gili; Naamad, Mira; Schtrechman, Gal; Zimran, Ari; Elstein, Deborah

2016-10-01

Thromboelastography (TEG) has long been available for routine monitoring of perisurgical and postpartum hemostasis, especially at point of care. The purpose of this study is to retrospectively compare TEG parameters to concomitant standard clotting test results in an unselected cohort of patients with Gaucher disease to ascertain whether TEG values are specific and sensitive enough to substitute for classic coagulation tests for decision making. This remains a cogent concern because of high incidence of thrombocytopenia in patients with Gaucher disease. Thromboelastography values were compared to concomitant platelet counts, partial thromboplastin time, international normalization ratio, and plasma fibrinogen. Demographic characteristics were collected from patients' files. There were 22 patients with Gaucher disease (2 children; 12.5%) for whom there were 24 TEG results at the same time as classic coagulation test results and 30% performed platelet function tests. The current study shows linear and/or monotonic relationships between platelet counts and several TEG values that were significant over a range of platelet counts including severe thrombocytopenia. The fibrinogen component, correlating only with the rate of clot lysis, played a lesser role. Based on these preliminary results albeit in a small cohort with only 1 case of hemorrhage, there is putative support for the intention to treat patients with Gaucher disease based on TEG results using the same TEG protocol as for other patients undergoing comparable procedures in our institution. © The Author(s) 2015.

Type I Gaucher disease: extraosseous extension of skeletal disease

International Nuclear Information System (INIS)

Poll, L.W.; Koch, J.A.; Moedder, U.; Dahl, S. vom; Haeussinger, D.; Sarbia, M.; Niederau, C.

2000-01-01

Objective. To investigate the frequency and morphology of extraosseous extension in patients with Gaucher disease type I.Design and patients. MRI examinations of the lower extremities were analyzed in 70 patients with Gaucher disease type I. Additionally, the thoracic spine and the midface were investigated on MRI in two patients.Results. Four cases are presented in which patients with Gaucher disease type I and severe skeletal involvement developed destruction or protrusion of the cortex with extraosseous extension into soft tissues. In one patient, Gaucher cell deposits destroyed the cortex of the mandible and extended into the masseter muscle. In the second patient, multiple paravertebral masses with localized destruction of the cortex were apparent in the thoracic spine. In the third and fourth patient, cortical destruction with extraosseous tissue extending into soft tissues was seen in the lower limbs.Conclusions. Extraosseous extension is a rare manifestation of Gaucher bone disease. While an increased risk of cancer, especially hematopoietic in origin, is known in patients with Gaucher disease, these extraosseous benign manifestations that may mimic malignant processes should be considered in the differential diagnosis of extraosseous extension into soft tissues. A narrow neck of tissue was apparent in all cases connecting bone and extraosseous extensions. (orig.)

Gaucher disease: Progress and ongoing challenges.

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Mistry, Pramod K; Lopez, Grisel; Schiffmann, Raphael; Barton, Norman W; Weinreb, Neal J; Sidransky, Ellen

Over the past decades, tremendous progress has been made in the field of Gaucher disease, the inherited deficiency of the lysosomal enzyme glucocerebrosidase. Many of the colossal achievements took place during the course of the sixty-year tenure of Dr. Roscoe Brady at the National Institutes of Health. These include the recognition of the enzymatic defect involved, the isolation and characterization of the protein, the localization and characterization of the gene and its nearby pseudogene, as well as the identification of the first mutant alleles in patients. The first treatment for Gaucher disease, enzyme replacement therapy, was conceived of, developed and tested at the Clinical Center of the National Institutes of Health. Advances including recombinant production of the enzyme, the development of mouse models, pioneering gene therapy experiments, high throughput screens of small molecules and the generation of induced pluripotent stem cell models have all helped to catapult research in Gaucher disease into the twenty-first century. The appreciation that mutations in the glucocerebrosidase gene are an important risk factor for parkinsonism further expands the impact of this work. However, major challenges still remain, some of which are described here, that will provide opportunities, excitement and discovery for the next generations of Gaucher investigators. Published by Elsevier Inc.

Juvenile Gaucher disease simulating osteomyelitis

International Nuclear Information System (INIS)

Miller, J.H.; Ortega, J.A.; Heisel, M.A.

1981-01-01

A case in which several imaging procedures suggested juvenile Gaucher disease in a child who presented with symptomatology of osteomyelitis is discussed. The 20-month girl was given a Technetium-99m radionuclide skeletal examination which revealed intense uptake of tracer agents along the shaft of the right femur. It was also found that the liver and spleen were dramatically Ga-67 avid. The bone pain symptomatology suggested an osteomyelitis of the femur, but skeletal scintigraphy with Tc-99m-labeled bone tracer demonstrated photopenic areas involving the femur, suggesting that the bone pain may have been due to marrow packed with Gaucher cells. This overexpansion of the marrow may lead to microfractures with remodeling seen radiographically as periosteal new bone and scintigraphically as increased periosteal deposition of tracer agent. The radiogallium study was useful to exclude an underlying osteomyelitis in the involved femurs. Although juvenile Gaucher disease is unusual, it should be considered in any child who presents with the constellation of hepatosplenomegaly and bone pain simulating osteomyelitis

Juvenile Gaucher disease simulating osteomyelitis

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Miller, J.H.; Ortega, J.A.; Heisel, M.A.

1981-10-01

A case in which several imaging procedures suggested juvenile Gaucher disease in a child who presented with symptomatology of osteomyelitis is discussed. The 20-month girl was given a Technetium-99m radionuclide skeletal examination which revealed intense uptake of tracer agents along the shaft of the right femur. It was also found that the liver and spleen were dramatically Ga-67 avid. The bone pain symptomatology suggested an osteomyelitis of the femur, but skeletal scintigraphy with Tc-99m-labeled bone tracer demonstrated photopenic areas involving the femur, suggesting that the bone pain may have been due to marrow packed with Gaucher cells. This overexpansion of the marrow may lead to microfractures with remodeling seen radiographically as periosteal new bone and scintigraphically as increased periosteal deposition of tracer agent. The radiogallium study was useful to exclude an underlying osteomyelitis in the involved femurs. Although juvenile Gaucher disease is unusual, it should be considered in any child who presents with the constellation of hepatosplenomegaly and bone pain simulating osteomyelitis.

Appendiceal involvement in a patient with Gaucher disease.

Science.gov (United States)

Kocic, Marija; Djuricic, Slavisa M; Djordjevic, Maja; Savic, Djordje; Kecman, Bozica; Sarajlija, Adrijan

2018-02-01

Almost any anatomical compartment may be involved in Gaucher disease (GD). Abdominal lymphadenopathy occurred during enzyme replacement therapy in more than a dozen children with GD so far. A fourteen-year-old boy from Serbia developed clinical signs of acute appendicitis six years after the onset of GD type 3 related abdominal lymphadenopathy. Ultrasound examination showed diffuse thickening of the intestinal wall in the ileocoecal region with periappendicular infiltration. An appendectomy was performed four months after conservative treatment with antibiotics. Histopathology revealed macrophages with cytological characteristics of Gaucher cells densely crammed in mesoappendiceal adipose tissue. Also the multifocal replacement of subserosal tissue by Gaucher cells and their infiltration to a variable depth of muscularis propria of the appendix were verified. Frank infiltration of the vermiform appendix with Gaucher cells represents a novel observation in a wide spectrum of manifestations reported in GD. A possible causative relationship of this infiltration with appendicitis is considered. Copyright © 2016 Elsevier Inc. All rights reserved.

The clinical management of Type 2 Gaucher disease.

Science.gov (United States)

Weiss, Karin; Gonzalez, Ashley; Lopez, Grisel; Pedoeim, Leah; Groden, Catherine; Sidransky, Ellen

2015-02-01

Gaucher disease, the inherited deficiency of the enzyme glucocerebrosidase, is the most common of the lysosomal storage disorders. Type 2 Gaucher disease, the most severe and progressive form, manifests either prenatally or in the first months of life, followed by death within the first years of life. The rarity of the many lysosomal storage disorders makes their diagnosis a challenge, especially in the newborn period when the focus is often on more prevalent illnesses. Thus, a heightened awareness of the presentation of these rare diseases is necessary to ensure their timely consideration. This review, designed to serve as a guide to physicians treating newborns and infants with Gaucher disease, discusses the presenting manifestations of Type 2 Gaucher disease, the diagnostic work-up, associated genotypes and suggestions for management. We also address the ethical concerns that may arise with this progressive and lethal disorder, since currently available treatments may prolong life, but do not impact the neurological manifestations of the disease. Published by Elsevier Inc.

A rare form of Gaucher disease resulting from saposin C deficiency.

Science.gov (United States)

Kang, Lulu; Zhan, Xia; Ye, Jun; Han, Lianshu; Qiu, Wenjuan; Gu, Xuefan; Zhang, Huiwen

2018-02-01

Gaucher disease is mainly caused by the deficiency of lysosomal acid β-glucosidase. Gaucher disease caused by the deficiency of saposin C is rare. Here we report a patient mainly presenting with hepatosplenomegaly, thrombocytopenia and anemia. EEG examination revealed increased theta waves. Gaucher cells identified in his bone marrow and the highly elevated plasma chitotriosidase activity and glucosylsphingosine supported a diagnosis of Gaucher disease. However, the leukocyte β-glucosidase activity was in a normal range. Sanger sequencing revealed a novel maternal exonic mutation c.1133C>G (p.Pro378Arg) in exon 10 of the PSAP gene, which codes the Sap C domain of PSAP protein. To search for other underlying mutations in this patient, whole genome sequencing was applied and revealed a deletion involving exon 2 to 7 of PSAP gene. The deletion appears as a de novo event on paternal chromosome. We concluded that biallelic mutations of PSAP gene were the cause of this patient's Gaucher disease. Our finding expands the mutation spectrum of Gaucher disease with saposin C deficiency. Copyright © 2017 Elsevier Inc. All rights reserved.

Mild thrombocytopenia as presenting symptom of type 1 Gauchers's disease.

Science.gov (United States)

Müzes, G; Pitlik, E; Somogyi, A; Tulassay, Z

2001-06-01

A young woman was examined for a mild thrombocytopenia which was present for some months. No signs of bleeding had so far occurred. Physical examination was normal except for a moderately enlarged spleen. Laboratory investigations showed a low platelet count. There was no evidence of an autoimmune or hematologic disease. Bone narrow aspirate indicated Gaucher's-like cells raising the suspicion of Gaucher's disease. This was further supported by electron microscopic demonstration of Gaucher's bodies in crista biopsy specimens. However, the definitive diagnosis was obtained by verifying deficient lysosomal glucosylceramide-beta-D-glucosidase activity in peripheral blood leukocytes. Upon the absence of neurologic involvement the patient was typical for the adult-onset or type 1 form of Gaucher's disease.

Quantification of glucosylceramide in plasma of Gaucher disease patients

Directory of Open Access Journals (Sweden)

Maria Viviane Gomes Muller

2010-12-01

Full Text Available Gaucher disease is a sphingolipidosis that leads to an accumulation of glucosylceramide. The objective of this study was to develop a methodology, based on the extraction, purification and quantification of glucosylceramide from blood plasma, for use in clinical research laboratories. Comparison of the glucosylceramide content in plasma from Gaucher disease patients, submitted to enzyme replacement therapy or otherwise, against that from normal individuals was also carried out. The glucosylceramide, separated from other glycosphingolipids by high performance thin layer chromatography (HPTLC was chemically developed (CuSO4 / H3PO4 and the respective band confirmed by immunostaining (human anti-glucosylceramide antibody / peroxidase-conjugated secondary antibody. Chromatogram quantification by densitometry demonstrated that the glucosylceramide content in Gaucher disease patients was seventeen times higher than that in normal individuals, and seven times higher than that in patients on enzyme replacement therapy. The results obtained indicate that the methodology established can be used in complementary diagnosis and for treatment monitoring of Gaucher disease patients.A doença de Gaucher é uma esfingolipidose caracterizada pelo acúmulo de glicosilceramida. O objetivo deste estudo foi desenvolver metodologia baseada na extração, purificação e quantificação da glicosilceramida plasmática a qual possa ser usada em laboratórios de pesquisa clínica. Após o desenvolvimento desta metodologia, foi proposto, também, comparar o conteúdo de glicosilceramida presente no plasma de pacientes com doença de Gaucher, submetidos ou não a tratamento, com aquele de indivíduos normais. A glicosilceramida, separada de outros glicoesfingolipídios por cromatografia de camada delgada de alto desempenho (HPTLC, foi revelada quimicamente (CuSO4/H3PO4 e a respectiva banda foi confirmada por imunorrevelação (anticorpo anti-glicosilceramida humana

Identification of a biomarker in cerebrospinal fluid for neuronopathic forms of Gaucher disease.

Science.gov (United States)

Zigdon, Hila; Savidor, Alon; Levin, Yishai; Meshcheriakova, Anna; Schiffmann, Raphael; Futerman, Anthony H

2015-01-01

Gaucher disease, a recessive inherited metabolic disorder caused by defects in the gene encoding glucosylceramidase (GlcCerase), can be divided into three subtypes according to the appearance of symptoms associated with central nervous system involvement. We now identify a protein, glycoprotein non-metastatic B (GPNMB), that acts as an authentic marker of brain pathology in neurological forms of Gaucher disease. Using three independent techniques, including quantitative global proteomic analysis of cerebrospinal fluid (CSF) in samples from Gaucher disease patients that display neurological symptoms, we demonstrate a correlation between the severity of symptoms and GPNMB levels. Moreover, GPNMB levels in the CSF correlate with disease severity in a mouse model of Gaucher disease. GPNMB was also elevated in brain samples from patients with type 2 and 3 Gaucher disease. Our data suggest that GPNMB can be used as a marker to quantify neuropathology in Gaucher disease patients and as a marker of treatment efficacy once suitable treatments towards the neurological symptoms of Gaucher disease become available.

Chronic pain in Gaucher disease: skeletal or neuropathic origin?

Science.gov (United States)

Devigili, Grazia; De Filippo, Michele; Ciana, Giovanni; Dardis, Andrea; Lettieri, Christian; Rinaldo, Sara; Macor, Daniela; Moro, Alessandro; Eleopra, Roberto; Bembi, Bruno

2017-08-31

Pain is one of the most disabling symptoms of Gaucher disease. It is referred by the majority of Gaucher patients and often persists despite long-term enzyme replacement treatment. It has been mainly considered as nociceptive pain secondary to skeletal involvement but it is described even in the absence of bone disease without a clear explanation. In the last years an increasing number of reports have described the presence of neurological manifestation in Gaucher type 1 patients, including subclinical large fibre neuropathy. In our Gaucher clinic we have observed the recurrence of painful symptoms in a group of type 1 Gaucher patients even after a long-term enzyme replacement therapy. A cross-sectional study was designed to investigate the pathophysiology of pain in a cohort of 25 Gaucher patients (13 females, 12 males). Twenty-two patients received enzyme replacement therapy for a period of time ranging from 10 to >20 years, while three were new diagnosis. Pain was classified as bone or neurologic related on the basis of anamnestic data, clinical and electrophysilogical examinations. Intensity and quality of pain were recorded by Douleur Neuropathique en 4 questionnaire and Neuropathic Pain Symptom Inventory. Neuroalgological evaluation, quantitative sensory testing, nerve conduction studies and evaluation of epidermal nerve fibres density were performed. Comorbidities for peripheral neuropathy were excluded. Thirteen patients complained of pain suggestive of neuropathic origin with proximal patchy distribution, six manifested severe pain paroxysmal, nine pinprick hypoesthesia and 17 thermal hypoesthesia. At quantitative sensory testing, all of them showed high cold thresholds with errata sensation (burning instead of cold), paradoxical heat sensation and mechanic hypoesthesia; three patients showed pressure pain hyperalgesia. Epidermal denervation was present in 19 patients, 12 of them with non-length dependent pattern. These results confirm the role of

Magnetic resonance spectroscopy in patients with Fabry and Gaucher disease

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Gruber, S., E-mail: stephan@nmr.at [Department of Radiology, MR-Centre of Excellence, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Bogner, W. [Department of Radiology, MR-Centre of Excellence, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Stadlbauer, A. [MR Physics Group, Department of Radiology, Landesklinikum St. Poelten (Austria); Krssak, M. [Department of Radiology, MR-Centre of Excellence, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Bodamer, O. [Department of Pediatrics, Medical University of Vienna (Austria)

2011-08-15

Objective: Fabry and Gaucher diseases are rare progressive inherited disorders of glycosphingolipid metabolism that affect multiple organ systems. The aim of this study was to investigate evidence for metabolic changes in the central nervous system involvement using proton magnetic resonance spectroscopic imaging. Methods: Seven Fabry and eight Gaucher patients were included into this study. A two-dimensional, spectroscopic imaging method with an ultra-short echo-time of 11 ms was used at a 3 T whole body magnet. Absolute metabolic values were retrieved using internal water scaling. Results were compared, with sex- and age-matched controls. Results: In contrast to previous findings, absolute and relative metabolite values of N-acetyl-aspartate (NAA) or NAA/Creatine (Cr), Cr, Choline (Cho) or Cho/Cr and myo-Inositol (mI) or mI/Cr revealed no, differences between Fabry and Gaucher Type 1 (GD1) patients and controls. Average values were, 10.22, 6.32, 2.15 and 5.39 mMol/kg wet weight for NAA, Cr, Cho and mI, respectively. In this study, we found significantly decreasing NAA/Cho with increasing age in all three groups (Fabry, GD1, patients and healthy controls) (between 5 and 8% per decade). Conclusions: There were no changes of the quantified metabolites detected by MRS in normal appearing white matter. This study shows the importance of sex- and age-matched controls.

Magnetic resonance spectroscopy in patients with Fabry and Gaucher disease

International Nuclear Information System (INIS)

Gruber, S.; Bogner, W.; Stadlbauer, A.; Krssak, M.; Bodamer, O.

2011-01-01

Objective: Fabry and Gaucher diseases are rare progressive inherited disorders of glycosphingolipid metabolism that affect multiple organ systems. The aim of this study was to investigate evidence for metabolic changes in the central nervous system involvement using proton magnetic resonance spectroscopic imaging. Methods: Seven Fabry and eight Gaucher patients were included into this study. A two-dimensional, spectroscopic imaging method with an ultra-short echo-time of 11 ms was used at a 3 T whole body magnet. Absolute metabolic values were retrieved using internal water scaling. Results were compared, with sex- and age-matched controls. Results: In contrast to previous findings, absolute and relative metabolite values of N-acetyl-aspartate (NAA) or NAA/Creatine (Cr), Cr, Choline (Cho) or Cho/Cr and myo-Inositol (mI) or mI/Cr revealed no, differences between Fabry and Gaucher Type 1 (GD1) patients and controls. Average values were, 10.22, 6.32, 2.15 and 5.39 mMol/kg wet weight for NAA, Cr, Cho and mI, respectively. In this study, we found significantly decreasing NAA/Cho with increasing age in all three groups (Fabry, GD1, patients and healthy controls) (between 5 and 8% per decade). Conclusions: There were no changes of the quantified metabolites detected by MRS in normal appearing white matter. This study shows the importance of sex- and age-matched controls.

Extraosseous extension of Gaucher cell deposits mimicking malignancy

International Nuclear Information System (INIS)

Hermann, G.; Shapiro, R.; Abdelwahab, I.F.; Klein, M.J.; Pastores, G.; Grabowski, G.

1994-01-01

Two cases are described in which patients with type I Gaucher disease developed extraosseous soft tissue masses consisting of Gaucher cell deposits. In one instance the mass destroyed the posterior cortex of the left distal femur and protruded into the soft tissues. In the second case the lesion involved the proximal tibia and gradually extended into the soft tissues. While the incidence of neoplastic disorder such as lymphoproliferative disease appears to be more common in Gaucher disease patients than in the general population, lesions of benign etiology that mimic these aggressive processes should be considered in the differential diagnosis when cortical destruction with coexisting soft tissue most is found in these patients. (orig.)

Extraosseous extension of Gaucher cell deposits mimicking malignancy

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Hermann, G. (Dept. of Radiology, Mount Sinai Medical Center of the City Univ. of New York, NY (United States)); Shapiro, R. (Dept. of Radiology, Mount Sinai Medical Center of the City Univ. of New York, NY (United States)); Abdelwahab, I.F. (Dept. of Radiology, Mount Sinai Medical Center of the City Univ. of New York, NY (United States)); Klein, M.J. (Dept. of Pathology, Mount Sinai Center of the City Univ. of New York, NY (United States)); Pastores, G. (Dept. of Human Genetics, Mount Sinai Medical Center of the City Univ. of New York, NY (United States)); Grabowski, G. (Cincinnati Children' s Hospital, Cincinnati Univ., Coll. of Medicine, OH (United States))

1994-05-01

Two cases are described in which patients with type I Gaucher disease developed extraosseous soft tissue masses consisting of Gaucher cell deposits. In one instance the mass destroyed the posterior cortex of the left distal femur and protruded into the soft tissues. In the second case the lesion involved the proximal tibia and gradually extended into the soft tissues. While the incidence of neoplastic disorder such as lymphoproliferative disease appears to be more common in Gaucher disease patients than in the general population, lesions of benign etiology that mimic these aggressive processes should be considered in the differential diagnosis when cortical destruction with coexisting soft tissue most is found in these patients. (orig.)

Pulmonary Gaucher's disease: high-resolution computed tomographic features

International Nuclear Information System (INIS)

Tunaci, A.; Berkmen, Y.M.; Goekmen, E.

1995-01-01

CT findings in pulmonary Gaucher's disease have not been previously reported. Chest radiograph of a patient with pulmonary involvement in type I Gaucher's disease proven by biopsy showed linear and reticulo-nodular opacities. High-resolution CT demonstrated thickening of the interlobular septa and between four and six small nodules within secondary lobules, probably each corresponding to an acinus. (orig.)

Increased basal glucose production in type 1 Gaucher's disease

NARCIS (Netherlands)

Corssmit, E. P.; Hollak, C. E.; Endert, E.; van Oers, M. H.; Sauerwein, H. P.; Romijn, J. A.

1995-01-01

To evaluate the metabolic effects of Gaucher's disease, glucose metabolism and parameters of fat metabolism were studied by indirect calorimetry and primed continuous infusion of [3-3H]glucose in seven clinically stable untreated patients with type 1 Gaucher's disease and in seven healthy matched

Identification of a biomarker in cerebrospinal fluid for neuronopathic forms of Gaucher disease.

Directory of Open Access Journals (Sweden)

Hila Zigdon

Full Text Available Gaucher disease, a recessive inherited metabolic disorder caused by defects in the gene encoding glucosylceramidase (GlcCerase, can be divided into three subtypes according to the appearance of symptoms associated with central nervous system involvement. We now identify a protein, glycoprotein non-metastatic B (GPNMB, that acts as an authentic marker of brain pathology in neurological forms of Gaucher disease. Using three independent techniques, including quantitative global proteomic analysis of cerebrospinal fluid (CSF in samples from Gaucher disease patients that display neurological symptoms, we demonstrate a correlation between the severity of symptoms and GPNMB levels. Moreover, GPNMB levels in the CSF correlate with disease severity in a mouse model of Gaucher disease. GPNMB was also elevated in brain samples from patients with type 2 and 3 Gaucher disease. Our data suggest that GPNMB can be used as a marker to quantify neuropathology in Gaucher disease patients and as a marker of treatment efficacy once suitable treatments towards the neurological symptoms of Gaucher disease become available.

Are transient and shear wave elastography useful tools in Gaucher disease?

Science.gov (United States)

Webb, Muriel; Zimran, Ari; Dinur, Tama; Shibolet, Oren; Levit, Stella; Steinberg, David M; Salomon, Ophira

2018-02-01

Up to now, there are no reliable biochemical markers or imaging that could reveal early tissue damage in Gaucher disease. Therefore, we addressed whether elastography technique can serve as a tool for evaluating patients with Gaucher disease. The study included 42 patients with Gaucher disease type I and 33 patients with liver cirrhosis as well as 22 healthy volunteers. Ultrasound and Doppler examination was performed on each participant prior to apply transient and 2D shear wave elastography. In Gaucher disease the median stiffness of the spleen as assessed by transient elastography (TE) and shear wave elastography (SWE) was 35KPa and 22KPa respectively in contrast to the median stiffness of healthy controls (16.95 and 17.5KPa, p=0.0028 and p=0.0002, respectively) and of patients with cirrhosis (45KPa and 34.5KPa, p=0.015 and pGaucher disease from healthy controls and among those with splenomegaly from cirrhotic patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Treatment patterns from 647 patients with Gaucher disease: An analysis from the Gaucher Outcome Survey.

Science.gov (United States)

Deegan, P; Fernandez-Sasso, D; Giraldo, P; Lau, H; Panahloo, Z; Zimran, A

2018-02-01

The Gaucher Outcome Survey (GOS) is an international disease-specific registry established in 2010 for patients with a confirmed diagnosis of Gaucher disease (GD), regardless of GD type or treatment status. For insight into how GD management varies among countries, we analyzed treatment patterns in GOS. As of October 30, 2015, data on GD-specific treatment (enzyme replacement therapy, substrate reduction therapy, or chemical chaperone therapy) received at any time were available for 647 patients. At analysis, velaglucerase alfa (316/573, 55.1%) and imiglucerase (184/573, 32.1%) were the treatments most widely used. Of the 647 treated patients, 446 (68.9%) had been treated for >5years and 368 (56.9%) had received only one GD-specific drug therapy. There were 377 patients who received velaglucerase alfa. Velaglucerase alfa was most widely used at 60U/kg every other week (134/492 dose entries, 27.2%), but there were differences in dosing between the three highest-enrolling countries (defined as >100 GOS patients enrolled in each), with most patients in Israel receiving <20U/kg, most patients in the United Kingdom receiving 20 to <40U/kg, and most in the United States receiving 60U/kg. This analysis provides a foundation upon which to examine real-life outcomes data from different treatment regimens globally. Copyright © 2016 Shire Human Genetic Therapies, Inc. Published by Elsevier Inc. All rights reserved.

Elevated plasma glucosylsphingosine in Gaucher disease: relation to phenotype, storage cell markers, and therapeutic response

Science.gov (United States)

Dekker, Nick; van Dussen, Laura; Hollak, Carla E. M.; Overkleeft, Herman; Scheij, Saskia; Ghauharali, Karen; van Breemen, Mariëlle J.; Ferraz, Maria J.; Groener, Johanna E. M.; Maas, Mario; Wijburg, Frits A.; Speijer, Dave; Tylki-Szymanska, Anna; Mistry, Pramod K.; Boot, Rolf G.

2011-01-01

Gaucher disease, caused by a deficiency of the lysosomal enzyme glucocerebrosidase, leads to prominent glucosylceramide accumulation in lysosomes of tissue macrophages (Gaucher cells). Here we show glucosylsphingosine, the deacylated form of glucosylceramide, to be markedly increased in plasma of symptomatic nonneuronopathic (type 1) Gaucher patients (n = 64, median = 230.7nM, range 15.6-1035.2nM; normal (n = 28): median 1.3nM, range 0.8-2.7nM). The method developed for mass spectrometric quantification of plasma glucosylsphingosine is sensitive and robust. Plasma glucosylsphingosine levels correlate with established plasma markers of Gaucher cells, chitotriosidase (ρ = 0.66) and CCL18 (ρ = 0.40). Treatment of Gaucher disease patients by supplementing macrophages with mannose-receptor targeted recombinant glucocerebrosidase results in glucosylsphingosine reduction, similar to protein markers of Gaucher cells. Since macrophages prominently accumulate the lysoglycosphingolipid on glucocerebrosidase inactivation, Gaucher cells seem a major source of the elevated plasma glucosylsphingosine. Our findings show that plasma glucosylsphingosine can qualify as a biomarker for type 1 Gaucher disease, but that further investigations are warranted regarding its relationship with clinical manifestations of Gaucher disease. PMID:21868580

Scintigraphic findings in Gaucher's disease

International Nuclear Information System (INIS)

Israel, O.; Jerushalmi, J.; Front, D.

1986-01-01

Gaucher's disease involves the liver, the spleen, and the bone. Liver-spleen and bone scintigraphy were used during an 8-yr period to evaluate changes caused by this disease. Patients were investigated with a liver-spleen scan for abdominal pain, mechanical discomfort, enlarged liver or spleen on physical examination, abdominal mass, abnormal liver function tests, and symptoms of hypersplenism. Fourteen liver-spleen scans were performed in nine patients. Liver scintigraphy showed various degrees of enlargement and inhomogeneous uptake. In two patients focal defects were detected. In one, focal defects were due to liver involvement with Gaucher's disease, but in the other they were caused by metastatic pancreatic carcinoma. The study was also useful in detecting splenic infarction and in following enlargement of the spleen after partial splenectomy. The main indication for bone scintigraphy in six patients was bone pain. This was found to be caused by either aseptic necrosis of the head of the femur, bone infarction, pathological fractures, or osteomyelitis. Loosening after total hip replacement was ruled out in three patients and missed in one patient. Scintigraphy appears to be a simple, sensitive test for evaluation of the liver, spleen, and bony skeleton in patients with symptomatic Gaucher's disease

Interruption of enzyme replacement therapy in Gaucher disease.

Science.gov (United States)

Goldblatt, J; Fletcher, J M; McGill, J; Szer, J; Wilson, M

2016-05-25

In Australia, 58 patients with Gaucher disease were managed by a Gaucher Disease Advisory Committee (GDAC) through a centrally adminis-tered national programme, the Life Savings Drug Program (LSDP). In June 2009, Genzyme Corporation, which manufactures imiglucerase (Cerezyme), the only enzyme replacement therapy (ERT) registered for the treatment of Gaucher disease in Australia at that time, announced that due to a viral contamination problem there would be no further shipments of Cerezyme to Australia prior to the end of 2009. The GDAC allocated available drug supplies in order to maintain treatment to those most in need on a hierarchal clinical severity basis. A cohort of 24 patients with Type 1 Gaucher disease was withdrawn from therapy, 22 of whom had no discernible clinically significant adverse effects when reviewed off therapy for up to 6 months. In this paper, we review the course of 20 of the patients who have been on imiglucerase for periods of at least 24 months after the end of their 'drug holiday'. No patient experienced a bone crisis nor clinical nor magnetic resonance imaging evidence of new avascular necrosis events during this period. Two years after recommencing ERT after a 6-month drug holiday, no patient had developed an overt irreversible complication of their Gaucher disease, with the majority returning to their previous clinical status.

Pathology of Gaucher's Disease

African Journals Online (AJOL)

1974-06-01

Jun 1, 1974 ... cytoplasm of the Gaucher cells, while ultrastructural examination has confirmed ... For light microscopy, sections from the spleen, bone marrow, liver and ... The dried grid was examined in a vacuum-coating unit at an angle of ...

Gaucher's disease

International Nuclear Information System (INIS)

Hainaux, B.; Christophe, C.; Hanquinet, S.; Perlmutter, N.

1992-01-01

We report our observations made by conventional radiography, ultrasound, computerized tomography (CT), and magnetic resonance imaging (MRI) on a 3 1/2-year-old girl with Gaucher's disease. The interest of the case consists in the exceptional lungs involvement, the demonstration by MRI of the bone marrow involvement and the necrosis and fibrosis of the liver, as shown by CT. This liver complication has been previously reported only once. (orig.)

[Progressive pulmonary hypertension in a patient with type 1 Gaucher disease].

Science.gov (United States)

Ponomarev, R V; Model, S V; Averbukh, O M; Gavrilov, A M; Galstyan, G M; Lukina, E A

Gaucher disease is the most common form of hereditary enzymopathies combined into a group of lysosomal storage diseases. The basis for the disease is a hereditary deficiency of the activity of acid β-glucosidase, a lysosomal enzyme involved in the catabolism of lipids, which results in the accumulation of nonutilized cellular metabolism products in the macrophage lysosomes. The main clinical manifestations of type 1 Gaucher disease are cytopenia, hepatomegaly, and splenomegaly, and bone lesion. One of the atypical clinical manifestations of Gaucher disease is damage to the lungs with the development of pulmonary hypertension, which is usually considered within the underlying disease - the development of pneumosclerosis due to macrophage dysfunction. The paper describes a case of progressive pulmonary hypertension in a patient with type 1 Gaucher disease.

Transgenic mice expressing human glucocerebrosidase variants: utility for the study of Gaucher disease.

Science.gov (United States)

Sanders, Angela; Hemmelgarn, Harmony; Melrose, Heather L; Hein, Leanne; Fuller, Maria; Clarke, Lorne A

2013-08-01

Gaucher disease is an autosomal recessively inherited storage disorder caused by deficiency of the lysosomal hydrolase, acid β-glucosidase. The disease manifestations seen in Gaucher patients are highly heterogeneous as is the responsiveness to therapy. The elucidation of the precise factors responsible for this heterogeneity has been challenging as the development of clinically relevant animal models of Gaucher disease has been problematic. Although numerous murine models for Gaucher disease have been described each has limitations in their specific utility. We describe here, transgenic murine models of Gaucher disease that will be particularly useful for the study of pharmacological chaperones. We have produced stable transgenic mouse strains that individually express wild type, N370S and L444P containing human acid β-glucosidase and show that each of these transgenic lines rescues the lethal phenotype characteristic of acid β-glucosidase null mice. Both the N370S and L444P transgenic models show early and progressive elevations of tissue sphingolipids with L444P mice developing progressive splenic Gaucher cell infiltration. We demonstrate the potential utility of these new transgenic models for the study of Gaucher disease pathogenesis. In addition, since these mice produce only human enzyme, they are particularly relevant for the study of pharmacological chaperones that are specifically targeted to human acid β-glucosidase and the common mutations underlying Gaucher disease. Copyright © 2013 Elsevier Inc. All rights reserved.

Varied autopsy findings in five treated patients with Gaucher disease and parkinsonism include the absence of Gaucher cells.

Science.gov (United States)

Monestime, Gianina; Borger, Daniel K; Kim, Jenny; Lopez, Grisel; Allgaeuer, Michael; Jain, Dhanpat; Vortmeyer, Alexander; Wang, Hao-Wei; Sidransky, Ellen

2016-05-01

Enzyme replacement therapy is standard of care for patients with Gaucher disease, as it significantly improves skeletal, visceral, and hematological symptoms. Few pathological studies have documented the extent of pathological findings in treated patients. Autopsy findings in five treated patients, who ultimately developed parkinsonism, ranged from the complete absence of Gaucher pathology to extensive involvement of multiple tissues, without correlation to age, genotype, spleen status, or dose/duration of therapy. Additional autopsies may elucidate modifiers and biomarkers contributing to disease burden and response to therapy. Published by Elsevier Inc.

A case of improved hearing with cochlear implantation in Gaucher disease type 1.

Science.gov (United States)

Endo, Shiori; Mizuta, Kunihiro; Yamatodani, Takashi; Nakanishi, Hiroshi; Hosokawa, Kumiko; Misawa, Kiyoshi; Hosokawa, Seiji; Mineta, Hiroyuki

2018-06-01

Gaucher disease is a lysosomal storage disorder that is caused by congenital defective function of the enzyme glucocerebrosidase. Glucocerebroside that is not hydrolyzed by glucocerebrosidase mainly accumulates in the reticular tissue. We describe a Japanese boy with Gaucher disease type 1 who developed bilateral profound sensorineural hearing loss within approximately 4years. We performed cochlear implantation initially on his right ear and again on his left ear 5 months later. The cochlear implants were successfully utilized with a speech discrimination score of 95% on a Japanese sentence recognition test. There are many reports of central hearing loss in Gaucher disease type 2 or 3. However, to the best of our knowledge, this is the first report of profound inner ear hearing loss with Gaucher disease. It also appears to be the first record of cochlear implantation for Gaucher disease. Cochlear implants may be useful for sensorineural hearing loss in patients with Gaucher disease without neurological symptoms other than hearing loss. Copyright © 2017 Elsevier B.V. All rights reserved.

An avascular necrosis in Gaucher's disease

International Nuclear Information System (INIS)

Mansberg, R.; Uren, R.; Howman-Giles, R.

1999-01-01

Full text: Avascular necrosis is frequently associated with sickle cell disease and other haemoglobinopathies. It is less commonly associated with Gaucher's disease. A case with multi-modality imaging is presented. A 33-year-old male patient presented with a 4-day history of severe right knee pain. He was a febrile with mild swelling of the right knee. A diagnosis of Gaucher's disease had been made by bone marrow biopsy on a clinical picture of hepatosplenomegaly and thrombocytopenia some years earlier. A radiograph of the knee demonstrated an Erlenmeyer flask deformity of the distal femur. A bone scan demonstrated reduced perfusion to the distal right femoral shaft and femoral condyles. Delayed images demonstrated decreased tracer uptake in the distal right femur extending to the right medial femoral condyle consistent with a vascular necrosis. An MRI of the thighs demonstrated lipid accumulation in the marrow space of both femora consistent with Gaucher's disease associated with changes of bone oedema in the metadiaphysis and epiphysis of the right femur. The patient was treated with supportive measures and made an uneventful recovery and is being commenced on enzyme replacement therapy (Algucerase)

International collaboration in medical radiation science.

Science.gov (United States)

Denham, Gary; Allen, Carla; Platt, Jane

2016-06-01

International collaboration is recognised for enhancing the ability to approach complex problems from a variety of perspectives, increasing development of a wider range of research skills and techniques and improving publication and acceptance rates. The aim of this paper is to describe the current status of international collaboration in medical radiation science and compare this to other allied health occupations. This study utilised a content analysis approach where co-authorship of a journal article was used as a proxy for research collaboration and the papers were assigned to countries based on the corporate address given in the by-line of the publication. A convenience sample method was employed and articles published in the professional medical radiation science journals in the countries represented within our research team - Australia, the United Kingdom (UK) and the United States of America (USA) were sampled. Physiotherapy, speech pathology, occupational therapy and nursing were chosen for comparison. Rates of international collaboration in medical radiation science journals from Australia, the UK and the USA have steadily increased over the 3-year period sampled. Medical radiation science demonstrated lower average rates of international collaboration than the other allied health occupations sampled. The average rate of international collaboration in nursing was far below that of the allied health occupations sampled. Overall, the UK had the highest average rate of international collaboration, followed by Australia and the USA, the lowest. Overall, medical radiation science is lagging in international collaboration in comparison to other allied health fields.

International tuberculosis research collaborations within Asia.

Science.gov (United States)

Molton, James S; Singh, Shweta; Chen, Ling Jun; Paton, Nicholas I

2017-09-07

Asia bears more than half the global tuberculosis (TB) burden. Economic development in the region has increased available funding for biomedical research and opportunity for collaboration. We explored the extent of international tuberculosis research collaborations between institutions within Asia. We conducted a Pubmed search for all articles with tuberculosis in the title published during a 12 month period with at least one author affiliation listed in Asia, then identified international collaborations from institution websites and internet searches. We identified 99 international collaborations involving an institution within Asia, of which only 8 (8.1%) were collaborations between Asian institutions. The remainder were with institutions outside of Asia. The paucity of intra-Asian international research collaboration represents a lost opportunity to optimise regional research funding, capacity building and the development of an Asia-relevant TB research agenda.

The Spectrum of Neurological Manifestations Associated with Gaucher Disease

Directory of Open Access Journals (Sweden)

Tamanna Roshan Lal

2017-03-01

Full Text Available Gaucher disease, the most common lysosomal storage disorder, is due to a deficiency in the enzyme glucocerebrosidase. This leads to the accumulation of its normal substrate, glucocerebroside, in tissue macrophages, affecting the hematological, visceral, bone and neurologic systems. Gaucher disease is classified into three broad phenotypes based upon the presence or absence of neurological involvement: type 1 (non-neuronopathic, type 2 (acute neuronopathic, and type 3 (subacute neuronopathic. Phenotypically, there is a wide spectrum of visceral and neurological manifestations. Enzyme replacement is effective in managing the visceral disease; however, treating the neurological manifestations has proved to be more challenging. This review discusses the various neurological manifestations encountered in Gaucher disease, and provides a brief overview regarding the treatment and ongoing research challenges.

'Non-neuronopathic' Gaucher disease reconsidered. Prevalence of neurological manifestations in a Dutch cohort of type I Gaucher disease patients and a systematic review of the literature

NARCIS (Netherlands)

Biegstraaten, M.; van Schaik, I. N.; Aerts, J. M. F. G.; Hollak, C. E. M.

2008-01-01

Gaucher disease is a lysosomal storage disorder, which is classically divided into three types. Type I Gaucher disease is differentiated from types II and III disease by the absence of nervous system involvement. However, an increasing number of reports has emerged on neurological manifestations in

Reported outcomes of 453 pregnancies in patients with Gaucher disease: An analysis from the Gaucher outcome survey.

Science.gov (United States)

Lau, Heather; Belmatoug, Nadia; Deegan, Patrick; Goker-Alpan, Ozlem; Schwartz, Ida Vanessa D; Shankar, Suma P; Panahloo, Zoya; Zimran, Ari

2018-02-01

Gaucher disease (GD) may worsen during pregnancy, leading to the discussion of continuing treatment during pregnancy. We examined fetal outcomes of pregnancies reported in the Gaucher Outcome Survey, an international GD-specific registry established in 2010. A total of 453 pregnancies were reported. Most pregnancies (336/453, 74.2%) were in women who did not receive GD-specific treatment during pregnancy, while enzyme replacement therapy (ERT) was received during 117/453 (25.8%) pregnancies. No pregnancies exposed to substrate reduction therapy were reported. The percentage of normal outcomes (live birth delivered at term with no congenital abnormalities) was similar in untreated and treated pregnancies (92.9% vs. 91.4%). The percentage of spontaneous abortions in untreated pregnancies was 3.6% (95% CI, 1.9%- 6.2%) compared with 6.9% (95% CI, 3.0%-13.1%) in treated pregnancies (p=0.1866). In women who received velaglucerase alfa <1month prior to conception and/or during pregnancy, 34/36 (94.4%) pregnancies had normal outcomes and 2 (5.6%) ended in spontaneous abortion. Normal outcomes were observed in the 20 pregnancies with velaglucerase alfa exposure starting <1month prior to conception and continuing through all trimesters. These observations, in addition to information in the literature, suggest that continuation of ERT during pregnancy may be appropriate for GD patients. Copyright © 2016 Shire Human Genetic Therapies, Inc. Published by Elsevier Inc. All rights reserved.

Radiologic findings of Korean gaucher disease

International Nuclear Information System (INIS)

Cho, Jae Hyun; Kim, Byoung Suck; Kim, Moon Kyu; Chung, Yoon Sok; Suh, Jung Ho; Kim, Hyon J; Ha, Doo Hoe

1999-01-01

To document the radiologic characteristics of Korean Gaucher disease. Fifteen bone marrow biopsy and laboratory data confirmed Gaucher disease patients (age 1-21, mean 10.9 yr) were undertaken plain X ray and MRI. Number of type I were 10, type II, 2, type III, 3. Seven were splencetomized on initial evaluation or during follow up. Five enzyme treated patient were undertaken follow-up MR examination during 6-40 month with 6 month interval. Conventional T1 and T2WI of spine and femur was performed and FMPSPGR in and out of phase image was also done. Volume of liver and spleen were measured, and bone marrow infiltration and presence of infarction were scored according to 6 scale scoring system. Clinical data were also reviewed and correlated with the MR findings. Marrow infiltration was noted in 71.4% of all patients in MRI, while it was in 45.7% with plain radiography. Type I group showed marrow infiltration in all but one cases, which was parallel with ages, SGPT, and presence of osteopenia, reversely correlated with spleen size. Severe bone complications (infarction of fracture) were noted in 7 of 10 type I group, and 6 patients showed severe growth retardation (below 3rd percentile). Follow up MR examination of 5 patient showed decrease in liver and spleen size first without bone change until 6 months. There showed bone regeneration in 2 patient 1 year after, and increased fat signal in one patient 3.5 years after. In and out of phase images couldn't help in quantifying fat composition in bone marrow. Korean Gaucher patients revealed as more severe skeletal complications than others reported from Western groups. MR examination is a effective modality to evaluate and monitor of Gaucher patients

Macrophage models of Gaucher disease for evaluating disease pathogenesis and candidate drugs.

Science.gov (United States)

Aflaki, Elma; Stubblefield, Barbara K; Maniwang, Emerson; Lopez, Grisel; Moaven, Nima; Goldin, Ehud; Marugan, Juan; Patnaik, Samarjit; Dutra, Amalia; Southall, Noel; Zheng, Wei; Tayebi, Nahid; Sidransky, Ellen

2014-06-11

Gaucher disease is caused by an inherited deficiency of glucocerebrosidase that manifests with storage of glycolipids in lysosomes, particularly in macrophages. Available cell lines modeling Gaucher disease do not demonstrate lysosomal storage of glycolipids; therefore, we set out to develop two macrophage models of Gaucher disease that exhibit appropriate substrate accumulation. We used these cellular models both to investigate altered macrophage biology in Gaucher disease and to evaluate candidate drugs for its treatment. We generated and characterized monocyte-derived macrophages from 20 patients carrying different Gaucher disease mutations. In addition, we created induced pluripotent stem cell (iPSC)-derived macrophages from five fibroblast lines taken from patients with type 1 or type 2 Gaucher disease. Macrophages derived from patient monocytes or iPSCs showed reduced glucocerebrosidase activity and increased storage of glucocerebroside and glucosylsphingosine in lysosomes. These macrophages showed efficient phagocytosis of bacteria but reduced production of intracellular reactive oxygen species and impaired chemotaxis. The disease phenotype was reversed with a noninhibitory small-molecule chaperone drug that enhanced glucocerebrosidase activity in the macrophages, reduced glycolipid storage, and normalized chemotaxis and production of reactive oxygen species. Macrophages differentiated from patient monocytes or patient-derived iPSCs provide cellular models that can be used to investigate disease pathogenesis and facilitate drug development. Copyright © 2014, American Association for the Advancement of Science.

Inhibition of UDP-glucosylceramide synthase in mice prevents Gaucher disease-associated B-cell malignancy.

Science.gov (United States)

Pavlova, Elena V; Archer, Joy; Wang, Susan; Dekker, Nick; Aerts, Johannes Mfg; Karlsson, Stefan; Cox, Timothy M

2015-01-01

Clonal B-cell proliferation is a frequent manifestation of Gaucher disease - a sphingolipidosis associated with a high risk of multiple myeloma and non-Hodgkin lymphoma. Gaucher disease is caused by genetic deficiency of acid β-glucosidase, the natural substrates of which (β-d-glucosylceramide and β-d-glucosylsphingosine) accumulate, principally in macrophages. Mice with inducible deficiency of β-glucosidase [Gba(tm1Karl/tm1Karl)Tg(MX1-cre)1Cgn/0] serve as an authentic model of human Gaucher disease; we have recently reported clonal B-cell proliferation accompanied by monoclonal serum paraproteins and cognate tumours in these animals. To explore the relationship between B-cell malignancy and the biochemical defect, we treated Gaucher mice with eliglustat tartrate (GENZ 112638), a potent and selective inhibitor of the first committed step in glycosphingolipid biosynthesis. Twenty-two Gaucher mice received 300 mg/kg of GENZ 112638 daily for 3-10 months from 6 weeks of age. Plasma concentrations of β-d-glucosylceramide and the unacylated glycosphingolipid, β-d-glucosylsphingosine, declined. After administration of GENZ 112638 to Gaucher mice for 3-10 months, serum paraproteins were not detected and there was a striking reduction in the malignant lymphoproliferation: neither lymphomas nor plasmacytomas were found in animals that had received the investigational agent. In contrast, 14 out of 60 Gaucher mice without GENZ 112638 treatment developed these tumours; monoclonal paraproteins were detected in plasma from 18 of the 44 age-matched mice with Gaucher disease that had not received GENZ 112638. Long-term inhibition of glycosphingolipid biosynthesis suppresses the development of spontaneous B-cell lymphoma and myeloma in Gaucher mice. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Mesenteric mass in a young girl - an unusual site for Gaucher's disease

International Nuclear Information System (INIS)

Lim, Adrian K.P.; Vellodi, Ashok; McHugh, Kieran

2002-01-01

We report the first case of a child with Gaucher's disease and a large mesenteric mass, confirmed histologically to be Gaucher's cell infiltrates. We describe the radiological findings and discuss further management. The advent of enzyme replacement therapy has prolonged survival and the emergence of previously undocumented manifestations of the disease is being observed. The radiologist and clinician should be alert to the possible development of these new problems and the fact that in Gaucher's disease a palpable right upper-quadrant mass need not necessarily represent hepatomegaly. (orig.)

Clinical manifestations and management of Gaucher disease.

Science.gov (United States)

Linari, Silvia; Castaman, Giancarlo

2015-01-01

Gaucher disease is a rare multi-systemic metabolic disorder caused by the inherited deficiency of the lysosomal enzyme β-glucocerebrosidase, which leads to the accumulation of its normal substrate, glucocerebroside, in tissue macrophages with damage to haematological, visceral and bone systems. Anaemia, thrombocytopenia, enlargement of liver and/or spleen, skeletal abnormalities (osteopenia, lytic lesions, pathological fractures, chronic bone pain, bone crisis, bone infarcts, osteonecrosis and skeletal deformities) are typical manifestations of the most prevalent form of the disease, the so-called non-neuronopathic type 1. However, severity and coexistence of different symptoms are highly variable. The determination of deficient β-glucocerebrosidase activity in leukocytes or fibroblasts by enzymatic assay is the gold standard for the diagnosis of Gaucher disease. Comprehensive and reproducible evaluation and monitoring of all clinically relevant aspects are fundamental for the effective management of Gaucher disease patients. Enzyme replacement therapy has been shown to be effective in reducing glucocerebroside storage burden and diminishing the deleterious effects caused by its accumulation. Tailored treatment plan for each patient should be directed to symptom relief, general improvement of quality of life, and prevention of irreversible damage.

Scintigraphic picture in Gaucher's disease

International Nuclear Information System (INIS)

Bykov, S.A.; Gafton, G.I.; Petrov, V.P.

1988-01-01

Analysis of the results of combined radionuclide investigation of the liver, spleen, kidney, lymph nodes and bones in a patient with Gaucher's disease is given. Scintigraphy was shown to be an important method for making correct diagnosis in patients with this rare disease

Gaucher disease in sheep.

Science.gov (United States)

Karageorgos, Litsa; Lancaster, Malcolm J; Nimmo, Judith S; Hopwood, John J

2011-02-01

Gaucher disease, an autosomal recessive lysosomal storage disorder caused by mutations in the β-glucocerebrosidase gene, was recently discovered in sheep on a "Southdown" sheep stud in Victoria, Australia. Clinical signs include neuropathy, thickened leathery skin, and ichthyosis, with lambs unable to stand from birth. Affected lambs were found to be deficient in glucocerebrosidase activity, and mutational analysis found them to be homozygous for the missense mutations c.1142G>A (p.C381Y) and c.1400C>T (p.P467L). In addition, four silent mutations were detected (c.777C>A [p.Y259Y], c1203A>G [p.Q401Q], c.1335T>C [p.I445I], c.1464C>G [p.L488L]). The human equivalent [C342Y] to the C381Y mutation leads to an acute neuronopathic phenotype in patients. Identification of an acute neuronopathic form of Gaucher disease in sheep provides a large animal model that will enable studies of pathology and evaluation of therapies to treat this common lysosomal storage disorder.

International collaborations through the internet

DEFF Research Database (Denmark)

Olson, Gary M.; David, Paul A.; Eksteen, Johan

2007-01-01

The past decade has seen remarkable advances in the availability of tools to support scientific collaboration at a distance. This is especially good news for international collaborations, where in the past constraints on collocation and travel have made such collaborations a major challenge. The ...

Gaucher's disease: Magnetic resonance findings

International Nuclear Information System (INIS)

Roca, M.; Gomez-Pereda, R.; Blasco, A.; Ros, L.

1996-01-01

The objective is to assess the role of magnetic resonance (MR) in determining the initial extension of Gaucher's disease and its complications. A retrospective study of eight patients diagnosed as having Gaucher's disease was carried out using MR. The study focused on pelvis, hip, femur, spine, liver parenchyma and splenic parenchyma. Infiltration of the cancellous portion of the vertebral bodies was observed in all but one of the patients. Three patients presented small hemangiomas in dorsal and lumbar vertebral bodies. Pelvic bone involvement was homogeneous in four cases and spotty in two, while the pelvic marrow was normal in the two patients with no vertebral infiltration. A vascular necrosis of the femoral head was detected in two cases. MR is very useful in determining the initial extension, in the early diagnosis of complications and in managing the posttreatment marrow response to assess the therapeutic efficacy. 16 refs

Low-dose N-butyldeoxynojirimycin (OGT 918) for type I Gaucher disease

NARCIS (Netherlands)

Heitner, Rene; Elstein, Deborah; Aerts, Johannes; Weely, Sonja van; Zimran, Ari

2002-01-01

The objective of this study was to evaluate the efficacy and safety of low-dose substrate balance therapy with OGT 918 for the treatment of adults with Gaucher disease. Eighteen patients with Gaucher disease from two centers were enrolled in an open-label 6-month study of OGT 918, 50 mg taken three

Pathology of Gaucher's Disease

African Journals Online (AJOL)

1974-06-01

Jun 1, 1974 ... disability in 2 of them. One patient also developed restric- tive lung disease, presumably on the ... Brother of case 9; diagnosed as Gaucher's. 8500 g disease at age 6 yrs on basis of hepato- ... other siblings, one of whom is said to have an enlarged spleen. Estimations of ,a-glucosidase on lymphocytes from.

Genetics Home Reference: Gaucher disease

Science.gov (United States)

... 500 to 1,000 people of Ashkenazi Jewish heritage. The other forms of Gaucher disease are uncommon and do not occur more frequently in people of Ashkenazi Jewish descent. Related Information What information about a genetic condition can statistics provide? Why are some genetic ...

Combination therapy in a patient with chronic neuronopathic Gaucher disease: a case report.

Science.gov (United States)

Ceravolo, Ferdinando; Grisolia, Michele; Sestito, Simona; Falvo, Francesca; Moricca, Maria Teresa; Concolino, Daniela

2017-01-20

The variants of neuronopathic Gaucher disease may be viewed as a clinical phenotypic continuum divided into acute and chronic forms. The chronic neuronopathic form of Gaucher disease is characterized by a later onset of neurological symptoms and protracted neurological and visceral involvement. The first-choice treatment for nonneuronopathic Gaucher disease is enzyme replacement therapy with recombinant analogues of the deficient human enzyme glucocerebrosidase. Enzyme replacement therapy has been shown to improve hematological and bone manifestations associated with Gaucher disease, but, as with most proteins, recombinant enzymes cannot cross the blood-brain barrier, which prevents effects on neurological manifestations. Substrate reduction therapy with miglustat (N-butyldeoxynojirimycin) inhibits glucosylceramide synthase, which catalyzes the first step in glycosphingolipid synthesis. Because miglustat can cross the blood-brain barrier, it has been suggested that, combined with enzyme replacement therapy, it might be effective in treating neurological symptoms in patients with neuronopathic Gaucher disease. We report observed effects of combined enzyme replacement therapy and substrate reduction therapy in a 7-year-old Caucasian boy with neuronopathic Gaucher disease who was homozygous for L444P mutations. He had received enzyme replacement therapy from the age of 18 months, and concomitant miglustat treatment was commenced, with dosing according to body surface area uptitrated over 1 month with dietary modifications when he reached the age of 30 months. He experienced mild diarrhea after commencing miglustat therapy, which decreased in frequency/severity over time. His splenomegaly was reduced, and his hematological values and plasma angiotensin-converting enzyme activity normalized. Plasma chitotriosidase also showed substantial and sustained decreases. After 5 years of combination therapy, the patient showed no signs of neurological impairment. This case

Gaucher disease in a family from Maranhão

Directory of Open Access Journals (Sweden)

Samira Shizuko Parreão Oi

2014-10-01

Full Text Available Background: Gaucher disease is an inborn, autosomal recessive error of the metabolism which belongs to the group of lysosomal storage disorders. Objective: This work reports on the treatment of Gaucher disease in several members of the same family from the countryside of Maranhão. Methods: This was an observational, retrospective and prospective, descriptive case study about the efficacy of enzyme replacement therapy. Results: The results showed that women were more affected (80% of patients by the disease, age at diagnosis ranged from 24 to 33 years, the predominant ethnicity was mulatto (80% and all cases were classified as type 1. The diagnosis of these patients was performed by measuring the levels of glucocerebrosidase and chitotriosidase enzymes and confirmed by genotyping. All patients suffering from Gaucher disease had low glucocerebrosidase levels. Before replacement therapy, hepatosplenomegaly was the most common clinical manifestation (100% and osteopenia was seen in 80% of the cases. Regarding hematological manifestations, anemia and leukopenia were found in 40% of patients at diagnosis; however the hemoglobin and leukocyte levels were normalized after four years of therapy. Thrombocytopenia, observed in 20% of cases, was normalized after the second year of treatment. Conclusion: In these cases, despite gaps in the treatment as the family resides in the rural region of the state, the patients with Gaucher disease showed satisfactory therapeutic response over time.

Skeletal Manifestations in Gaucher Disease: A Case Report

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Altınay Göksel Karatepe

2005-09-01

Full Text Available Gauchers disease is the most frequent hereditary lysosomal deposit storage disorder. It is characterized by a deficiency of the enzyme glucocerebrosidase that leads to an accumulation of glucocerebroside in the macrophage lysosomes. It is classified in three types, according to the presence of central nervous system involvement (type 2 and 3 or not (type 1. In the majority of patients there are hepatosplenomegaly, anemia and thrombocytopenia. Skeletal involvement is also important and it is the most disabling manifestation. In this case report, there is presented a case of Gauchers disease with multiple skeletal involvement and the literature is reviewed.

Validating glycoprotein non-metastatic melanoma B (gpNMB, osteoactivin), a new biomarker of Gaucher disease.

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Murugesan, Vagishwari; Liu, Jun; Yang, Ruhua; Lin, Haiquin; Lischuk, Andrew; Pastores, Gregory; Zhang, Xiaokui; Chuang, Wei-Lien; Mistry, Pramod K

2018-02-01

In the spleens of Gaucher disease mice and patients, there is a striking elevation of expression of glycoprotein non-Metastatic Melanoma B (gpNMB). We conducted a study in a large cohort of patients with Gaucher disease to assess the utility of serum levels of soluble fragment of gpNMB as a biomarker of disease activity. There was >15-fold elevation of gpNMB in sera of untreated patients with Gaucher disease. gpNMB levels correlated with overall disease severity as well as the severity of individual organ compartments: liver, spleen, bone and hematological disease. Imiglucerase enzyme replacement therapy resulted in significant reduction of gpNMB. Serum levels of gpNMB were highly correlated with accumulation of bioactive lipid substrate of Gaucher disease, glucosylsphingosine as well as established biomarkers, chitotriosidase and chemokine, CCL18. Our results suggest utility of gpNMB as a biomarker of Gaucher disease to monitor individual patients and cohorts of patients for disease progression or response to therapy. Investigation of gpNMB in Gaucher disease pathophysiology is likely to illuminate our understanding disease mechanisms. Copyright © 2016 Elsevier Inc. All rights reserved.

Impaired IL-10 transcription and release in animal models of Gaucher disease macrophages.

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Kacher, Yaacov; Futerman, Anthony H

2009-01-01

A number of studies have shown altered cytokine levels in serum from Gaucher disease patients, including changes in levels of the anti-inflammatory cytokine, interleukin-10 (IL-10). However, the source of IL-10, or the mechanisms leading to changes in IL-10 serum levels are not known. We now show that mouse macrophages treated with an active site-directed inhibitor of glucocerebrosidase, or macrophages from a mouse model of Gaucher disease, the L444P mouse, release significantly less IL-10 than their untreated counterparts, but that TNFalpha release is unaffected. These changes are due to reduced transcription of IL-10 mRNA in macrophages. The reduction in IL-10 secretion observed in animal models of Gaucher disease macrophages may be of relevance to explain the increase in inflammation that is often observed in Gaucher disease.

Gaucher Disease: The Metabolic Defect, Pathophysiology, Phenotypes And Natural History

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Baris, Hagit N.; Cohen, Ian J.; Mistry, Pramod K.

2015-01-01

Gaucher disease (GD), a prototype lysosomal storage disorder, results from inherited deficiency of lysosomal glucocerebrosidase due to biallelic mutations in GBA. The result is widespread accumulation of macrophages engorged with predominantly lysosomal glucocerebroside. A complex multisystem phenotype arises involving the liver, spleen, bone marrow and occasionally the lungs in type 1 Gaucher disease; in neuronopathic fulminant type 2 and chronic type 3 disease there is in addition progressive neurodegenerative disease. Manifestations of Gaucher disease type 1 (GD1) include hepatosplenomegaly, cytopenia, a complex pattern of bone involvement with avascular osteonecrosis (AVN), osteoporosis, fractures and lytic lesions. Enzyme replacement therapy became the standard of care in 1991, and this has transformed the natural history of GD1. This article reviews the clinical phenotypes of GD, diagnosis, pathophysiology and its natural history. A subsequent chapter discusses the treatment options. PMID:25345088

Gaucher disease diagnosed after bone marrow trephine biopsy — a report of two cases

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Anna Dmoszyńska

2011-07-01

Full Text Available The hematologist is at the forefront of specialists to whom patients with Gaucher disease present because of cytopenia and hepatosplenomegaly. Usually, patients with such symptoms have undergone trephine biopsy. We present the cases of two patients in whom Gaucher disease was suspected because of the discovery of Gaucher cells in trephine biopsy, and subsequently confirmed via enzymatic and molecular investigations. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 2, pp. 352–356

Gaucher disease and other storage disorders.

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Grabowski, Gregory A

2012-01-01

In 1882, Philippe Gaucher described a 32-year-old woman with massive splenomegaly and unusually large cells in the spleen, which he called a "primary epithelioma of the spleen." The systemic nature and inheritance of the disease and its variants involving the viscera and CNS were described over the next century. The delineation of the causal enzymatic defects, genetics, molecular pathology, and genomics have provided pathogenic insights into the phenotypic spectrum and the bases for development of specific therapies for what is now known as Gaucher disease. As a prototype, the clinically and economically successful intracellular enzyme therapy provided the impetus for the expansion of similar research and therapeutic developments for other lysosomal storage diseases (LSDs) and orphan diseases, including Fabry, Pompe, and Niemann-Pick diseases, as well as several mucopolysaccharidoses. Continuing studies of such LSDs, which occur as a group in more than 7000 live births, have revealed the complex molecular interdigitation with the autophagy and apoptotic pathways and proteostasis and the impact of disruptions of the lysosomal/autophagy and proteostasis systems on more common diseases has been recognized. Examples include age-related neurodegenerative diseases (eg, Parkinson disease and Gaucher disease), idiopathic hypertrophic myocardiopathies, stroke and renal failure (eg, Fabry disease), and Nonalcoholic Fatty Liver Disease/Nonalcoholic SteatoHepatitis (NAFLD/NASH) and atherosclerosis (eg, lysosomal acid lipase deficiencies). Although perceived as rare, the availability of treatment and the impact of the LSDs on more common diseases require their integration into routine clinical practice.

An Adult Form of Gaucher Disease Associated with Portal Hypertension: A Case

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Ahmet Dulger

2013-04-01

Full Text Available Gaucher disease (GD is an inborn error of metabolism that affects the recycling of cellular glycolipids. Glucosylceramide (also called glucocerebroside accumulate within the lysosomes of cells. Gaucher%u2019s disease is most common lysosomal storage disease and its incidence is 1/75.000. Three types of this disease have been defined. During the course of disease, it was reported that hepatosplenomegaly, portal hypertension, hyperferritinemia, splenic infarcts and splenic nodules might develop. Therefore, as in our case; Gaucher%u2019s disease must be remembered in the setting of hepatosplenomegaly, portal hypertension, hyperferritinemia, splenic infarcts and splenic nodules of unknown etiology.

Diagnosis features of pediatric Gaucher disease patients in the era of enzymatic therapy, a national-base study from the Spanish Registry of Gaucher Disease.

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Andrade-Campos, Marcio; Alfonso, Pilar; Irun, Pilar; Armstrong, Judith; Calvo, Carmen; Dalmau, Jaime; Domingo, Maria-Rosario; Barbera, Jose-Luis; Cano, Horacio; Fernandez-Galán, Maria-Angeles; Franco, Rafael; Gracia, Inmaculada; Gracia-Antequera, Miguel; Ibañez, Angela; Lendinez, Francisco; Madruga, Marcos; Martin-Hernández, Elena; O'Callaghan, Maria Del Mar; Del Soto, Alberto Pérez; Del Prado, Yolanda Ruiz; Sancho-Val, Ignacio; Sanjurjo, Pablo; Pocovi, Miguel; Giraldo, Pilar

2017-05-03

The enzymatic replacement therapy (ERT) availability for Gaucher disease (GD) has changed the landscape of the disease, several countries have screening programs. These actions have promoted the early diagnosis and avoided many complications in pediatric patients. In Spain ERT has been available since 1993 and 386 patients have been included in the Spanish Registry of Gaucher Disease (SpRGD). The aim of this study is to analyze the impact of ERT on the characteristics at time of diagnosis and initial complications in pediatric Gaucher disease patients. To analyze the impact of ERT on the characteristics at time of diagnosis and initial complications in pediatric Gaucher disease patients. A review of data in SpRGD from patients' diagnosed before 18 years old was performed. The cohort was split according the year of diagnosis (≤1994, cohort A; ≥1995, cohort B). A total of 98 pediatric patients were included, GD1: 80, GD3: 18; mean age: 7.2 (0.17-16.5) years, 58 (59.2%) males and 40 (40.8%) females. Forty-five were diagnosed ≤ 1994 and 53 ≥ 1995. Genotype: N370S/N370S: 2 (2.0%), N370S/L444P: 27 (27.5%), N370S/other: 47 (48%), L444P/L444P: 7 (7.1%), L444P/D409H: 2 (2.0%), L444P/other: 3 (6.2%), other/other: 10 (10.2%). The mean age at diagnosis was earlier in patients diagnosed after 1995 (p Gaucher disease in the era of ERT availability has permitted to reduce the incidence of severe and irreversible initial complication in pediatric patients, and this has permitted better development of these patients. This is the largest pediatric cohort from a national registry.

Gaucher disease of the liver: CT appearance

International Nuclear Information System (INIS)

Glass, R.B.J.; Poznanski, A.K.; Young, S.; Urban, M.A.

1987-01-01

We present a child with Gaucher disease with hepatic involvement that caused portal hypertension. Computerized tomography (CT) showed distortion of liver parenchyma and central necrosis of the liver. (orig.)

International scientific collaboration in nonproliferation

International Nuclear Information System (INIS)

Travelli, A.

1998-01-01

International collaboration is a vital component of every serious nonproliferation effort. Several examples of the experiences that the Argonne Arms Control and Nonproliferation Program has had in this area are given and, in the process, important components of the program come to light. Some of the main principles that the program has learned to follow while pursuing international collaboration projects are shared, as are the pitfalls that the program has learned to avoid. (author)

Coenzyme Q10 partially restores pathological alterations in a macrophage model of Gaucher disease.

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de la Mata, Mario; Cotán, David; Oropesa-Ávila, Manuel; Villanueva-Paz, Marina; de Lavera, Isabel; Álvarez-Córdoba, Mónica; Luzón-Hidalgo, Raquel; Suárez-Rivero, Juan M; Tiscornia, Gustavo; Sánchez-Alcázar, José A

2017-02-06

Gaucher disease (GD) is caused by mutations in the GBA1 gene which encodes lysosomal β-glucocerebrosidase (GCase). In GD, partial or complete loss of GCase activity causes the accumulation of the glycolipids glucosylceramide (GlcCer) and glucosylsphingosine in the lysosomes of macrophages. In this manuscript, we investigated the effects of glycolipids accumulation on lysosomal and mitochondrial function, inflammasome activation and efferocytosis capacity in a THP-1 macrophage model of Gaucher disease. In addition, the beneficial effects of coenzyme Q 10 (CoQ) supplementation on cellular alterations were evaluated. Chemically-induced Gaucher macrophages were developed by differentiateing THP-1 monocytes to macrophages by treatment with phorbol 12-myristate 13-acetate (PMA) and then inhibiting intracellular GCase with conduritol B-epoxide (CBE), a specific irreversible inhibitor of GCase activity, and supplementing the medium with exogenous GlcCer. This cell model accumulated up to 16-fold more GlcCer compared with control THP-1 cells. Chemically-induced Gaucher macrophages showed impaired autophagy flux associated with mitochondrial dysfunction and increased oxidative stress, inflammasome activation and impaired efferocytosis. All abnormalities were partially restored by supplementation with CoQ. These data suggest that targeting mitochondria function and oxidative stress by CoQ can ameliorate the pathological phenotype of Gaucher cells. Chemically-induced Gaucher macrophages provide cellular models that can be used to investigate disease pathogenesis and explore new therapeutics for GD.

A specific and potent inhibitor of glucosylceramide synthase for substrate inhibition therapy of Gaucher disease.

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McEachern, Kerry Anne; Fung, John; Komarnitsky, Svetlana; Siegel, Craig S; Chuang, Wei-Lien; Hutto, Elizabeth; Shayman, James A; Grabowski, Gregory A; Aerts, Johannes M F G; Cheng, Seng H; Copeland, Diane P; Marshall, John

2007-07-01

An approach to treating Gaucher disease is substrate inhibition therapy which seeks to abate the aberrant lysosomal accumulation of glucosylceramide. We have identified a novel inhibitor of glucosylceramide synthase (Genz-112638) and assessed its activity in a murine model of Gaucher disease (D409V/null). Biochemical characterization of Genz-112638 showed good potency (IC(50) approximately 24nM) and specificity against the target enzyme. Mice that received drug prior to significant accumulation of substrate (10 weeks of age) showed reduced levels of glucosylceramide and number of Gaucher cells in the spleen, lung and liver when compared to age-matched control animals. Treatment of older mice that already displayed significant amounts of tissue glucosylceramide (7 months old) resulted in arrest of further accumulation of the substrate and appearance of additional Gaucher cells in affected organs. These data indicate that substrate inhibition therapy with Genz-112638 represents a viable alternate approach to enzyme therapy to treat the visceral pathology in Gaucher disease.

Characteristics of 26 patients with type 3 Gaucher disease: A descriptive analysis from the Gaucher Outcome Survey.

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Schwartz, Ida Vanessa D; Göker-Alpan, Özlem; Kishnani, Priya S; Zimran, Ari; Renault, Lydie; Panahloo, Zoya; Deegan, Patrick

2018-03-01

The Gaucher Outcome Survey (GOS) is an international disease-specific registry established in 2010 for patients with a confirmed diagnosis of Gaucher disease (GD), regardless of GD type or treatment status. Historically, there has been a limited understanding of type 3 GD (GD3) and its natural history in patients irrespective of their treatment status. Here, we describe the disease characteristics of patients with GD3 enrolled in GOS. As of October 2015, 1002 patients had been enrolled, 26 of whom were reported as GD3. The majority of patients with GD3 were from the US (13; 50.0%), seven (26.9%) were from the UK, three (11.5%) from Israel, and three (11.5%) from Brazil. No patients were of Ashkenazi Jewish origin. Median age of symptom onset was 1.4 (interquartile range: 0.5-2.0) years. The most common GBA1 mutation genotype was L444P/L444P, occurring in 16 (69.6%) of 23 patients who had genotyping information available. Nine patients reported a family history of GD (any type). Of 21 patients with treatment status information, 20 (95.2%) had received GD-specific treatment at any time, primarily imiglucerase (14 patients) and/or velaglucerase alfa (13 patients). Hemoglobin concentrations and platelet counts at GOS entry were within normal ranges for most patients, and there were no reports of severe hepatomegaly or of splenomegaly in non-splenectomized patients, most likely indicative of the effects of treatment received prior to GOS entry. This analysis provides information on the characteristics of patients with GD3 that could be used as the baseline for longitudinal follow-up of these patients.

Characteristics of 26 patients with type 3 Gaucher disease: A descriptive analysis from the Gaucher Outcome Survey

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Ida Vanessa D. Schwartz

2018-03-01

Full Text Available The Gaucher Outcome Survey (GOS is an international disease-specific registry established in 2010 for patients with a confirmed diagnosis of Gaucher disease (GD, regardless of GD type or treatment status. Historically, there has been a limited understanding of type 3 GD (GD3 and its natural history in patients irrespective of their treatment status. Here, we describe the disease characteristics of patients with GD3 enrolled in GOS. As of October 2015, 1002 patients had been enrolled, 26 of whom were reported as GD3. The majority of patients with GD3 were from the US (13; 50.0%, seven (26.9% were from the UK, three (11.5% from Israel, and three (11.5% from Brazil. No patients were of Ashkenazi Jewish origin. Median age of symptom onset was 1.4 (interquartile range: 0.5–2.0 years. The most common GBA1 mutation genotype was L444P/L444P, occurring in 16 (69.6% of 23 patients who had genotyping information available. Nine patients reported a family history of GD (any type. Of 21 patients with treatment status information, 20 (95.2% had received GD-specific treatment at any time, primarily imiglucerase (14 patients and/or velaglucerase alfa (13 patients. Hemoglobin concentrations and platelet counts at GOS entry were within normal ranges for most patients, and there were no reports of severe hepatomegaly or of splenomegaly in non-splenectomized patients, most likely indicative of the effects of treatment received prior to GOS entry. This analysis provides information on the characteristics of patients with GD3 that could be used as the baseline for longitudinal follow-up of these patients.

International Collaboration Activities in Different Geologic Disposal Environments

International Nuclear Information System (INIS)

Birkholzer, Jens

2015-01-01

This report describes the current status of international collaboration regarding geologic disposal research in the Used Fuel Disposition (UFD) Campaign. Since 2012, in an effort coordinated by Lawrence Berkeley National Laboratory, UFD has advanced active collaboration with several international geologic disposal programs in Europe and Asia. Such collaboration allows the UFD Campaign to benefit from a deep knowledge base with regards to alternative repository environments developed over decades, and to utilize international investments in research facilities (such as underground research laboratories), saving millions of R&D dollars that have been and are being provided by other countries. To date, UFD's International Disposal R&D Program has established formal collaboration agreements with five international initiatives and several international partners, and national lab scientists associated with UFD have conducted specific collaborative R&D activities that align well with its R&D priorities.

International Collaboration Activities in Different Geologic Disposal Environments

Energy Technology Data Exchange (ETDEWEB)

Birkholzer, Jens [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

2015-09-01

This report describes the current status of international collaboration regarding geologic disposal research in the Used Fuel Disposition (UFD) Campaign. Since 2012, in an effort coordinated by Lawrence Berkeley National Laboratory, UFD has advanced active collaboration with several international geologic disposal programs in Europe and Asia. Such collaboration allows the UFD Campaign to benefit from a deep knowledge base with regards to alternative repository environments developed over decades, and to utilize international investments in research facilities (such as underground research laboratories), saving millions of R&D dollars that have been and are being provided by other countries. To date, UFD’s International Disposal R&D Program has established formal collaboration agreements with five international initiatives and several international partners, and national lab scientists associated with UFD have conducted specific collaborative R&D activities that align well with its R&D priorities.

Processes of international collaboration in management research

DEFF Research Database (Denmark)

Jonsen, Karsten; Butler, Christina; Mäkelä, Kristiina

2013-01-01

Scientists and academics increasingly work on collaborative projects and write papers in international research teams. This trend is driven by greater publishing demands in terms of the quality and breadth of data and analysis methods, which tend to be difficult to achieve without collaborating...... across institutional and national boundaries. Yet, our understanding of the collaborative processes in an academic setting and the potential tensions associated with them remains limited. We use a reflexive, autoethnographic approach to explicitly investigate our own experiences of international...... collaborative research. We offer systematic insights into the social and intellectual processes of academic collaborative writing, identifying six lessons and two key tensions that influence the success of international research teams. Our findings may benefit the formation of future coauthor teams...

Doppler ultrasound study of portal hemodynamics in patients with Gaucher disease

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Šarenac-Kovač Radmila

2015-01-01

Full Text Available Gaucher disease is a lysosomal storage disorder caused by a deficiency of the enzyme glucocerebrosidase and characterized by the presence of pathological macrophages laden with glucosylceramide. Hepatosplenomegaly is a common manifestation of Gaucher disease, but symptomatic portal hypertension is rarely seen. The study included 20 untreated adult patients with Gaucher disease (non-neuronopathic type 1 diagnosed with the presence of Gaucher cells in the bone marrow, and 20 healthy subjects as controls. The examination of patients included color Doppler ultrasonography (pulsed Doppler mode, resistive index (RI and Doppler perfusion index (DPI using a Toshiba Xario ultrasound machine and a convex array probe PVT-375AX (1.9-6 MHz with the objective of analyzing portal hemodynamics. Results showed that all patients had enlarged liver and spleen, and their average sizes were significantly larger than those in the healthy controls (liver: 17.04 vs.14.02 cm; spleen: 22.2 vs. 10.74 cm. DPI values were significantly different between patients and controls (0.15 vs. 0.21. Considering DPI <0.15 indicates arterial liver hypoperfusion and hypoxia, it can be concluded that a number of patients had a problem with liver oxygenation, which may be linked to the high angiotensin-converting enzyme (ACE levels obtained in the patients (339.42 U/L, 10 times greater than in control subjects. Since ACE is a potent vasoconstrictor produced by spleen macrophages in Gaucher disease, we can suppose that elevated ACE is associated with effects on the blood vessels of the liver and spleen. [Projekat Ministarstva nauke Republike Srbije, br. 175056

Pathogenesis of Bone Alterations in Gaucher Disease: The Role of Immune System

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Juan Marcos Mucci

2015-01-01

Full Text Available Gaucher, the most prevalent lysosomal disorder, is an autosomal recessive inherited disorder due to a deficiency of glucocerebrosidase. Glucocerebrosidase deficiency leads to the accumulation of glucosylceramide primarily in cells of mononuclear-macrophage lineage. Clinical alterations are visceral, hematological, and skeletal. Bone disorder in Gaucher disease produces defects on bone metabolism and structure and patients suffer from bone pain and crisis. Skeletal problems include osteopenia, osteoporosis, osteolytic lesions, and osteonecrosis. On the other hand a chronic stimulation of the immune system is a well-accepted hallmark in this disease. In this review we summarize the latest findings in the mechanisms leading to the bone pathology in Gaucher disease in relationship with the proinflammatory state.

Haematological Problems Associated with Gaucher's Disease ...

African Journals Online (AJOL)

Five recent cases of Gaucher's disease seen at Groote Schuur Hospital illustrate the haematological complications. The main problem is hypersplenism with secondary thrombocytopenia. Two patients underwent splenectomy for this reason, and one gained lasting improvement. None of the more rare haematological ...

The saccadic and neurological deficits in type 3 Gaucher disease.

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William Benko

Full Text Available Our objective was to characterize the saccadic eye movements in patients with type 3 Gaucher disease (chronic neuronopathic in relationship to neurological and neurophysiological abnormalities. For approximately 4 years, we prospectively followed a cohort of 15 patients with Gaucher type 3, ages 8-28 years, by measuring saccadic eye movements using the scleral search coil method. We found that patients with type 3 Gaucher disease had a significantly higher regression slope of duration vs amplitude and peak duration vs amplitude compared to healthy controls for both horizontal and vertical saccades. Saccadic latency was significantly increased for horizontal saccades only. Downward saccades were more affected than upward saccades. Saccade abnormalities increased over time in some patients reflecting the slowly progressive nature of the disease. Phase plane plots showed individually characteristic patterns of abnormal saccade trajectories. Oculo-manual dexterity scores on the Purdue Pegboard test were low in virtually all patients, even in those with normal cognitive function. Vertical saccade peak duration vs amplitude slope significantly correlated with IQ and with the performance on the Purdue Pegboard but not with the brainstem and somatosensory evoked potentials. We conclude that, in patients with Gaucher disease type 3, saccadic eye movements and oculo-manual dexterity are representative neurological functions for longitudinal studies and can probably be used as endpoints for therapeutic clinical trials.ClinicalTrials.gov NCT00001289.

Gaucher's disease in a black child in South Africa. A case report.

Science.gov (United States)

Patel, R; MacDougall, L G

1984-09-01

A 7-year-old Black boy presented with massive splenomegaly and a tendency to haemorrhage due to type 1 Gaucher's disease. After splenectomy he became asymptomatic and the haematological parameters returned to normal. Although type 1 Gaucher's disease has been described in adult Blacks, it has not been reported previously in a Black child in southern Africa.

Manifestações esqueléticas da doença de gaucher Skeletal manifestations in Gaucher's disease

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Vinicius França de Mendonça

2001-06-01

Full Text Available A doença de Gaucher é manifestação genética causada pela deficiência da enzima glicocerebrosidase, resultando no acúmulo secundário de glicocerebrosídeos nos órgãos do sistema reticuloendotelial. Apresenta-se sob três formas clínicas distintas, podendo ser rapidamente fatal ou crônica com poucos sintomas. O presente trabalho tem o objetivo de analisar os achados da radiografia simples do esqueleto em 32 pacientes comprovadamente portadores da doença, de ambos os sexos e em diferentes faixas etárias. Foram observadas as seguintes alterações: osteopenia difusa em todos os casos, deformidade em "frasco de Erlenmeyer" em 93,7%, alterações articulares em 40,6%, necrose da cabeça do fêmur e lesões líticas em 28,1%, respectivamente, fratura patológica em 9,3% e necrose da cabeça do úmero em 6,2% dos casos. Estes resultados encontram-se de acordo com as descrições da literatura, demonstrando a importância da radiologia convencional como método complementar no diagnóstico desta enfermidade.Gaucher's disease has a genetic background and is characterized by the deficiency of enzyme glucocerebrosidase, resulting in secondary accumulation of glucocerebrosides in the reticuloendothelial organs. The objective of the present study is to evaluate the x-ray findings in the skeleton of a group of 32 male and female patients of different ages, with biochemical diagnosis of Gaucher's disease. The following bone lesions were observed: diffuse osteopenia (100% of the patients, "Erlenmeyer flask" deformities (93.7% of the patients, abnormalities of the joints (40.6% of the patients, necrosis of the femoral head (28.1% of the patients, lytic lesions (28.1% of the patients, pathological fractures (9.3% of the patients and necrosis of the humeral head (6.2% of the patients. These results are concordant with the literature, and demonstrate the importance of conventional x-ray as a complementary method in the diagnosis of Gaucher's disease.

Evaluation of neopterin as a biomarker for the monitoring of Gaucher disease patients.

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Drugan, Cristina; Drugan, Tudor C; Miron, Nicolae; Grigorescu-Sido, Paula; Naşcu, Ioana; Cătană, Cristina

2016-07-01

Biomarker research is an important area of investigation in Gaucher disease, caused by an inherited deficiency of a lysosomal enzyme, glucocerebrosidase. We evaluated the usefulness of neopterin, as a novel biomarker reflecting chronic inflammation and immune system activation in Gaucher disease and analysed its evolution in response to enzyme replacement therapy (ERT). Circulating plasma neopterin levels in 31 patients with non-neuronopathic Gaucher disease were measured before and after the onset of ERT and were compared with those of 18 healthy controls. Plasma chitotriosidase activity was also monitored, as a reference biomarker, against which we evaluated the evolution of neopterin. Neopterin levels were significantly increased in treatment-naïve patients (mean 11.90 ± 5.82 nM) compared with controls (6.63 ± 5.59 nM, Mann-Whitney U test P = 0.001), but returned to normal levels (6.92 ± 4.66 nM) following ERT. Investigating the diagnostic value of neopterin by receiver operating characteristic analysis, we found a cut-off value of 7.613 nM that corresponds to an area under the curve of 0.780 and indicates a good discrimination capacity, with a sensitivity of 0.774 and a specificity of 0.778. Our results suggest that measurement of circulating neopterin may be considered as a novel test for the confirmation of diagnosis and monitoring of the efficacy of therapeutic intervention in Gaucher disease. Plasma neopterin levels reflect the global accumulation and activation of Gaucher cells and the extent of chronic immune activation in this disorder. Neopterin may be an alternative storage cell biomarker in Gaucher disease, especially in chitotriosidase-deficient patients.

INTERNATIONAL COLLABORATION: Panelling

International Nuclear Information System (INIS)

Anon.

1991-01-01

At the meeting of the International Committee for Future Accelerators (ICFA), in Geneva in July, Chairman A.N. Skrinsky of Novosibirsk reviewed ICFA progress, particularly the activities of the specialist Panels which pursue specific Committee objectives in guiding worldwide collaboration in high energy physics

INTERNATIONAL COLLABORATION: Panelling

Energy Technology Data Exchange (ETDEWEB)

Anon.

1991-10-15

At the meeting of the International Committee for Future Accelerators (ICFA), in Geneva in July, Chairman A.N. Skrinsky of Novosibirsk reviewed ICFA progress, particularly the activities of the specialist Panels which pursue specific Committee objectives in guiding worldwide collaboration in high energy physics.

Gaucher disease: plasmalogen levels in relation to primary lipid abnormalities and oxidative stress.

Science.gov (United States)

Moraitou, Marina; Dimitriou, Evangelia; Dekker, Nick; Monopolis, Ioannis; Aerts, Johannes; Michelakakis, Helen

2014-01-01

Plasmalogens represent a unique class of phospholipids. Reduced red blood cell plasmalogen levels in Gaucher disease patients were reported, correlating to total disease burden. The relation between plasmalogen abnormalities in Gaucher disease patients and primary glycosphingolipid abnormalities, malonyldialdehyde levels, an indicator of lipid peroxidation, and the total antioxidant status was further investigated. Significant reduction of C16:0 and C18:0 plasmalogens in red blood cells of Gaucher disease patients was confirmed. In parallel, a significant increase in the glucosylceramide/ceramide ratio in red blood cell membranes, as well as an average 200-fold increase in plasma glucosylsphingosine levels was observed. Red blood cell malonyldialdehyde levels were significantly increased in patients, whereas their total antioxidant status was significantly reduced. A negative correlation between plasmalogen species and glucosylceramide, ceramide, glucosylceramide/ceramide ratio, glucosylsphingosine and malonyldialdehyde, significant for the C16:0 species and all the above parameters with the exception of malonyldialdehyde levels, was found along with a positive non-significant correlation with the total antioxidant status. Our results indicate that increased lipid peroxidation and reduced total antioxidant status exist in Gaucher disease patients. They demonstrate a clear link between plasmalogen levels and the primary glycolipid abnormalities characterizing the disorder and an association with the increased oxidative stress observed in Gaucher disease patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Glycosphingolipid analysis in a naturally occurring ovine model of acute neuronopathic Gaucher disease.

Science.gov (United States)

Karageorgos, Litsa; Hein, Leanne; Rozaklis, Tina; Adams, Melissa; Duplock, Stephen; Snel, Marten; Hemsley, Kim; Kuchel, Tim; Smith, Nicholas; Hopwood, John J

2016-07-01

Gaucher disease arises from mutations in the β-glucocerebrosidase gene which encodes an enzyme required for the lysosomal catabolism of glucosylceramide. We have identified a naturally occurring mutation in the β-glucocerebrosidase gene in sheep that leads to Gaucher disease with acute neurological symptoms. Here we have examined the clinical phenotype at birth and subsequently quantified lipids in Gaucher lamb brain, in order to characterise the disorder. Enzyme activity assessments showed that a reduction in β-glucocerebrosidase activity to 1-5% of wild-type occurs consistently across newborn Gaucher lamb brain regions. We analyzed glucosylceramide, glucosylsphingosine, bis(monoacylglycero)phosphate and ganglioside profiles in brain, liver, and spleen, and observed 30- to 130-fold higher glucosylceramide, and 500- to 2000-fold higher glucosylsphingosine concentrations in Gaucher diseased lambs compared to wild-type. Significant increases of bis(monoacylglycero)phosphate and gangliosides [GM1, GM2, GM3] concentrations were also detected in the brain. As these glycosphingolipids are involved in many cellular events, an imbalance or disruption of the cell membrane lipid homeostasis would be expected to impair normal neuronal function. To our knowledge, this is the first detailed analysis of glycosphingolipids in various brain regions in a large animal model of neuronal disease, which permits the mechanistic investigation of lipid deregulation and their contribution to neurodegenerative process. Copyright © 2016 Elsevier Inc. All rights reserved.

Integrating Diverse Data Systems for International Collaboration

Science.gov (United States)

Fox, Peter

2014-05-01

International collaborations, especially ones that arise with little or no financial resources, still face challenges in opening up data collections via a wide variety of differing and often non-interoperable means. In turn, this hampers the collaborative process, slows or even prevents scientific exchange. Early efforts that proposed a centralized, and project specific data archive encountered many difficulties, ranging from little or no adoption, to the inability to provide required documentation and metadata to make the datasets findable or usable. In time, virtualized approaches appeared to gain traction, for e.g. virtual observatories. In this contribution, we report on several international collaboration case studies with distributed data systems; their needs, successes, challenges and failures and synthesize a set of suggested practices to inform future international collaboration efforts.

Gaucher disease: MR evaluation of bone marrow features during treatment with enzyme replacement; Morbus Gaucher: Analyse der Knochenmarkveraenderungen in der MRT waehrend Enzymersatztherapie

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Poll, L.W.; Koch, J.A.; Boerner, D.; Cohnen, M.; Jung, G.; Scherer, A.; Moedder, U. [Duesseldorf Univ. (DF). Inst. fuer Diagnostische Radiologie; Dahl, S. vom; Haeussinger, D. [Duesseldorf Univ. (Germany). Klinik fuer Gastroenterologie, Hepatologie und Infektiologie; Willers, R. [Rechenzentrum, Heinrich-Heine-Univ. Duesseldorf (Germany); Niederau, C. [Innere Abt., St. Josef-Hospital Oberhausen, Akademisches Lehrkrankenhaus der Univ. Essen (Germany)

2001-10-01

Purpose: Enzyme replacement therapy (ERT) arrests and reverses the hematological and visceral symptoms of adult Gaucher disease, the most frequent lysosomal storage disorder. There are only a few studies available evaluating bone disease during ERT. The aim of this study was to investigate the features of bone marrow (bm) by magnetic resonance imaging (MRI) in these patients during ERT. Materials and Methods: MRI was performed prospectively in thirty adult type I Gaucher patients before and during ERT with a mean follow-up of 3 years. Spin-echo sequences (T{sub 1}/T{sub 2}) of the lower extremities were obtained and the reconversion (response) or lack of reconversion (non-response) to fatty marrow during treatment was analyzed. The morphological features of bm involvement, a homogeneous or non-homogeneous distribution of bm changes and focal bone lesions surrounded by a rim of reduced signal intensity (SI), were analyzed. Results: Infiltration of bm by Gaucher cells is characterized by a reduction of Sl on both T{sub 1}- and T{sub 2}-weighted sequences. Bone marrow responses were seen in 19 patients (63%) during treatment. Focal bone lesions, surrounded by a rim of reduced Sl, did not respond to ERT and correlated with a non-homogenous distribution of bone involvement and splenectomy. (orig.) [German] Ziel: Unter Enzymersatztherapie (enzyme replacement therapy = ERT) zeigen Patienten mit adulter Form des Morbus Gaucher, der haeufigsten lysosomalen Speicherkrankheit, eine deutliche Besserung der haematologischen und visceralen Symptome. Bislang liegen nur wenige Untersuchungen zur Analyse der Knochenveraenderungen waehrend der ERT vor. Ziel war es, die Knochenmarkveraenderungen bei Gaucher-Patienten waehrend der Enzymersatztherapie mit Alglucerase/Imiglucerase in der Magnetresonanztomographie (MRT) zu evaluieren. Material und Methoden: In einer prospektiven Untersuchung wurden 30 adulte Patienten mit gesichertem Morbus Gaucher vor und waehrend der ERT in der MRT

Learning Together Through International Collaborative Writing Groups

Directory of Open Access Journals (Sweden)

Mick Healey

2017-03-01

Full Text Available The International Collaborative Writing Groups (ICWG initiative creates a space for ongoing collaboration amongst scholars of teaching and learning who co-author a manuscript on a topic of shared interest. The second ICWG, linked to the 2015 International Society for the Scholarship of Teaching and Learning Conference in Melbourne, Australia, involved 59 scholars from 11 countries. In this piece, we describe the aims, process, and outcomes for the ICWG, comparing it with the first ICWG in 2012. While international collaboration around a topic of shared interest is generally viewed positively, the realities of collaborating online with limited face-to-face interactions to complete a manuscript can be challenging. We argue, despite such challenges, that ongoing collaboration amongst scholars is vital to the scholarship of teaching and learning (SoTL movement. Drawing on our experience of leading the overall ICWG initiative and our research into participants’ experiences, we suggest there are individual dispositions toward collaboration that enrich and enable successful participation in ICWG experiences. We end by highlighting the final products arising from almost two year of collaborative thinking and writing from six groups.

Inhibition of UDP-glucosylceramide synthase in mice prevents Gaucher disease-associated B-cell malignancy

NARCIS (Netherlands)

Pavlova, Elena V.; Archer, Joy; Wang, Susan; Dekker, Nick; Aerts, Johannes Mfg; Karlsson, Stefan; Cox, Timothy M.

2015-01-01

Clonal B-cell proliferation is a frequent manifestation of Gaucher disease - a sphingolipidosis associated with a high risk of multiple myeloma and non-Hodgkin lymphoma. Gaucher disease is caused by genetic deficiency of acid β-glucosidase, the natural substrates of which (β-d-glucosylceramide and

MRI bone marrow findings in 63 patients with type I Gaucher's disease

International Nuclear Information System (INIS)

Poll, L.W.; Willers, R.; Haeussinger, D.; Moedder, U.; Dahl, S. vom

2010-01-01

Purpose: To determine whether MR bone marrow findings in Gaucher patients may help to identify patients at high risk of developing severe Gaucher bone complications exemplified by avascular necrosis (AVN) of the femoral head. Materials and Methods: MR images were obtained in 63 Type I Gaucher patients through a standard protocol using coronal T1 and T2-weighted sequences of the lower extremities. The location and extent of infiltrated marrow was established using a semi-quantitative MRI scoring method (Duesseldorf Gaucher score, DGS) and the morphological pattern of bone marrow involvement determined (whether homogeneous type A or non-homogeneous type B). The active marrow process with bone edema and AVN of the femoral head were also analyzed. Results: Bone marrow involvement was observed in femoral sites more than in tibial sites. A high DGS was significantly correlated with type B morphology and femoral AVN (both p < 0.0001). Splenectomized patients showed a significantly higher Duesseldorf Gaucher score and type B morphology than non-splenectomized patients (both p < 0.05). AVN was seen in 46 % of patients with type B morphology versus 3 % in type A morphology (p < 0.0001). DGS and morphology of bone marrow involvement were not significantly correlated with active marrow processes. Conclusion: Type B marrow morphology and extensive marrow packing were significantly associated with AVN of the femoral head (both p < 0.0001). These patterns are considered predictive and may be employed in a disease management context to alert physicians to the need for urgent therapeutic measures. (orig.)

Novel insertion mutation in a non-Jewish Caucasian type 1 Gaucher disease patient

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Choy, F.Y.M.; Humphries, M.L. [Univ. of Victoria, British Columbia (Canada); Ferreira, P. [Univ. of Alberta, Edmonton (Canada)

1997-01-20

Gaucher disease is the most prevalent lysosomal storage disorder. It is autosomal recessive, resulting in lysosomal glucocerebrosidase deficiency. Three clinical forms of Gaucher disease have been described: type 1 (nonneuronopathic), type 2 (acute neuronopathic), and type 3 (subacute neuronopathic). We performed PCR-thermal cycle sequence analysis of glucocerebrosidase genomic DNA and identified a novel mutation in a non-Jewish type 1 Gaucher disease patient. It is a C insertion in exon 3 at cDNA nucleotide position 122 and genomic nucleotide position 1626. This mutation causes a frameshift and, subsequently, four of the five codons immediately downstream of the insertion were changed while the sixth was converted to a stop codon, resulting in premature termination of protein translation. The 122CC insertion abolishes a Cac81 restriction endonuclease cleavage site, allowing a convenient and reliable method for detection using RFLP analysis of PCR-amplified glucocerebrosidase genomic DNA. The mutation in the other Gaucher allele was found to be an A{r_arrow}G substitution at glucocerebrosidase cDNA nucleotide position 1226 that so far has only been reported among type 1 Gaucher disease patients. Since mutation 122CC causes a frameshift and early termination of protein translation, it most likely results in a meaningless transcript and subsequently no residual glucocerebrosidase enzyme activity. We speculate that mutation 122CC may result in a worse prognosis than mutations associated with partial activity. When present in the homozygous form, it could be a lethal allele similar to what has been postulated for the other known insertion mutation, 84GG. Our patient, who is a compound heterozygote 122CC/1226G, has moderately severe type 1 Gaucher disease. Her clinical response to Ceredase{reg_sign} therapy that began 31 months ago has been favorable, though incomplete. 30 refs., 3 figs., 2 tabs.

Collaborating internationally on physician leadership development: why now?

Science.gov (United States)

Chan, Ming-Ka; de Camps Meschino, Diane; Dath, Deepak; Busari, Jamiu; Bohnen, Jordan David; Samson, Lindy Michelle; Matlow, Anne; Sánchez-Mendiola, Melchor

2016-07-04

Purpose This paper aims to highlight the importance of leadership development for all physicians within a competency-based medical education (CBME) framework. It describes the importance of timely international collaboration as a key strategy in promoting physician leadership development. Design/methodology/approach The paper explores published and Grey literature around physician leadership development and proposes that international collaboration will meet the expanding call for development of leadership competencies in postgraduate medical learners. Two grounding frameworks were used: complexity science supports adding physician leadership training to the current momentum of CBME adoption, and relational cultural theory supports the engagement of diverse stakeholders in multiple jurisdictions around the world to ensure inclusivity in leadership education development. Findings An international collaborative identified key insights regarding the need to frame physician leadership education within a competency-based model. Practical implications International collaboration can be a vehicle for developing a globally relevant, generalizable physician leadership curriculum. This model can be expanded to encourage innovation, scholarship and program evaluation. Originality/value A competency-based leadership development curriculum is being designed by an international collaborative. The curriculum is based on established leadership and education frameworks. The international collaboration model provides opportunities for ongoing sharing, networking and diversification.

The absence of later wave components in auditory brainstem responses as an initial manifestation of type 2 Gaucher disease.

Science.gov (United States)

Okubo, Yusuke; Goto, Masahiro; Sakakibara, Hiroshi; Terakawa, Toshiro; Kaneko, Takashi; Miyama, Sahoko

2014-12-01

Type 2 Gaucher disease is the most severe neuronopathic form of Gaucher disease and is characterized by severe neurodegeneration with brainstem involvement and organ failure. Prediction or diagnosis of type 2 Gaucher disease before the development of neurological complications is difficult. A 5-month-old female infant presented with deafness without other neurological abnormalities. Auditory brainstem response analysis revealed the absence of later wave components. Two months later, muscular rigidity became evident, followed by the development of opisthotonus and strabismus. Rapid progression of splenomegaly led to the diagnosis of type 2 Gaucher disease. Abnormal auditory brainstem response findings may already exist before the development of severe brainstem abnormalities such as muscular rigidity and opisthotonus in type 2 Gaucher disease. When patients present with deafness and absent later wave components on auditory brainstem response, type 2 Gaucher disease should be included in the differential diagnosis even in the absence of other neurological abnormalities. Copyright © 2014 Elsevier Inc. All rights reserved.

Elevated plasma glucosylsphingosine in Gaucher disease: relation to phenotype, storage cell markers, and therapeutic response

NARCIS (Netherlands)

Dekker, Nick; van Dussen, Laura; Hollak, Carla E. M.; Overkleeft, Herman; Scheij, Saskia; Ghauharali, Karen; van Breemen, Mariëlle J.; Ferraz, Maria J.; Groener, Johanna E. M.; Maas, Mario; Wijburg, Frits A.; Speijer, Dave; Tylki-Szymanska, Anna; Mistry, Pramod K.; Boot, Rolf G.; Aerts, Johannes M.

2011-01-01

Gaucher disease, caused by a deficiency of the lysosomal enzyme glucocerebrosidase, leads to prominent glucosylceramide accumulation in lysosomes of tissue macrophages (Gaucher cells). Here we show glucosylsphingosine, the deacylated form of glucosylceramide, to be markedly increased in plasma of

Mass spectrometric quantification of glucosylsphingosine in plasma and urine of type 1 Gaucher patients using an isotope standard.

Science.gov (United States)

Mirzaian, Mina; Wisse, Patrick; Ferraz, Maria J; Gold, Henrik; Donker-Koopman, Wilma E; Verhoek, Marri; Overkleeft, Herman S; Boot, Rolf G; Kramer, Gertjan; Dekker, Nick; Aerts, Johannes M F G

2015-04-01

Deficiency of glucocerebrosidase (GBA) leads to Gaucher disease (GD), an inherited disorder characterised by storage of glucosylceramide (GlcCer) in lysosomes of tissue macrophages. Recently, we reported marked increases of deacylated GlcCer, named glucosylsphingosine (GlcSph), in plasma of GD patients. To improve quantification, [5-9] (13)C5-GlcSph was synthesised for use as internal standard with quantitative LC-ESI-MS/MS. The method was validated using plasma of 55 GD patients and 20 controls. Intra-assay variation was 1.8% and inter-assay variation was 4.9% for GlcSph (m/z 462.3). Plasma GlcSph levels with the old and new methods closely correlate (r=0.968, slope=1.038). Next, we analysed GlcSph in 24h urine samples of 30 GD patients prior to therapy. GlcSph was detected in the patient samples (median 1.20nM, range 0.11-8.92nM), but was below the limit of quantification in normal urine. Enzyme replacement therapy led to a decrease of urinary GlcSph of GD patients, coinciding with reductions in plasma GlcSph and markers of Gaucher cells (chitotriosidase and CCL18). In analogy to globotriaosylsphingsone in urine of Fabry disease patients, additional isoforms of GlcSph differing in structure of the sphingosine moiety were identified in GD urine samples. In conclusion, GlcSph can be sensitively detected by LC-ESI-MS/MS with an internal isotope standard. Abnormalities in urinary GlcSph are a hallmark of Gaucher disease allowing biochemical confirmation of diagnosis. Copyright © 2015. Published by Elsevier Inc.

Image-guided, direct convective delivery of glucocerebrosidase for neuronopathic Gaucher disease.

Science.gov (United States)

Lonser, R R; Schiffman, R; Robison, R A; Butman, J A; Quezado, Z; Walker, M L; Morrison, P F; Walbridge, S; Murray, G J; Park, D M; Brady, R O; Oldfield, E H

2007-01-23

To determine if convection-enhanced delivery (CED) of glucocerebrosidase could be used to treat targeted sites of disease progression in the brain and brainstem of a patient with neuronopathic Gaucher disease while monitoring enzyme distribution using MRI. A CED paradigm in rodents (n = 8) and primates (n = 5) that employs co-infusion of a surrogate MRI tracer (gadolinium diethylenetriamine penta-acetic acid [Gd-DTPA]) with glucocerebrosidase to permit real-time monitoring of distribution was developed. The safety and feasibility of this delivery and monitoring paradigm were evaluated in a patient with type 2 Gaucher disease. Animal studies revealed that real-time, T1-weighted, MRI of Gd-DTPA accurately tracked enzyme distribution during CED. Targeted perfusion of clinically affected anatomic sites in a patient with neuronopathic Gaucher disease (frontal lobe and brainstem) with glucocerebrosidase was successfully performed. Real-time MRI revealed progressive and complete filling of the targeted region with enzyme and Gd-DTPA infusate. The patient tolerated the infusions without evidence of toxicity. Convection-enhanced delivery can be used to safely perfuse large regions of the brain and brainstem with therapeutic levels of glucocerebrosidase. Co-infused imaging surrogate tracers can be used to monitor and control the distribution of therapeutic agents in vivo. Patients with neuronopathic Gaucher disease and other intrinsic CNS disorders may benefit from a similar treatment paradigm.

Exploring the patient journey to diagnosis of Gaucher disease from the perspective of 212 patients with Gaucher disease and 16 Gaucher expert physicians.

Science.gov (United States)

Mehta, Atul; Belmatoug, Nadia; Bembi, Bruno; Deegan, Patrick; Elstein, Deborah; Göker-Alpan, Özlem; Lukina, Elena; Mengel, Eugen; Nakamura, Kimitoshi; Pastores, Gregory M; Pérez-López, Jordi; Schwartz, Ida; Serratrice, Christine; Szer, Jeffrey; Zimran, Ari; Di Rocco, Maja; Panahloo, Zoya; Kuter, David J; Hughes, Derralynn

2017-11-01

Gaucher disease (GD) is a rare hereditary disorder caused by a deficiency of the lysosomal enzyme β-glucocerebrosidase. Diagnosis is challenging owing to a wide variability in clinical manifestations and severity of symptoms. Many patients may experience marked delays in obtaining a definitive diagnosis. The two surveys reported herein aimed to explore the patient journey to diagnosis of GD from the perspectives of Gaucher expert physicians and patients. Findings from the surveys revealed that many patients experienced diagnostic delays and misdiagnoses, with nearly 1 in 6 patients stating that they were not diagnosed with GD for 7years or more after first consulting a doctor. Physicians and patients both reported multiple referrals to different specialties before a diagnosis of GD was obtained, with primary care, haematology/haematology-oncology and paediatrics the main specialties to which patients first presented. Splenomegaly, thrombocytopenia, anaemia and bone pain were reported as the most common medical problems at first presentation in both surveys. These findings support a clear need for straightforward and easy-to-follow guidance designed to assist non-specialists to identify earlier patients who are at risk of GD. Copyright © 2017 The Authors and Shire HGT Inc. Published by Elsevier Inc. All rights reserved.

Enzyme replacement and substrate reduction therapy for Gaucher disease.

Science.gov (United States)

Shemesh, Elad; Deroma, Laura; Bembi, Bruno; Deegan, Patrick; Hollak, Carla; Weinreb, Neal J; Cox, Timothy M

2015-03-27

Gaucher disease, a rare disorder, is caused by inherited deficiency of the enzyme glucocerebrosidase. It is unique among the ultra-orphan disorders in that four treatments are currently approved by various regulatory authorities for use in routine clinical practice. Hitherto, because of the relatively few people affected worldwide, many of whom started therapy during a prolonged period when there were essentially no alternatives to imiglucerase, these treatments have not been systematically evaluated in studies such as randomized controlled trials now considered necessary to generate the highest level of clinical evidence. To summarize all available randomized controlled study data on the efficacy and safety of enzyme replacement therapies and substrate reduction therapy for treating Gaucher disease. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register. Additional searches were conducted on ClinicalTrials.gov for any ongoing studies with potential interim results, and through PubMed. We also searched the reference lists of relevant articles and reviews.Date of last search: 07 August 2014. All randomized and quasi-randomized controlled studies (including open-label studies and cross-over studies) assessing enzyme replacement therapy or substrate reduction therapy, or both, in all types of Gaucher disease were included. Two authors independently assessed the risk of bias in the included studies, and extracted relevant data. Of the 488 studies retrieved by the electronic searches, eight met the inclusion criteria and were analysed (300 participants). Response parameters were restricted to haemoglobin concentration, platelet count, spleen and liver volume and serum biomarkers (chitotriosidase and CCL18). Only one publication reported a 'low risk of bias' score in all parameters assessed, and all studies included were randomized.Four studies reported the responses to enzyme replacement therapy of previously

The use of technology in international collaboration

DEFF Research Database (Denmark)

Livonen, Mirja; Sonnenwald, Diane H.

2000-01-01

International collaboration is emerging as an essential function for organizations, playing an important role in organizational strategy, performance and knowledge management. Two case studies of international collaboration are discussed in this paper. Participants' perceptions and use...... of technology to collaborate are examined from the perspective of sense of presence, participation, task type, productivity and ease of use. The data suggest that technology compatibility with cultural and work style preferences and technology infrastructure is more important than media richness, in contrast...

Demographics and patient characteristics of 1209 patients with Gaucher disease: Descriptive analysis from the Gaucher Outcome Survey (GOS)

Science.gov (United States)

Belmatoug, Nadia; Bembi, Bruno; Deegan, Patrick; Elstein, Deborah; Fernandez‐Sasso, Diego; Giraldo, Pilar; Goker‐Alpan, Ozlem; Lau, Heather; Lukina, Elena; Panahloo, Zoya; Schwartz, Ida Vanessa D.

2017-01-01

Abstract The Gaucher Outcome Survey (GOS) is an international Gaucher disease (GD) registry established in 2010 for patients with a confirmed GD diagnosis, regardless of GD type or treatment status, designed to evaluate the safety and long‐term effectiveness of velaglucerase alfa and other GD‐related treatments. As of February 25, 2017, 1209 patients had enrolled, the majority from Israel (44.3%) and the US (31.4%). Median age at GOS entry was 40.4 years, 44.1% were male, and 13.3% had undergone a total splenectomy. Most patients had type 1 GD (91.5%) and were of Ashkenazi Jewish ethnicity (55.8%). N370S/N370S was the most prevalent genotype, accounting for 44.2% of genotype‐confirmed individuals (n = 847); however, there was considerable variation between countries. A total of 887 (73.4%) patients had received ≥1 GD‐specific treatment at any time, most commonly imiglucerase (n = 587), velaglucerase alfa (n = 507), and alglucerase (n = 102). Hematological and visceral findings at the time of GOS entry were close to normal for most patients, probably a result of previous treatment; however, spleen volume of patients in Israel was almost double that of patients elsewhere (7.2 multiples of normal [MN] vs. 2.7, 2.9 and 4.9 MN in the US, UK and rest of world), which may be explained by a greater disease severity in this cohort. This analysis aimed to provide an overview of GOS and present baseline demographic and disease characteristics of participating patients to help improve the understanding of the natural history of GD and inform the overall management of patients with the disease. PMID:29090476

Investigation of novel pharmacological chaperones for Gaucher Disease.

Science.gov (United States)

Yilmazer, Buge; Yagci, Z Begum; Bakar, Emre; Ozden, Burcu; Ulgen, Kutlu; Ozkirimli, Elif

2017-09-01

Beta-Glucocerebrosidase (GBA) is a lysosomal protein that is responsible for the hydrolysis of glycosylceramide into glucose and ceramide. Mutations in GBA lead to the accumulation of glycosylceramide in the lysosome causing an enlargement of the spleen and the liver and skeletal deformations. This disease is called Gaucher Disease. Enzyme replacement therapies and substrate reduction methods that are used to treat Gaucher Disease fail when the disease is neuropathic because they fail to pass the blood brain barrier. In this work, QSAR, virtual screening, docking and molecular dynamics simulations were performed to obtain a set of compounds that might be pharmacological chaperones for GBA. ZINC Database was screened using ligand-based and structure-based pharmacophore hypotheses. After docking of these molecules and filtration based on druglikeness, top ranking ligands were identified and their binding stabilities were examined using MD simulations. As a result, seven new compounds that can potentially cross the blood brain barrier were proposed as GBA inhibitors. Three of the seven compounds have a tricyclic pyrido-thieno-pyrimidine scaffold and one has the dioxino quinolone scaffold. Derivatives of these scaffolds have been reported as antiallergic agents, antibiotic and anticancer compounds. These results offer a new approach for the development of new drugs against neuropathic Gaucher Disease Type 2 and Type 3. Copyright © 2017 Elsevier Inc. All rights reserved.

Involvement of Gaucher Disease Mutations in Parkinson Disease.

Science.gov (United States)

Vilageliu, Lluisa; Grinberg, Daniel

2017-01-01

Gaucher disease is an autosomal recessive lysosomal storage disorder, caused by mutations in the GBA gene. The frequency of Gaucher disease patients and heterozygote carriers that developed Parkinson disease has been found to be above that of the control population. This fact suggests that mutations in the GBA gene can be involved in Parkison's etiology. Analysis of large cohorts of patients with Parkinson disease has shown that there are significantly more cases bearing GBA mutations than those found among healthy individuals. Functional studies have proven an interaction between α-synuclein and GBA, the levels of which presented an inverse correlation. Mutant GBA proteins cause increases in α-synuclein levels, while an inhibition of GBA by α-synuclein has been also demonstrated. Saposin C, a coactivator of GBA, has been shown to protect GBA from this inhibition. Among the GBA variants associated with Parkinson disease, E326K seems to be one of the most prevalent. Interestingly, it is involved in Gaucher disease only when it forms part of a double-mutant allele, usually with the L444P mutation. Structural analyses have revealed that both residues (E326 and L444) interact with Saposin C and, probably, also with α-synuclein. This could explain the antagonistic role of these two proteins in relation to GBA. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Insights into the structural biology of Gaucher disease.

Science.gov (United States)

Smith, Laura; Mullin, Stephen; Schapira, Anthony H V

2017-12-01

Gaucher disease, the most common lysosomal storage disorder, is caused by mutations in the gene encoding the acid-β-glucosidase lysosomal hydrolase enzyme that cleaves glucocerebroside into glucose and ceramide. Reduced enzyme activity and impaired structural stability arise due to >300 known disease-causing mutations. Several of these mutations have also been associated with an increased risk of Parkinson disease (PD). Since the discovery of the acid-β-glucosidase X-ray structure, there have been major advances in our understanding of the structural properties of the protein. Analysis of specific residues has provided insight into their functional and structural importance and provided insight into the pathogenesis of Gaucher disease and the contribution to PD. Disease-causing mutations are positioned throughout the acid-β-glucosidase structure, with many located far from the active site and thus retaining some enzymatic activity however, thus far no clear relationship between mutation location and disease severity has been established. Here, we review the crystal structure of acid-β-glucosidase, while highlighting important structural aspects of the protein in detail. This review discusses the structural stability of acid-β-glucosidase, which can be altered by pH and glycosylation, and explores the relationship between known Gaucher disease and PD mutations, structural stability and disease severity. Copyright © 2017. Published by Elsevier Inc.

Multiple pathogenic proteins implicated in neuronopathic Gaucher disease mice.

Science.gov (United States)

Xu, You-hai; Xu, Kui; Sun, Ying; Liou, Benjamin; Quinn, Brian; Li, Rong-hua; Xue, Ling; Zhang, Wujuan; Setchell, Kenneth D R; Witte, David; Grabowski, Gregory A

2014-08-01

Gaucher disease, a prevalent lysosomal storage disease (LSD), is caused by insufficient activity of acid β-glucosidase (GCase) and the resultant glucosylceramide (GC)/glucosylsphingosine (GS) accumulation in visceral organs (Type 1) and the central nervous system (Types 2 and 3). Recent clinical and genetic studies implicate a pathogenic link between Gaucher and neurodegenerative diseases. The aggregation and inclusion bodies of α-synuclein with ubiquitin are present in the brains of Gaucher disease patients and mouse models. Indirect evidence of β-amyloid pathology promoting α-synuclein fibrillation supports these pathogenic proteins as a common feature in neurodegenerative diseases. Here, multiple proteins are implicated in the pathogenesis of chronic neuronopathic Gaucher disease (nGD). Immunohistochemical and biochemical analyses showed significant amounts of β-amyloid and amyloid precursor protein (APP) aggregates in the cortex, hippocampus, stratum and substantia nigra of the nGD mice. APP aggregates were in neuronal cells and colocalized with α-synuclein signals. A majority of APP co-localized with the mitochondrial markers TOM40 and Cox IV; a small portion co-localized with the autophagy proteins, P62/LC3, and the lysosomal marker, LAMP1. In cultured wild-type brain cortical neural cells, the GCase-irreversible inhibitor, conduritol B epoxide (CBE), reproduced the APP/α-synuclein aggregation and the accumulation of GC/GS. Ultrastructural studies showed numerous larger-sized and electron-dense mitochondria in nGD cerebral cortical neural cells. Significant reductions of mitochondrial adenosine triphosphate production and oxygen consumption (28-40%) were detected in nGD brains and in CBE-treated neural cells. These studies implicate defective GCase function and GC/GS accumulation as risk factors for mitochondrial dysfunction and the multi-proteinopathies (α-synuclein-, APP- and Aβ-aggregates) in nGD. © The Author 2014. Published by Oxford University

Is there a role for scintigraphic imaging of bone manifestations in Gaucher disease? A review of the literature

International Nuclear Information System (INIS)

Mikosch, P.; State Hospital Klagenfurt; Kohlfuerst, S.; Gallowitsch, H.J.; Kresnik, E.; Lind, P.; Mehta, A.B.; Hughes, D.A.

2008-01-01

Gaucher disease is the most prevalent inherited, lysosomal storage disease and is caused by deficient activity of the enzyme β-glucocerebrosidase. Bone and bone marrow alterations are frequent in the most prevalent non-neuronopathic form of Gaucher disease. Imaging of bone manifestations in Gaucher disease is performed by a variety of imaging methods, conventional X-ray and MRI as the most frequently and most important ones. However, different modalities of scintigraphic imaging have also been used. This article gives an overview on scintigraphic imaging with respect to bone manifestations in Gaucher disease discussing the advantages and limitations of scintigraphic imaging in comparison to other imaging methods. (orig.)

Radiographic findings in type 3 b Gaucher disease

International Nuclear Information System (INIS)

Hill, S.C.; Damaska, B.M.; Tsokos, M.; Kreps, C.; Brady, R.O.; Barton, N.W.

1996-01-01

The purpose of this paper is to describe the radiographic findings in type 3 b Gaucher disease, a chronic neuronopathic form of the illness with severe systemic manifestations. Between 1980 and 1985 17 consecutive patients were evaluated with radiography of the chest, long bones and spine, CT of the head and chest, abdominal sonography, and MRI of the head, abdomen and spine. Clinical manifestations were severe, and led to death from hepatic, pulmonary or cardiac failure in nine patients. Type 3 b Gaucher disease shares the same spectrum of radiographic findings observed in type 1 disease, but the systemic manifestations are more severe. Pulmonary infiltrates, thoracic lymph node enlargement, vertebral compression fractures and osteonecrosis of the long bones occur much more frequently in patients with type 3 b disease. (orig.). With 7 figs., 2 tabs

International Collaboration Patterns and Effecting Factors of Emerging Technologies.

Directory of Open Access Journals (Sweden)

Xu Bai

Full Text Available With the globalization of the world economy, international innovation collaboration has taken place all over the world. This study selects three emerging technologies (3D printing, big data and carbon nanotubes and graphene technology among 20 countries as the research objects, using three patent-based indicators and network relationship analysis to reflect international collaboration patterns. Then we integrate empirical analyses to show effecting factors of international collaboration degrees by using panel data. The results indicate that while 3D printing technology is associated with a "balanced collaboration" mode, big data technology is more accurately described by a radial pattern, centered on the United States, and carbon nanotubes and graphene technology exhibits "small-world" characteristics in this respect. It also shows that the factors GDP per capita (GPC, R&D expenditure (RDE and the export of global trade value (ETV negatively affect the level of international collaboration. It could be useful for China and other developing countries to make international scientific and technological collaboration strategies and policies in the future.

Conversion in the framework of international collaboration. Proceedings

International Nuclear Information System (INIS)

Akhmetov, T.; Vagin, S.; Urezchenko, V.

1996-01-01

22-26 October 1996 the Republic of Kazakhstan Ministry of Science - Academy of Science, International Science and Technology Center with collaboration of National Nuclear Center of the Republic of Kazakhstan conducted an international workshop C onversion in the framework of international collaboration . In the workshop scientists and specialists from different countries participated. 84 reports were presented in this workshop

Lysosomal storage and impaired autophagy lead to inflammasome activation in Gaucher macrophages.

Science.gov (United States)

Aflaki, Elma; Moaven, Nima; Borger, Daniel K; Lopez, Grisel; Westbroek, Wendy; Chae, Jae Jin; Marugan, Juan; Patnaik, Samarjit; Maniwang, Emerson; Gonzalez, Ashley N; Sidransky, Ellen

2016-02-01

Gaucher disease, the inherited deficiency of lysosomal glucocerebrosidase, is characterized by the presence of glucosylcer-amide macrophages, the accumulation of glucosylceramide in lysosomes and the secretion of inflammatory cytokines. However, the connection between this lysosomal storage and inflammation is not clear. Studying macrophages derived from peripheral monocytes from patients with type 1 Gaucher disease with genotype N370S/N370S, we confirmed an increased secretion of interleukins IL-1β and IL-6. In addition, we found that activation of the inflammasome, a multiprotein complex that activates caspase-1, led to the maturation of IL-1β in Gaucher macrophages. We show that inflammasome activation in these cells is the result of impaired autophagy. Treatment with the small-molecule glucocerebrosidase chaperone NCGC758 reversed these defects, inducing autophagy and reducing IL-1β secretion, confirming the role of the deficiency of lysosomal glucocerebrosidase in these processes. We found that in Gaucher macrophages elevated levels of the autophagic adaptor p62 prevented the delivery of inflammasomes to autophagosomes. This increase in p62 led to activation of p65-NF-kB in the nucleus, promoting the expression of inflammatory cytokines and the secretion of IL-1β. This newly elucidated mechanism ties lysosomal dysfunction to inflammasome activation, and may contribute to the massive organomegaly, bone involvement and increased susceptibility to certain malignancies seen in Gaucher disease. Moreover, this link between lysosomal storage, impaired autophagy, and inflammation may have implications relevant to both Parkinson disease and the aging process. Defects in these basic cellular processes may also provide new therapeutic targets. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Benefits of International Collaboration on the International Space Station

Science.gov (United States)

Hasbrook, Pete; Robinson, Julie A.; Brown Tate, Judy; Thumm, Tracy; Cohen, Luchino; Marcil, Isabelle; De Parolis, Lina; Hatton, Jason; Umezawa, Kazuo; Shirakawa, Masaki;

Conversion in the framework of international collaboration. Proceedings

Energy Technology Data Exchange (ETDEWEB)

Akhmetov, T; Vagin, S; Urezchenko, V [eds.

1997-12-31

22-26 October 1996 the Republic of Kazakhstan Ministry of Science - Academy of Science, International Science and Technology Center with collaboration of National Nuclear Center of the Republic of Kazakhstan conducted an international workshop {sup C}onversion in the framework of international collaboration{sup .} In the workshop scientists and specialists from different countries participated. 84 reports were presented in this workshop

Phenotype/genotype correlations in Gaucher disease type 1: Clinical and therapeutic implications

Energy Technology Data Exchange (ETDEWEB)

Sibille, A.; Eng, C.M.; Kim, S.J.; Pastores, G. (Mount Sinai School of Medicine, New York, NY (United States)); Grabowski, G.A. (Mount Sinai School of Medicine, New York, NY (United States) Univ. of Cincinnati, OH (United States))

1993-06-01

Gaucher disease is the most frequent lysosomal storage disease and the most prevalent genetic disease among Ashkenazi Jews. Gaucher disease type 1 is characterized by marked variability of the phenotype and by the absence of neuronopathic involvement. To test the hypothesis that this phenotypic variability was due to genetic compounds of several different mutant alleles, 161 symptomatic patients with Gaucher disease type 1 (> 90% Ashkenazi Jewish) were analyzed for clinical involvement, and their genotypes were determined. Qualitative and quantitative measures of disease involvement included age at onset of the disease manifestations, hepatic and splenic volumes, age at splenectomy, and severity of bony disease. High statistically significant differences (P < .005) were found in each clinical parameter in patients with the N370S/N370S genotype compared with those patients with the N370S/84GG, N370S/L444P, and N370/ genotypes. The symptomatic N370S homozygotes had onset of their disease two to three decades later than patients with the other genotypes. In addition, patients with the latter genotypes have much more severely involved livers, spleens, and bones and had a higher incidence of splenectomy at an earlier age. These predictive genotype analyses provide the basis for genetic care delivery and therapeutic recommendations in patients affected with Gaucher disease type 1. 38 refs., 1 fig., 4 tabs.

International research collaboration as social relation: an Ethiopian-Canadian example.

Science.gov (United States)

Bender, Amy; Guruge, Sepali; Aga, Fekadu; Hailemariam, Damen; Hyman, Ilene; Tamiru, Melesse

2011-06-01

International collaboration in nursing and other health disciplines is vital for addressing global health issues. While the results and processes of such collaborations have been reported, few publications have addressed their philosophical or theoretical underpinnings, particularly with respect to collaboration between those in low- and high-income countries. Piaget's notion of social relations of cooperation and constraint and Habermas's notion of "lifeworld" provide a theoretical lens through which to examine international collaboration as a construction of knowledge. This article is an exploration of these ideas as seen in the collective experience of Canadians and Ethiopians organizing an interdisciplinary forum on intimate partner violence in Ethiopia. The project is presented as a case study for reflecting on international collaboration as a manifestation of social relations. Such re-visioning of international collaboration may be useful for improving collaborative processes and their outcomes.

Four Gaucher disease type II patients with three novel mutations: a single centre experience from Turkey.

Science.gov (United States)

Bulut, Fatma Derya; Kör, Deniz; Şeker-Yılmaz, Berna; Hergüner, Özlem; Ceylaner, Serdar; Özkınay, Ferda; Kılavuz, Sebile; Önenli-Mungan, Neslihan

2018-04-14

Gaucher disease is the most common lysosomal storage disorder due to glucosylceramidase enzyme deficiency. There are three subtypes of the disease. Neurological involvement accompanies visceral and haematological findings only in type II and type III Gaucher patients. Type II is the acute progressive neuronopathic form which is the most severe and rare subtype. Clinical findings are recognized prenatally or in the first months of life and followed by death within the first two years of age. Among our 81 Gaucher patients, we identified 4 (4,9%) type II patients in our metabolic centre. This rate is significantly higher than the rate reported in the literature (Gaucher patients with three novel mutations and one perinatal lethal form with generalized ichthyosis which is a very rare disorder. Additionally, we would like to highlight the phenotypic heterogeneity not only between the subtypes, also even in the same type.

Femoral neck fractures complicating gaucher disease in children

International Nuclear Information System (INIS)

Goldman, A.B.; Jacobs, B.

1984-01-01

In normal children, fractures of the femoral neck are uncommon and accompany severe trauma and multiple injuries elsewhere in the skeleton. In children with Gaucher disease, a rare hereditary disorder of lipid metabolism, midcervical or basicervical fractures can occur with minor or no trauma and without other injury to the skeleton. Three children with Gaucher disease who developed pathologic fractures of the femoral neck are described. In all three, the fractures occurred between five and nine years of age, and the fracture lines passed through areas of abnormal bone characterized by poorly defined patches of increased and decreased density and cortical thinning along the medial femoral necks. In the affected hips, there was no evidence of avascular necrosis of the femoral heads at the time of injury. One child's fracture was preceeded by multiple bone 'crisis' localized to the proximal femora. (orig.)

Femoral neck fractures complicating gaucher disease in children

Energy Technology Data Exchange (ETDEWEB)

Goldman, A B; Jacobs, B

1984-09-01

In normal children, fractures of the femoral neck are uncommon and accompany severe trauma and multiple injuries elsewhere in the skeleton. In children with Gaucher disease, a rare hereditary disorder of lipid metabolism, midcervical or basicervical fractures can occur with minor or no trauma and without other injury to the skeleton. Three children with Gaucher disease who developed pathologic fractures of the femoral neck are described. In all three, the fractures occurred between five and nine years of age, and the fracture lines passed through areas of abnormal bone characterized by poorly defined patches of increased and decreased density and cortical thinning along the medial femoral necks. In the affected hips, there was no evidence of avascular necrosis of the femoral heads at the time of injury. One child's fracture was preceeded by multiple bone 'crisis' localized to the proximal femora.

Clinical evaluation of chitotriosidase enzyme activity in Gaucher and Niemann Pick A/B diseases: A retrospective study from India.

Science.gov (United States)

Kadali, Srilatha; Kolusu, Anusha; Sunkara, Satish; Gummadi, Maheshwar Reddy; Undamatla, Jayanthi

2016-06-01

Plasma chitotriosidase originates from activated macrophages and is reported to be elevated in many Lysosomal Storage Disorders. Measurement of this enzyme activity has been an available tool for monitoring therapy of Gaucher disease. The degree of elevation of chitotriosidase is useful for differential diagnosis of Gaucher disease and Niemann Pick A/B. However the potential utility of this chitotriosidase assay depends on the frequency of deficient chitotriosidase activity in a particular population. We therefore aim to study the clinical utility of this assay Gaucher and Niemann Pick A/B diseases in the backdrop of chitotriosidase deficiency in our population. The study comprises 173 patients with clinical suspicion of either Gaucher disease (n=108) or Niemann Pick A/B (n=65) and 92 healthy controls. The plasma samples of controls, Gaucher disease, and Niemann Pick A/B showed chitotriosidase deficiency of 12%, 25% and 27% respectively. The degree of elevation of chitotriosidase in Gaucher disease and Niemann Pick A/B patients is 40-326 (11,325.7±6395.4nmol/h/ml) and 7-22 folds (1192.5±463.0nmol/h/ml) respectively. In view of these findings of distinguishable fold elevation of chitotriosidase in Gaucher disease or Niemann Pick A/B, it can be a potential surrogate differential diagnostic marker for these groups of diseases, except in the patients in whom this enzyme is deficient. Copyright © 2016 Elsevier B.V. All rights reserved.

ACC International Academic Collaborative receives special award

OpenAIRE

Felker, Susan B.

2006-01-01

The Atlantic Coast Conference's new International Academic Collaborative (ACC/IAC) has been singled out by the New York-based Institute of International Education (IIE) for a special award for innovation in international education.

International Collaboration Patterns and Effecting Factors of Emerging Technologies

Science.gov (United States)

Bai, Xu; Liu, Yun

2016-01-01

With the globalization of the world economy, international innovation collaboration has taken place all over the world. This study selects three emerging technologies (3D printing, big data and carbon nanotubes and graphene technology) among 20 countries as the research objects, using three patent-based indicators and network relationship analysis to reflect international collaboration patterns. Then we integrate empirical analyses to show effecting factors of international collaboration degrees by using panel data. The results indicate that while 3D printing technology is associated with a “balanced collaboration” mode, big data technology is more accurately described by a radial pattern, centered on the United States, and carbon nanotubes and graphene technology exhibits “small-world” characteristics in this respect. It also shows that the factors GDP per capita (GPC), R&D expenditure (RDE) and the export of global trade value (ETV) negatively affect the level of international collaboration. It could be useful for China and other developing countries to make international scientific and technological collaboration strategies and policies in the future. PMID:27911926

MRI bone marrow findings in 63 patients with type I Gaucher's disease

Energy Technology Data Exchange (ETDEWEB)

Poll, L.W. [Berufsgenossenschaftliche Unfallklinik Duisburg GmbH (Germany). Abt. Radiologie; Willers, R. [Duesseldorf Univ. (Germany). Zentrum fuer Information, Kommunikation und Medientechnologie; Haeussinger, D. [Universitaetsklinikum Duesseldorf (Germany). Klinik fuer Gastroenterologie, Hepatologie und Infektiologie; Moedder, U. [Universitaetsklinikum Duesseldorf (Germany). Inst. fuer Radiologie; Dahl, S. vom [St.-Franziskus-Hospital Koeln, Akademisches Lehrkrankenhaus der Koeln Univ. (Germany). Klinik fuer Innere Medizin.

2010-11-15

Purpose: To determine whether MR bone marrow findings in Gaucher patients may help to identify patients at high risk of developing severe Gaucher bone complications exemplified by avascular necrosis (AVN) of the femoral head. Materials and Methods: MR images were obtained in 63 Type I Gaucher patients through a standard protocol using coronal T1 and T2-weighted sequences of the lower extremities. The location and extent of infiltrated marrow was established using a semi-quantitative MRI scoring method (Duesseldorf Gaucher score, DGS) and the morphological pattern of bone marrow involvement determined (whether homogeneous type A or non-homogeneous type B). The active marrow process with bone edema and AVN of the femoral head were also analyzed. Results: Bone marrow involvement was observed in femoral sites more than in tibial sites. A high DGS was significantly correlated with type B morphology and femoral AVN (both p < 0.0001). Splenectomized patients showed a significantly higher Duesseldorf Gaucher score and type B morphology than non-splenectomized patients (both p < 0.05). AVN was seen in 46 % of patients with type B morphology versus 3 % in type A morphology (p < 0.0001). DGS and morphology of bone marrow involvement were not significantly correlated with active marrow processes. Conclusion: Type B marrow morphology and extensive marrow packing were significantly associated with AVN of the femoral head (both p < 0.0001). These patterns are considered predictive and may be employed in a disease management context to alert physicians to the need for urgent therapeutic measures. (orig.)

Complement drives glucosylceramide accumulation and tissue inflammation in Gaucher disease.

Science.gov (United States)

Pandey, Manoj K; Burrow, Thomas A; Rani, Reena; Martin, Lisa J; Witte, David; Setchell, Kenneth D; Mckay, Mary A; Magnusen, Albert F; Zhang, Wujuan; Liou, Benjamin; Köhl, Jörg; Grabowski, Gregory A

2017-03-02

Gaucher disease is caused by mutations in GBA1, which encodes the lysosomal enzyme glucocerebrosidase (GCase). GBA1 mutations drive extensive accumulation of glucosylceramide (GC) in multiple innate and adaptive immune cells in the spleen, liver, lung and bone marrow, often leading to chronic inflammation. The mechanisms that connect excess GC to tissue inflammation remain unknown. Here we show that activation of complement C5a and C5a receptor 1 (C5aR1) controls GC accumulation and the inflammatory response in experimental and clinical Gaucher disease. Marked local and systemic complement activation occurred in GCase-deficient mice or after pharmacological inhibition of GCase and was associated with GC storage, tissue inflammation and proinflammatory cytokine production. Whereas all GCase-inhibited mice died within 4-5 weeks, mice deficient in both GCase and C5aR1, and wild-type mice in which GCase and C5aR were pharmacologically inhibited, were protected from these adverse effects and consequently survived. In mice and humans, GCase deficiency was associated with strong formation of complement-activating GC-specific IgG autoantibodies, leading to complement activation and C5a generation. Subsequent C5aR1 activation controlled UDP-glucose ceramide glucosyltransferase production, thereby tipping the balance between GC formation and degradation. Thus, extensive GC storage induces complement-activating IgG autoantibodies that drive a pathway of C5a generation and C5aR1 activation that fuels a cycle of cellular GC accumulation, innate and adaptive immune cell recruitment and activation in Gaucher disease. As enzyme replacement and substrate reduction therapies are expensive and still associated with inflammation, increased risk of cancer and Parkinson disease, targeting C5aR1 may serve as a treatment option for patients with Gaucher disease and, possibly, other lysosomal storage diseases.

A schedule for fusion research development and international collaboration

International Nuclear Information System (INIS)

Kakihana, H.

1983-01-01

In order to reach their goal of commercial fusion power reactors, development must proceed in a series of basic stages. Each step is expected to incur an increased level of cost. The cost-sharing benefits of international collaboration will become increasingly important and attractive with each successive step preceding commercialization. Outstanding examples of implementation of international collaboration in fusion include the JET project and the INTOR workshop which lend encouragement for the prospects for international collaboration in fusion in the future. (author)

Role of Scientific Societies in International Collaboration

Science.gov (United States)

Fucugauchi, J. U.

2007-12-01

Geophysical research increasingly requires global multidisciplinary approaches. Understanding how deeply interrelated are Earth components and processes, population growth, increased needs of mineral and energy resources, global impact of human activities, and view of our planet as an interconnected system emphasizes the need of international cooperation. International research collaboration has an immense potential and is needed for further development of Earth science research and education. The Union Session is planned to provide a forum for analysis and discussion of the status of research and education of geosciences in developing countries, international collaboration programs and new initiatives for promoting and strengthening scientific cooperation. A theme of particular relevance in the analyses and discussions is the role of scientific societies in international collaboration. Societies organize meetings, publish journals and books and promote cooperation through academic exchange activities. They may further assist communities in developing countries in providing and facilitating access to scientific literature, attendance to international meetings, short and long-term stays and student and young researcher mobility. What else can be done? This is a complex subject and scientific societies may not be seen independently from the many factors involved in research and education. Developing countries present additional challenges resulting from limited economic resources and social and political problems, while urgently requiring improved educational and research programs. Needed are in-depth analyses of infrastructure and human resources, and identification of major problems and needs. What are the major limitations and needs in research and postgraduate education in developing countries? What and how should international collaboration do? What are the roles of individuals, academic institutions, funding agencies, scientific societies? Here we attempt to

Dose-response relationships for enzyme replacement therapy with imiglucerase/alglucerase in patients with Gaucher disease type 1

NARCIS (Netherlands)

Grabowski, Gregory A.; Kacena, Katherine; Cole, J. Alexander; Hollak, Carla E. M.; Zhang, Lin; Yee, John; Mistry, Pramod K.; Zimran, Ari; Charrow, Joel; vom Dahl, Stephan

2009-01-01

Purpose: To determine whether enzyme therapy with imiglucerase/ alglucerase demonstrates dose-response relationships with doses and disease parameters used in routine clinical practice for Gaucher disease type 1 patients. Methods: Analyses included all patients with Gaucher disease type 1 on enzyme

Management and monitoring recommendations for the use of eliglustat in adults with type 1 Gaucher disease in Europe.

Science.gov (United States)

Belmatoug, Nadia; Di Rocco, Maja; Fraga, Cristina; Giraldo, Pilar; Hughes, Derralynn; Lukina, Elena; Maison-Blanche, Pierre; Merkel, Martin; Niederau, Claus; Plӧckinger, Ursula; Richter, Johan; Stulnig, Thomas M; Vom Dahl, Stephan; Cox, Timothy M

2017-01-01

In Gaucher disease, diminished activity of the lysosomal enzyme, acid β-glucosidase, leads to accumulation of glucosylceramides and related substrates, primarily in the spleen, liver, and bone marrow. Eliglustat is an oral substrate reduction therapy approved in the European Union and the United States as a first-line treatment for adults with type 1 Gaucher disease who have compatible CYP2D6 metabolism phenotypes. A European Advisory Council of experts in Gaucher disease describes the characteristics of eliglustat that are distinct from enzyme augmentation therapy (the standard of care) and miglustat (the other approved substrate reduction therapy) and recommends investigations and monitoring for patients on eliglustat therapy within the context of current recommendations for Gaucher disease management. Eliglustat is a selective, potent inhibitor of glucosylceramide synthase, the enzyme responsible for biosynthesis of glucosylceramides which accumulate in Gaucher disease. Extensive metabolism of eliglustat by CYP2D6, and, to a lesser extent, CYP3A of the cytochrome P450 pathway, necessitates careful consideration of the patient's CYP2D6 metaboliser status and use of concomitant medications which share metabolism by these pathways. Guidance on specific assessments and monitoring required for eliglustat therapy, including an algorithm to determine eligibility for eliglustat, are provided. As a first-line therapy for type 1 Gaucher disease, eliglustat offers eligible patients a daily oral therapy alternative to biweekly infusions of enzyme therapy. Physicians will need to carefully assess individual Gaucher patients to determine their appropriateness for eliglustat therapy. The therapeutic response to eliglustat and use of concomitant medications will require long-term monitoring. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Demographic, Clinical and Genetic Characteristics of Child Gaucher Disease Patients in Russia: Pediatric Register Data

Directory of Open Access Journals (Sweden)

G. B. Movsisyan

2016-01-01

Full Text Available Background: Registers are an effective tool for tracing the dynamics of patients with rare pathologies.Objective: Our aim was to examine the demographic, clinical and genetic features of child Gaucher disease patients in Russia.Methods: We held a retrospective survey of the pediatric register data with regard to children suffering from Gaucher disease. The period of data accounting was from 2006 to 2016.Results: 115 children with Gaucher disease aged from 3 months to 17 years (the median age of diagnosis is 5 years were registered; 62 them (53.9% are girls. The prevalence of the disease was 0.32 cases for 100,000 children. 95 (82.6% children had 1st type of Gaucher disease, 6 (5.2% — 2nd, and 1 (12.2% — 3rd. Maximum morbidity was in Central (27; 23.5% and Volga (27; 23.5% Federal Districts; minimal — in the Far East (3; 2.6%. By the time of diagnosis all the patients were suffering from splengomegaly. The genotype and phenotype correlations in 90 children with Gaucher disease were as follows: in case of 1st type (n = 77, in 21 (27.3% cases, the p.N370S/р.L444P genotype was set, in 12 (15.6% — the р.N370S/other mutation; in case of 2nd and 3rd types, in 13 children with neuropathic forms, in 9 (62.9% cases — the p.L444P/p.L444P, in 3 (231% — the p.L444P/p. D409H. The rest of genotypes were presented by other mutations, 13 of which were revealed for the first time. The p.W223R (p.W184R mutation is specific for Russian patients. Enzyme replacement therapy was carried out for 109 patients (94.8%: in 105 (96.3% children (1st and 3rd types of Gaucher disease with imiglucerase, in 4 (3.7% children with 1st type — with velaglucerase alfa. Pathogenetic treatment stops the main symptoms in most patients.Conclusion: The pediatric Gaucher disease register allows to systemize the data concerning the disease course in children and optimizing the approaches to its monitoring in Russia.

Femoral neck fractures complicating gaucher disease in children

Energy Technology Data Exchange (ETDEWEB)

Goldman, A.B.; Jacobs, B.

1984-09-01

In normal children, fractures of the femoral neck are uncommon and accompany severe trauma and multiple injuries elsewhere in the skeleton. In children with Gaucher disease, a rare hereditary disorder of lipid metabolism, midcervical or basicervical fractures can occur with minor or no trauma and without other injury to the skeleton. Three children with Gaucher disease who developed pathologic fractures of the femoral neck are described. In all three, the fractures occurred between five and nine years of age, and the fracture lines passed through areas of abnormal bone characterized by poorly defined patches of increased and decreased density and cortical thinning along the medial femoral necks. In the affected hips, there was no evidence of avascular necrosis of the femoral heads at the time of injury. One child's fracture was preceeded by multiple bone 'crisis' localized to the proximal femora.

Collaborative entrepreneurship: On the Influence of Internal and External Collaboration on Corporate Entrepreneurial Innovation

DEFF Research Database (Denmark)

Lassen, Astrid Heidemann; Timenes Laugen, Bjørge; Middel, Rick

2008-01-01

The present paper empirically tests the effect which internal/external collaboration has on innovation height and identifies characteristics of collaboration patterns leading to entrepreneurial innovation in particular. Doing so adds to the understanding of how corporate entrepreneurship best...... unfolds as interfirm activity, which here is termed collaborative entrepreneurship, and provides details on the particular patterns of Open Innovation. The empirical analysis is based on a data set with responses from 512 Danish engineers. The analysis finds that external collaboration has significantly...... different effects on innovation height depending on the type of partners involved, and furthermore suggests that the development of entrepreneurial innovation is not only dependent on high external involvement, but also on involvement and collaboration among internal functional departments and people....

GBAmutations in Gaucher type I Venezuelan patients: ethnic origins ...

Indian Academy of Sciences (India)

Gilberto GÓmez

2017-09-08

Sep 8, 2017 ... In Venezuela, 20 unrelated index cases with GD type I were ..... S, splenomegaly; T, thrombocytopenia; Bc, bone crisis; Hy, hypotonia; NA, data not available; ..... Management of neuronopathic Gaucher disease: a European.

Bone- and bone marrow scintigraphy in Gaucher disease type 1

International Nuclear Information System (INIS)

Mikosch, P.; Zitter, F.; Gallowitsch, H.J.; Lind, P.; Wuertz, F.; Mehta, A.B.; Hughes, D.A.

2008-01-01

Scintigraphy is a method for imaging metabolism and should be viewed as complimentary to morphological imaging. Bone and bone marrow scintigraphy can particularly contribute to the detection of focal disease in Gaucher disease. In bone crises it can discriminate within three days after pain onset between local infection and aseptic necrosis. A further advantage of bone- and bone marrow scintigraphy is the visualization of the whole skeleton within one setting. Whole body imaging for focal lesions might thus be an objective in GD, in particular in patients complaining of several painful sites. Direct imaging of bone marrow deposits in GD by MIBI scintigraphy might be of special interest in children in whom bone marrow undergoes a developmental conversion from red to yellow marrow in the ap-pendicular skeleton. MRI interpretation in young GD patients is thus difficult in order to estimate the exact amount and extent of bone marrow infiltration by Gaucher cells. 99mTc-MIBI scintigraphy with its direct visualization of lipid storage could thus add interesting additional information not shown with other methods including MRI. Although MRI is the most accepted imaging modality in assessing the skeletal status in GD, a selective use of scintigraphy for imaging bone and bone marrow may add information in the evaluation of patients with Gaucher disease

Diagnosis and Management of Gaucher Disease in India - Consensus Guidelines of the Gaucher Disease Task Force of the Society for Indian Academy of Medical Genetics and the Indian Academy of Pediatrics.

Science.gov (United States)

Puri, Ratna Dua; Kapoor, Seema; Kishnani, Priya S; Dalal, Ashwin; Gupta, Neerja; Muranjan, Mamta; Phadke, Shubha R; Sachdeva, Anupam; Verma, Ishwar C; Mistry, Pramod K

2018-02-15

Gaucher disease (GD) is amongst the most frequently occurring lysosomal storage disorder in all ethnicities. The clinical manifestations and natural history of GD is highly heterogeneous with extreme geographic and ethnic variations. The literature on GD has paucity of information and optimal management guidelines for Indian patients. Gaucher Disease Task Force was formed under the auspices of the Society for Indian Academy of Medical Genetics. Invited experts from various specialties formulated guidelines for the management of patients with GD. A writing committee was formed and the draft guidelines were circulated by email to all members for comments and inputs. The guidelines were finalized in December 2016 at the annual meeting of the Indian Academy of Medical Genetics. These guidelines are intended to serve as a standard framework for treating physicians and the health care systems for optimal management of Gaucher disease in India and to define unique needs of this patient population. Manifestations of GD are protean and a high index of suspicion is essential for timely diagnosis. Patients frequently experience diagnostic delays during which severe irreversible complications occur. Leucocyte acid b-glucosidase activity is mandatory for establishing the diagnosis of Gaucher disease; molecular testing can help identify patients at risk of neuronopathic disease. Enzyme replacement therapy for type 1 and type 3 Gaucher disease is the standard of care. Best outcomes are achieved by early initiation of therapy before onset of irreversible complications. However, in setting of progressive neurological symptoms such as seizures and or/ neuroregression, ERT is not recommended, as it cannot cross the blood brain barrier. The recommendations herein are for diagnosis, for initiation of therapy, therapeutic goals, monitoring and follow up of patients. We highlight that prevention of recurrence of the disease through genetic counseling and prenatal diagnosis is essential

Partial splenectomy in children with Gaucher's disease

International Nuclear Information System (INIS)

Bar-Maor, J.A.; Govrin-Yehudain, J.

1985-01-01

Because of hypersplenism and mechanical problems, partial splenectomy was performed in four children with Gaucher's disease. Subsequently, one of the patients underwent a total splenectomy due to bleeding from the remnant of the spleen. At the follow-up of the other three patients, an isotope scan showed that the remaining spleen was functioning well

Radiopharmacology of inhaled 133Xe in skeletal sites containing deposits of Gaucher cells

International Nuclear Information System (INIS)

Castronovo, F.P. Jr.; McKusick, K.A.; Doppelt, S.H.; Barton, N.W.

1993-01-01

Gaucher's disease is a lysomal storage disease in which cells of the reticuloendothelial system accumulate the lipid glucocerebroside. It is characterized by slowly progressive visceral and osseous involvement. One of the latter manifestations includes lipid infiltration of bone marrow. We monitored the rate of the inhaled 133 Xe uptake and wash-out over diseased and normal metaphyseal and epiphyseal areas of the knee. Twenty-two patients (15 adults, 7 children) with various degrees of previously diagnosed Gaucher's disease were positioned supine under a γ-camera interfaced to a computer system. All patients rebreathed 133 Xe gas from a closed system for 10 min followed by 14 min of wash-out. Digitized images of the lung, liver, spleen, bony sites and soft tissue were obtained at 1 min intervals during the wash-in and wash-out phases. Counts for each ROI were normalized per 100 pixels and plotted as a function (time). Maximum uptake was also calculated by relating the counts/ROI/100 pixels to the 10 min integrated lung count during equilibrium (the administered ''dose''). There was essentially no 133 Xe uptake in liver and spleen involved with Gaucher's disease. Monophasic uptake and biphasic wash-out curves were observed in the limited investigative population. Gaucher deposits released the 133 Xe at a greater rate relative to soft tissue. (Author)

Histological characterisation of visceral changes in a patient with type 2 Gaucher disease treated with enzyme replacement therapy.

Science.gov (United States)

Tezuka, Yuko; Fukuda, Mitsumasa; Watanabe, Shohei; Nakano, Takeshi; Okamoto, Kentaro; Kuzume, Kazuyo; Yano, Yoshiaki; Eguchi, Mariko; Ishimae, Minenori; Ishii, Eiichi; Miyazaki, Tatsuhiko

2018-02-01

Gaucher disease is a lysosomal storage disease caused by deficiency of glucocerebrosidase and accumulation of glucocerebroside. Three major sub-types have been described, type 2 is an acute neurological form that exhibits serious general symptoms and poor prognosis, compared with the other types. This case was a girl diagnosed with type 2 Gaucher disease at 12months of age who presented with poor weight gain from infancy, stridor, hypertonia, hepatosplenomegaly, trismus and an eye movement disorder. Enzyme replacement therapy (ERT) was administered, but she had frequent myoclonus and developmental regression. She needed artificial ventilation because of respiratory failure. She died at 11years of age. An autopsy demonstrated infiltrating CD68-positive large cells containing abundant lipids in alveoli, while in the liver, kidney and bone marrow CD68-positive cells were small and round. In the bone marrow, myelodysplastic changes were present without Gaucher cells. The infiltration of Gaucher cells in alveoli was marked, suggesting that ERT was relatively ineffective in pulmonary involvement, particularly intra-alveolar. Additional treatments are necessary to improve the neurological and pulmonary prognosis of type 2Gaucher disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Reduced cerebral vascularization in experimental neuronopathic Gaucher disease.

Science.gov (United States)

Smith, Nicholas Jc; Fuller, Maria; Saville, Jennifer T; Cox, Timothy M

2018-01-01

The glycosphingolipidosis, Gaucher disease, in which a range of neurological manifestations occur, results from a deficiency of acid β-glucocerebrosidase, with subsequent accumulation of β-glucocerebroside, its upstream substrates, and the non-acylated congener β-glucosylsphingosine. However, the mechanisms by which end-organ dysfunction arise are poorly understood. Here, we report strikingly diminished cerebral microvascular density in a murine model of disease, and provide a detailed analysis of the accompanying cerebral glycosphingolipidome in these animals, with marked elevations of β-glucosylsphingosine. Further in vitro studies confirmed a concentration-dependent impairment of endothelial cytokinesis upon exposure to quasi-pathological concentrations of β-glucosylsphingosine. These findings support a premise for pathogenic disruption of cerebral angiogenesis as an end-organ effect, with potential for therapeutic modulation in neuronopathic Gaucher disease. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Investigation of original multivalent iminosugars as pharmacological chaperones for the treatment of Gaucher disease.

Science.gov (United States)

Laigre, Eugénie; Hazelard, Damien; Casas, Josefina; Serra-Vinardell, Jenny; Michelakakis, Helen; Mavridou, Irene; Aerts, Johannes M F G; Delgado, Antonio; Compain, Philippe

2016-06-24

Multivalent iminosugars conjugated with a morpholine moiety and/or designed as prodrugs have been prepared and evaluated as new classes of pharmacological chaperones for the treatment of Gaucher disease. This study further confirms the interest of the prodrug concept and shows that the addition of a lysosome-targeting morpholine unit into iminosugar cluster structures has no significant impact on the chaperone activity on Gaucher cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

Increased glucocerebrosidase (GBA) 2 activity in GBA1 deficient mice brains and in Gaucher leucocytes.

Science.gov (United States)

Burke, Derek G; Rahim, Ahad A; Waddington, Simon N; Karlsson, Stefan; Enquist, Ida; Bhatia, Kailash; Mehta, Atul; Vellodi, Ashok; Heales, Simon

2013-09-01

Lysosomal glucocerebrosidase (GBA1) deficiency is causative for Gaucher disease. Not all individuals with GBA1 mutations develop neurological involvement raising the possibility that other factors may provide compensatory protection. One factor may be the activity of the non-lysosomal β-glucosidase (GBA2) which exhibits catalytic activity towards glucosylceramide and is reported to be highly expressed in brain tissue. Here, we assessed brain GBA2 enzymatic activity in wild type, heterozygote and GBA1 deficient mice. Additionally, we determined activity in leucocytes obtained from 13 patients with Gaucher disease, 10 patients with enzymology consistent with heterozygote status and 19 controls. For wild type animals, GBA2 accounted for over 85 % of total brain GBA activity and was significantly elevated in GBA1 deficient mice when compared to heterozygote and wild types (GBA1 deficient; 92.4 ± 5.6, heterozygote; 71.5 ± 2.4, wild type 76.8 ± 5.1 nmol/h/mg protein). For the patient samples, five Gaucher patients had GBA2 leucocyte activities markedly greater than controls. No difference in GBA2 activity was apparent between the control and carrier groups. Undetectable GBA2 activity was identified in four leucocyte preparations; one in the control group, two in the carrier group and one from the Gaucher disease group. Work is now required to ascertain whether GBA2 activity is a disease modifying factor in Gaucher disease and to identify the mechanism(s) responsible for triggering increased GBA2 activity in GBA1 deficiency states.

Generation of a conditional knockout of murine glucocerebrosidase: utility for the study of Gaucher disease.

Science.gov (United States)

Sinclair, Graham B; Jevon, Gareth; Colobong, Karen E; Randall, Derrick R; Choy, Francis Y M; Clarke, Lorne A

2007-02-01

Gaucher disease is a disorder of sphingolipid metabolism resulting from an inherited deficiency of the lysosomal hydrolase glucocerebrosidase. Affected individuals present with a spectrum of clinical symptoms ranging from hepatosplenomegaly, haematological abnormalities, and bone pain in type 1 disease, to severe neurodegeneration and premature death in types 2 and 3 disease. Although the basic biochemical defect is well characterized, there remains a poor understanding of the underlying pathophysiology of disease. In vitro studies suggest that macrophage glucocerebroside storage leads to tissue dysfunction through complex mechanisms involving altered intracellular calcium homeostasis and apoptosis. In order to study the pathogenic roles of these complex interactions, a viable animal model for Gaucher disease is needed. The complexity of this single gene disorder has been emphasized by the varied results of previous murine Gaucher models, ranging from perinatal lethality to phenotypically and biochemically asymptomatic animals. Recognizing the need to modulate the biochemical phenotype in mice to produce a relevant model, we have created a murine strain with key exons of the glucocerebrosidase gene flanked by loxP sites. We show that expression of Cre-recombinase in cells of hematopoietic and endothelial origin results in deficiency of glucocerebrosidase in the liver, spleen, bone marrow, and peripheral white cells. Glucocerebroside storage in this model leads to progressive splenomegaly with Gaucher cell infiltration and modest storage in the liver by 26 weeks of age. These results indicate the utility of this loxP GBA targeted murine strain for understanding the complex pathophysiology of Gaucher disease.

How Do I Talk to My Family about Gaucher?

Science.gov (United States)

... to my parents and the rest of our family. My father and mother did not want to accept the ... holding fundraisers and speaking to Jewish organizations. My family also got tested: My father had asymptomatic Gaucher, my mother is a carrier, ...

Global gene expression profile progression in Gaucher disease mouse models

Directory of Open Access Journals (Sweden)

Zhang Wujuan

2011-01-01

Full Text Available Abstract Background Gaucher disease is caused by defective glucocerebrosidase activity and the consequent accumulation of glucosylceramide. The pathogenic pathways resulting from lipid laden macrophages (Gaucher cells in visceral organs and their abnormal functions are obscure. Results To elucidate this pathogenic pathway, developmental global gene expression analyses were conducted in distinct Gba1 point-mutated mice (V394L/V394L and D409 V/null. About 0.9 to 3% of genes had altered expression patterns (≥ ± 1.8 fold change, representing several categories, but particularly macrophage activation and immune response genes. Time course analyses (12 to 28 wk of INFγ-regulated pro-inflammatory (13 and IL-4-regulated anti-inflammatory (11 cytokine/mediator networks showed tissue differential profiles in the lung and liver of the Gba1 mutant mice, implying that the lipid-storage macrophages were not functionally inert. The time course alterations of the INFγ and IL-4 pathways were similar, but varied in degree in these tissues and with the Gba1 mutation. Conclusions Biochemical and pathological analyses demonstrated direct relationships between the degree of tissue glucosylceramides and the gene expression profile alterations. These analyses implicate IFNγ-regulated pro-inflammatory and IL-4-regulated anti-inflammatory networks in differential disease progression with implications for understanding the Gaucher disease course and pathophysiology.

[Cathepsin K as a biomarker of bone involvement in type 1 Gaucher disease].

Science.gov (United States)

Bobillo Lobato, Joaquín; Durán Parejo, Pilar; Núñez Vázquez, Ramiro J; Jiménez Jiménez, Luis M

2015-10-05

Gaucher disease is an inherited disorder caused by deficit of acid β-glucocerebrosidase, responsible for the degradation of glucosylceramide to ceramide and glucose. Although the disorder is primarily hematologic, bone is the second most commonly affected structure. Cathepsin K (CATK) is an enzyme involved in bone remodelling process. It has been proposed that determination of its serum concentrations may provide additional information to other biomarkers. The study included 20 control subjects and 20 Gaucher type 1 patients from Andalusia and Extremadura regions. We analyzed the biomarkers of bone remodelling: the bone alkaline phosphatase (B-ALP), the N-terminal propeptide of type 1 procollagen (P1NP), the β carboxyterminal telopeptide of type 1 collagen (CTx) and the CATK through electrochemiluminescence and immunoassay techniques. There is an increase in levels of CATK, CATK/P1NP and CATK/B-ALP ratios in type 1 Gaucher patients compared to the control group. Considering the existence of skeletal manifestations in the patient group, the CATK and CATK/P1NP ratio showed higher levels in patients with bone damage compared to those without it. Although imaging studies are the gold standard for monitoring bone disease in type 1 Gaucher patients, the utility of CATK should be considered as a possible indicator of bone damage in these patients. Furthermore, this parameter can be used in the monitoring of the treatment of bone pathology. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Legal Considerations for International Collaborative Research Contract

International Nuclear Information System (INIS)

Lee, D. S.; Oh, K. B.; Kim, H. J.; Lee, J. H.

2007-01-01

Though collaborative research is pure academic activity the research plan and resource allocation for the research are shaped under foam of contract. Thus, legal binding effect and compulsive instrument is adopted at the research contract. This paper aimed at guiding equal collaborative research contract in legal aspect. To reach the goal (1) enforceability and elements of international collaborative contract, (2) damage calculation and related issues with those topics shall be discussed in each section

International Medical Collaboration: Lessons from Cuba

Science.gov (United States)

Castelló González, Mauro; Pons Vásquez, Reinaldo; Rodriguez Bencomo, David; Choonara, Imti

2016-01-01

Over 50,000 Cuban health professionals are currently working overseas in 67 different countries. They work in conjunction with local health professionals. The majority work in primary care in deprived areas. The aim is to reduce morbidity and mortality but also improve health in the long term by training local health professionals, and building both institutions and a structure to deliver health care alongside educating the local population. Cuba is a small, middle-income country. It has, however, made a significant international contribution in relation to medical collaboration. Cuba’s international collaboration is based on the principles of social justice and equity for all. It has set an example for other countries to emulate. PMID:27763571

International Medical Collaboration: Lessons from Cuba

Directory of Open Access Journals (Sweden)

Mauro Castelló González

2016-10-01

Full Text Available Over 50,000 Cuban health professionals are currently working overseas in 67 different countries. They work in conjunction with local health professionals. The majority work in primary care in deprived areas. The aim is to reduce morbidity and mortality but also improve health in the long term by training local health professionals, and building both institutions and a structure to deliver health care alongside educating the local population. Cuba is a small, middle-income country. It has, however, made a significant international contribution in relation to medical collaboration. Cuba’s international collaboration is based on the principles of social justice and equity for all. It has set an example for other countries to emulate.

Clinical and genetic assessment of pediatric patients with Gaucherâ ...

African Journals Online (AJOL)

Tahia H. Saleem

2016-09-24

Sep 24, 2016 ... were squint, seizures and delayed mental development. Five different .... or miscarriages or genetically affected siblings with GD was also included. ..... with Gaucher disease and relation to disease phenotypes. World J.

Intracerebroventricular delivery of glucocerebrosidase reduces substrates and increases lifespan in a mouse model of neuronopathic Gaucher disease.

Science.gov (United States)

Cabrera-Salazar, M A; Bercury, S D; Ziegler, R J; Marshall, J; Hodges, B L; Chuang, W-L; Pacheco, J; Li, L; Cheng, S H; Scheule, R K

2010-10-01

Gaucher disease is caused by a deficit in the enzyme glucocerebrosidase. As a consequence, degradation of the glycolipids glucosylceramide (GluCer) and glucosylsphingosine (GluSph) is impaired, and their subsequent buildup can lead to significant pathology and early death. Type 1 Gaucher patients can be treated successfully with intravenous replacement enzyme, but this enzyme does not reach the CNS and thus does not ameliorate the neurological involvement in types 2 and 3 Gaucher disease. As one potential approach to treating these latter patients, we have evaluated intracerebroventricular (ICV) administration of recombinant human glucocerebrosidase (rhGC) in a mouse model of neuronopathic Gaucher disease. ICV administration resulted in enzyme distribution throughout the brain and alleviated neuropathology in multiple brain regions of this mouse model. Treatment also resulted in dose-dependent decreases in GluCer and GluSph and significantly extended survival. To evaluate the potential of continuous enzyme delivery, a group of animals was treated ICV with an adeno-associated viral vector encoding hGC and resulted in a further extension of survival. These data suggest that ICV administration of rhGC may represent a potential therapeutic approach for type 2/3 Gaucher patients. Preclinical evaluation in larger animals will be needed to ascertain the translatability of this approach to the clinic. Copyright © 2010 Elsevier Inc. All rights reserved.

Treatment options for patients with Gaucher disease | Shawky ...

African Journals Online (AJOL)

Gaucher disease is the most common lysosomal storage disorder due to deficiency of ß-glucocerebrosidase. Since the introduction of Ceredase in 1991, enzyme replacement therapy has been the mainstay of treatment with its major disadvantage of long life dependency on biweekly IV therapy. It was more than a decade ...

Progress and potential of non-inhibitory small molecule chaperones for the treatment of Gaucher disease and its implications for Parkinson disease.

Science.gov (United States)

Jung, Olive; Patnaik, Samarjit; Marugan, Juan; Sidransky, Ellen; Westbroek, Wendy

2016-05-01

Gaucher disease, caused by pathological mutations GBA1, encodes the lysosome-resident enzyme glucocerebrosidase, which cleaves glucosylceramide into glucose and ceramide. In Gaucher disease, glucocerebrosidase deficiency leads to lysosomal accumulation of substrate, primarily in cells of the reticulo-endothelial system. Gaucher disease has broad clinical heterogeneity, and mutations in GBA1 are a risk factor for the development of different synucleinopathies. Insights into the cell biology and biochemistry of glucocerebrosidase have led to new therapeutic approaches for Gaucher disease including small chemical chaperones. Such chaperones facilitate proper enzyme folding and translocation to lysosomes, thereby preventing premature breakdown of the enzyme in the proteasome. This review discusses recent progress in developing chemical chaperones as a therapy for Gaucher disease, with implications for the treatment of synucleinopathies. It focuses on the development of non-inhibitory glucocerebrosidase chaperones and their therapeutic advantages over inhibitory chaperones, as well as the challenges involved in identifying and validating chemical chaperones.

Hemorrhage associated with 'bone crisis' in Gaucher's disease identified by magnetic resonance imaging

International Nuclear Information System (INIS)

Horev, G.; Kornreich, L.; Hadar, H.; Katz, K.

1991-01-01

Children suffering from Gaucher's disease were examined by magnetic resonance imaging (MRI) during a characteristic episode of 'bone crisis'. An unexpectedly high intramedullary as well as subperiosteal signal was observed on both the T1- and T2-weighted sequences in 5 patients, suggesting a subacute hemorrhage or hematoma. It is conceivable that such a painful hemorrhage is an important component of the 'bone crisis' phenomenon. Furthermore, in these cases this is a specific sign which may enable differentiation of bone crises from other types of bone pain associated with Gaucher's disease. (orig.)

Augmentation of phenotype in a transgenic Parkinson mouse heterozygous for a Gaucher mutation.

Science.gov (United States)

Fishbein, Ianai; Kuo, Yien-Ming; Giasson, Benoit I; Nussbaum, Robert L

2014-12-01

The involvement of the protein α-synuclein (SNCA) in the pathogenesis of Parkinson's disease is strongly supported by the facts that (i) missense and copy number mutations in the SNCA gene can cause inherited Parkinson's disease; and (ii) Lewy bodies in sporadic Parkinson's disease are largely composed of aggregated SNCA. Unaffected heterozygous carriers of Gaucher disease mutations have an increased risk for Parkinson's disease. As mutations in the GBA gene encoding glucocerebrosidase (GBA) are known to interfere with lysosomal protein degradation, GBA heterozygotes may demonstrate reduced lysosomal SNCA degradation, leading to increased steady-state SNCA levels and promoting its aggregation. We have created mouse models to investigate the interaction between GBA mutations and synucleinopathies. We investigated the rate of SNCA degradation in cultured primary cortical neurons from mice expressing wild-type mouse SNCA, wild-type human SNCA, or mutant A53T SNCA, in a background of either wild-type Gba or heterozygosity for the L444P GBA mutation associated with Gaucher disease. We also tested the effect of this Gaucher mutation on motor and enteric nervous system function in these transgenic animals. We found that human SNCA is stable, with a half-life of 61 h, and that the A53T mutation did not significantly affect its half-life. Heterozygosity for a naturally occurring Gaucher mutation, L444P, reduced GBA activity by 40%, reduced SNCA degradation and triggered accumulation of the protein in culture. This mutation also resulted in the exacerbation of motor and gastrointestinal deficits found in the A53T mouse model of Parkinson's disease. This study demonstrates that heterozygosity for a Gaucher disease-associated mutation in Gba interferes with SNCA degradation and contributes to its accumulation, and exacerbates the phenotype in a mouse model of Parkinson's disease. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain

Identification of a feedback loop involving β-glucosidase 2 and its product sphingosine sheds light on the molecular mechanisms in Gaucher disease.

Science.gov (United States)

Schonauer, Sophie; Körschen, Heinz G; Penno, Anke; Rennhack, Andreas; Breiden, Bernadette; Sandhoff, Konrad; Gutbrod, Katharina; Dörmann, Peter; Raju, Diana N; Haberkant, Per; Gerl, Mathias J; Brügger, Britta; Zigdon, Hila; Vardi, Ayelet; Futerman, Anthony H; Thiele, Christoph; Wachten, Dagmar

2017-04-14

The lysosomal acid β-glucosidase GBA1 and the non-lysosomal β-glucosidase GBA2 degrade glucosylceramide (GlcCer) to glucose and ceramide in different cellular compartments. Loss of GBA2 activity and the resulting accumulation of GlcCer results in male infertility, whereas mutations in the GBA1 gene and loss of GBA1 activity cause the lipid-storage disorder Gaucher disease. However, the role of GBA2 in Gaucher disease pathology and its relationship to GBA1 is not well understood. Here, we report a GBA1-dependent down-regulation of GBA2 activity in patients with Gaucher disease. Using an experimental approach combining cell biology, biochemistry, and mass spectrometry, we show that sphingosine, the cytotoxic metabolite accumulating in Gaucher cells through the action of GBA2, directly binds to GBA2 and inhibits its activity. We propose a negative feedback loop, in which sphingosine inhibits GBA2 activity in Gaucher cells, preventing further sphingosine accumulation and, thereby, cytotoxicity. Our findings add a new chapter to the understanding of the complex molecular mechanism underlying Gaucher disease and the regulation of β-glucosidase activity in general. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

12th International Symposium on Open Collaboration Companion

CERN Document Server

2016-01-01

Welcome to the proceedings of OpenSym 2016, the 12th international symposium on open collaboration! Open collaboration is collaboration that is egalitarian (everyone can join, no principled or artificial barriers to participation exist), meritocratic (decisions and status are merit-based rather than imposed) and self-organizing (processes adapt to people rather than people adapt to predefined processes).

International and interlaboratory collaboration on Neutron Science Project

Energy Technology Data Exchange (ETDEWEB)

Oyama, Yukio [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

1997-11-01

For effectiveness of facility development for Neutron Science Projects at JAERI, international and interlaboratory collaborations have been extensively planned and promoted, especially in the areas of accelerator and target technology. Here status of two collaborations relevant to a spallation neutron target development is highlighted from those collaborations. The two collaborations are experiments on BNL-AGS spallation target simulation and PSI materials irradiation. Both are planned to start in spring of 1997. (author)

A case of traction retinal detachment in a patient with Gaucher disease.

Science.gov (United States)

Watanabe, Akira; Gekka, Tamaki; Arai, Kota; Tsuneoka, Hiroshi

2017-01-01

This is the first report of vitreous surgery for traction retinal detachment in a patient with type III Gaucher disease with multiple vitreous opacities. A 16-year-old boy who was diagnosed with Gaucher disease at age two and was undergoing enzyme replacement therapy presented with numerous white opacities of varying sizes in the vitreous bodies of both eyes. Visual acuity was 20/40 in the right eye and 20/2000 in the left eye. The retina of the left eye was completely detached, and vitreous surgery was performed. Liquefaction of the vitreous body was advanced, and the central part of the vitreous cavity contained almost no vitreous humor. The macular region was successfully aspirated with a vitreous cutter to form a posterior vitreous detachment. From the optic disk to the nasal side, however, posterior vitreous detachment formation was prevented by strong adhesions between the retina and the vitreous body. The traction retinal detachment of the posterior fundus improved after vitreous body resection alone. Traction retinal detachment may occur as a result of severe vitreous liquefaction in cases of Gaucher disease with numerous vitreous opacities.

Case report of unexpected gastrointestinal involvement in type 1 Gaucher disease: comparison of eliglustat tartrate treatment and enzyme replacement therapy.

Science.gov (United States)

Kim, Yoo-Mi; Shin, Dong Hoon; Park, Su Bum; Cheon, Chong Kun; Yoo, Han-Wook

2017-05-15

Gastrointestinal involvement in Gaucher disease is very rare, and appears to be unresponsive to enzyme replacement therapy (ERT). Here, we describe identical twin, splenectomized, non-neuronopathic Gaucher patients on long-term ERT for 9 years, who complained of epigastric discomfort due to Gaucher cell infiltration of the gastroduodenal mucosa. Rare compound heterozygous mutations (p.Arg48Trp and p.Arg257Gln) of the GBA gene were found in both. Improvement in the gastroduodenal infiltration and reduced chitotriosidase levels were observed in one who switched to eliglustat tartrate for 1 year, whereas the other one who maintained ERT showed no improvement of chitotriosidase level and persistent duodenal lesions. This shows that eliglustat might be an effective treatment for Gaucher disease patients having lesions resistant to ERT.

Gaucher disease: from fundamental research to effective therapeutic interventions

NARCIS (Netherlands)

de Fost, M.; Aerts, J. M. F. G.; Hollak, C. E. M.

2003-01-01

Gaucher disease type I is the most common lysosomal storage disorder, with a prevalence Of 1:50,000 in most countries. It is caused by an autosomally recessive inherited deficiency of the lysosomal enzyme glucocerebrosidase, leading to the accumulation of glucocerebroside in the macrophages. The

Cytokines in Gaucher disease: Role in the pathogenesis of bone ...

African Journals Online (AJOL)

Azza A.G. Tantawy

2015-03-03

Mar 3, 2015 ... The impact of therapy on bone manifestations of Gaucher disease . ... types: classical or alternative, depending on the predominant cytokine in the .... avascular necrosis, bone infarcts and localised cortical thin- ning may be ...

Animal models for Gaucher disease research

OpenAIRE

Farfel-Becker, Tamar; Vitner, Einat B.; Futerman, Anthony H.

2011-01-01

Gaucher disease (GD), the most common lysosomal storage disorder (LSD), is caused by the defective activity of the lysosomal hydrolase glucocerebrosidase, which is encoded by the GBA gene. Generation of animal models that faithfully recapitulate the three clinical subtypes of GD has proved to be more of a challenge than first anticipated. The first mouse to be produced died within hours after birth owing to skin permeability problems, and mice with point mutations in Gba did not display sympt...

Outcome of Gaucher Disease in India: Lessons from Prevalent Diagnostic and Therapeutic Practices.

Science.gov (United States)

Muranjan, Mamta; Patil, Smita

2016-08-08

To study disease severity and response to enzyme replacement therapy in Gaucher disease. Updated data was captured from records of 37 patients (35 reported previously) with confirmed diagnosis of Gaucher disease from January 1995 through December 2011 (31, 83.8 %) and prospectively from January 2012 through June 2013 (6, 16.2 %). Severity of manifestations was determined by Gaucher disease Severity Score Index. Response to enzyme replacement therapy was assessed in terms of attainment of therapeutic goals. Moderate to severe manifestations (domain score of > 2) were observed in treated patients at baseline (83%, 58%, 66% and 25% for anemia, thrombocytopenia, hepatomegaly and leucopenia, respectively and 100% for splenomegaly and elevated plasma chitotriosidase). None of the 11 patients treated with synthetic enzyme (average annual dose 23 to 53 units/kg) attained all therapeutic goals in the recommended time frame, particularly the visceral, skeletal and growth domains. Early onset of moderate to severe disease in Indian patients mandates early therapy with optimum doses to ensure attainment of all recommended therapeutic goals.

Enhancing international collaboration among early-career researchers

Science.gov (United States)

Carroll, Jennifer K; Albada, Akke; Farahani, Mansoureh; Lithner, Maria; Neumann, Melanie; Sandhu, Harbinder; Shepherd, Heather L

2010-01-01

Objective The European Association of Communication in Healthcare (EACH) Early Career Researchers Network (ECRN) aims are to (1) promote international collaboration among young investigators and (2) provide a support network for future innovative communication research projects. In October 2009, Miami, USA at a workshop facilitated by the ECRN at the International Conference on Communication in Healthcare (ICCH) hosted by the American Academy of Communication in Healthcare we explored common facilitators and challenges faced by early career researchers in health communication research. Methods Attendees introduced themselves, their research area(s) of interest, and listed one facilitator and one barrier for their career development. EACH ECRN members then led a discussion of facilitators and challenges encountered in communication research projects and career development. We discussed potential collaboration opportunities, future goals, and activities. Results Having supportive collegial relationships, institutional support, job security, and funding are critical facilitators for early career investigators. Key challenges include difficulty with time management and prioritizing, limited resources, and contacts. Conclusion International collaboration among early career researchers is a feasible and effective means to address important challenges, by increasing opportunities for professional support and networking, problem-solving, discussion of data, and ultimately publishing. Practice Implications Future AACH-EACH Early Career Researcher Networks should continue to build collaborations by developing shared research projects, papers, and other scholarly products. PMID:20663630

Health literacy: setting an international collaborative research agenda

Directory of Open Access Journals (Sweden)

Rowlands Gillian

2009-07-01

Full Text Available Abstract Background Health literacy is an increasingly important topic in both the policy and research agendas of many countries. During the recent 36th Annual Meeting of the North American Primary Care Research Group, the authors led an audio-taped 3-hour forum, "Studying Health Literacy: Developing an International Collaboration," where the current state of health literacy (HL in the United States (US and United Kingdom (UK was presented and attendees were encouraged to debate a future research agenda. Discussion of Forum Themes The debate centred around three distinct themes, including: (1 refining HL definitions and conceptual models, (2 HL measurement and assessment tools, and (3 developing a collaborative international research agenda. The attendees agreed that future research should be theoretically grounded and conceptual models employed in studies should be explicit to allow for international comparisons to be drawn. Summary and Authors Reflections The importance of HL research and its possible contribution to health disparities is becoming increasingly recognised internationally. International collaborations and comparative studies could illuminate some of the possible determinants of disparities, and also possibly provide a vehicle to examine other research questions of interest.

Imiglucerase in the management of Gaucher disease type 1: an evidence-based review of its place in therapy

Science.gov (United States)

Serratrice, Christine; Carballo, Sebastian; Serratrice, Jacques; Stirnemann, Jérome

2016-01-01

Introduction Gaucher disease is the first lysosomal disease to benefit from enzyme replacement therapy, thus serving as model for numerous other lysosomal diseases. Alglucerase was the first glucocerebrosidase purified from placental extracts, and this was then replaced by imiglucerase – a Chinese hamster ovary cell-derived glucocerebrosidase. Aim The aim was to review the evidence underlying the use of imiglucerase in Gaucher disease type 1 Evidence review Data from clinical trials and Gaucher Registries were analyzed. Conclusion Imiglucerase has been prescribed and found to have an excellent efficacy and safety profile. We report herein the evidence-based data published for 26 years justifying the use of imiglucerase. PMID:27790078

The challenges of international collaboration: Perspectives from Princess Nourah Bint Abdulrahman University

Directory of Open Access Journals (Sweden)

Sana Almansour

2015-12-01

Full Text Available This case study addresses the international collaboration challenges faced by Princess Nourah Bint Abdulrahman University for women in Saudi Arabia. The objectives of this investigation are to define the challenging sources of international program collaboration between Princess Nourah Bint Abdulrahman University and foreign institutions from the perspective of the university staff who are involved in initiating these collaborations. A total of 27 university staff members who were involved in initiating institutional collaborations participated in semi-structured interviews. A thematic analysis of the interviews suggested that the major sources of challenges to the university’s international collaboration efforts are difficulties in making contacts with international institutions, language barriers, faculty resistance to international partnerships, cross-cultural issues, and establishing partnership agreements.

Enfermedad de Gaucher en Latinoamérica: Un informe del Registro Internacional y del Grupo Latinoamericano para la Enfermedad de Gaucher

Directory of Open Access Journals (Sweden)

Guillermo Drelichman

2012-08-01

Full Text Available La enfermedad de Gaucher, por su escasa frecuencia, está incluida dentro de las llamadas enfermedades huérfanas. En 1991 se creó el Registro Internacional de Gaucher y en 1992 se incorporaron los primeros pacientes de Latinoamérica. En el año 2008 se creó el Grupo Latinoamericano para la Enfermedad de Gaucher (GLAEG cuyos principales objetivos son fomentar la realización de consensos regionales, difundir el ingreso de pacientes al registro internacional y aumentar el conocimiento sobre la enfermedad para lograr mejorar la atención y la calidad de vida de los pacientes. Hasta abril del 2010 ingresaron 5828 pacientes de todo el mundo, 911 (15.6% son de Latinoamérica. Este es el primer informe global de la enfermedad en la Región: hay un predominio del sexo femenino, la forma clínica más frecuente es el tipo I (95%; al diagnóstico la mayoría son <20 años (68%. Las manifestaciones clínicas más frecuentes al diagnóstico son esplenomegalia (96% y anemia (49%, el 80% presentó hallazgos radiológicos de compromiso óseo. En nuestra Región, la gran mayoría de los pacientes (89% ha recibido alguna vez terapia de reemplazo enzimática con imiglucerasa logrando, con un seguimiento prolongado (hasta10 años, las metas terapéuticas que muestran la gran eficacia de la terapia. Si bien el porcentaje de pacientes con terapia es alto, las suspensiones de tratamiento son frecuentes. Las principales deficiencias en nuestra Región son: la carencia de evaluaciones viscerales volumétricas, de densitometría y de estudios moleculares en algunos pacientes. El principal problema es el subdiagnóstico.

B cell lymphoma and myeloma in murine Gaucher's disease

NARCIS (Netherlands)

Pavlova, E. V.; Wang, S. Z.; Archer, J.; Dekker, N. [=Nick; Aerts, J. M. F. G.; Karlsson, S.; Cox, T. M.

2013-01-01

Multiple myeloma and B cell lymphoma are leading causes of death in Gaucher's disease but the nature of the stimulus driving the often noted clonal expansion of immunoglobulin-secreting B cells and cognate lymphoid malignancy is unknown. We investigated the long-term development of B cell

A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments.

Science.gov (United States)

Stirnemann, Jérôme; Belmatoug, Nadia; Camou, Fabrice; Serratrice, Christine; Froissart, Roseline; Caillaud, Catherine; Levade, Thierry; Astudillo, Leonardo; Serratrice, Jacques; Brassier, Anaïs; Rose, Christian; Billette de Villemeur, Thierry; Berger, Marc G

2017-02-17

Gaucher disease (GD, ORPHA355) is a rare, autosomal recessive genetic disorder. It is caused by a deficiency of the lysosomal enzyme, glucocerebrosidase, which leads to an accumulation of its substrate, glucosylceramide, in macrophages. In the general population, its incidence is approximately 1/40,000 to 1/60,000 births, rising to 1/800 in Ashkenazi Jews. The main cause of the cytopenia, splenomegaly, hepatomegaly, and bone lesions associated with the disease is considered to be the infiltration of the bone marrow, spleen, and liver by Gaucher cells. Type-1 Gaucher disease, which affects the majority of patients (90% in Europe and USA, but less in other regions), is characterized by effects on the viscera, whereas types 2 and 3 are also associated with neurological impairment, either severe in type 2 or variable in type 3. A diagnosis of GD can be confirmed by demonstrating the deficiency of acid glucocerebrosidase activity in leukocytes. Mutations in the GBA1 gene should be identified as they may be of prognostic value in some cases. Patients with type-1 GD-but also carriers of GBA1 mutation-have been found to be predisposed to developing Parkinson's disease, and the risk of neoplasia associated with the disease is still subject to discussion. Disease-specific treatment consists of intravenous enzyme replacement therapy (ERT) using one of the currently available molecules (imiglucerase, velaglucerase, or taliglucerase). Orally administered inhibitors of glucosylceramide biosynthesis can also be used (miglustat or eliglustat).

A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments

Directory of Open Access Journals (Sweden)

Jérôme Stirnemann

2017-02-01

Full Text Available Gaucher disease (GD, ORPHA355 is a rare, autosomal recessive genetic disorder. It is caused by a deficiency of the lysosomal enzyme, glucocerebrosidase, which leads to an accumulation of its substrate, glucosylceramide, in macrophages. In the general population, its incidence is approximately 1/40,000 to 1/60,000 births, rising to 1/800 in Ashkenazi Jews. The main cause of the cytopenia, splenomegaly, hepatomegaly, and bone lesions associated with the disease is considered to be the infiltration of the bone marrow, spleen, and liver by Gaucher cells. Type-1 Gaucher disease, which affects the majority of patients (90% in Europe and USA, but less in other regions, is characterized by effects on the viscera, whereas types 2 and 3 are also associated with neurological impairment, either severe in type 2 or variable in type 3. A diagnosis of GD can be confirmed by demonstrating the deficiency of acid glucocerebrosidase activity in leukocytes. Mutations in the GBA1 gene should be identified as they may be of prognostic value in some cases. Patients with type-1 GD—but also carriers of GBA1 mutation—have been found to be predisposed to developing Parkinson’s disease, and the risk of neoplasia associated with the disease is still subject to discussion. Disease-specific treatment consists of intravenous enzyme replacement therapy (ERT using one of the currently available molecules (imiglucerase, velaglucerase, or taliglucerase. Orally administered inhibitors of glucosylceramide biosynthesis can also be used (miglustat or eliglustat.

Recommendations for the use of eliglustat in the treatment of adults with Gaucher disease type 1 in the United States.

Science.gov (United States)

Balwani, Manisha; Burrow, Thomas Andrew; Charrow, Joel; Goker-Alpan, Ozlem; Kaplan, Paige; Kishnani, Priya S; Mistry, Pramod; Ruskin, Jeremy; Weinreb, Neal

2016-02-01

In Gaucher disease, deficient activity of acid β-glucosidase results in accumulation of its substrates, glucosylceramide and glucosylsphingosine, within the lysosomes of cells primarily in the spleen, liver, bone marrow, and occasionally the lung. The multisystem disease is predominantly characterized by hepatosplenomegaly, anemia, thrombocytopenia, and skeletal disease. Enzyme replacement therapy with recombinant human acid β-glucosidase has been the first-line therapy for Gaucher disease type 1 for more than two decades. Eliglustat, a novel oral substrate reduction therapy, was recently approved in the United States and the European Union as a first-line treatment for adults with Gaucher disease type 1. Eliglustat inhibits glucosylceramide synthase, thereby decreasing production of the substrate glucosylceramide and reducing its accumulation. Although existing recommendations for the care of patients with Gaucher disease remain in effect, unique characteristics of eliglustat require additional investigation and monitoring. A panel of physicians with expertise in Gaucher disease and experience with eliglustat in the clinical trials provide guidance regarding the use of eliglustat, including considerations before starting therapy and monitoring of patients on eliglustat therapy. Copyright © 2015 Shire Development LLC. Published by Elsevier Inc. All rights reserved.

Radiopharmacology of inhaled [sup 133]Xe in skeletal sites containing deposits of Gaucher cells

Energy Technology Data Exchange (ETDEWEB)

Castronovo, F.P. Jr. (Brigham and Women' s Hospital, Boston, MA (United States) Harvard Medical School, Boston, MA (United States)); McKusick, K.A.; Doppelt, S.H. (Massachusetts General Hospital, Boston, MA (United States) Harvard Medical School, Boston, MA (United States)); Barton, N.W. (National Insts. of Health, Bethesda, MD (United States))

1993-07-01

Gaucher's disease is a lysomal storage disease in which cells of the reticuloendothelial system accumulate the lipid glucocerebroside. It is characterized by slowly progressive visceral and osseous involvement. One of the latter manifestations includes lipid infiltration of bone marrow. We monitored the rate of the inhaled [sup 133]Xe uptake and wash-out over diseased and normal metaphyseal and epiphyseal areas of the knee. Twenty-two patients (15 adults, 7 children) with various degrees of previously diagnosed Gaucher's disease were positioned supine under a [gamma]-camera interfaced to a computer system. All patients rebreathed [sup 133]Xe gas from a closed system for 10 min followed by 14 min of wash-out. Digitized images of the lung, liver, spleen, bony sites and soft tissue were obtained at 1 min intervals during the wash-in and wash-out phases. Counts for each ROI were normalized per 100 pixels and plotted as a function (time). Maximum uptake was also calculated by relating the counts/ROI/100 pixels to the 10 min integrated lung count during equilibrium (the administered ''dose''). There was essentially no [sup 133]Xe uptake in liver and spleen involved with Gaucher's disease. Monophasic uptake and biphasic wash-out curves were observed in the limited investigative population. Gaucher deposits released the [sup 133]Xe at a greater rate relative to soft tissue. (Author).

Studies in the use of liposomes in the development of an animal model of Gaucher's disease

OpenAIRE

Weereratne, Elaine Annmarie Hishani

1982-01-01

Gaucher's disease is characterised by a malfunction of the enzyme glucocerebrosidase which hydrolyses the glycolipid glucocerebroside. Mammalian tissues contain at least two beta-glucosidases capable of releasing glucose from the synthetic substrate 4-methylumbelliferyl-beta-D-glucopyranoside (4-MUGlc). One of these enzymes, a membrane bound 'acid' form, also hydrolyses glucocerebroside and is deficient in patients with Gaucher's disease. The synthetic substrate is used to measure this latter...

AAV8-mediated expression of glucocerebrosidase ameliorates the storage pathology in the visceral organs of a mouse model of Gaucher disease.

Science.gov (United States)

McEachern, Kerry Anne; Nietupski, Jennifer B; Chuang, Wei-Lien; Armentano, Donna; Johnson, Jennifer; Hutto, Elizabeth; Grabowski, Gregory A; Cheng, Seng H; Marshall, John

2006-06-01

Gaucher disease is the most common of the lysosomal storage disorders. The primary manifestation is the accumulation of glucosylceramide (GL-1) in the macrophages of liver and spleen (Gaucher cells), due to a deficiency in the lysosomal hydrolase glucocerebrosidase (GC). A Gaucher mouse model (D409V/null) exhibiting reduced GC activity and accumulation of GL-1 was used to evaluate adeno-associated viral (AAV)-mediated gene therapy. A recombinant AAV8 serotype vector bearing human GC (hGC) was administered intravenously to the mice. The levels of hGC in blood and tissues were determined, as were the effects of gene transfer on the levels of GL-1. Histopathological evaluation was performed on liver, spleen and lungs. Vector administration to pre-symptomatic Gaucher mice resulted in sustained hepatic secretion of hGC at levels that prevented GL-1 accumulation and the appearance of Gaucher cells in the liver, spleen and lungs. AAV administration to older mice with established disease resulted in normalization of GL-1 levels in the spleen and liver and partially reduced that in the lung. Analysis of the bronchoalveolar lavage fluid (BALF) from treated mice showed significant correction of the abnormal cellularity and cell differentials. No antibodies to the expressed hGC were detected following a challenge with recombinant enzyme suggesting the animals were tolerized to human enzyme. These data demonstrate the effectiveness of AAV-mediated gene therapy at preventing and correcting the biochemical and pathological abnormalities in a Gaucher mouse model, and thus support the continued consideration of this vector as an alternative approach to treating Gaucher disease. Copyright 2006 John Wiley & Sons, Ltd.

Association Between Progranulin and Gaucher Disease

OpenAIRE

Jian, Jinlong; Zhao, Shuai; Tian, Qing-Yun; Liu, Helen; Zhao, Yunpeng; Chen, Wen-Chi; Grunig, Gabriele; Torres, Paola A.; Wang, Betty C.; Zeng, Bai; Pastores, Gregory; Tang, Wei; Sun, Ying; Grabowski, Gregory A.; Kong, Max Xiangtian

2016-01-01

Background: Gaucher disease (GD) is a genetic disease caused by mutations in the GBA1 gene which result in reduced enzymatic activity of β-glucocerebrosidase (GCase). This study identified the progranulin (PGRN) gene (GRN) as another gene associated with GD. Methods: Serum levels of PGRN were measured from 115 GD patients and 99 healthy controls, whole GRN gene from 40 GD patients was sequenced, and the genotyping of 4 SNPs identified in GD patients was performed in 161 GD and 142 healthy ...

Clinical and genetic assessment of pediatric patients with Gaucher's ...

African Journals Online (AJOL)

Background: Gaucher's disease (GD) is an autosomal recessive genetic disorder that results from pathogenic mutations of GBA gene encoding the enzyme glucocerebrosidase (acid b-glucosidase). Of the approximately 300 mutations associated with GD, 4 accounts for the majority of mutations seen in GD patients: N370S, ...

Genetic heterogeneity in type 1 Gaucher disease: Multiple genotypes in Ashkenazic and non-Ashkenazic individuals

International Nuclear Information System (INIS)

Tsuji, Shoji; Martin, B.M.; Stubblefield, B.K.; LaMarca, M.E.; Ginns, E.I.; Barranger, J.A.

1988-01-01

Nucleotide sequence analysis of a genomic clone from an Ashkenazic Jewish patient with type 1 Gaucher disease revealed a single-base mutation (adenosine to guanosine transition) in exon 9 of the glucocerebrosidase gene. This change results in the amino acid substitution of serine for asparagine. Transient expression studies following oligonucleotide-directed mutagenesis of the normal cDNA confirmed that the mutation results in loss of glucocerebrosidase activity. Allele-specific hybridization with oligonucleotide probes demonstrated that this mutation was found exclusively in type 1 phenotype. None of the 6 type 2 patients, 11 type 3 patients, or 12 normal controls had this allele. In contrast, 15 of 24 type 1 patients had one allele with this mutation, and 3 others were homozygous for the mutation. Furthermore, some of the Ashkenazic Jewish type 1 patients had only one allele with this mutation, suggesting that even in this population there is allelic heterozygosity. These findings indicate that there are multiple allelic mutations responsible for type 1 Gaucher disease in both the Jewish and non-Jewish populations. Allelic-specific hybridization demonstrating this mutation in exon 9, used in conjunction with the Nci I restriction fragment length polymorphism described as a marker for neuronopathic Gaucher disease, provides a tool for diagnosis and genetic counseling that is ∼80% informative in all Gaucher patients studied

Genetic heterogeneity in type 1 Gaucher disease: Multiple genotypes in Ashkenazic and non-Ashkenazic individuals

Energy Technology Data Exchange (ETDEWEB)

Tsuji, Shoji; Martin, B.M.; Stubblefield, B.K.; LaMarca, M.E.; Ginns, E.I. (National Institute of Mental Health, Bethesda, MD (USA)); Barranger, J.A. (Childrens Hospital of Los Angeles, CA (USA))

1988-04-01

Nucleotide sequence analysis of a genomic clone from an Ashkenazic Jewish patient with type 1 Gaucher disease revealed a single-base mutation (adenosine to guanosine transition) in exon 9 of the glucocerebrosidase gene. This change results in the amino acid substitution of serine for asparagine. Transient expression studies following oligonucleotide-directed mutagenesis of the normal cDNA confirmed that the mutation results in loss of glucocerebrosidase activity. Allele-specific hybridization with oligonucleotide probes demonstrated that this mutation was found exclusively in type 1 phenotype. None of the 6 type 2 patients, 11 type 3 patients, or 12 normal controls had this allele. In contrast, 15 of 24 type 1 patients had one allele with this mutation, and 3 others were homozygous for the mutation. Furthermore, some of the Ashkenazic Jewish type 1 patients had only one allele with this mutation, suggesting that even in this population there is allelic heterozygosity. These findings indicate that there are multiple allelic mutations responsible for type 1 Gaucher disease in both the Jewish and non-Jewish populations. Allelic-specific hybridization demonstrating this mutation in exon 9, used in conjunction with the Nci I restriction fragment length polymorphism described as a marker for neuronopathic Gaucher disease, provides a tool for diagnosis and genetic counseling that is {approx}80% informative in all Gaucher patients studied.

Achievement of Therapeutic Goals with Low-Dose Imiglucerase in Gaucher Disease: A Single-Center Experience

Directory of Open Access Journals (Sweden)

Irina Tukan

2013-01-01

Full Text Available Gaucher disease, a lysosomal storage disorder, is a multisystem disorder with variable and unpredictable onset and severity. Disease-specific enzyme replacement therapy (ERT has been shown to reverse or ameliorate disease-specific hepatosplenomegaly and anemia and thrombocytopenia. ERT also impacts bone manifestations, including bone crises, bone pain, and appearance of new osteonecrosis, and improves bone mineral density to varying degrees. The objective of this study was to assess achievement of predefined therapeutic goals based on international registry outcomes for Israeli patients with Gaucher disease receiving imiglucerase for four consecutive years on a low-dose regimen followed in a single center. All data were taken from patient files. The therapeutic goals were taken from standards published in the literature for disease-specific clinical parameters. Among 164 patients at baseline, values for spleen and liver volumes, hemoglobin and platelet counts, and Z-scores for lumbar spine and femoral were significantly different from the goal. After four years ERT, there was a significant improvement ( in each of the therapeutic goal parameters from baseline. 15.2% of these patients achieved all hematology-visceral goals. In children, there was achievement of linear growth and puberty. This survey highlights the good overall response in symptomatic patients receiving low-dose ERT with imiglucerase in Israel.

Effects of switching from a reduced dose imiglucerase to velaglucerase in type 1 Gaucher disease: clinical and biochemical outcomes

NARCIS (Netherlands)

van Dussen, Laura; Cox, Timothy M.; Hendriks, Erik J.; Morris, Elizabeth; Akkerman, Erik M.; Maas, Mario; Groener, Johanna E. M.; Aerts, Johannes M. F. G.; Deegan, Patrick B.; Hollak, Carla E. M.

2012-01-01

This paper describes the effects of a switch to velaglucerase alfa in a group of adult patients with type 1 Gaucher disease, all of whom had previously had their dose reduced as a consequence of the worldwide imiglucerase shortage. Thirty-two patients from two large European Gaucher centers switched

Successful switch from enzyme replacement therapy to miglustat in an adult patient with type 1 Gaucher disease: a case report.

Science.gov (United States)

Giuffrida, Gaetano; Lombardo, Rita; Di Francesco, Ernesto; Parrinello, Laura; Di Raimondo, Francesco; Fiumara, Agata

2016-11-08

Gaucher disease is one of the most common lipid-storage disorders, affecting approximately 1 in 75,000 births. Enzyme replacement therapy with recombinant glucocerebrosidase is currently considered the first-line treatment choice for patients with symptomatic Gaucher disease type 1. Oral substrate reduction therapy is generally considered a second-line treatment option for adult patients with mild to moderate Gaucher disease type 1 who are unable or unwilling to receive lifelong intravenous enzyme infusions. The efficacy and safety of the oral substrate reduction therapy miglustat (Zavesca®) in patients with Gaucher disease type 1 have been established in both short-term clinical trials and long-term, open-label extension studies. Published data indicate that miglustat can be used as maintenance therapy in patients with stable Gaucher disease type 1 switched from previous enzyme replacement therapy. We report a case of a 44-year-old Caucasian man with Gaucher disease type 1 who was initially treated with enzyme replacement therapy but, owing to repeated cutaneous allergic reactions, had to be switched to miglustat after several attempts with enzyme replacement therapy. Despite many attempts, desensitization treatment did not result in improved toleration of imiglucerase infusions, and the patient became unwilling to continue with any intravenous enzyme replacement therapy. He subsequently agreed to switch to oral substrate reduction therapy with miglustat 100 mg twice daily titrated up to 100 mg three times daily over a short period. Long-term miglustat treatment maintained both hemoglobin and platelet levels within acceptable ranges over 8 years. The patient's spleen volume decreased, his plasma chitotriosidase levels stayed at reduced levels, and his bone mineral density findings have remained stable throughout follow-up. The patient's quality of life has remained satisfactory. Miglustat showed good gastrointestinal tolerability in this patient, and no

Review: Cytokines in Gaucher disease: Role in the pathogenesis of ...

African Journals Online (AJOL)

Gaucher disease (GD) is the most frequently encountered lysosomal storage disease caused by inborn defects of themembrane-bound lysosomal enzyme, acid b-glucosidase or glucocerebrosidase. This defective activity causes an accumulation of glucocerebroside (glucosylceramide) in the lysosomes of cells derived from ...

Clinical evaluation of chemokine and enzymatic biomarkers of Gaucher disease

NARCIS (Netherlands)

Deegan, Patrick B.; Moran, Mary Teresa; McFarlane, Ian; Schofield, J. Paul; Boot, Rolf G.; Aerts, Johannes M. F. G.; Cox, Timothy M.

2005-01-01

Purpose: Gaucher disease is an exemplary orphan disorder. Enzyme replacement therapy with imiglucerase is effective, but very expensive. To improve the assessment of severity of disease and responses to this costly treatment, we have evaluated several enzymatic biomarkers and a newly-described

Connecting Gaucher and Parkinson Disease: Considerations for Clinical and Research Genetic Counseling Settings.

Science.gov (United States)

Cook, Lola; Schulze, Jeanine

2017-12-01

There are multiple autosomal recessive disorders in which carriers may be at risk for other diseases. This observation calls into question the previous understanding that carriers of autosomal recessive disorders escape clinical consequences. We also know that childhood genetic conditions may have adult disease counterparts (Zimran et al., The Israel Medical Association Journal: IMAJ, 16(11), 723-724, 2014). Individuals who have Gaucher disease and carriers of the disorder are at increased risk for a seemingly unrelated and complex neurological condition, Parkinson disease. Parkinson disease is, in part, caused by the same mutations in the GBA gene that lead to Gaucher disease, and the two conditions are thought to have shared pathophysiology. Briefly reviewed are how these two diseases historically became linked, where their paths cross, potential problems and considerations in disclosure of the link, and current guidelines and research in this area. Genetic counseling experience with a large Parkinson disease cohort is used as a starting point to question the state of clinical and nonclinical practice in disclosing this unusual connection We conclude that more research and discussion are needed to inform practice regarding the crossroads of Gaucher and Parkinson disease.

Plasma glucosylceramide and ceramide in type 1 Gaucher disease patients: correlations with disease severity and response to therapeutic intervention

NARCIS (Netherlands)

Groener, J. E. M.; Poorthuis, B. J. H. M.; Kuiper, S.; Hollak, C. E. M.; Aerts, J. M. F. G.

2008-01-01

The concentrations of plasma glucosylceramide (GlcCer) and ceramide (Cer) were determined in a cohort of type 1 Gaucher disease patients. In plasma of untreated patients, GlcCer concentrations were on average 3-fold increased (median Gaucher: 17.5 nmol/ml, range: 6.5-45.5 (n=27); median control: 5.9

Trend and impact of international collaboration in clinical medicine papers published in Malaysia.

Science.gov (United States)

Low, Wah Yun; Ng, Kwan Hoong; Kabir, M A; Koh, Ai Peng; Sinnasamy, Janaki

2014-01-01

Research collaboration is the way forward in order to improve quality and impact of its research findings. International research collaboration has resulted in international co-authorship in scientific communications and publications. This study highlights the collaborating research and authorship trend in clinical medicine in Malaysia from 2001 to 2010. Malaysian-based author affiliation in the Web of Science (Science Citation Index Expanded) and clinical medicine journals ( n  = 999) and articles ( n  = 3951) as of 30th Oct 2011 were downloaded. Types of document analyzed were articles and reviews, and impact factors (IF) in the 2010 Journal Citation Report Science Edition were taken to access the quality of the articles. The number of publications in clinical medicine increased from 4.5 % ( n  = 178) in 2001 to 23.9 % ( n  = 944) in 2010. The top three contributors in the subject categories are Pharmacology and Pharmacy (13.9 %), General and Internal Medicine (13.6 %) and Tropical Medicine (7.3 %). By journal tier system: Tier 1 (18.7 %, n  = 738), Tier 2 (22.5 %, n  = 888), Tier 3 (29.6 %, n  = 1170), Tier 4 (27.2 %, n  = 1074), and journals without IF (2.1 %, n  = 81). University of Malaya was the most productive. Local collaborators accounted for 60.3 % and international collaborations 39.7 %. Articles with international collaborations appeared in journals with higher journal IFs than those without international collaboration. They were also cited more significantly than articles without international collaborations. Citations, impact factor and journal tiers were significantly associated with international collaboration in Malaysia's clinical medicine publications. Malaysia has achieved a significant number of ISI publications in clinical medicine participation in international collaboration.

Project-based learning with international collaboration for training biomedical engineers.

Science.gov (United States)

Krishnan, Shankar

2011-01-01

Training biomedical engineers while effectively keeping up with the fast paced scientific breakthroughs and the growth in technical innovations poses arduous challenges for educators. Traditional pedagogical methods are employed for coping with the increasing demands in biomedical engineering (BME) training and continuous improvements have been attempted with some success. Project-based learning (PBL) is an academic effort that challenges students by making them carry out interdisciplinary projects aimed at accomplishing a wide range of student learning outcomes. PBL has been shown to be effective in the medical field and has been adopted by other fields including engineering. The impact of globalization in healthcare appears to be steadily increasing which necessitates the inclusion of awareness of relevant international activities in the curriculum. Numerous difficulties are encountered when the formation of a collaborative team is tried, and additional difficulties occur as the collaboration team is extended to international partners. Understanding and agreement of responsibilities becomes somewhat complex and hence the collaborative project has to be planned and executed with clear understanding by all partners and participants. A model for training BME students by adopting PBL with international collaboration is proposed. The results of previous BME project work with international collaboration fit partially into the model. There were many logistic issues and constraints; however, the collaborative projects themselves greatly enhanced the student learning outcomes. This PBL type of learning experience tends to promote long term retention of multidisciplinary material and foster high-order cognitive activities such as analysis, synthesis and evaluation. In addition to introducing the students to experiences encountered in the real-life workforce, the proposed approach enhances developing professional contracts and global networking. In conclusion, despite

De ziekte van Gaucher op de kinderleeftijd: presentatie en behandeling

NARCIS (Netherlands)

Maaswinkel-Mooij, P. D.; Kerstjens-Frederikse, W. S.; de Koning, J.; Kok, A. J.; Poorthuis, B. J.

1992-01-01

M. Gaucher is a lysosomal storage disorder. Patients present with hepatosplenomegaly or with complaints of the bones. Clinically 3 subtypes can be distinguished; the 'adult' type I is most frequent found. On the basis of 10 case histories the presentation in childhood is reported. Only recently

GBA mutations in Gaucher type I Venezuelan patients: ethnic origins ...

Indian Academy of Sciences (India)

Gaucher disease (GD), the most frequent lysosomal storage disease, is caused by heterogeneous mutations in the locus coding for glucocerebrosidase (GBA). It is an autosomal recessive disorder with different phenotypes of which the most frequent is the nonneuronopathic or type 1, prevalent worldwide. To date, more ...

Type gaucher disease: radiographic and MRI manifestations

International Nuclear Information System (INIS)

Dong Yanqing; Li Kuncheng; Wang Yunzhao; Tian Ding

1999-01-01

Objective: To enhance the understanding of Gaucher disease (GD) type I bone involvement on imaging findings. Methods: The X-ray plain film and MRI findings of GD type I were reported, and literature reviewed. Results: The X-ray plain film of GD had characteristic change. The extent of bone involvement demonstrated could be depicted in longitudinal direction and the changes of marrow involvement on MRI. Conclusions: MRI is the best way to diagnose the bone involvement of GD

International Collaboration in Satellite Observations for Disaster Management

Science.gov (United States)

Duda, Kenneth A.; Abrams, Michael

2012-01-01

When lives are threatened or lost due to catastrophic disasters, and when massive financial impacts are experienced, international emergency response teams rapidly mobilize to provide urgently required support. Satellite observations of affected areas often provide essential insight into the magnitude and details of the impacts. The large cost and high complexity of developing and operating satellite flight and ground systems encourages international collaboration in acquiring imagery for such significant global events in order to speed delivery of critical information to help those affected, and optimize spectral, spatial, and temporal coverage of the areas of interest. The International Charter-Space and Major Disasters was established to enable such collaboration in sensor tasking during times of crisis and is often activated in response to calls for assistance from authorized users. Insight is provided from a U.S. perspective into sensor support for Charter activations and other disaster events through a description of the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER), which has been used to support emergency situations for over a decade through its expedited tasking and near real-time data delivery capabilities. Examples of successes achieved and challenges encountered in international collaboration to develop related systems and fulfill tasking requests suggest operational considerations for new missions as well as areas for future enhancements.

Women in global science advancing academic careers through international collaboration

CERN Document Server

Zippel, Kathrin

2017-01-01

Scientific and engineering research is increasingly global, and international collaboration can be essential to academic success. Yet even as administrators and policymakers extol the benefits of global science, few recognize the diversity of international research collaborations and their participants, or take gendered inequalities into account. Women in Global Science is the first book to consider systematically the challenges and opportunities that the globalization of scientific work brings to U.S. academics, especially for women faculty. Kathrin Zippel looks to the STEM fields as a case study, where gendered cultures and structures in academia have contributed to an underrepresentation of women. While some have approached underrepresentation as a national concern with a national solution, Zippel highlights how gender relations are reconfigured in global academia. For U.S. women in particular, international collaboration offers opportunities to step outside of exclusionary networks at home. International ...

International Collaboration in the Development of NPP Software

International Nuclear Information System (INIS)

Jiang, S.; Liu, L.; Yu, H.

2015-01-01

In this paper, we first review the progress and current status of international collaboration and technical exchange in the development of nuclear power plant (NPP) software by The State Nuclear Power Software Development Center (SNPSDC) in China. Then we discuss the importance of the international collaboration and exchange in the trend of globalisation of NPP technology. We also identify the role and contribution of professional women in this process. SNPSDC, the first professional software development centre for NPP in China, has been developing COSINE — a self-reliance NPP design and analysis software product with China brand—since 2010. Through participating in OECD/NEA’s joint projects, such as ROSA-2 Project, PKL–3 Project, HYMERES Project and ATLAS Project, SNPSDC shared data with other countries involved with respect to particular areas, such as high quality reactor thermal hydraulics test data. SNPSDC’s engineers have also been actively participating in international technical and research exchange for presenting their innovative work to the community while learning from peers. Our record shows that over 30 papers have been presented in international conferences with respect to nuclear reactor thermal hydraulics, safety analysis, reactor physics and software engineering within the past 4 years. The above international collaboration and technical exchange helped SNPSDC’s engineers to keep up with the state-of-art technology in this field. The large amount of valuable experimental data transferred to SNPSDC ensured the functionality, usability and reliability of software while greatly reduced the cost and shortened the cycle of development. Female engineers and other employees of SNPSDC either drove or got actively involved in a lot of aspects of the above collaboration and exchange, such as technical communication, business negotiation and overseas affairs management. These professional women played an irreplaceable role in this project by

Osteocyte Alterations Induce Osteoclastogenesis in an In Vitro Model of Gaucher Disease

Directory of Open Access Journals (Sweden)

Constanza Bondar

2017-01-01

Full Text Available Gaucher disease (GD is caused by mutations in the glucosylceramidase β (GBA 1 gene that confer a deficient level of activity of glucocerebrosidase (GCase. This deficiency leads to the accumulation of the glycolipid glucocerebroside in the lysosomes of cells, mainly in the monocyte/macrophage lineage. Its mildest form is Type I GD, characterized by non-neuronopathic involvement. Bone compromise is the most disabling aspect of the Gaucher disease. However, the pathophysiological aspects of skeletal alterations are not yet fully understood. The bone tissue homeostasis is maintained by a balance between resorption of old bone by osteoclasts and new bone formation by osteoblasts. A central player in this balance is the osteocyte as it controls both processes. We studied the involvement of osteocytes in an in vitro chemical model of Gaucher disease. The osteocyte cell line MLO-Y4 was exposed to conduritol-β-epoxide (CBE, an inhibitor of GCase, for a period of 7, 14 and 21 days. Conditioned media from CBE-treated osteocytes was found to induce osteoclast differentiation. GCase inhibition caused alterations in Cx43 expression and distribution pattern and an increase in osteocyte apoptosis. Osteoclast differentiation involved osteocyte apoptotic bodies, receptor activator of nuclear factor κ-B ligand (RANKL and soluble factors. Thus, our results indicate that osteocytes may have a role to play in the bone pathophysiology of GD.

Ocean Drilling: Forty Years of International Collaboration

Science.gov (United States)

Smith, Deborah K.; Exon, Neville; Barriga, Fernando J. A. S.; Tatsumi, Yoshiyuki

2010-10-01

International cooperation is an essential component of modern scientific research and societal advancement [see Ismail-Zadeh and Beer, 2009], and scientific ocean drilling represents one of Earth science's longest-running and most successful international collaborations. The strength of this collaboration and its continued success result from the realization that scientific ocean drilling provides a unique and powerful tool to study the critical processes of both short-term change and the long-term evolution of Earth systems. A record of Earth's changing tectonics, climate, ocean circulation, and biota is preserved in marine sedimentary deposits and the underlying basement rocks. And because the ocean floor is the natural site for accumulation and preservation of geological materials, it may preserve a continuous record of these processes.

Gaucher disease in the liver on hepatocyte specific contrast agent enhanced MR imaging

International Nuclear Information System (INIS)

Ayyala, Rama S.; Teot, Lisa A.; Perez Rossello, Jeanette M.

2017-01-01

Gaucher disease is a hereditary lipid storage disorder that affects the enzyme beta glucocerebrosidase, causing accumulation of glucocerebroside in macrophages of the reticuloendothelial system. Accumulation can occur in the liver and spleen, manifesting as hepatosplenomegaly, as well as within the bone marrow. Hepatic involvement is usually diffuse but can occasionally manifest as focal liver lesions. We present a case of a 2-year-old boy with Gaucher disease and an infiltrating liver lesion detected on imaging, which was pathologically shown to be focal changes related to the disease. Imaging characteristics of this lesion using hepatocyte specific contrast agent enhanced MRI, which have not been previously discussed in the literature, are described. (orig.)

Gaucher disease in the liver on hepatocyte specific contrast agent enhanced MR imaging

Energy Technology Data Exchange (ETDEWEB)

Ayyala, Rama S. [Morgan Stanley Children' s Hospital, Department of Radiology, Columbia University Medical Center, New York, NY (United States); Teot, Lisa A. [Boston Children' s Hospital, Department of Pathology, Harvard Medical School, Boston, MA (United States); Perez Rossello, Jeanette M. [Boston Children' s Hospital, Department of Radiology, Harvard Medical School, Boston, MA (United States)

2017-04-15

Gaucher disease is a hereditary lipid storage disorder that affects the enzyme beta glucocerebrosidase, causing accumulation of glucocerebroside in macrophages of the reticuloendothelial system. Accumulation can occur in the liver and spleen, manifesting as hepatosplenomegaly, as well as within the bone marrow. Hepatic involvement is usually diffuse but can occasionally manifest as focal liver lesions. We present a case of a 2-year-old boy with Gaucher disease and an infiltrating liver lesion detected on imaging, which was pathologically shown to be focal changes related to the disease. Imaging characteristics of this lesion using hepatocyte specific contrast agent enhanced MRI, which have not been previously discussed in the literature, are described. (orig.)

International collaboration on CESR-TA program

International Nuclear Information System (INIS)

Flanagan, John; Suetsugu, Yusuke

2009-01-01

An international collaboration on the CESR-TA (Cornell Electron Storage Ring-Test Accelerator) program, which is a program to investigate electron cloud instability (ECI) issues in the positron damping ring of the ILC (International Linear-Collider), is currently underway a Cornell University, KEK is supporting the program through the development of an X-ray beam profile monitor system to measure the extremely small beam size, and through the development of clearing electrodes to mitigate the ECI. (author)

The biology of the Gaucher cell: the cradle of human chitinases

NARCIS (Netherlands)

Bussink, Anton P.; van Eijk, Marco; Renkema, G. Herma; Aerts, Johannes M.; Boot, Rolf G.

2006-01-01

Gaucher disease (GD) is the most common lysosomal storage disorder and is caused by inherited deficiencies of glucocerebrosidase, the enzyme responsible for the lysosomal breakdown of the lipid glucosylceramide. GD is characterized by the accumulation of pathological, lipid laden macrophages,

Gaucher disease: MR evaluation of bone marrow features during treatment with enzyme replacement

International Nuclear Information System (INIS)

Poll, L.W.; Koch, J.A.; Boerner, D.; Cohnen, M.; Jung, G.; Scherer, A.; Moedder, U.; Niederau, C.

2001-01-01

Purpose: Enzyme replacement therapy (ERT) arrests and reverses the hematological and visceral symptoms of adult Gaucher disease, the most frequent lysosomal storage disorder. There are only a few studies available evaluating bone disease during ERT. The aim of this study was to investigate the features of bone marrow (bm) by magnetic resonance imaging (MRI) in these patients during ERT. Materials and Methods: MRI was performed prospectively in thirty adult type I Gaucher patients before and during ERT with a mean follow-up of 3 years. Spin-echo sequences (T 1 /T 2 ) of the lower extremities were obtained and the reconversion (response) or lack of reconversion (non-response) to fatty marrow during treatment was analyzed. The morphological features of bm involvement, a homogeneous or non-homogeneous distribution of bm changes and focal bone lesions surrounded by a rim of reduced signal intensity (SI), were analyzed. Results: Infiltration of bm by Gaucher cells is characterized by a reduction of Sl on both T 1 - and T 2 -weighted sequences. Bone marrow responses were seen in 19 patients (63%) during treatment. Focal bone lesions, surrounded by a rim of reduced Sl, did not respond to ERT and correlated with a non-homogenous distribution of bone involvement and splenectomy. (orig.) [de

Reconversion of bone marrow in Gaucher disease treated with enzyme therapy documented by MR

International Nuclear Information System (INIS)

Allison, J.W.; James, C.A.; Arnold, G.L.; Stine, K.C.; Becton, D.L.; Bell, J.M.

1998-01-01

Background. Skeletal complications are responsible for significant morbidity in Gaucher patients. Plain radiographs have been unreliable in assessing bone marrow infiltration and activity. A way to assess bone marrow improvement is needed during enzyme therapy. Objective. The purpose of this paper is to assess the usefulness of MR in following improvement of abnormal bone marrow in Gaucher patients on enzyme therapy. Materials and methods. Three patients aged 2, 7, and 24 years underwent serial MR scans of the lower extremities before and during treatment with Alglucerase (two patients) and Imiglucerase (one patient). T1-weighted, T2-weighted, STIR and FSE T2-weighted images were utilized. Two patients were imaged after 16 months of therapy, and one patient was imaged after 6 months of therapy. Results. All patients had improvement in marrow signal consistent with partial reconversion to fatty marrow during treatment. The findings were more marked after prolonged therapy. T1-weighted images demonstrated findings most clearly. Conclusion. MR consistently showed improvement in marrow signal in Gaucher patients on enzyme therapy. As smaller doses of enzyme therapy are the trend, MR can be utilized to determine if therapy is effecting a change in the bone marrow. (orig.)

ICFA: Protvino meeting looks at trends in international collaboration

Energy Technology Data Exchange (ETDEWEB)

Anon.

1991-01-15

International collaboration is the lifeblood of Big Science, and in high energy physics the triennial 'Future Perspectives' meeting organized by the International Committee for Future Accelerators (ICFA) provides a valuable opportunity to reappraise trends in this collaboration. The latest meeting was held in October at Protvino, near Moscow, where the Institute for High Energy Physics is the scene of construction work for the 21-kilometre UNK proton rings and the projected home of a big new linear collider for electrons and positrons.

Combined miglustat and enzyme replacement therapy in two patients with type 1 Gaucher disease: two case reports.

Science.gov (United States)

Amato, Dominick; Patterson, Mary Anne

2018-01-27

Intravenous enzyme replacement therapy is a first-line therapy for Gaucher disease type 1, and substrate reduction therapy represents an oral treatment alternative. Both enzyme replacement therapy and substrate reduction therapy are generally used as monotherapies in Gaucher disease. However, one randomized study and several case reports have described combination therapy over short time periods. We report two female Gaucher disease type 1 patients of mainly Anglo-Saxon descent, where combined enzyme replacement therapy and miglustat substrate reduction therapy were administered to overcome refractory clinical symptoms. The first patient was diagnosed at age 17 and developed Gaucher disease-related bone manifestations that worsened despite starting imiglucerase enzyme replacement therapy. After switching to miglustat substrate reduction therapy, her bone symptoms improved, but she developed tremors and eventually switched back to enzyme replacement therapy. Miglustat was later recommenced in combination with ongoing enzyme replacement therapy due to continued bone pain, and her bone symptoms improved along with maintained visceral manifestations. Enzyme replacement therapy was subsequently tapered off and the patient has since been successfully maintained on miglustat. The second patient was diagnosed aged 3, and commenced imiglucerase enzyme replacement therapy aged 15. After 9 years on enzyme replacement therapy she switched to miglustat substrate reduction therapy and her core symptoms were maintained/stable for 3 years. Imiglucerase enzyme replacement therapy was later added as a boost to therapy and her symptoms were subsequently maintained over a 2.3-year period. However, miglustat was discontinued due to her relocation, necessitating an increase in enzyme replacement therapy dose. Overall, both patients benefited from combination therapy. While the majority of Gaucher disease type 1 patients will not need treatment with both substrate reduction therapy

Gaucher's disease: Report of 11 cases with review of literature ...

African Journals Online (AJOL)

Gaucher's disease (GD) is a lysosomal storage disorder due to glucocerebrosidase deficiency; it's one of the rare genetic diseases for which therapy is now available. The purpose of this work is to study the epidemiological features of the disease and to highlight the diagnostic difficulties. We performed an 11-year ...

Association Between Progranulin and Gaucher Disease.

Science.gov (United States)

Jian, Jinlong; Zhao, Shuai; Tian, Qing-Yun; Liu, Helen; Zhao, Yunpeng; Chen, Wen-Chi; Grunig, Gabriele; Torres, Paola A; Wang, Betty C; Zeng, Bai; Pastores, Gregory; Tang, Wei; Sun, Ying; Grabowski, Gregory A; Kong, Max Xiangtian; Wang, Guilin; Chen, Ying; Liang, Fengxia; Overkleeft, Herman S; Saunders-Pullman, Rachel; Chan, Gerald L; Liu, Chuan-Ju

2016-09-01

Gaucher disease (GD) is a genetic disease caused by mutations in the GBA1 gene which result in reduced enzymatic activity of β-glucocerebrosidase (GCase). This study identified the progranulin (PGRN) gene (GRN) as another gene associated with GD. Serum levels of PGRN were measured from 115 GD patients and 99 healthy controls, whole GRN gene from 40 GD patients was sequenced, and the genotyping of 4 SNPs identified in GD patients was performed in 161 GD and 142 healthy control samples. Development of GD in PGRN-deficient mice was characterized, and the therapeutic effect of rPGRN on GD analyzed. Serum PGRN levels were significantly lower in GD patients (96.65±53.45ng/ml) than those in healthy controls of the general population (164.99±43.16ng/ml, pGaucher-like cells in lung, spleen, and bone marrow. Moreover, lysosomes in PGRN KO mice exhibit a tubular-like appearance. PGRN is required for the lysosomal appearance of GCase and its deficiency leads to GCase accumulation in the cytoplasm. More importantly, recombinant PGRN is therapeutic in various animal models of GD and human fibroblasts from GD patients. Our data demonstrates an unknown association between PGRN and GD and identifies PGRN as an essential factor for GCase's lysosomal localization. These findings not only provide new insight into the pathogenesis of GD, but may also have implications for diagnosis and alternative targeted therapies for GD. Copyright © 2016 Forschungsgesellschaft für Arbeitsphysiologie und Arbeitschutz e.V. Published by Elsevier B.V. All rights reserved.

A New Glucocerebrosidase Chaperone Reduces α-Synuclein and Glycolipid Levels in iPSC-Derived Dopaminergic Neurons from Patients with Gaucher Disease and Parkinsonism.

Science.gov (United States)

Aflaki, Elma; Borger, Daniel K; Moaven, Nima; Stubblefield, Barbara K; Rogers, Steven A; Patnaik, Samarjit; Schoenen, Frank J; Westbroek, Wendy; Zheng, Wei; Sullivan, Patricia; Fujiwara, Hideji; Sidhu, Rohini; Khaliq, Zayd M; Lopez, Grisel J; Goldstein, David S; Ory, Daniel S; Marugan, Juan; Sidransky, Ellen

2016-07-13

Among the known genetic risk factors for Parkinson disease, mutations in GBA1, the gene responsible for the lysosomal disorder Gaucher disease, are the most common. This genetic link has directed attention to the role of the lysosome in the pathogenesis of parkinsonism. To study how glucocerebrosidase impacts parkinsonism and to evaluate new therapeutics, we generated induced human pluripotent stem cells from four patients with Type 1 (non-neuronopathic) Gaucher disease, two with and two without parkinsonism, and one patient with Type 2 (acute neuronopathic) Gaucher disease, and differentiated them into macrophages and dopaminergic neurons. These cells exhibited decreased glucocerebrosidase activity and stored the glycolipid substrates glucosylceramide and glucosylsphingosine, demonstrating their similarity to patients with Gaucher disease. Dopaminergic neurons from patients with Type 2 and Type 1 Gaucher disease with parkinsonism had reduced dopamine storage and dopamine transporter reuptake. Levels of α-synuclein, a protein present as aggregates in Parkinson disease and related synucleinopathies, were selectively elevated in neurons from the patients with parkinsonism or Type 2 Gaucher disease. The cells were then treated with NCGC607, a small-molecule noninhibitory chaperone of glucocerebrosidase identified by high-throughput screening and medicinal chemistry structure optimization. This compound successfully chaperoned the mutant enzyme, restored glucocerebrosidase activity and protein levels, and reduced glycolipid storage in both iPSC-derived macrophages and dopaminergic neurons, indicating its potential for treating neuronopathic Gaucher disease. In addition, NCGC607 reduced α-synuclein levels in dopaminergic neurons from the patients with parkinsonism, suggesting that noninhibitory small-molecule chaperones of glucocerebrosidase may prove useful for the treatment of Parkinson disease. Because GBA1 mutations are the most common genetic risk factor for

International Education Hubs: Collaboration for Competitiveness and Sustainability

Science.gov (United States)

Knight, Jane

2014-01-01

This chapter focuses on the development of education hubs, a recent phenomenon in international higher education. Three models of hubs are examined in relation to the forces, risks, and opportunities of globalization and how local and international collaborations are essential for both global competitiveness and sustainability.

Building international collaborative capacity: contributions of community psychologists to a European network.

Science.gov (United States)

García-Ramírez, Manuel; Paloma, Virginia; Suarez-Balcazar, Yolanda; Balcazar, Fabricio

2009-09-01

Europe is in the process of building a more participative, just, and inclusive European Union. The European Social Fund, which is an initiative developed to actively promote multinational partnerships that address pressing social issues, is a good example of the European transformation. This article describes the steps taken to develop and evaluate the activities of an international network promoting collaborative capacity among regional partners involved in the prevention of labor discrimination toward immigrants in three European countries-Spain, Belgium, and Italy. An international team of community psychologists proposed an empowering approach to assess the collaborative capacity of the network. This approach consisted of three steps: (1) establishing a collaborative relationship among partners, (2) building collaborative capacity, and (3) evaluating the collaborative capacity of the network. We conclude with lessons learned from the process and provide recommendations for addressing the challenges inherent in international collaboration processes.

The world network of scientific collaborations between cities: domestic or international dynamics?

Energy Technology Data Exchange (ETDEWEB)

Maisonobe, M.; Eckert, D.; Grossetti, M.; Jégou, L.; Milard, B.

2016-07-01

Earlier publication (Grossetti et al., 2014) has established that we are attending a decreasing concentration of scientific activities within “world-cities”. Given that more and more cities and countries are contributing to the world production of knowledge, this article analyzes the evolution of the world network of collaborations both at the domestic and international levels during the 2000s. Using data from the Science Citation Index Expanded, scientific authors’ addresses are geo-localized and grouped by urban areas. Our data suggests that interurban collaborations within countries have increased together with international linkages. In most countries, domestic collaborations have increased faster than international collaborations. Even among the top collaborating cities, sometimes referred to as “world cities”, the share of domestic collaborations is gaining momentum. Our results suggest that, contrary to common beliefs about the globalization process, national systems of research have been strengthening during the 2000s. (Author)

A new glucocerebrosidase-deficient neuronal cell model provides a tool to probe pathophysiology and therapeutics for Gaucher disease.

Science.gov (United States)

Westbroek, Wendy; Nguyen, Matthew; Siebert, Marina; Lindstrom, Taylor; Burnett, Robert A; Aflaki, Elma; Jung, Olive; Tamargo, Rafael; Rodriguez-Gil, Jorge L; Acosta, Walter; Hendrix, An; Behre, Bahafta; Tayebi, Nahid; Fujiwara, Hideji; Sidhu, Rohini; Renvoise, Benoit; Ginns, Edward I; Dutra, Amalia; Pak, Evgenia; Cramer, Carole; Ory, Daniel S; Pavan, William J; Sidransky, Ellen

2016-07-01

Glucocerebrosidase is a lysosomal hydrolase involved in the breakdown of glucosylceramide. Gaucher disease, a recessive lysosomal storage disorder, is caused by mutations in the gene GBA1 Dysfunctional glucocerebrosidase leads to accumulation of glucosylceramide and glycosylsphingosine in various cell types and organs. Mutations in GBA1 are also a common genetic risk factor for Parkinson disease and related synucleinopathies. In recent years, research on the pathophysiology of Gaucher disease, the molecular link between Gaucher and Parkinson disease, and novel therapeutics, have accelerated the need for relevant cell models with GBA1 mutations. Although induced pluripotent stem cells, primary rodent neurons, and transfected neuroblastoma cell lines have been used to study the effect of glucocerebrosidase deficiency on neuronal function, these models have limitations because of challenges in culturing and propagating the cells, low yield, and the introduction of exogenous mutant GBA1 To address some of these difficulties, we established a high yield, easy-to-culture mouse neuronal cell model with nearly complete glucocerebrosidase deficiency representative of Gaucher disease. We successfully immortalized cortical neurons from embryonic null allele gba(-/-) mice and the control littermate (gba(+/+)) by infecting differentiated primary cortical neurons in culture with an EF1α-SV40T lentivirus. Immortalized gba(-/-) neurons lack glucocerebrosidase protein and enzyme activity, and exhibit a dramatic increase in glucosylceramide and glucosylsphingosine accumulation, enlarged lysosomes, and an impaired ATP-dependent calcium-influx response; these phenotypical characteristics were absent in gba(+/+) neurons. This null allele gba(-/-) mouse neuronal model provides a much-needed tool to study the pathophysiology of Gaucher disease and to evaluate new therapies. © 2016. Published by The Company of Biologists Ltd.

A new glucocerebrosidase-deficient neuronal cell model provides a tool to probe pathophysiology and therapeutics for Gaucher disease

Directory of Open Access Journals (Sweden)

Wendy Westbroek

2016-07-01

Full Text Available Glucocerebrosidase is a lysosomal hydrolase involved in the breakdown of glucosylceramide. Gaucher disease, a recessive lysosomal storage disorder, is caused by mutations in the gene GBA1. Dysfunctional glucocerebrosidase leads to accumulation of glucosylceramide and glycosylsphingosine in various cell types and organs. Mutations in GBA1 are also a common genetic risk factor for Parkinson disease and related synucleinopathies. In recent years, research on the pathophysiology of Gaucher disease, the molecular link between Gaucher and Parkinson disease, and novel therapeutics, have accelerated the need for relevant cell models with GBA1 mutations. Although induced pluripotent stem cells, primary rodent neurons, and transfected neuroblastoma cell lines have been used to study the effect of glucocerebrosidase deficiency on neuronal function, these models have limitations because of challenges in culturing and propagating the cells, low yield, and the introduction of exogenous mutant GBA1. To address some of these difficulties, we established a high yield, easy-to-culture mouse neuronal cell model with nearly complete glucocerebrosidase deficiency representative of Gaucher disease. We successfully immortalized cortical neurons from embryonic null allele gba−/− mice and the control littermate (gba+/+ by infecting differentiated primary cortical neurons in culture with an EF1α-SV40T lentivirus. Immortalized gba−/− neurons lack glucocerebrosidase protein and enzyme activity, and exhibit a dramatic increase in glucosylceramide and glucosylsphingosine accumulation, enlarged lysosomes, and an impaired ATP-dependent calcium-influx response; these phenotypical characteristics were absent in gba+/+ neurons. This null allele gba−/− mouse neuronal model provides a much-needed tool to study the pathophysiology of Gaucher disease and to evaluate new therapies.

ICFA: Protvino meeting looks at trends in international collaboration

International Nuclear Information System (INIS)

Anon.

1991-01-01

International collaboration is the lifeblood of Big Science, and in high energy physics the triennial 'Future Perspectives' meeting organized by the International Committee for Future Accelerators (ICFA) provides a valuable opportunity to reappraise trends in this collaboration. The latest meeting was held in October at Protvino, near Moscow, where the Institute for High Energy Physics is the scene of construction work for the 21-kilometre UNK proton rings and the projected home of a big new linear collider for electrons and positrons

Bibliometric Analysis of International Collaboration in Wind and Solar Energy

Directory of Open Access Journals (Sweden)

Ichiro Sakata

2013-09-01

Full Text Available Modern technology is increasingly complex and demands an ever-widening range of knowledge and skills. No single country will possess all the knowledge and skills required for addressing global issues such as climate change. Technology collaboration between leading countries is important to promptly and efficiently address the problem. Previous studies have shown that a high level of collaboration is correlated with high paper productivity. This paper first aims to use objective data and create maps that enable us to see both the distribution of worldwide research competency and the relationship of international collaboration in clean energy research. In the international research network of wind power and solar cell, 4,189 institutions located in 121 countries and 6,600 institutions located in 125 countries are included respectively. This paper discusses various factors that would have an impact on research capability and support strong international relationships. With respect to research capability, governmental policies, stability of governmental commitment, natural conditions and historical and institutional differences have a significant impact on it. For research collaborations, factors such as geographical proximity, international science and technology policy, and developmental stage of technology have been brought to attention. This study demonstrates that bibliometrics is a methodology that is capable of providing a knowledge base that is useful in the development of the international science and technology policy and technological management strategy.

Trust Management - Building Trust for International Cross Disciplinary Collaboration on Climate Change

Science.gov (United States)

Oakley, K. V.; Gurney, R. J.

2014-12-01

Successful communication and collaboration entails mutual understanding, and transfer, of information. The risk of misunderstanding and/or miscommunication between collaborating groups is tackled in different ways around the globe; some are well documented whereas others may be unknown outside particular groups, whether defined geographically or by specialism. For example; in some countries legally binding contracts define the terms of collaboration. Some regions place greater emphasis on developing trust relationships, and sometimes an official agreement is implied, such as many electronic data transfers on the web. International collaboration on climate change increasingly involves electronic data exchange (e.g. open access publications, shared documents, data repositories etc.) and with this increased reliance on electronic data a need has arisen for scientists to collaborate both internationally and cross-disciplinarily particularly with information technology and data management specialists. Trust of data and metadata on the internet (e.g. privacy, legitimacy etc.) varies, possibly due to a lack of internationally agreed standards for data governance and management, leaving many national, regional and institutional practices tailored to the needs of that group only. It is proposed that building trust relationships between cross-disciplinary and international groups could help facilitate further communication, understanding and benefits from the relationship, while still maintaining independence as separate groups. Complex international cross-disciplinary group relationship dynamics are not easily mapped and producing a set of trust building rules that can be applied to any current and future collaboration with equal validity may be unfeasible. An alternative to such a set of rules may be found in a Trust Manager, whose role is to improve mutually beneficial knowledge exchange between groups, build trust and increase future collaborative potential. This

Imaging features of skeletal changes in children with Gaucher disease

International Nuclear Information System (INIS)

Zhang Ningning; Duan Xiaomin; Duan Yanlong

2011-01-01

Objective: To discuss the imaging features of skeletal changes in children with Gaucher disease on X-ray and MRI images. Methods: One hundred and nine children with Gaucher disease were enrolled in this study. They all received routine X-ray for spine with anterior-posterior (A-P) and lateral view and bilateral femurs with A-P view. Among them, 18 patients received X-ray for pelvic with A-P view, 14 patients received X-ray for left wrist with A-P view, and 14 patients received MRI scan for femur. The MRI scan included T 1 -weighted imaging, T 2 -weighted imaging and fat-suppressed T 2 -weighted imaging with short tau inversion recovery (STIR) sequence. The imaging features of the X-ray and MRI images were analyzed retrospectively. Results: The most common feature is osteoporosis, which presented in 91 cases (83.5%). Besides this, decreased density of metaphysis occurred in 86 cases (78.9%), erlenmeyer flask deformity of metaphysis occurred in 89 patients (81.7%), thinner cortex occurred in 69 cases (63.3%), osteolytic destruction occurred in. 31 cases (28.4%), pathological fractures occurred in 26 cases (23.9%), osteosclerosis occurred in 12 cases (11.0%). cystic degeneration of bone occurred in 16 cases (14.7%), and dislocation of the hip occurred in 4 cases. All 14 patients received MRI presented abnormal signals. Among them, 4 patients presented low signal intensity both on T 1 -weighted and T 2 -weighted images in bone marrow, the other ten presented high signal intensity mixed in low signal intensity areas on T 2 - weighted and fat-suppressed T 2 -weighted images. Conclusions: The imaging features of skeletal changes in children with Gaucher disease are of some characteristics, which could provide useful information for the clinical treatment. (authors)

How international is internationally collaborated research? A bibliometric study of Russian surname holder collaboration networks

Energy Technology Data Exchange (ETDEWEB)

Karaulova, M.; Goek, A.; Shapira, P.

2016-07-01

International research performance indicators attain increased attention in science policy. They are seen to reflect relative competitiveness of a country in producing leading research (in terms of cited papers) and its commercialisation (in terms of assigned patents). However, more studies point to ongoing global bias in production, composition and assessment of research performance metrics (Rafols et al., 2012; van Leeuwen et al., 2001). As research performance indicators are used increasingly in national science policy and in influential international rankings, it is important to understand their inherent bias. For instance, explosive growth of international collaboration in science is widely reported (Glänzel, 2001), and is generally perceived as having beneficial ‘knowledge exchange’ effect for involved parties. It is recognised as a capacity-building factor of domestic research indicating the increase in research quality (Bornmann et al., 2015). However, existing research has reported reproduction of uneven global relations between countries in terms of science and technology. For example, patterns of international cooperation in nanotechnology are still centred on the developed countries, which are key nodes in international networks (Shapira and Wang, 2010). (Author)

Evolutionary convergence of the patterns of international research collaborations across scientific fields

NARCIS (Netherlands)

Wang, L.; Coccia, M.

2015-01-01

Frame and Carpenter (1979) analysed the pattern of international research collaboration among scientific fields in 1970s. Starting from this pioneering work, this paper investigates international collaborations over 1997-2012 and compares the critical results with earlier studies to detect the

Glucocerebrosidase genotype of Gaucher patients in The Netherlands: limitations in prognostic value

NARCIS (Netherlands)

Boot, R. G.; Hollak, C. E.; Verhoek, M.; Sloof, P.; Poorthuis, B. J.; Kleijer, W. J.; Wevers, R. A.; van Oers, M. H.; Mannens, M. M.; Aerts, J. M.; van Weely, S.

1997-01-01

Gaucher disease is a recessively inherited lysosomal storage disorder that is caused by a deficiency in glucocerebrosidase activity. The clinical expression is markedly heterogeneous with respect to age of onset, progression, severity, and neurological involvement. The relative incidence of

Lipid composition of microdomains is altered in neuronopathic Gaucher disease sheep brain and spleen.

Science.gov (United States)

Hein, Leanne K; Rozaklis, Tina; Adams, Melissa K; Hopwood, John J; Karageorgos, Litsa

2017-07-01

Gaucher disease is a lysosomal storage disorder caused by a deficiency in glucocerebrosidase activity that leads to accumulation of glucosylceramide and glucosylsphingosine. Membrane raft microdomains are discrete, highly organized microdomains with a unique lipid composition that provide the necessary environment for specific protein-lipid and protein-protein interactions to take place. In this study we purified detergent resistant membranes (DRM; membrane rafts) from the occipital cortex and spleen from sheep affected with acute neuronopathic Gaucher disease and wild-type controls. We observed significant increases in the concentrations of glucosylceramide, hexosylsphingosine, BMP and gangliosides and decreases in the percentage of cholesterol and phosphatidylcholine leading to an altered DRM composition. Altered sphingolipid/cholesterol homeostasis would dramatically disrupt DRM architecture making them less ordered and more fluid. In addition, significant changes in the length and degree of lipid saturation within the DRM microdomains in the Gaucher brain were also observed. As these DRM microdomains are involved in many cellular events, an imbalance or disruption of the cell membrane homeostasis may impair normal cell function. This disruption of membrane raft microdomains and imbalance within the environment of cellular membranes of neuronal cells may be a key factor in initiating a cascade process leading to neurodegeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

Histologic findings of femoral heads from patients with Gaucher disease treated with enzyme replacement.

Science.gov (United States)

Lebel, Ehud; Elstein, Deborah; Peleg, Ariel; Reinus, Constantine; Zimran, Ari; Amir, Gail

2013-07-01

To assess correlations of patient demographics, including enzyme replacement therapy (ERT) with bone histology, to facilitate decisions of whether and when to perform hip replacement surgery in patients with Gaucher disease. We examined the histology of surgically removed femoral heads and categorized findings by the presence or extent of osteonecrosis, Gaucher cell (GC) infiltration, and bone regeneration qualifiers using a tripartite histology-based scoring system. Twenty-two patients with 26 bone specimens were evaluated. Seventeen patients (77%) were splenectomized, 16 (73%) received ERT, and 12 (55%) had the putatively milder genotype (N370S/N370S), with the rest putatively at increased risk for skeletal disease (N370S/other). The 3 histology subscores were applicable to all specimens. Osteonecrotic bone was seen in 19 of 26 (73%); osteoarthritis was seen in all cartilage specimens. Gaucher cell infiltration was not correlated with demographics or disease severity. A trend was noted between reduced GC infiltration and ERT (ρ = 0.407), but regeneration qualifiers were not correlated with ERT or other features. Histologic findings of GC infiltration and bone regeneration qualifiers did not correlate with demographics or with exposure to ERT. Most specimens unexpectedly showed good regenerative responses to osteonecrosis despite heavy GC infiltration.

Clinical potential of eliglustat tartrate in the treatment of type 1 Gaucher disease

Directory of Open Access Journals (Sweden)

Kaplan P

2014-05-01

Full Text Available Paige KaplanLysosomal Disorders Center, Section of Metabolic Diseases, Children's Hospital of Philadelphia, Philadelphia, PA, USAAbstract: Nonneuropathic type 1 Gaucher disease is an autosomal recessive inherited disease caused by the deficiency or absence of beta glucocerebrosidase (beta glucosidase. The highest prevalence of type 1 is in Ashkenazi Jews, but it affects all ethnic groups. It manifests at any age but is seen predominantly in the first two decades. The phenotype is characterized by painless splenomegaly and secondary hypersplenism (low hemoglobin concentration and low platelet and white blood cell counts. Symptoms and signs include splenomegaly; chronic fatigue, frequent nose bleeds, prolonged bleeding, and/or bruising; hepatomegaly; bone pain, bone destruction and low bone density; and poor growth in childhood and delayed pubertal development. Current treatment with intravenous enzyme replacement has been generally successful. However, oral treatments have been developed because enzyme replacement is time-consuming and invasive, and intravenous infusions are not universally available for patients who live far from medical centers or home infusion nurses. Furthermore, it may become difficult to access veins after repeated infusions. Orally administered substrate reduction is a newer treatment approach. The aim is to limit the synthesis of the substrate, glucosylceramide. The residual intrinsic enzyme, acting alone or with recombinant enzyme, can then completely catabolize the smaller amounts of glucosylceramide that are transported into lysosomes. Eliglustat tartrate is a new specific inhibitor of glucosylceramide synthase. Phase III trials in humans have been completed. Eliglustat tartrate has been shown to be efficacious and safe in adult humans. The results are as good or better compared with intravenous replacement with regard to reductions in spleen and liver enlargement and improvements in hemoglobin concentrations, platelet

Pseudo-osteomyelitic crisis upon presentation of Gaucher disease

International Nuclear Information System (INIS)

Weisstein, J.S.; Steinbach, L.S.; Diamond, C.A.; Huang, S.J.; O'Donnell, R.J.

2001-01-01

We report on a 4-year-old boy adopted from Paraguay who presented with an acute onset of thigh pain. Initial clinical, imaging, and histopathologic findings suggested florid osteomyelitis. However, the development of pancytopenia on intravenous antibiotics prompted further investigation and the ultimate diagnosis of Gaucher disease. In retrospect, characteristic changes on conventional radiographic and MR images, as well as growth of a contaminant organism, pointed to the diagnosis of pseudo-osteomyelitis rather than osteomyelitis. (orig.)

Plasma tumor necrosis factor-a (TNF-a) levels in Gaucher disease

NARCIS (Netherlands)

Michelakakis, H.; Spanou, C.; Kondyli, A.; Dimitriou, E.; van Weely, S.; Hollak, C. E.; van Oers, M. H.; Aerts, J. M.

1996-01-01

Tumor necrosis factor-a (TNF-a) levels were measured in the plasma of patients with different types of Gaucher disease (GD) and patients with other lysosomal storage diseases. The highest TNF-a levels were observed in the most severe neuronopathic type of GD, exceeding those found in healthy

Therapeutic response to intravenous infusions of glucocerebrosidase in a patient with Gaucher disease

International Nuclear Information System (INIS)

Barton, N.W.; Furbish, F.S.; Murray, G.J.; Garfield, M.; Brady, R.O.

1990-01-01

Enzyme replacement has been under consideration as a therapeutic strategy for patients with Gaucher disease for more than two decades. Previous studies indicated that single injections of purified glucocerebrosidase reduced the amount of storage material in the liver. It was important to determine whether administration of exogenous enzyme on a regular basis would be of clinical benefit. The authors weekly i.v. infusions of a macrophage-targeted preparation of human placental glucocerebrosidase in a child with type 1 Gaucher disease increased hemoglobin over a 20-week period. The platelet count also increased. Phagocytic activity in the spleen decreased during the period of enzyme administration, and there was radiographic evidence of skeletal improvement. These observations document objective clinical responses to enzyme supplementation in a patient with a sphingolipid storage disorder

Pleural tuberculosis in a patient with untreated type 1 Gaucher disease.

Science.gov (United States)

Dulgar, Ozgecan; Eskazan, Ahmet Emre; Ersen, Ezel; Demiroz, Ahu Senem; Turna, Akif; Oz, Buge; Tuzuner, Nukhet

2016-01-01

Gaucher disease (GD) is an autosomal recessive glycolipid storage disorder, due to deficiency of the lysosomal enzyme glucocerebrosidase, leading to accumulation of the substrate glucocerebroside in the cells of the macrophage-monocyte system. Patients with GD have alteration in their immune system and impaired microbicidal capacity of mononuclear phagocytes. It has also been demonstrated that monocyte dysfunction may correlate with the plasma glucocerebrosidase concentrations. Tuberculosis (TB) is a major public health problem in developing countries. Pleural TB is one of the most common forms of extra-pulmonary TB. Since immune system can be impaired due to the deficiency of glucocerebrosidase in various ways, TB can be observed in patients with GD especially when left untreated. Cytopenia(s) is also general finding in untreated Gaucher patients, and they may be observed most frequently due to the infiltration of the bone marrow with Gaucher cells together with the additional factor of splenomegaly. We herein present a case of an adult patient with heterozygous untreated GD1, who developed pleural TB complicated by ipsilateral pulmonary fibrosis. Before his admission to our clinic, pleurectomy operation was performed and 4-drug combination anti-TB therapy was initiated including isoniazid, rifampicin, ethambutol and pyrazinamide. Fever complaint was disappeared with anti-TB treatment but he also had fatigue and pain. After initiation of enzyme replacement therapy in addition to anti-TB treatment, clinical and hematological improvement was observed. To our knowledge, this is the first reported case of GD1 with pleural TB. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Sustaining an International Partnership: An Evolving Collaboration

Science.gov (United States)

Pierson, Melinda R.; Myck-Wayne, Janice; Stang, Kristin K.; Basinska, Anna

2015-01-01

Universities across the United States have an increasing interest in international education. Increasing global awareness through educational collaborations will promote greater cross-cultural understanding and build effective relationships with diverse communities. This paper documents one university's effort to build an effective international…

INL - NNL an International Technology Collaboration Case Study - Advanced Fogging Technologies for Decommissioning - 13463

International Nuclear Information System (INIS)

Banford, Anthony; Edwards, Jeremy; Demmer, Rick; Rankin, Richard; Hastings, Jeremy

2013-01-01

International collaboration and partnerships have become a reality as markets continue to globalize. This is the case in nuclear sector where over recent years partnerships commonly form to bid for capital projects internationally in the increasingly contractorized world and international consortia regularly bid and lead Management and Operations (M and O) / Parent Body Organization (PBO) site management contracts. International collaboration can also benefit research and technology development. The Idaho National Laboratory (INL) and the UK National Nuclear Laboratory (NNL) are internationally recognized organizations delivering leading science and technology development programmes both nationally and internationally. The Laboratories are actively collaborating in several areas with benefits to both the laboratories and their customers. Recent collaborations have focused on fuel cycle separations, systems engineering supporting waste management and decommissioning, the use of misting for decontamination and in-situ waste characterisation. This paper focuses on a case study illustrating how integration of two technologies developed on different sides of the Atlantic are being integrated through international collaboration to address real decommissioning challenges using fogging technology. (authors)

INL - NNL an International Technology Collaboration Case Study - Advanced Fogging Technologies for Decommissioning - 13463

Energy Technology Data Exchange (ETDEWEB)

Banford, Anthony; Edwards, Jeremy [National Nuclear Laboratory, 5th Floor Chadwick House, Birchwood Park, Warrington WA3 6AE(United Kingdom); Demmer, Rick; Rankin, Richard [Idaho National Laboratory, Idaho Falls, ID 83401(United States); Hastings, Jeremy [National Nuclear Laboratory, Central Laboratory Sellafield, Seascale, Cumbria CA20 1PG (United Kingdom)

2013-07-01

International collaboration and partnerships have become a reality as markets continue to globalize. This is the case in nuclear sector where over recent years partnerships commonly form to bid for capital projects internationally in the increasingly contractorized world and international consortia regularly bid and lead Management and Operations (M and O) / Parent Body Organization (PBO) site management contracts. International collaboration can also benefit research and technology development. The Idaho National Laboratory (INL) and the UK National Nuclear Laboratory (NNL) are internationally recognized organizations delivering leading science and technology development programmes both nationally and internationally. The Laboratories are actively collaborating in several areas with benefits to both the laboratories and their customers. Recent collaborations have focused on fuel cycle separations, systems engineering supporting waste management and decommissioning, the use of misting for decontamination and in-situ waste characterisation. This paper focuses on a case study illustrating how integration of two technologies developed on different sides of the Atlantic are being integrated through international collaboration to address real decommissioning challenges using fogging technology. (authors)

International stem cell collaboration: how disparate policies between the United States and the United Kingdom impact research.

Science.gov (United States)

Luo, Jingyuan; Flynn, Jesse M; Solnick, Rachel E; Ecklund, Elaine Howard; Matthews, Kirstin R W

2011-03-08

As the scientific community globalizes, it is increasingly important to understand the effects of international collaboration on the quality and quantity of research produced. While it is generally assumed that international collaboration enhances the quality of research, this phenomenon is not well examined. Stem cell research is unique in that it is both politically charged and a research area that often generates international collaborations, making it an ideal case through which to examine international collaborations. Furthermore, with promising medical applications, the research area is dynamic and responsive to a globalizing science environment. Thus, studying international collaborations in stem cell research elucidates the role of existing international networks in promoting quality research, as well as the effects that disparate national policies might have on research. This study examined the impact of collaboration on publication significance in the United States and the United Kingdom, world leaders in stem cell research with disparate policies. We reviewed publications by US and UK authors from 2008, along with their citation rates and the political factors that may have contributed to the number of international collaborations. The data demonstrated that international collaborations significantly increased an article's impact for UK and US investigators. While this applied to UK authors whether they were corresponding or secondary, this effect was most significant for US authors who were corresponding authors. While the UK exhibited a higher proportion of international publications than the US, this difference was consistent with overall trends in international scientific collaboration. The findings suggested that national stem cell policy differences and regulatory mechanisms driving international stem cell research in the US and UK did not affect the frequency of international collaborations, or even the countries with which the US and UK most

Immersion research education: students as catalysts in international collaboration research.

Science.gov (United States)

Anderson, K H; Friedemann, M L; Bűscher, A; Sansoni, J; Hodnicki, D

2012-12-01

This paper describes an international nursing and health research immersion program. Minority students from the USA work with an international faculty mentor in teams conducting collaborative research. The Minority Health International Research Training (MHIRT) program students become catalysts in the conduct of cross-cultural research. To narrow the healthcare gap for disadvantaged families in the USA and partner countries. Faculty from the USA, Germany, Italy, Colombia, England, Austria and Thailand formed an international research and education team to explore and compare family health issues, disparities in chronic illness care, social inequities and healthcare solutions. USA students in the MHIRT program complete two introductory courses followed by a 3-month research practicum in a partner country guided by faculty mentors abroad. The overall program development, student study abroad preparation, research project activities, cultural learning, and student and faculty team outcomes are explored. Cross-fertilization of research, cultural awareness and ideas about improving family health occur through education, international exchange and research immersion. Faculty research and international team collaboration provide opportunities for learning about research, health disparities, cultural influences and healthcare systems. The students are catalysts in the research effort, the dissemination of research findings and other educational endeavours. Five steps of the collaborative activities lead to programmatic success. MHIRT scholars bring creativity, enthusiasm, and gain a genuine desire to conduct health research about families with chronic illness. Their cultural learning stimulates career plans that include international research and attention to vulnerable populations. © 2012 The Authors. International Nursing Review © 2012 International Council of Nurses.

Heterogeneous pattern of bone disease in adult type 1 Gaucher disease: clinical and pathological correlates.

Science.gov (United States)

van Dussen, L; Lips, P; van Essen, H W; Hollak, C E M; Bravenboer, N

2014-09-01

Gaucher disease (GD) is a lysosomal storage disorder characterized by accumulation of glucosylceramide in macrophages, so-called Gaucher cells, as a result of a deficiency of the lysosomal enzyme glucocerebrosidase. Bone complications are an important cause of morbidity of GD and are thought to result from imbalance in bone remodeling. Bone manifestations among GD patients demonstrate a large variation including increased osteoclastic bone resorption, low bone formation and osteonecrosis. The purpose of the current case series is to describe the histological features observed in undecalcified bone samples, obtained from three GD patients, and evaluate the relationship with clinical features in these patients. Bone fragments were obtained from three adult type 1 GD patients with variable degrees of bone disease during orthopedic surgery. Specimens were embedded without prior decalcification in methylmethacrylate and prepared for histology according to standardized laboratory procedures. Histology revealed a heterogeneous pattern of bone involvement. High cellularity of bone marrow, abundant presence of Gaucher cells (GCs) and high turnover were observed in a patient with a history of multiple bone complications, while minimal bone turnover and few GCs were detected in the mildest affected patient in this series. An intermediate picture with relatively low bone turnover and a substantial amount of Gaucher cells was demonstrated in the third, moderately affected patient. No gross abnormalities in three biochemical markers of bone turnover (osteocalcin, N-terminal propeptide of type 1 procollagen and type 1 collagen C-terminal telopeptide) were noted. Plastic embedding and subsequent Goldner and TRAP staining offered a unique possibility to study bone histological findings in GD. Our data show that bone manifestations in GD may vary both clinically as well as histologically and bone disease in GD will likely require a personalized approach. Copyright © 2014 Elsevier

Internal and External Scripts in Computer-Supported Collaborative Inquiry Learning

Science.gov (United States)

Kollar, Ingo; Fischer, Frank; Slotta, James D.

2007-01-01

We investigated how differently structured external scripts interact with learners' internal scripts with respect to individual knowledge acquisition in a Web-based collaborative inquiry learning environment. Ninety students from two secondary schools participated. Two versions of an external collaboration script (high vs. low structured)…

Gaucher iPSC-derived macrophages produce elevated levels of inflammatory mediators and serve as a new platform for therapeutic development.

Science.gov (United States)

Panicker, Leelamma M; Miller, Diana; Awad, Ola; Bose, Vivek; Lun, Yu; Park, Tea Soon; Zambidis, Elias T; Sgambato, Judi A; Feldman, Ricardo A

2014-09-01

Gaucher disease (GD) is an autosomal recessive disorder caused by mutations in the acid β-glucocerebrosidase (GCase; GBA) gene. The hallmark of GD is the presence of lipid-laden Gaucher macrophages, which infiltrate bone marrow and other organs. These pathological macrophages are believed to be the sources of elevated levels of inflammatory mediators present in the serum of GD patients. The alteration in the immune environment caused by GD is believed to play a role in the increased risk of developing multiple myeloma and other malignancies in GD patients. To determine directly whether Gaucher macrophages are abnormally activated and whether their functional defects can be reversed by pharmacological intervention, we generated GD macrophages by directed differentiation of human induced pluripotent stem cells (hiPSC) derived from patients with types 1, 2, and 3 GD. GD hiPSC-derived macrophages expressed higher levels of tumor necrosis factor α, IL-6, and IL-1β than control cells, and this phenotype was exacerbated by treatment with lipopolysaccharide. In addition, GD hiPSC macrophages exhibited a striking delay in clearance of phagocytosed red blood cells, recapitulating the presence of red blood cell remnants in Gaucher macrophages from bone marrow aspirates. Incubation of GD hiPSC macrophages with recombinant GCase, or with the chaperones isofagomine and ambroxol, corrected the abnormal phenotypes of GD macrophages to an extent that reflected their known clinical efficacies. We conclude that Gaucher macrophages are the likely source of the elevated levels of inflammatory mediators in the serum of GD patients and that GD hiPSC are valuable new tools for studying disease mechanisms and drug discovery. © 2014 AlphaMed Press.

Improved management of lysosomal glucosylceramide levels in a mouse model of type 1 Gaucher disease using enzyme and substrate reduction therapy.

Science.gov (United States)

Marshall, John; McEachern, Kerry Anne; Chuang, Wei-Lien; Hutto, Elizabeth; Siegel, Craig S; Shayman, James A; Grabowski, Greg A; Scheule, Ronald K; Copeland, Diane P; Cheng, Seng H

2010-06-01

Gaucher disease is caused by a deficiency of the lysosomal enzyme glucocerebrosidase (acid beta-glucosidase), with consequent cellular accumulation of glucosylceramide (GL-1). The disease is managed by intravenous administrations of recombinant glucocerebrosidase (imiglucerase), although symptomatic patients with mild to moderate type 1 Gaucher disease for whom enzyme replacement therapy (ERT) is not an option may also be treated by substrate reduction therapy (SRT) with miglustat. To determine whether the sequential use of both ERT and SRT may provide additional benefits, we compared the relative pharmacodynamic efficacies of separate and sequential therapies in a murine model of Gaucher disease (D409V/null). As expected, ERT with recombinant glucocerebrosidase was effective in reducing the burden of GL-1 storage in the liver, spleen, and lung of 3-month-old Gaucher mice. SRT using a novel inhibitor of glucosylceramide synthase (Genz-112638) was also effective, albeit to a lesser degree than ERT. Animals administered recombinant glucocerebrosidase and then Genz-112638 showed the lowest levels of GL-1 in all the visceral organs and a reduced number of Gaucher cells in the liver. This was likely because the additional deployment of SRT following enzyme therapy slowed the rate of reaccumulation of GL-1 in the affected organs. Hence, in patients whose disease has been stabilized by intravenously administered recombinant glucocerebrosidase, orally administered SRT with Genz-112638 could potentially be used as a convenient maintenance therapy. In patients naïve to treatment, ERT followed by SRT could potentially accelerate clearance of the offending substrate.

Splenomegali og dårlig trivselsom følge af morbus Gaucher

DEFF Research Database (Denmark)

Hansen, Grith Lærkholm; Lund, Allan Meldgaard; Børresen, Malene Landbo

2015-01-01

Gaucher disease (GD) is the most common lysosomal storage disease with a prevalence of 1:75,000. The disease is caused by a defiency of the lysosomal enzyme glucocerebrosidase which leads to an accumulation of the substrate glycosylceramide within macrophages. GD presents with a wide spectrum...

Gaucher disease: N370S glucocerebrosidase gene frequency in the Portuguese population

NARCIS (Netherlands)

Lacerda, L.; Amaral, O.; Pinto, R.; Oliveira, P.; Aerts, J.; Sá Miranda, M. C.

1994-01-01

In the Portuguese population the most frequent form of Gaucher disease is type 1. The N370S glucocerebrosidase gene mutation accounts for 63% of mutated alleles. The frequency of this mutation was accurately determined in the Portuguese population, which does not present an Ashkenazi Jewish genetic

International Collaborative Research Partnerships: Blending Science with Management and Diplomacy.

Science.gov (United States)

Lau, Chuen-Yen; Wang, Crystal; Orsega, Susan; Tramont, Edmund C; Koita, Ousmane; Polis, Michael A; Siddiqui, Sophia

2014-12-01

As globalization progressively connects and impacts the health of people across the world, collaborative research partnerships provide mutual advantages by sharing knowledge and resources to address locally and globally relevant scientific and public health questions. Partnerships undertaken for scientific research are similar to business collaborations in that they require attention to partner systems, whether local, international, political, academic, or non-academic. Scientists, like diplomats or entrepreneurs, are representatives of their field, culture, and country and become obligatory agents in health diplomacy. This role significantly influences current and future collaborations with not only the immediate partner but with other in country partners as well. Research partnerships need continuous evaluation of the collaboration's productivity, perspectives of all partners, and desired outcomes for success to avoid engaging in "research tourism", particularly in developing regions. International engagement is a cornerstone in addressing the impact of infectious diseases globally. Global partnerships are strategically aligned with national, partner and global health priorities and may be based on specific requests for assistance from the partnering country governments. Here we share experiences from select research collaborations to highlight principles that we have found key in building long-term relationships with collaborators and in meeting the aim to address scientific questions relevant to the host country and strategic global health initiatives.

Splenomegaly, Cardiomegaly, and Osteoporosis in a Child with Gaucher Disease

Directory of Open Access Journals (Sweden)

J. J. Sheth

2011-01-01

Full Text Available A 15-month-old girl, born to the consanguineous parents, was referred with the sign of massive splenomegaly associated with thrombocytopenia and anemia. Plasma Chitotriosidase estimation was carried out as a screening test and was found to be normal with reduced activity of β-glucosidase in leucocytes suggestive of Gaucher disease. At the age of 4 years, severe osteoporosis and cardiomegaly with pulmonary congestion were observed in the child. Molecular analysis for GBA gene has revealed homozygous status for L444P (c.1448C in the proband, whereas parents and two elder sisters were found to be heterozygote. Prenatal study during the fourth pregnancy was carried out from cultured chorionic villi for β-glucosidase, which was in the carrier range. Further confirmation of the carrier status was carried out from amniotic fluid DNA and was found to be heterozygous for L444P (c.1448C in the GBA gene. This case demonstrates that children with the sign of splenomegaly with anemia and thrombocytopenia need to be screened for Gaucher disease, and molecular study can further help to confirm the heterozygous status, where prenatal study by enzyme investigation demonstrate heterozygous condition.

Mongolize or Westernize - international collaboration in educational change

DEFF Research Database (Denmark)

Baltzersen, Johnny

The paper presented at the 10th International Congress of Mongolists, Ulaanbaatar, August 2011 discuss conflicting approaches to international collaboration in development aid with Mongolia as a case. The paper introduces the dilemmas facing education reform in Mongolia after the collapse of soci...... of socialism in 1990 and Mongolia's struggle to find a balance between (re)defining a Mongolian-based philosophical and practical foundation guiding education development and the flood of Western-based ideas following the international donor funded aid programs....

Towards a measurement of internalization of collaboration scripts in the medical context - results of a pilot study.

Science.gov (United States)

Kiesewetter, Jan; Gluza, Martin; Holzer, Matthias; Saravo, Barbara; Hammitzsch, Laura; Fischer, Martin R

2015-01-01

Collaboration as a key qualification in medical education and everyday routine in clinical care can substantially contribute to improving patient safety. Internal collaboration scripts are conceptualized as organized - yet adaptive - knowledge that can be used in specific situations in professional everyday life. This study examines the level of internalization of collaboration scripts in medicine. Internalization is understood as fast retrieval of script information. The goals of the current study were the assessment of collaborative information, which is part of collaboration scripts, and the development of a methodology for measuring the level of internalization of collaboration scripts in medicine. For the contrastive comparison of internal collaboration scripts, 20 collaborative novices (medical students in their final year) and 20 collaborative experts (physicians with specialist degrees in internal medicine or anesthesiology) were included in the study. Eight typical medical collaborative situations as shown on a photo or video were presented to the participants for five seconds each. Afterwards, the participants were asked to describe what they saw on the photo or video. Based on the answers, the amount of information belonging to a collaboration script (script-information) was determined and the time each participant needed for answering was measured. In order to measure the level of internalization, script-information per recall time was calculated. As expected, collaborative experts stated significantly more script-information than collaborative novices. As well, collaborative experts showed a significantly higher level of internalization. Based on the findings of this research, we conclude that our instrument can discriminate between collaboration novices and experts. It therefore can be used to analyze measures to foster subject-specific competency in medical education.

Advancing Diversity and Inclusion within the IceCube Collaboration: Lessons from an International Particle Astrophysics Research Collaboration

Science.gov (United States)

Knackert, J.

2017-12-01

The IceCube Collaboration is comprised of 300 scientists, engineers, students, and support staff at 48 institutions in 12 countries. IceCube recognizes the value of increased diversity within STEM fields and is committed to improving this situation both within the collaboration and more broadly. The process of establishing and maintaining a focus on diversity and inclusion within an international research collaboration has yielded many lessons and best practices relevant for broader STEM diversity efforts. Examples of events, training activities, and workshops to promote diversity both internally and within the broader STEM community will be provided. We will outline strategies to promote an environment of inclusivity and increase diversity in hiring within IceCube. We will describe collaborations with local networks and advocacy groups that have helped to guide our efforts and maximize their impact. We will also discuss methods for getting community members interested, informed, and invested, while helping them better understand the benefits associated with increased STEM diversity. This work has been informed by the American Association for the Advancement of Science's inaugural cohort of the Community Engagement Fellows Program. The author has made this submission on behalf of the IceCube Collaboration Diversity Task Force.

Collaborating internationally on physician leadership education: first steps.

Science.gov (United States)

Matlow, Anne; Chan, Ming-Ka; Bohnen, Jordan David; Blumenthal, Daniel Mark; Sánchez-Mendiola, Melchor; de Camps Meschino, Diane; Samson, Lindy Michelle; Busari, Jamiu

2016-07-04

Purpose Physicians are often ill-equipped for the leadership activities their work demands. In part, this is due to a gap in traditional medical education. An emergent international network is developing a globally relevant leadership curriculum for postgraduate medical education. The purpose of this article is to share key learnings from this process to date. Design/methodology/approach The Toronto International Summit on Leadership Education for Physicians (TISLEP) was hosted by the Royal College of Physicians and Surgeons of Canada, and the University of Toronto's Faculty of Medicine and Institute of Health Policy, Management and Evaluation. Of 64 attendees from eight countries, 34 joined working groups to develop leadership competencies. The CanMEDS Competency Framework, stage of learner development and venue of learning formed the scaffold for the work. Emotional intelligence was selected as the topic to test the feasibility of fruitful international collaboration; results were presented at TISLEP 2015. Findings Dedicated international stakeholders engaged actively and constructively through defined working groups to develop a globally relevant, competency-based curriculum for physician leadership education. Eleven principles are recommended for consideration in physician leadership curriculum development. Defining common language and taxonomy is essential for a harmonized product. The importance of establishing an international network to support implementation, evaluation, sustainability and dissemination of the work was underscored. Originality/value International stakeholders are collaborating successfully on a graduated, competency-based leadership curriculum for postgraduate medical learners. The final product will be available for adaptation to local needs. An international physician leadership education network is being developed to support and expand the work underway.

ICTP: A Successful Model of International Scientific Collaboration

CERN Multimedia

CERN. Geneva

2012-01-01

The importance of international scientific collaboration in the changing world where the centre of gravity of fundamental research may be moving towards the east and the south is addressed. The unique role of ICTP in supporting global science is highlighted.

Gendered patterns in international research collaborations in academia

NARCIS (Netherlands)

Uhly, K.M.; Visser, L.M.; Zippel, K.S.

2017-01-01

Although women's representation in higher education nears parity with men at the undergraduate level, this representation diminishes as one ascends the academic ranks. Because gender gaps in the ‘elite’ activity of international research collaborations might contribute to the underrepresentation of

International collaboration for nuclear competence building

International Nuclear Information System (INIS)

Haapalehto, T.; Storey, P.

2004-01-01

The life cycle of the nuclear industry is no different to that of any other industry, indeed to most forms of human activity: birth, growth, maturity, decline, rebirth and renewal or death. As a result of the twin facets of long time scales and essential technical competence the industry now faces two problems: how to retain existing skills and competences for the 50 plus years that a plant is operating and how to develop and retain new skills and competences in the areas of decommissioning and radioactive waste management. Different countries are at different stages of the nuclear technology life cycle, a competence that may have declined or be lost in one country may be strong in another. And therein lies one solution to the problems the sector faces - international collaboration. The initiatives such as the NEA Halden project and the Generation IV International Forum lay a ground for quiet optimism that collaboration, information exchange and exchange of personnel continue to be an integral part of the development of nuclear power. Also there is evidence that myriad initiatives are underway in the area of nuclear education and training. Though, national surveys show that still more engineers and scientists having nuclear knowledge are required than are graduating. (author)

Reasoning about the value of cultural awareness in international collaboration

Directory of Open Access Journals (Sweden)

Helena Bernáld

Full Text Available As international collaborations become a part of everyday life, cultural awareness becomes crucial for our ability to work with people from other countries. People see, evaluate, and interpret things differently depending on their cultural background and cultural awareness. This includes aspects such as appreciation of different communication patterns, the awareness of different value systems and, not least, to become aware of our own cultural values, beliefs and perceptions. This paper addresses the value of cultural awareness in general through describing how it was introduced in two computer science courses with a joint collaboration between students from the US and Sweden. The cultural seminars provided to the students are presented, as well as a discussion of the students\\' reflections and the teachers\\' experiences. The cultural awareness seminars provided students with a new understanding of cultural differences which greatly improved the international collaboration. Cultural awareness may be especially important for small countries like New Zealand and Sweden, since it could provide an essential edge in collaborations with representatives from more \\'powerful\\' countries.

Comparative therapeutic effects of velaglucerase alfa and imiglucerase in a Gaucher disease mouse model.

Directory of Open Access Journals (Sweden)

You-Hai Xu

2010-05-01

Full Text Available Gaucher disease type 1 is caused by the defective activity of the lysosomal enzyme, acid beta-glucosidase (GCase. Regular infusions of purified recombinant GCase are the standard of care for reversing hematologic, hepatic, splenic, and bony manifestations. Here, similar in vitro enzymatic properties, and in vivo pharmacokinetics and pharmacodynamics (PK/PD and therapeutic efficacy of GCase were found with two human GCases, recombinant GCase (CHO cell, imiglucerase, Imig and gene-activated GCase (human fibrosarcoma cells, velaglucerase alfa, Vela, in a Gaucher mouse, D409V/null. About 80+% of either enzyme localized to the liver interstitial cells and <5% was recovered in spleens and lungs after bolus i.v. injections. Glucosylceramide (GC levels and storage cell numbers were reduced in a dose (5, 15 or 60 U/kg/wk dependent manner in livers (60-95% and in spleens ( approximately 10-30%. Compared to Vela, Imig (60 U/kg/wk had lesser effects at reducing hepatic GC (p = 0.0199 by 4 wks; this difference disappeared by 8 wks when nearly WT levels were achieved by Imig. Anti-GCase IgG was detected in GCase treated mice at 60 U/kg/wk, and IgE mediated acute hypersensitivity and death occurred after several injections of 60 U/kg/wk (21% with Vela and 34% with Imig. The responses of GC levels and storage cell numbers in Vela- and Imig-treated Gaucher mice at various doses provide a backdrop for clinical applications and decisions.

International energy technology collaboration: benefits and achievements

International Nuclear Information System (INIS)

1996-01-01

The IEA Energy Technology Collaboration Programme facilitates international collaboration on energy technology research, development and deployment. More than 30 countries are involved in Europe, America, Asia, Australasia and Africa. The aim is to accelerate the development and deployment of new energy technologies to meet energy security, environmental and economic development goals. Costs and resources are shared among participating governments, utilities, corporations and universities. By co-operating, they avoid unproductive duplication and maximize the benefits from research budgets. The IEA Programme results every year in hundreds of publications which disseminate information about the latest energy technology developments and their commercial utilisation. The IEA Energy Technology Collaboration Programme operates through a series of agreements among governments. This report details the activities and achievements of all 41 agreements, covering energy technology information centres and Research and Development projects in fossil fuels, renewable energy efficient end-use, and nuclear fusion technologies. (authors). 58 refs., 9 tabs

Strengthening International Collaboration: Geosciences Research and Education in Developing Countries

Science.gov (United States)

Fucugauchi, J. U.

2009-05-01

Geophysical research increasingly requires global multidisciplinary approaches and global integration. Global warming, increasing CO2 levels and increased needs of mineral and energy resources emphasize impact of human activities. The planetary view of our Earth as a deeply complex interconnected system also emphasizes the need of international scientific cooperation. International collaboration presents an immense potential and is urgently needed for further development of geosciences research and education. In analyzing international collaboration a relevant aspect is the role of scientific societies. Societies organize meetings, publish journals and books and promote cooperation through academic exchange activities and can further assist communities in developing countries providing and facilitating access to scientific literature, attendance to international meetings, short and long-term stays and student and young researcher mobility. Developing countries present additional challenges resulting from limited economic resources and social and political problems. Most countries urgently require improved educational and research programs. Needed are in-depth analyses of infrastructure and human resources and identification of major problems and needs. Questions may include what are the major limitations and needs in research and postgraduate education in developing countries? what and how should international collaboration do? and what are the roles of individuals, academic institutions, funding agencies, scientific societies? Here we attempt to examine some of these questions with reference to case examples and AGU role. We focus on current situation, size and characteristics of research community, education programs, facilities, economic support, and then move to perspectives for potential development in an international context.

Evaluation of Bone Marrow Infiltration in Non-Neuropathic Gaucher Disease Patients with Use of Whole-Body MRI--A Retrospective Data Analysis.

Science.gov (United States)

Laudemann, K; Moos, L; Mengel, K E; Lollert, A; Reinke, J; Brixius-Huth, M; Wagner, D; Düber, C; Staatz, G

2015-12-01

To evaluate whole-body magnetic resonance imaging (WB-MRI) for the assessment of bone marrow infiltration in patients with confirmed Gaucher disease type 1 under long-term enzyme replacement therapy (ERT). This retrospective data analysis included 38 patients in two subgroups. Group A: 10 females, 9 males, 15-29 years, mean age 22 years and Group B: 11 females, 8 males, 29-77 years, mean age 49 years, all treated with alglucerase or imiglucerase for at least 12.5 years. Whole-body MRI was carried out in all patients using a standard MRI protocol. Two radiologists assessed all MR images retrospectively with the use of three different MRI score systems: The bone marrow burden (BMB) score, the Düsseldorf-Gaucher score (DGS) and the vertebra disc ratio (VDR). As a clinical component, severity score index type 1 (GD-DS3) was determined. In both groups the MR scores showed low to moderate pathologic levels but no statistically significant difference was found between both groups. The median scores in group A/group B were 7.00/9.00 for the BMB score (p=0.07), 4.00/3.00 for the DGS score (p=0.062) and 1.54/1.62 for the VDR score (p=0.267). The GD-DS3 score was statistically significantly different between both groups (1.6/3.9, p=0.000) and osseous Gaucher disease complications were only found in group B. Bone marrow involvement and typical clinical manifestations are reduced to a minimum, when ERT starts immediately after the confirmed diagnosis of Gaucher disease type 1. The applied MR scores are useful markers to control bone marrow infiltration under enzyme replacement therapy in older patients. Pathologic MR scores in young patients may reflect postponed fat conversion of the juvenile bone marrow. This issue has to be examined in further studies. Whole-body MRI is valuable for the staging of Gaucher disease type 1. Osseous complications are reduced to a minimum in early treated patients. MR score systems have to be adjusted in young Gaucher patients. © Georg Thieme

DOCTOR’S AUTOMATIZED WORK PLACE FOR THE TREATMENT OF PATIENTS WITH GAUCHER DISEASE

Directory of Open Access Journals (Sweden)

N. H. Horovenko

2015-05-01

Full Text Available The program was designed to account the registry of patients with Gaucher disease. During the investigation of object domain a medical documentation and work regime of centre were analyzed including medical forms and questionnaires, medical cards, the order of filling appointment of treatment, report forms. The program provides the creation of automatized work place for interaction with patients with Gaucher disease on a personal computer of doctor. The purpose of development system is to perform a range of functions, which correspond to the full cycle of interaction doctor with patients. General function: introduction and correction of data, analysis and preservation of the history of this treatment, filtration patient records, construction of schedules based on the results of blood tests and examinations which reflect the dynamics of the patient. Special functions: calculation of required quantity of the medicine to the patient, tracing of human health standards depending on the age of the patient, the cost of the medicine.

Profile of eliglustat tartrate in the management of Gaucher disease

Directory of Open Access Journals (Sweden)

Sechi A

2016-01-01

Full Text Available Annalisa Sechi, Andrea Dardis, Bruno Bembi Regional Coordinator Center for Rare Diseases, Academic Hospital of Udine, Udine, Italy Abstract: Gaucher disease (GD is a lysosomal storage disorder caused by the deficient activity of acid beta glucosidase, with consequent accumulation of glucosylceramide in the spleen, liver, bone marrow, and various organs and tissues. Currently, the gold standard for GD treatment is enzyme replacement therapy (ERT. The efficacy of ERT in improving or stabilizing the visceral and hematological symptoms of GD is well-proven. However, since ERT has to be administered by frequent intravenous infusions, this therapeutic approach has an important impact on the patient’s quality of life. Eliglustat tartrate is a new substrate reduction therapy for GD, which acts as a specific and potent inhibitor of glucosylceramide synthase and can be administered orally. This review summarizes the results of the preclinical and clinical trials, which experimented with eliglustat, and discusses its possible role in the management of GD, when compared to the currently available treatments and the new experimental approaches. Keywords: Gaucher disease, enzyme replacement therapy, substrate reduction therapy, eliglustat tartrate

Ocular manifestations of Gaucher disease: case report and literature review

Directory of Open Access Journals (Sweden)

Mejía-Turizo, Juan Carlos

2017-07-01

Full Text Available We report the case of a patient with Gaucher disease (GD type 3b, with a homozygous GBA gene mutation (c.1448T > C p.L483P (L444P. Ocular findings characteristic of this mutation are described, including vitreous condensation and macular edema. To our knowledge this is the first case reported in Colombia with these characteristics. A review of the ocular manifestations of this disease is also presented.

Hampered Vitamin B12 Metabolism in Gaucher Disease?

Directory of Open Access Journals (Sweden)

Luciana Hannibal PhD

2017-02-01

Full Text Available Untreated vitamin B 12 deficiency manifests clinically with hematological abnormalities and combined degeneration of the spinal cord and polyneuropathy and biochemically with elevated homocysteine (Hcy and methylmalonic acid (MMA. Vitamin B 12 metabolism involves various cellular compartments including the lysosome, and a disruption in the lysosomal and endocytic pathways induces functional deficiency of this micronutrient. Gaucher disease (GD is characterized by dysfunctional lysosomal metabolism brought about by mutations in the enzyme beta-glucocerebrosidase (Online Mendelian Inheritance in Man (OMIM: 606463; Enzyme Commission (EC 3.2.1.45, gene: GBA1 . In this study, we collected and examined available literature on the associations between GD, the second most prevalent lysosomal storage disorder in humans, and hampered vitamin B 12 metabolism. Results from independent cohorts of patients show elevated circulating holotranscobalamin without changes in vitamin B 12 levels in serum. Gaucher disease patients under enzyme replacement therapy present normal levels of Hcy and MMA. Although within the normal range, a significant increase in Hcy and MMA with normal serum vitamin B 12 was documented in treated GD patients with polyneuropathy versus treated GD patients without polyneuropathy. Thus, a functional deficiency of vitamin B 12 caused by disrupted lysosomal metabolism in GD is a plausible mechanism, contributing to the neurological form of the disorder but this awaits confirmation. Observational studies suggest that an assessment of vitamin B 12 status prior to the initiation of enzyme replacement therapy may shed light on the role of vitamin B 12 in the pathogenesis and progression of GD.

(International Collaboration on Advanced Neutron Sources)

Energy Technology Data Exchange (ETDEWEB)

Hayter, J.B.

1990-11-08

The International Collaboration on Advanced Neutron Sources was started about a decade ago with the purpose of sharing information throughout the global neutron community. The collaboration has been extremely successful in optimizing the use of resources, and the discussions are open and detailed, with reasons for failure shared as well as reasons for success. Although the meetings have become increasingly oriented toward pulsed neutron sources, many of the neutron instrumentation techniques, such as the development of better monochromators, fast response detectors and various data analysis methods, are highly relevant to the Advanced Neutron Source (ANS). I presented one paper on the ANS, and another on the neutron optical polarizer design work which won a 1989 R D-100 Award. I also gained some valuable design ideas, in particular for the ANS hot source, in discussions with individual researchers from Canada, Western Europe, and Japan.

Advances in Wilms Tumor Treatment and Biology: Progress Through International Collaboration.

Science.gov (United States)

Dome, Jeffrey S; Graf, Norbert; Geller, James I; Fernandez, Conrad V; Mullen, Elizabeth A; Spreafico, Filippo; Van den Heuvel-Eibrink, Marry; Pritchard-Jones, Kathy

2015-09-20

Clinical trials in Wilms tumor (WT) have resulted in overall survival rates of greater than 90%. This achievement is especially remarkable because improvements in disease-specific survival have occurred concurrently with a reduction of therapy for large patient subgroups. However, the outcomes for certain patient subgroups, including those with unfavorable histologic and molecular features, bilateral disease, and recurrent disease, remain well below the benchmark survival rate of 90%. Therapy for WT has been advanced in part by an increasingly complex risk-stratification system based on patient age; tumor stage, histology, and volume; response to chemotherapy; and loss of heterozygosity at chromosomes 1p and 16q. A consequence of this system has been the apportionment of patients into such small subgroups that only collaboration between large international WT study groups will support clinical trials that are sufficiently powered to answer challenging questions that move the field forward. This article gives an overview of the Children's Oncology Group and International Society of Pediatric Oncology approaches to WT and focuses on four subgroups (stage IV, initially inoperable, bilateral, and relapsed WT) for which international collaboration is pressing. In addition, biologic insights resulting from collaborative laboratory research are discussed. A coordinated expansion of international collaboration in both clinical trials and laboratory science will provide real opportunity to improve the treatment and outcomes for children with renal tumors on a global level. © 2015 by American Society of Clinical Oncology.

Role of international collaboration in PNC's R ampersand D programme for HLW disposal

International Nuclear Information System (INIS)

Masuda, Sumio; Umeki, Hiroyuki; Yamakawa, Minoru

1996-01-01

PNC has been active in promoting international cooperation in connection with the Japanese HLW disposal programme, based on both a bilateral and multilateral approach. Both types of cooperation are extremely useful; in particular, bilateral cooperation has the advantage of providing opportunities for in-depth discussions in mutual areas of interest. By way of contrast, multilateral cooperation also provides an international arena for broader discussion and corroboration of output from individual R ampersand D programmes. International collaboration also provides young researchers with an opportunity to learn from experience. Depending on the issues to be tackled, appropriate forms of collaboration have been integrated into PNC's strategy for maximizing output. The lessons learned from collaboration are very valuable and can be used directly in their programme to enhance its credibility. The format of collaboration has also been extensively developed: it has been found that resources can be utilized more effectively by sharing them appropriately

Initiatives in national and international collaborations at Variable Energy Cyclotron Centre

International Nuclear Information System (INIS)

Viyogi, Yogendra Pathak; Chakrabarti, Alok

2008-01-01

Over the last two decades VECC scientists, under the leadership of their director Bikash Sinha, have pursued experimental physics studies under international collaboration programmes, which would not have been possible with the existing facilities at home. The collaboration extended from RIKEN (Japan) in the east to CERN (Switzerland) in the west. It spanned the energy scales from a few tens of MeV per nucleon to several hundred GeV per nucleon and the physics topics on one extreme being the structure of exotic nuclei and their decay modes and on other extreme being the phase transition of hadronic matter and the formation of quark gluon plasma. The dynamic leadership of Dr. Sinha not only helped to shed the initial inhibitions towards such activities, going beyond the national frontiers, but also gave a new dimension to the experimental physics research in the country. It helped to organize an Indian team of scientists from various national institutes and universities. It paved way for full scale funding of the projects and set the trend that enabled many other Indian groups to join several international collaborations in various fields. Here we reflect on the evolution of these national and international collaboration programmes and the physics, technological and sociological benefits resulting from these activities. (author)

Partial splenic embolization in a child with Gaucher disease, massive splenomegaly and severe thrombocytopenia

International Nuclear Information System (INIS)

Pena, Andres H.; Clevac, Egor; Marie Cahill, Anne; Kaplan, Paige; Ganesh, Jaya

2009-01-01

A 13-month-old boy with Gaucher disease presented with severe thrombocytopenia, anemia and massive splenomegaly. In addition he had significant respiratory compromise caused by abdominal compartment syndrome, requiring mechanical ventilation. Because of the degree of respiratory compromise and his existing bone marrow suppression, splenic artery embolization was chosen as an alternative to splenectomy. Splenic artery embolization was performed using 355-500-μm polyvinyl alcohol particles, with 70% ablation achieved. Within 24 h of the procedure the platelet count had risen to greater than 70,000/mm 3 and to more than 170,000/mm 3 on postoperative day 4. At the 8-month follow-up the splenic size had decreased from 18 cm to 8 cm, with a platelet count of 578,000/mm 3 . Partial splenic embolization provides a minimally invasive alternative to splenectomy in patients with Gaucher disease with massive splenomegaly and bone marrow suppression. (orig.)

Expanding NASA and Roscosmos Scientific Collaboration on the International Space Station

Science.gov (United States)

Hasbrook, Pete

2016-01-01

The International Space Station (ISS) is a world-class laboratory orbiting in space. NASA and Roscosmos have developed a strong relationship through the ISS Program Partnership, working together and with the other ISS Partners for more than twenty years. Since 2013, based on a framework agreement between the Program Managers, NASA and Roscosmos are building a joint program of collaborative research on ISS. This international collaboration is developed and implemented in phases. Initially, members of the ISS Program Science Forum from NASA and TsNIIMash (representing Roscosmos) identified the first set of NASA experiments that could be implemented in the "near term". The experiments represented the research categories of Technology Demonstration, Microbiology, and Education. Through these experiments, the teams from the "program" and "operations" communities learned to work together to identify collaboration opportunities, establish agreements, and jointly plan and execute the experiments. The first joint scientific activity on ISS occurred in January 2014, and implementation of these joint experiments continues through present ISS operations. NASA and TsNIIMash have proceeded to develop "medium term" collaborations, where scientists join together to improve already-proposed experiments. A major success is the joint One-Year Mission on ISS, with astronaut Scott Kelly and cosmonaut Mikhail Kornienko, who returned from ISS in March, 2016. The teams from the NASA Human Research Program and the RAS Institute for Biomedical Problems built on their considerable experience to design joint experiments, learn to work with each other's protocols and processes, and share medical and research data. New collaborations are being developed between American and Russian scientists in complex fluids, robotics, rodent research and space biology, and additional human research. Collaborations are also being developed in Earth Remote Sensing, where scientists will share data from imaging

Poor results of drilling in early stages of juxta-articular osteonecrosis in 12 joints affected by Gaucher disease

Science.gov (United States)

Lebel, Ehud; Phillips, Mici; Zimran, Ari; Itzchaki, Menachem

2009-01-01

Background and purpose Gaucher disease is heterogeneous. One of the most devastating complications is bone involvement, ranging from mild osteopenia to osteonecrosis, but no markers have been discovered to predict onset and/or progression. We describe our experience in a large referral center using drilling for juxta-articular osteonecrosis in young patients with Gaucher disease. Patients and methods We retrospectively reviewed medical data from all patients who were recommended to undergo drilling for osteonecrosis of juxta-articular bone of the femoral head, the humeral head, or upper tibia for acute osteonecrosis at a pre-collapse stage. Results 11 patients (mean age 34 years) underwent drilling of 12 joints with juxta-articular osteonecrosis; 3 (mean age 51 years) refused intervention. 9 joints that were drilled showed advancing joint degeneration within 0.5 to 4 years. 3 joints have undergone replacement. Of the 3 joints that did not undergo drilling, 2 have undergone replacement and 1 has collapsed with osteoarthritis. Interpretation We found equally poor outcome with and without drilling. Effective intervention can only be achieved by improving our understanding of bone physiology and pathophysiology in Gaucher disease. PMID:19404804

Gendered Patterns in International Research Collaborations in Academia

Science.gov (United States)

Uhly, K. M.; Visser, L. M.; Zippel, K. S.

2017-01-01

Although women's representation in higher education nears parity with men at the undergraduate level, this representation diminishes as one ascends the academic ranks. Because gender gaps in the "elite" activity of international research collaborations might contribute to the underrepresentation of women in the upper ranks, we ask if…

Cirurgias conservadoras do baço para tratamento da doença de Gaucher Partial splenectomy in the treatment of Gaucher's disease

Directory of Open Access Journals (Sweden)

Andy Petroianu

2004-03-01

Full Text Available As complicações da esplenomegalia na doença de Gaucher, com repercussões de hiperesplenismo e compressões mecânicas, têm sido tratadas por meio de esplenectomia parcial. Contudo, verificou-se que o remanescente esplênico suprido pelos vasos hilares volta a crescer, com conseqüente recorrência da esplenomegalia e de todo o quadro clínico que a acompanha. Uma experiência superior a dezoito anos no tratamento da hipertensão porta, trauma esplênico, esplenomegalia mielóide, hipodesenvolvimento somático e sexual esplenomegálico, linfomas e cistoadenoma de cauda pancreática por meio de esplenectomia subtotal, preservando o pólo superior do baço irrigado apenas pelos vasos esplenogástricos, mostrou que o remanescente esplênico não aumenta as suas dimensões. Com base em evidências de que o pólo superior esplênico é suficiente para manter todas as funções do baço, realizamos em cinco pacientes com doença de Gaucher esplenectomia subtotal, mantendo o pólo superior do baço e sua vascularização esplenogástrica. O remanescente esplênico não modificou as suas dimensões durante o acompanhamento pós-operatório superior a doze anos e os parâmetros hematológicos normalizaram. Uma outra paciente, que possuía vasos esplenogástricos insuficientes para nutrir o pólo superior do baço, foi submetida a esplenectomia total, com implantes autógenos de tecido esplênico no omento maior. Os auto-implantes sobreviveram e foram funcionantes. Todos os seis pacientes tiveram evolução pós-operatória sem anormalidades relacionadas ao procedimento de conservação esplênica. Concluindo, em presença de esplenomegalia gigante, acompanhada de quadro clínico e hematológico grave, a cirurgia do baço conservadora, com destaque para a esplenectomia subtotal ou a esplenectomia total seguida de auto-implantes de tecido esplênico.Complications of splenomegaly in Gaucher's disease, such as hypersplenism and mechanical compressions

The North American Career Development Partnership: Experiment in International Collaboration.

Science.gov (United States)

Carslon, Burton L.; Goguen, Robert A.; Jarvis, Phillip S.; Lester, Juliette N.

2000-01-01

Describes how career development programs became the focus of an international partnership between the United States and Canada. Traces the history of each country's efforts, beginning in the 1970s, which led to this significant international collaboration. Concludes with a discussion of the lessons learned from these experiences. (Author/JDM)

Recommendations for the management of the haematological and onco-haematological aspects of Gaucher disease

NARCIS (Netherlands)

Hughes, Derralynn; Cappellini, Maria Domenica; Berger, Marc; van Droogenbroeck, Jan; de Fost, Maaike; Janic, Dragana; Marinakis, Theodore; Rosenbaum, Hanna; Villarubia, Jesús; Zhukovskaya, Elena; Hollak, Carla

2007-01-01

Current knowledge of the haematological and onco-haematological complications of type 1 Gaucher disease has been reviewed with the aim of identifying best clinical practice for treatment and disease management. It was concluded that: (i) Awareness of typical patterns of cytopenia can help clinicians

Systemic Delivery of a Glucosylceramide Synthase Inhibitor Reduces CNS Substrates and Increases Lifespan in a Mouse Model of Type 2 Gaucher Disease

OpenAIRE

Cabrera-Salazar, Mario A.; DeRiso, Matthew; Bercury, Scott D.; Li, Lingyun; Lydon, John T.; Weber, William; Pande, Nilesh; Cromwell, Mandy A.; Copeland, Diane; Leonard, John; Cheng, Seng H.; Scheule, Ronald K.

2012-01-01

Neuropathic Gaucher disease (nGD), also known as type 2 or type 3 Gaucher disease, is caused by a deficiency of the enzyme glucocerebrosidase (GC). This deficiency impairs the degradation of glucosylceramide (GluCer) and glucosylsphingosine (GluSph), leading to their accumulation in the brains of patients and mouse models of the disease. These accumulated substrates have been thought to cause the severe neuropathology and early death observed in patients with nGD and mouse models. Substrate a...

The International Nucleotide Sequence Database Collaboration.

Science.gov (United States)

Cochrane, Guy; Karsch-Mizrachi, Ilene; Nakamura, Yasukazu

2011-01-01

Under the International Nucleotide Sequence Database Collaboration (INSDC; http://www.insdc.org), globally comprehensive public domain nucleotide sequence is captured, preserved and presented. The partners of this long-standing collaboration work closely together to provide data formats and conventions that enable consistent data submission to their databases and support regular data exchange around the globe. Clearly defined policy and governance in relation to free access to data and relationships with journal publishers have positioned INSDC databases as a key provider of the scientific record and a core foundation for the global bioinformatics data infrastructure. While growth in sequence data volumes comes no longer as a surprise to INSDC partners, the uptake of next-generation sequencing technology by mainstream science that we have witnessed in recent years brings a step-change to growth, necessarily making a clear mark on INSDC strategy. In this article, we introduce the INSDC, outline data growth patterns and comment on the challenges of increased growth.

Crossing boundaries to improve mental health in the Americas: international collaborative authorship.

Science.gov (United States)

Killion, Chery M

2007-01-01

A nurse anthropologist with a background in international collaborations attended Project LEAD for two years, which enabled her to continue to serve as an advocate for the mentally ill in Belize. The anthropologist collaborated with a psychiatrist from Belize to develop a cross-cultural, cross-discipline publication, "Mental Health in Belize: A National Priority, " which highlights the work of psychiatric nurse practitioners in the country. The researcher learned to collaborate with her peer in Belize through face to face discussions and e-mail and overcame technological difficulties and cultural barriers to produce an international publication. Project LEAD gave the author a sense of self-discovery and self-knowledge, reinforced core values, and developed a frame of reference for leadership. The author also benefited from discussions by local, national, and international leaders on leadership in terms of its key components, contexts, challenges, triumphs, and styles.

Status Report on Laboratory Testing and International Collaborations in Salt.

Energy Technology Data Exchange (ETDEWEB)

Kuhlman, Kristopher L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Matteo, Edward N. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hadgu, Teklu [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Reedlunn, Benjamin [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Sobolik, Steven R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Mills, Melissa Marie [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Kirkes, Leslie Dawn [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Xiong, Yongliang [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Icenhower, Jonathan [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2017-09-01

This report is a summary of the international collaboration and laboratory work funded by the US Department of Energy Office of Nuclear Energy Spent Fuel and Waste Science & Technology (SFWST) as part of the Sandia National Laboratories Salt R&D work package. This report satisfies milestone levelfour milestone M4SF-17SN010303014. Several stand-alone sections make up this summary report, each completed by the participants. The first two sections discuss international collaborations on geomechanical benchmarking exercises (WEIMOS) and bedded salt investigations (KOSINA), while the last three sections discuss laboratory work conducted on brucite solubility in brine, dissolution of borosilicate glass into brine, and partitioning of fission products into salt phases.

International energy technology collaboration and climate change mitigation. Case study 1. Concentrating Solar Power Technologies

Energy Technology Data Exchange (ETDEWEB)

Philibert, C. [Energy and Environment Division, International Energy Agency IEA, Paris (France)

2004-07-01

Mitigating climate change and achieving stabilisation of greenhouse gas atmospheric concentrations will require deep reductions in global emissions of energy-related carbon dioxide emissions. Developing and disseminating new, low-carbon energy technology will thus be needed. Two previous AIXG papers have focused on possible drivers for such a profound technological change: Technology Innovation, Development and Diffusion, released in June 2003, and International Energy Technology Collaboration and Climate Change Mitigation, released in June 2004. The first of these papers assesses a broad range of technical options for reducing energy-related CO2 emissions. It examines how technologies evolve and the role of research and development efforts, alternative policies, and short-term investment decisions in making long-term options available. It considers various policy tools that may induce technological change, some very specific, and others with broader expected effects. Its overall conclusion is that policies specifically designed to promote technical change, or 'technology push', could play a critical role in making available and affordable new energy technologies. However, such policies would not be sufficient to achieve the Convention's objective in the absence of broader policies. First, because there is a large potential for cuts that could be achieved in the short run with existing technologies; and second, the development of new technologies requires a market pull as much as a technology push. The second paper considers the potential advantages and disadvantages of international energy technology collaboration and transfer for promoting technological change. Advantages of collaboration may consist of lowering R and D costs and stimulating other countries to invest in R and D; disadvantage may include free-riding and the inefficiency of reaching agreement between many actors. This paper sets the context for further discussion on the role of

Partial splenic embolization in a child with Gaucher disease, massive splenomegaly and severe thrombocytopenia

Energy Technology Data Exchange (ETDEWEB)

Pena, Andres H.; Clevac, Egor; Marie Cahill, Anne [Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); Kaplan, Paige; Ganesh, Jaya [Children' s Hospital of Philadelphia, Division of Metabolic Diseases, Philadelphia, PA (United States)

2009-09-15

A 13-month-old boy with Gaucher disease presented with severe thrombocytopenia, anemia and massive splenomegaly. In addition he had significant respiratory compromise caused by abdominal compartment syndrome, requiring mechanical ventilation. Because of the degree of respiratory compromise and his existing bone marrow suppression, splenic artery embolization was chosen as an alternative to splenectomy. Splenic artery embolization was performed using 355-500-{mu}m polyvinyl alcohol particles, with 70% ablation achieved. Within 24 h of the procedure the platelet count had risen to greater than 70,000/mm{sup 3} and to more than 170,000/mm{sup 3} on postoperative day 4. At the 8-month follow-up the splenic size had decreased from 18 cm to 8 cm, with a platelet count of 578,000/mm{sup 3}. Partial splenic embolization provides a minimally invasive alternative to splenectomy in patients with Gaucher disease with massive splenomegaly and bone marrow suppression. (orig.)

Clinical course and prognosis in patients with Gaucher disease and parkinsonism

Science.gov (United States)

Lopez, Grisel; Kim, Jenny; Wiggs, Edythe; Cintron, Dahima; Groden, Catherine; Tayebi, Nahid; Mistry, Pramod K.; Pastores, Gregory M.; Zimran, Ari; Goker-Alpan, Ozlem

2016-01-01

Objective: The goal of this study was to characterize the parkinsonian phenotype in patients with Gaucher disease (GD) who developed parkinsonism in order to evaluate clinical course and prognosis. Methods: This is a retrospective observational study conducted at the Clinical Center of the NIH, Bethesda, MD, over a period of 10 years. The study included 19 patients with GD and parkinsonism. The severity of Gaucher and parkinsonian symptoms was determined from clinical data including physical, neurologic, pathologic, and neurocognitive evaluations, family histories, imaging studies, olfactory testing, and validated questionnaires. Results: We found an earlier age at onset of parkinsonism and evidence of mild cognitive dysfunction in our cohort. Although the clinical course in some patients was similar to that of idiopathic Parkinson disease with a favorable levodopa response, others exhibited features characteristic of dementia with Lewy bodies. When we examined the patients as a group, we did not observe a uniformly aggressive form of parkinsonism after the initial onset of symptoms, contrary to other published reports. Conclusions: Appreciable clinical variation was seen in this cohort with GD and parkinsonism. Although some patients had early onset and prominent cognitive changes, others had a later, slower course, indicating that GBA1 mutations may not be a reliable prognostic indicator in Parkinson disease in clinical settings. PMID:27123476

International Collaboration on CO2 Sequestration

Energy Technology Data Exchange (ETDEWEB)

Peter H. Israelsson; E. Eric Adams

2007-06-30

On December 4, 1997, the US Department of Energy (USDOE), the New Energy and Industrial Technology Development Organization of Japan (NEDO), and the Norwegian Research Council (NRC) entered into a Project Agreement for International Collaboration on CO{sub 2} Ocean Sequestration. Government organizations from Japan, Canada, and Australia, and a Swiss/Swedish engineering firm later joined the agreement, which outlined a research strategy for ocean carbon sequestration via direct injection. The members agreed to an initial field experiment, with the hope that if the initial experiment was successful, there would be subsequent field evaluations of increasingly larger scale to evaluate environmental impacts of sequestration and the potential for commercialization. The evolution of the collaborative effort, the supporting research, and results for the International Collaboration on CO{sub 2} Ocean Sequestration were documented in almost 100 papers and reports, including 18 peer-reviewed journal articles, 46 papers, 28 reports, and 4 graduate theses. These efforts were summarized in our project report issued January 2005 and covering the period August 23, 1998-October 23, 2004. An accompanying CD contained electronic copies of all the papers and reports. This report focuses on results of a two-year sub-task to update an environmental assessment of acute marine impacts resulting from direct ocean sequestration. The approach is based on the work of Auerbach et al. [6] and Caulfield et al. [20] to assess mortality to zooplankton, but uses updated information concerning bioassays, an updated modeling approach and three modified injection scenarios: a point release of negatively buoyant solid CO{sub 2} hydrate particles from a moving ship; a long, bottom-mounted diffuser discharging buoyant liquid CO{sub 2} droplets; and a stationary point release of hydrate particles forming a sinking plume. Results suggest that in particular the first two discharge modes could be

Focal changes of the spleen in one case of Gaucher disease - assessed by ultrasonography, CT, MRI and angiography

International Nuclear Information System (INIS)

Aspestrand, F.; Charania, B.; Scheel, B.; Kolmannskog, F.; Jacobsen, M.

1989-01-01

Focal lesions of the spleen in one case of Gaucher disease are demonstrated by ultrasonography, CT, MRI and angiography. The sonographic and angiographic features differ from the findings presented in previous reports. The Gaucher manifestations in the spleen as demonstrated by CT, do not seem to have been reported previously. An earlier report on the MR findings in the liver and spleen in this disease did not disclose any focal abnormalities. In this case, ultrasonography and MRI revealed a targetlike configuration of the focal lesions. An attempt is made to analyze the more complex patterns disclosed by MRI against the background of the manifestations by the other imaging modalities and previous reports. (orig.) [de

Activity of glucocerebrosidase in extracts of different cell types from type 1 Gaucher disease patients

NARCIS (Netherlands)

Sa Miranda, M. C.; Aerts, J. M.; Pinto, R.; Fontes, A.; de Lacerda, L. W.; van Weely, S.; Barranger, J.; Tager, J. M.

1990-01-01

Glucocerebrosidase activity in extracts of leukocytes, Epstein-Barr virus transformed lymphocytes and fibroblasts from Portuguese Type 1 Gaucher disease patients was studied. The residual glucocerebrosidase activity in all extracts from patients was less than 25% if measured in the presence of bile

International R&D collaboration networks and free trade agreements

OpenAIRE

Song, Hua Sheng

2006-01-01

This thesis contributes to the analysis of optimal industrial and strategic trade policy in the presence of oligopoly and other forms of imperfect competition, so as to make contact with important empirical regularities and policy concerns, such as international R&D collaboration, unionization and free trade. First, in the context of international competition in which R&D plays an important role, we study the consequences of allowing governments to subsidize R&D and coalition devi...

ICFA on international collaboration

International Nuclear Information System (INIS)

Anon.

1993-01-01

International collaboration in high energy physics is what ICFA - the International Committee for Future Accelerators - is all about. Progress is highlighted every three years when ICFA convenes its 'Future Perspectives in High Energy Physics' seminar to focus attention on major issues and to identify evolving trends. The latest such seminar, held at the DESY Laboratory in Hamburg from 3-7 May, looked at international cooperation in the construction of major facilities. Status reports across the whole range of existing experimental programmes and ongoing plans gave valuable pointers to future needs. For electron-positron linear colliders (EPLC), research and development work towards the next generation of machines is underway in Laboratories throughout the world. At previous such seminars, at Tsukuba, Japan (1984), Brookhaven, USA (1987) and Protvino (1990), ICFA, which has no direct power, could sometimes only stand on the sidelines and comment on the emergence of major new national plans. The lessons learnt, ICFA is keen to make sure that the EPLC debut on the world stage will be better choreographed. In addition to plans for new major experimental facilities, the Hamburg seminar also provided a valuable snapshot of the current scene and the directions in which ongoing research is poised to take. This covered existing facilities and projects, 'factories' to mass-produce specific particles, fixed target studies and non-accelerator experiments as well as the key EPLC development theme. B-physics, the study of particles containing the fifth, or 'beauty' (b) quark, emerged as an important thread running across several machine scenarios

Correction of glucocerebrosidase deficiency after retroviral-mediated gene transfer into hematopoietic progenitor cells from patients with Gaucher disease

International Nuclear Information System (INIS)

Fink, J.K.; Correll, P.H.; Perry, L.K.; Brady, R.O.; Karlsson, S.

1990-01-01

Retroviral gene transfer has been used successfully to correct the glucocerebrosidase (GCase) deficiency in primary hematopoietic cells from patients with Gaucher disease. For this model of somatic gene therapy, the authors developed a high-titer, amphotropic retroviral vector designated NTG in which the human GCase gene was driven by the mutant polyoma virus enhancer/herpesvirus thymidine kinase gene (tk) promoter (Py + /Htk). NTG normalized GCase activity in transduced Gaucher fibroblasts and efficiently infected human monocytic and erythroleukemic cell lines. RNA blot-hybridization (Northern blot) analysis of these hemaptopoietic cell lines showed unexpectedly high-level expression from the Moloney murine leukemia virus long terminal repeat (Mo-MLV LTR) and levels of Py + /Htk enhancer/promoter-initiated human GCase RNA that approximated endogenous GCase RNA levels. Furthermore, NTG efficiently infected human hematopoietic progenitor cells. Detection of the provirus in approximately one-third of NTG-infected progenitor colonies that had not been selected in G418-containing medium indicates that relative resistance to G418 underestimated the actual gene transfer efficiency. Northern blot analysis of NTG-infected, progenitor-derived cells showed expression from both the Mo-MLV LTR and the Py + /Htk enhancer/promoter. NTG-transduced hematopoietic progenitor cells from patients with Gaucher disease generated progeny in which GCase activity has been normalized

Correction of glucocerebrosidase deficiency after retroviral-mediated gene transfer into hematopoietic progenitor cells from patients with Gaucher disease

Energy Technology Data Exchange (ETDEWEB)

Fink, J.K.; Correll, P.H.; Perry, L.K.; Brady, R.O.; Karlsson, S. (National Institutes of Health, Bethesda, MD (USA))

1990-03-01

Retroviral gene transfer has been used successfully to correct the glucocerebrosidase (GCase) deficiency in primary hematopoietic cells from patients with Gaucher disease. For this model of somatic gene therapy, the authors developed a high-titer, amphotropic retroviral vector designated NTG in which the human GCase gene was driven by the mutant polyoma virus enhancer/herpesvirus thymidine kinase gene (tk) promoter (Py{sup +}/Htk). NTG normalized GCase activity in transduced Gaucher fibroblasts and efficiently infected human monocytic and erythroleukemic cell lines. RNA blot-hybridization (Northern blot) analysis of these hemaptopoietic cell lines showed unexpectedly high-level expression from the Moloney murine leukemia virus long terminal repeat (Mo-MLV LTR) and levels of Py{sup +}/Htk enhancer/promoter-initiated human GCase RNA that approximated endogenous GCase RNA levels. Furthermore, NTG efficiently infected human hematopoietic progenitor cells. Detection of the provirus in approximately one-third of NTG-infected progenitor colonies that had not been selected in G418-containing medium indicates that relative resistance to G418 underestimated the actual gene transfer efficiency. Northern blot analysis of NTG-infected, progenitor-derived cells showed expression from both the Mo-MLV LTR and the Py{sup +}/Htk enhancer/promoter. NTG-transduced hematopoietic progenitor cells from patients with Gaucher disease generated progeny in which GCase activity has been normalized.

Human Acid β-Glucosidase Inhibition by Carbohydrate Derived Iminosugars: Towards New Pharmacological Chaperones for Gaucher Disease.

Science.gov (United States)

Parmeggiani, Camilla; Catarzi, Serena; Matassini, Camilla; D'Adamio, Giampiero; Morrone, Amelia; Goti, Andrea; Paoli, Paolo; Cardona, Francesca

2015-09-21

A collection of carbohydrate-derived iminosugars belonging to three structurally diversified sub-classes (polyhydroxylated pyrrolidines, piperidines, and pyrrolizidines) was evaluated for inhibition of human acid β-glucosidase (glucocerebrosidase, GCase), the deficient enzyme in Gaucher disease. The synthesis of several new pyrrolidine analogues substituted at the nitrogen or α-carbon atom with alkyl chains of different lengths suggested an interpretation of the inhibition data and led to the discovery of two new GCase inhibitors at sub-micromolar concentration. In the piperidine iminosugar series, two N-alkylated derivatives were found to rescue the residual GCase activity in N370S/RecNcil mutated human fibroblasts (among which one up to 1.5-fold). This study provides the starting point for the identification of new compounds in the treatment of Gaucher disease. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evaluation of an international and interprofessional collaboration forum.

Science.gov (United States)

Stone, Teresa; Hua, Susan; Turale, Sue

2016-11-01

International and interprofessional collaborations are increasingly becoming a core requirement for health professionals in our globalized world. The aim of this study was to evaluate the effectiveness of the Asia Pacific Alliance of Health Leaders (APAHL) Forum to enhance the development of international perspectives and leadership among students and faculty in the discipline of health. This pilot study used a student-designed questionnaire to evaluate the views of students and faculty members about the effectiveness of APAHL in meeting its goals. Quantitative data from the scaled items on the questionnaire were analyzed by aggregating the data. Qualitative data were analyzed using a qualitative descriptive approach. Study participants comprised of 22 health science (nursing and laboratory science) students and 15 faculty members. Both faculty and students agreed that APAHL was effective in leadership development of students, as well as in advancing internationalization, interprofessional collaboration, and cultural awareness among students. A clear theme among the students was acknowledgement of the importance of communication, in particular being proficient in English. Difficulties in communication were an issue for both students and faculty members. This pilot study has shown the benefits of a student-focused international forum in developing cross-cultural awareness, and will provide the groundwork for evaluating the effectiveness of cross-cultural and interprofessional leadership forums aimed particularly at students of health. Copyright © 2016 Elsevier Ltd. All rights reserved.

Deep Learning: Enriching Teacher Training through Mobile Technology and International Collaboration

Science.gov (United States)

Naylor, Amanda; Gibbs, Janet

2018-01-01

This article presents results from an international collaboration between college students and pre-service teachers in Norway and the UK. This research is part of a large, international project exploring and developing the interrelationship between mobile technology and teachers' perceptions of teaching and learning. Data was collected for this…

Evaluation of treatment response to enzyme replacement therapy with Velaglucerase alfa in patients with Gaucher disease using whole-body magnetic resonance imaging.

Science.gov (United States)

Laudemann, K; Moos, L; Mengel, E; Lollert, A; Hoffmann, C; Brixius-Huth, M; Wagner, D; Düber, C; Staatz, G

2016-03-01

This was a retrospective data analysis to evaluate the treatment response to enzyme replacement therapy (ERT) with Velaglucerase alfa using whole-body magnetic resonance imaging (MRI). A baseline and follow-up MRI were performed on 18 Gaucher Type 1 patients at an interval of 11.6 months. The MRI score systems determined the Bone-Marrow-Burden (BMB) score, the Düsseldorf-Gaucher score (DGS), and the Vertebra-Disc-Ratio (VDR). The Severity Score Index Type 1 (GD-DS3) was also assessed. The baseline MRI medians were: BMB, 7.00; DGS, 3.00; and VDR: 1.70; while, the follow-up MRI medians were: BMB, 7.00; DGS, 3.00; and VDR: 1.73. The baseline GD-DS3 median was 2.40 (BMB excl.: 0.50) and the follow-up median was 2.00 (BMB excl.: 0.50). There was weak statistical significance with the Wilcoxon signed-rank test for the DGS (p=0.034) and GD-DS3 (p=0.047) between both MRIs. Velaglucerase alfa therapy is a effective long-term treatment for Gaucher Type 1 patients who are newly diagnosed or switching therapies. Measurements with whole-body MRI and an objective scoring system were reliable tools for detecting early stage bone marrow activity. Further research is needed to evaluate the "Booster-Effect" of Velaglucerase alfa therapy in Gaucher skeletal disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Neurolymphomatosis: An International Primary CNS Lymphoma Collaborative Group report

NARCIS (Netherlands)

S. Grisariu (Sigal); B. Avni (Batia); T.T. Batchelor (Tracy); M.J. van den Bent (Martin); F. Bokstein (Felix); D. Schiff (David); O. Kuittinen (Outi); M.C. Chamberlain (Marc C.); P. Roth (Patrick); A. Nemets (Anatoly); E. Shalom (Edna); D. Ben-Yehuda (Dina); T. Siegal (Tali)

2010-01-01

textabstractNeurolymphomatosis (NL) is a rare clinical entity. The International Primary CNS Lymphoma Collaborative Group retrospectively analyzed 50 patients assembled from 12 centers in 5 countries over a 16-year period. NL was related to non-Hodgkin lymphoma in 90% and to acute leukemia in 10%.

Teaching Social Research Methods on an International, Collaborative Environment & Sustainability Degree Programme: Exploring plagiarism, group work, and formative feedback

OpenAIRE

Laycock, R

2017-01-01

International collaboration is central to the Sustainable Development agenda given environmental challenges that span national boundaries. Education for Sustainability therefore needs to account for international/intercultural understandings, such as though international collaborative degree programmes in Higher Education. This paper evaluates a module taught on an international collaborative Bachelor’s degree programme in Environment & Sustainability taught between Nanjing Xiaozhuang Univers...

International Collaboration on Spent Fuel Disposition in Crystalline Media: FY17 Progress Report

Energy Technology Data Exchange (ETDEWEB)

Wang, Yifeng [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hadgu, Teklu [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Kainina, Elena [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Jove-Colon, Carlos [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2017-09-01

Active participation in international R&D is crucial for achieving the Spent Fuel Waste Science & Technology (SFWST) long-term goals of conducting “experiments to fill data needs and confirm advanced modeling approaches” and of having a “robust modeling and experimental basis for evaluation of multiple disposal system options” (by 2020). DOE’s Office of Nuclear Energy (NE) has developed a strategic plan to advance cooperation with international partners. The international collaboration on the evaluation of crystalline disposal media at Sandia National Laboratories (SNL) in FY17 focused on the collaboration through the Development of Coupled Models and their Validation against Experiments (DECOVALEX-2019) project. The DECOVALEX project is an international research and model comparison collaboration, initiated in 1992, for advancing the understanding and modeling of coupled thermo-hydro-mechanical-chemical (THMC) processes in geological systems. SNL has been participating in three tasks of the DECOVALEX project: Task A. Modeling gas injection experiments (ENGINEER), Task C. Modeling groundwater recovery experiment in tunnel (GREET), and Task F. Fluid inclusion and movement in the tight rock (FINITO).

Iron storage in liver, bone marrow and splenic Gaucheroma reflects residual disease in type 1 Gaucher disease patients on treatment.

Science.gov (United States)

Regenboog, Martine; Bohte, Anneloes E; Akkerman, Erik M; Stoker, Jaap; Hollak, Carla E M

2017-11-01

Gaucher disease (GD) is a lysosomal storage disorder characterized by the storage of glycosphingolipids in macrophages. Despite effective therapy, residual disease is present in varying degrees and may be associated with late complications, such as persistent bone or liver disease and increased cancer risk. Gaucher macrophages are capable of storing iron and locations of residual disease may thus be detectable with iron imaging. Forty type 1 GD (GD1) patients and 40 matched healthy controls were examined using a whole-body magnetic resonance imaging protocol consisting of standard sequences, allowing analysis of iron content per organ, expressed as R2* (Hz). Median R2* values were significantly elevated in GD1 patients as compared to healthy controls in liver [41 Hz (range 29-165) vs. 38 Hz (range 28-53), P Gaucher lesions known as Gaucheroma were found to have increased R2* values. R2* values of liver, spleen and vertebral bone marrow strongly correlated with serum ferritin levels. GD1 patients with persistent hyperferritinaemia demonstrate increased iron levels in liver and bone marrow, which may carry a risk for liver fibrosis and cancer. © 2017 John Wiley & Sons Ltd.

BRICS and International Collaborations in Higher Education in India

Science.gov (United States)

Varghese, N. V.

2015-01-01

International cooperation and collaborations played an important role in the economic and educational development of several countries. In the 1950s and 1960s external aid was an important modality to establish cooperation between countries, especially between developing and developed countries. Cross-border activities in higher education used to…

Force Majeure: Therapeutic measures in response to restricted supply of imiglucerase (Cerezyme) for patients with Gaucher disease

NARCIS (Netherlands)

Hollak, Carla E. M.; vom Dahl, Stephan; Aerts, Johannes M. F. G.; Belmatoug, Nadia; Bembi, Bruno; Cohen, Yossi; Collin-Histed, Tanya; Deegan, Patrick; van Dussen, Laura; Giraldo, Pilar; Mengel, Eugen; Michelakakis, Helen; Manuel, Jeremy; Hrebicek, Martin; Parini, Rosella; Reinke, Jörg; Di Rocco, Maja; Pocovi, Miguel; Sa Miranda, Maria Clara; Tylki-Szymanska, Anna; Zimran, Ari; Cox, Timothy M.

2010-01-01

Gaucher disease is the first lysosomal disorder for which clinically effective enzyme replacement therapy has been introduced. Lifelong treatment with imiglucerase, the recombinant glucocerebrosidase manufactured by the Genzyme Corporation (MA, USA), is administered intravenously - usually at

[Treatment of Gaucher disease with allogeneic hematopoietic stem cell transplantation: report of three cases and review of literatures].

Science.gov (United States)

Tang, Xiangfeng; Luan, Zuo; Wu, Nanhai; Zhang, Bo; Jing, Yuanfang; Du, Hong; Lu, Wei; Xu, Shixia

2015-11-01

To explore the efficacy of unrelated umbilical cord blood transplantation (UCBT) in the treatment of Gaucher disease. The clinical characteristics of three children with Gaucher disease underwent UCBT in our hospital between April 2013 and September 2014 were retrospectively analyzed. Literature on allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of Gaucher disease was searched at Wanfang and Pubmed databases between 1983 and 2015 and was reviewed and summaried. Three children with Gaucher disease, all were female, received UCBT. These patients' age at receiving transplantation was 3.8 years, 7.1 years and 2.6 years, respectively. The second case received the second transplantation. The first and third case received splenectomy before UCBT. The pretreatment regimen was busulfan (Bu)/fludarabine (Flu)/cyclophosphamide (CTX)/antithymocyte globulin (ATG), and for the patient received the second transplantation melphalan was added to the myeloablative conditioning regimen of Bu/Flu/CTX/ATG. Cyclosporine and mycophenolate mofetil (MMF) wee used for prophylaxis of acute graft versus host disease (aGVHD). The dose of cord blood stem cell nucleated cell counts was 9.7 × 10⁷ /kg,11.9 × 10⁷ /kg and 7.6 × 10⁷/kg respectively. The dose of cord blood stem cell CD34⁺ cell counts was 5.4 × 10⁵/kg , 3.5 × 10⁵/kg and 3.2 × 10⁵/kg respectively. The day of granulocytes exceeding 0.5 × 10⁹/L was day 11, 12 and 19 after transplantation, respectively. The day of platelets exceeding 20 × 10⁹/L was day 14, 33 and 74 after transplantation, respectively. At one month after transplantation the rate of chimerism was over 95% and all patients got donor complete chimerism. The level of β-glucocerebrosidase recovered to normal at one month after transplantation. During transplantation, all patients developed cytomegalovirus (CMV) and Epstein-Barr virus (EBV) viremia. In case 1 immune thrombocytopenia occurred at five month after

Animal models for Gaucher disease research

Directory of Open Access Journals (Sweden)

Tamar Farfel-Becker

2011-11-01

Full Text Available Gaucher disease (GD, the most common lysosomal storage disorder (LSD, is caused by the defective activity of the lysosomal hydrolase glucocerebrosidase, which is encoded by the GBA gene. Generation of animal models that faithfully recapitulate the three clinical subtypes of GD has proved to be more of a challenge than first anticipated. The first mouse to be produced died within hours after birth owing to skin permeability problems, and mice with point mutations in Gba did not display symptoms correlating with human disease and also died soon after birth. Recently, conditional knockout mice that mimic some features of the human disease have become available. Here, we review the contribution of all currently available animal models to examining pathological pathways underlying GD and to testing the efficacy of new treatment modalities, and propose a number of criteria for the generation of more appropriate animal models of GD.

Animal models for Gaucher disease research.

Science.gov (United States)

Farfel-Becker, Tamar; Vitner, Einat B; Futerman, Anthony H

2011-11-01

Gaucher disease (GD), the most common lysosomal storage disorder (LSD), is caused by the defective activity of the lysosomal hydrolase glucocerebrosidase, which is encoded by the GBA gene. Generation of animal models that faithfully recapitulate the three clinical subtypes of GD has proved to be more of a challenge than first anticipated. The first mouse to be produced died within hours after birth owing to skin permeability problems, and mice with point mutations in Gba did not display symptoms correlating with human disease and also died soon after birth. Recently, conditional knockout mice that mimic some features of the human disease have become available. Here, we review the contribution of all currently available animal models to examining pathological pathways underlying GD and to testing the efficacy of new treatment modalities, and propose a number of criteria for the generation of more appropriate animal models of GD.

International collaborative fire modeling project (ICFMP). Summary of benchmark

International Nuclear Information System (INIS)

Roewekamp, Marina; Klein-Hessling, Walter; Dreisbach, Jason; McGrattan, Kevin; Miles, Stewart; Plys, Martin; Riese, Olaf

2008-09-01

This document was developed in the frame of the 'International Collaborative Project to Evaluate Fire Models for Nuclear Power Plant Applications' (ICFMP). The objective of this collaborative project is to share the knowledge and resources of various organizations to evaluate and improve the state of the art of fire models for use in nuclear power plant fire safety, fire hazard analysis and fire risk assessment. The project is divided into two phases. The objective of the first phase is to evaluate the capabilities of current fire models for fire safety analysis in nuclear power plants. The second phase will extend the validation database of those models and implement beneficial improvements to the models that are identified in the first phase of ICFMP. In the first phase, more than 20 expert institutions from six countries were represented in the collaborative project. This Summary Report gives an overview on the results of the first phase of the international collaborative project. The main objective of the project was to evaluate the capability of fire models to analyze a variety of fire scenarios typical for nuclear power plants (NPP). The evaluation of the capability of fire models to analyze these scenarios was conducted through a series of in total five international Benchmark Exercises. Different types of models were used by the participating expert institutions from five countries. The technical information that will be useful for fire model users, developers and further experts is summarized in this document. More detailed information is provided in the corresponding technical reference documents for the ICFMP Benchmark Exercises No. 1 to 5. The objective of these exercises was not to compare the capabilities and strengths of specific models, address issues specific to a model, nor to recommend specific models over others. This document is not intended to provide guidance to users of fire models. Guidance on the use of fire models is currently being

Power Institutions and International Collaboration on the Kola Peninsula

Directory of Open Access Journals (Sweden)

Geir Hønneland

2006-05-01

Full Text Available The article discusses how international cooperative projects have contributed to increased interaction between civilian authorities and the military or other power agencies in Murmansk Oblast. The cases of fisheries enforcement, nuclear safety and the fight against communicable diseases, especially tuberculosis in prisons, are reviewed. The main lesson is that international collaboration ventures can sometimes provide arenas for initiating new coordination patterns that would otherwise not have evolved. Occasionally, the international project is simply the pretext necessary for changing a situation that both civilian and power agencies view as irrational. Whether these changes are fundamental and structural, however, remains to be seen.

Optimal therapy in Gaucher disease

Directory of Open Access Journals (Sweden)

Ozlem Goker-Alpan

2010-07-01

Full Text Available Ozlem Goker-AlpanLysosomal Diseases Research and Treatment Unit, Center for Clinical Trials, O&O Alpan LLC, Springfield, VA, USAAbstract: Gaucher disease (GD, the inherited deficiency of the lysosomal enzyme glucocerebrosidase, presents with a wide range of symptoms of varying severity, and primarily affects the skeletal, hematologic and nervous systems. To date, the standard of care has included enzyme replacement therapy with imiglucerase. Although imiglucerase is highly effective in reversing the visceral and hematologic manifestations, skeletal disease is slow to respond, pulmonary involvement is relatively resistant, and the CNS involvement is not impacted. Because of the recent manufacturing and processing problems, the research and development of alternative therapeutics has become more pressing. The divergent phenotypes and the heterogeneity involving different organ systems implicates the involvement of several pathological processes that include enzyme deficiency, substrate accumulation, protein misfolding, and macrophage activation, that differ in each patient with GD. Thus, the therapy should be tailored individually in order to target multiple pathways that interplay in GD.Keywords: glucocerebrosidase, enzyme replacement therapy, substrate reduction therapy, protein misfolding and chaperone therapy, macrophage

Apparent diffusion coefficient vale of the brain in patients with Gaucher's disease type II and type III

International Nuclear Information System (INIS)

Abdel Razek, Ahmed Abdel Khalek; Abd El-Gaber, Nahed; Abdalla, Ahmed; Fathy, Abeer; Azab, Ahmed; Rahman, Ashraf Abdel

2009-01-01

The aim of this work is to assess the usefulness of apparent diffusion coefficient (ADC) value of the brain for diagnosis of patients with Gaucher's disease type II and type III. Prospective study was conducted upon 13 patients (nine boys and four girls aged 8 months-14 years: mean 6.1 years) with Gaucher's disease type II and III and for age-matched control group (n = 13). Diffusion-weighted magnetic resonance imaging using a single-shot echo-planar imaging with a diffusion-weighted factor b of 0, 500, and 1,000 s/mm 2 was done for all patients and volunteers. The ADC value was calculated in ten regions of the brain parenchyma and correlated with genotyping. There was significantly lower ADC value of the cortical frontal (P = 0.003), cortical temporal (P = 0.04), frontal subcortical white matter (P = 0.02), corticospinal tract (P = 0.001), cerebellum (P = 0.001), medulla (P = 0.002), and midbrain (P = 0.02) between patients and volunteers. There was significant difference in the ADC value of the frontal and temporal gray matter (P = 0.04 and 0.05, respectively) between patients with heterozygous and homozygous gene mutation. We concluded that ADC value is a new promising quantitative imaging parameter that can be used for the detection of brain abnormalities in patients with Gaucher's disease type II and type III and has a correlation with genotyping. (orig.)

Facilitating learning through an international virtual collaborative practice: A case study.

Science.gov (United States)

Wihlborg, Monne; Friberg, Elizabeth E; Rose, Karen M; Eastham, Linda

2018-02-01

Internationalisation of higher education involving information and communication technology such as e-learning opens opportunities for innovative learning approaches across nations and cultures. Describe a case in practice of collaborative and transformative learning in relation to 'internationalisation on home grounds' with the broader learning objective of 'becoming aware and knowledgeable'. A mutually developed project established a virtual international collaborative exchange for faculty and students using a course management software (MOODLE) and open access technology (Adobe CONNECT). Two research universities in Sweden and the United States. Approximately 90 nursing students from each university per semester over several semesters. A collaborative process to develop a joint learning community to construct a virtual module and learning activity involving academics and nursing students in two countries using principles of meaning construction and negotiated learning. Developed possibilities for dealing with the challenges and finding strategies for a future higher education system that opens dialogues worldwide. Virtual international exchanges open innovative communication and learning contexts across nations and cultures. Internationalisation is so much more than students and teachers' mobility. 'Internationalisation on home grounds' (internationalisation for all) should receive more attention to support faculty and student collaboration, learning, and professional development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Radiopharmacology of inhaled 133Xe in skeletal sites containing deposits of Gaucher cells

International Nuclear Information System (INIS)

Castronovo, F.P. Jr.; Mckusick, K.A.; Doppelt, S.H.; Barton, N.W.

1993-01-01

Gaucher's disease is a lysosomal storage disease in which cells of the reticuloendothelial system accumulate the lipid gluococerebroside. It is characterized by slowly progressive visceral and osseous involvement. One of the latter manifestations includes lipid infiltration of bone marrow. The authors monitored the rate of inhaled 133 Xe uptake and wash-out over diseased and normal metaphyseal and epiphyseal areas of the knee. (author)

Modelling Gaucher disease progression: long-term enzyme replacement therapy reduces the incidence of splenectomy and bone complications

NARCIS (Netherlands)

van Dussen, Laura; Biegstraaten, Marieke; Dijkgraaf, Marcel Gw; Hollak, Carla Em

2014-01-01

Long-term complications and associated conditions of type 1 Gaucher Disease (GD) can include splenectomy, bone complications, pulmonary hypertension, Parkinson disease and malignancies. Enzyme replacement therapy (ERT) reverses cytopenia and reduces organomegaly. To study the effects of ERT on

Gaucher disease: haematological presentations and complications.

Science.gov (United States)

Thomas, Alison S; Mehta, Atul; Hughes, Derralynn A

2014-05-01

Gaucher disease (GD) is an autosomal recessive lysosomal storage disease, caused by deficiency of the enzyme glucocerebrosidase, required for the degradation of glycosphingolipids. Clinical manifestations include hepatosplenomegaly, thrombocytopenia, bone disease and a bleeding diathesis, frequently resulting in presentation to haematologists. Historically managed by splenectomy, transfusions and orthopaedic surgery, the development of specific therapy in the form of intravenous enzyme replacement therapy in the 1990s has resulted in dramatic improvements in haematological and visceral disease. Recognition of complications, including multiple myeloma and Parkinson disease, has challenged the traditional macrophage-centric view of the pathophysiology of this disorder. The pathways by which enzyme deficiency results in the clinical manifestations of this disorder are poorly understood; altered inflammatory cytokine profiles, bioactive sphingolipid derivatives and alterations in the bone marrow microenvironment have been implicated. Further elucidating these pathways will serve to advance our understanding not only of GD, but of associated disorders. © 2014 John Wiley & Sons Ltd.

Norway's role in international collaboration towards rehabilitation of Andreeva Bay.

Science.gov (United States)

Dowdall, M; Sneve, M; Standring, W J F; Amundsen, I

2009-12-01

Andreeva Bay is one of the largest and most hazardous nuclear legacy sites in northwest Russia. The site is the location of large amounts of Spent Nuclear Fuel (SNF) and radioactive wastes and the risks associated with the site have precipitated an extensive international collaborative effort towards securing and rehabilitating the site. Given the location and proximity of the site, Norway has and continues to contribute in a number of ways towards this effort. Norway's activities in relation to rehabilitative efforts at Andreeva Bay are focused on both infrastructural and remediative initiatives as well as regulatory collaboration with Russia towards ensuring effective and safe operations during handling and removal of SNF and radioactive materials. This article describes Norway's role within international efforts in the context of the rehabilitation of Andreeva Bay and outlines previous activities and Norway's future direction with respect to the site.

Isofagomine in vivo effects in a neuronopathic Gaucher disease mouse.

Directory of Open Access Journals (Sweden)

Ying Sun

2011-04-01

Full Text Available The pharmacological chaperone, isofagomine (IFG, enhances acid β-glucosidase (GCase function by altering folding, trafficking, and activity in wild-type and Gaucher disease fibroblasts. The in vivo effects of IFG on GCase activity, its substrate levels, and phenotype were evaluated using a neuronopathic Gaucher disease mouse model, 4L;C* (V394L/V394L + saposin C-/- that has CNS accumulation of glucosylceramide (GC and glucosylsphingosine (GS as well as progressive neurological deterioration. IFG administration to 4L;C* mice at 20 or 600 mg/kg/day resulted in life span extensions of 10 or 20 days, respectively, and increases in GCase activity and protein levels in the brain and visceral tissues. Cerebral cortical GC and GS levels showed no significant reductions with IFG treatment. Increases of GC or GS levels were detected in the visceral tissues of IFG treated (600 mg/kg/day mice. The attenuations of brain proinflammatory responses in the treated mice were evidenced by reductions in astrogliosis and microglial cell activation, and decreased p38 phosphorylation and TNFα levels. Terminally, axonal degeneration was present in the brain and spinal cord from untreated and treated 4L;C* mice. These data demonstrate that IFG exerts in vivo effects by enhancing V394L GCase protein and activity levels, and in mediating suppression of proinflammation, which led to delayed onset of neurological disease and extension of the life span of 4L;C* mice. However, this was not correlated with a reduction in the accumulation of lipid substrates.

Case report 387: Gaucher disease affecting the skeleton (left femur)

International Nuclear Information System (INIS)

Tabas, J.H.; Daffner, R.H.; Hartsock, R.J.; Blakley, J.B.

1986-01-01

A case is described of a non-Jewish (Italian) 49-year-old man who presented to the hospital with pain in the left hip. Radionuclide studies showed decreased tracer activity with 99m Tc MDP over a lytic area in the subtrochanteric region of the left femur. Increased activity, however, was present in the right temporal bone, low anterior rib cage and right tenth posterior rib. The presence of subendosteal sclerosis with some cortical thickening adjacent to the femoral lesion, suggested the possibility of malignant neoplasm, (e.g. chondrosarcoma). Biopsy of the bone marrow showed the presence of Gaucher disease. (orig./SHA)

Case report 387: Gaucher disease affecting the skeleton (left femur)

Energy Technology Data Exchange (ETDEWEB)

Tabas, J.H.; Daffner, R.H.; Hartsock, R.J.; Blakley, J.B.

1986-08-01

A case is described of a non-Jewish (Italian) 49-year-old man who presented to the hospital with pain in the left hip. Radionuclide studies showed decreased tracer activity with /sup 99m/Tc MDP over a lytic area in the subtrochanteric region of the left femur. Increased activity, however, was present in the right temporal bone, low anterior rib cage and right tenth posterior rib. The presence of subendosteal sclerosis with some cortical thickening adjacent to the femoral lesion, suggested the possibility of malignant neoplasm, (e.g. chondrosarcoma). Biopsy of the bone marrow showed the presence of Gaucher disease. (orig./SHA).

Cross-border data exchange - a case study on international collaboration gone wrong

Science.gov (United States)

Yanko-Hombach, Valentina

2016-04-01

The subject of ethics in science has become a hot topic recently (Gleick, 2011). As publication pressure on researchers increases and use of the internet allows faster turn-around, the quality of the peer review process has suffered. This presentation describes one case of scientific ethics violation in which the editors of a high-ranking scientific journal improperly permitted publication of a paper that was based upon unethical acquisition of data and failed to acknowledge scientific collaboration and exchange of intellectual property. We will present "Case description" and "Ethical issues" with a hope that our experience draws attention to important ethical issues in international collaborative research, and prevents such misconduct in the future. Since international research involves cooperation and coordination among many people in different disciplines and institutions across national borders, ethical standards should promote values that are essential to integrity and collaborative work, including trust, accountability, mutual respect, and fairness. One lesson to be learned is not to engage in collaboration without a written agreement stating clearly who is responsible for what and how the results of collaborative research are to be shared. This is especially important in cases of international collaborations, particularly those involving smaller or developing nations who often do not have the high-tech facilities of developed nations. There is also need to establish clear regulations regarding co-authorship on papers in which intellectual property and significant financial investment was made to allow the research to proceed. As such, a system of ethics to guide the practice of science from data collection to publication and beyond is timely and much needed to protect the integrity of scientific collaboration. It will keep science moving forward by validating research findings and confirming or raising questions about results. References Benos, D. J., Fabres

A Study on planning of the international collaboration foundation for the Advanced Nuclear Technology Development Project

Energy Technology Data Exchange (ETDEWEB)

Chang, Moon Hee; Kim, H. R.; Kim, H. J. and others

2005-03-15

Korea has participated in the international collaboration programs for the development of future nuclear energy systems driven by the countries holding advanced nuclear technology and Korea and U.S. have cooperated in the INERI. This study aimed mainly at developing the plan for participation in the collaborative development of the Gen IV, searching the participation strategy for INERI and the INPRO, and the international cooperation in these programs. Contents and scope of the study for successful achievement are as follows; Investigation and analysis of international and domestic trends related to advanced nuclear technologies, Development of the plan for collaborative development of the Gen IV and conducting the international cooperation activities, Support for the activities related to I-NERI between Korea and U.S. and conducting the international cooperation, International cooperation activities for the INPRO. This study can be useful for planning the research plan and setting up of the strategy of integrating the results of the international collaboration and the domestic R and D results by combining the Gen IV and the domestic R and D in the field of future nuclear technology. Futhermore, this study can contribute to establishing the effective foundation and broadening the cooperation activities not only with the advanced countries for acquisition of the advanced technologies but also with the developing countries for the export of the domestic nuclear energy systems.

A Study on planning of promotion for international collaborative development of Generation IV Nuclear Energy Systems

International Nuclear Information System (INIS)

Hee, Chang Moon; Yang, M. S.; Ha, J. J.

2006-06-01

Korea has participated in the international collaboration programs for the development of future nuclear energy systems driven by the countries holding advanced nuclear technology and Korea and U. S. have cooperated in the INERI. This study is mainly at developing the plan for participation in the collaborative development of the Gen IV, searching the participation strategy for INERI and the INPRO, and the international cooperation in these programs. Contents and scope of the study for successful achievement are as follows; - Investigation and analysis of international and domestic trends related to advanced nuclear technologies - Development of the plan for collaborative development of the Gen IV and conducting the international cooperation activities - Support for the activities related to I-NERI between Korea and U. S. and conducting the international cooperation - International cooperation activities for the INPRO This study can be useful for planning the research plan and setting up of the strategy of integrating the results of the international collaboration and the domestic R and D results by combining the Gen IV and the domestic R and D in the field of future nuclear technology. Furthermore, this study can contribute to establishing the effective foundation and broadening the cooperation activities not only with the advanced countries for acquisition of the advanced technologies but also with the developing countries for the export of the domestic nuclear energy systems

A Study on planning of the international collaboration foundation for the Advanced Nuclear Technology Development Project

International Nuclear Information System (INIS)

Chang, Moon Hee; Kim, H. R.; Kim, H. J. and others

2005-03-01

Korea has participated in the international collaboration programs for the development of future nuclear energy systems driven by the countries holding advanced nuclear technology and Korea and U.S. have cooperated in the INERI. This study aimed mainly at developing the plan for participation in the collaborative development of the Gen IV, searching the participation strategy for INERI and the INPRO, and the international cooperation in these programs. Contents and scope of the study for successful achievement are as follows; Investigation and analysis of international and domestic trends related to advanced nuclear technologies, Development of the plan for collaborative development of the Gen IV and conducting the international cooperation activities, Support for the activities related to I-NERI between Korea and U.S. and conducting the international cooperation, International cooperation activities for the INPRO. This study can be useful for planning the research plan and setting up of the strategy of integrating the results of the international collaboration and the domestic R and D results by combining the Gen IV and the domestic R and D in the field of future nuclear technology. Futhermore, this study can contribute to establishing the effective foundation and broadening the cooperation activities not only with the advanced countries for acquisition of the advanced technologies but also with the developing countries for the export of the domestic nuclear energy systems

Celebrating international collaboration: reflections on the first Virtual International Practice Development Conference

Directory of Open Access Journals (Sweden)

Moira Stephens

2016-11-01

Full Text Available This article reports on the first Virtual International Practice Development Conference, held in May 2015 to celebrate International Nurses Day. The article describes key aspects of its planning, offers a flavour of the event itself and sets out an evaluation, including learning points and recommendations to assist with planning similar events in the future. Central to our learning are: The need for practice developers to grasp skills in technology associated with virtual space The need to embrace virtual space itself as another means by which creative and communicative spaces can be established for active learning and practice development activities The potential advantages that international virtual engagement has over face-to-face national or international engagement The delivery of this virtual event made a significant international contribution to global practice development activity within the International Practice Development Collaborative and to enabling practice developers to connect and celebrate on a more global basis. Implications for practice: Virtual space technology skills can assist with sharing and translating practice development research, innovations and critical commentary Virtual space can provide an adjunct to creative and communicative learning spaces Global networking opportunities can be developed and enhanced through the use of virtual space technology Practice developers need to role model the use of virtual technologies

Skeletal improvement in patients with Gaucher disease type 1: a phase 2 trial of oral eliglustat

Energy Technology Data Exchange (ETDEWEB)

Kamath, Ravi S. [Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Fairfax Radiological Consultants, Fairfax, VA (United States); Lukina, Elena [Russian Academy of Medical Sciences, Moscow (Russian Federation); Watman, Nora [Hospital Ramos Mejia, Buenos Aires (Argentina); Dragosky, Marta [Instituto Mexicano del Seguro Social Hospital de Especialidades, Col. La Raza (Mexico); Pastores, Gregory M. [New York University, New York (United States); Yale University School of Medicine, New Haven, CT (United States); Arreguin, Elsa Avila [Instituto Argentino de Diagnostico y Tratamiento, Buenos Aires (Argentina); Rosenbaum, Hanna [Rambam Medical Center, Haifa (Israel); Zimran, Ari [Sha' are Zedek Hebrew University and Hadassah Medical School, Jerusalem (Israel); Aguzzi, Rasha [Genzyme, a Sanofi company, Cambridge, MA (United States); Alexion Pharmaceuticals, Cambridge, MA (United States); Puga, Ana Cristina; Norfleet, Andrea M.; Peterschmitt, M.J. [Genzyme, a Sanofi company, Cambridge, MA (United States); Rosenthal, Daniel I. [Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Massachusetts General Hospital, Department of Radiology, Boston, MA (United States)

2014-10-15

Eliglustat is an investigational oral substrate reduction therapy for Gaucher disease type 1 (GD1). Its skeletal effects were evaluated by prospective monitoring of bone mineral density (BMD), fractures, marrow infiltration by Gaucher cells, focal bone lesions, and infarcts during an open-label, multi-site, single-arm phase 2 trial (NCT00358150). Institutional review board approval and patient informed consent were obtained. Eliglustat (50 or 100 mg) was self-administered by mouth twice daily; 19 patients completed 4 years of treatment. All were skeletally mature (age range, 18-55 years). DXA and MRI assessments were conducted at baseline and annually thereafter. X-rays were obtained annually until month 24, and then every other year. Lumbar spine BMD increased significantly (p = 0.02; n = 15) by a mean (SD) of 9.9 % (14.2 %) from baseline to year 4; corresponding T-scores increased significantly (p = 0.01) from a mean (SD) of -1.6 (1.1) to -0.9 (1.3). Mean femur T-score remained normal through 4 years. Femur MRI showed that 10/18 (56 %) patients had decreased Gaucher cell infiltration compared to baseline; one patient with early improvement had transient worsening at year 4. There were no lumbar spine or femoral fractures and no reported bone crises during the study. At baseline, 8/19 (42 %) patients had focal bone lesions, which remained stable, and 7/19 (37 %) patients had bone infarctions, which improved in one patient by year 2. At year 4, one new asymptomatic, indeterminate bone lesion was discovered that subsequently resolved. Eliglustat may be a therapeutic option for treating the skeletal manifestations of GD1. (orig.)

Skeletal improvement in patients with Gaucher disease type 1: a phase 2 trial of oral eliglustat

International Nuclear Information System (INIS)

Kamath, Ravi S.; Lukina, Elena; Watman, Nora; Dragosky, Marta; Pastores, Gregory M.; Arreguin, Elsa Avila; Rosenbaum, Hanna; Zimran, Ari; Aguzzi, Rasha; Puga, Ana Cristina; Norfleet, Andrea M.; Peterschmitt, M.J.; Rosenthal, Daniel I.

2014-01-01

Eliglustat is an investigational oral substrate reduction therapy for Gaucher disease type 1 (GD1). Its skeletal effects were evaluated by prospective monitoring of bone mineral density (BMD), fractures, marrow infiltration by Gaucher cells, focal bone lesions, and infarcts during an open-label, multi-site, single-arm phase 2 trial (NCT00358150). Institutional review board approval and patient informed consent were obtained. Eliglustat (50 or 100 mg) was self-administered by mouth twice daily; 19 patients completed 4 years of treatment. All were skeletally mature (age range, 18-55 years). DXA and MRI assessments were conducted at baseline and annually thereafter. X-rays were obtained annually until month 24, and then every other year. Lumbar spine BMD increased significantly (p = 0.02; n = 15) by a mean (SD) of 9.9 % (14.2 %) from baseline to year 4; corresponding T-scores increased significantly (p = 0.01) from a mean (SD) of -1.6 (1.1) to -0.9 (1.3). Mean femur T-score remained normal through 4 years. Femur MRI showed that 10/18 (56 %) patients had decreased Gaucher cell infiltration compared to baseline; one patient with early improvement had transient worsening at year 4. There were no lumbar spine or femoral fractures and no reported bone crises during the study. At baseline, 8/19 (42 %) patients had focal bone lesions, which remained stable, and 7/19 (37 %) patients had bone infarctions, which improved in one patient by year 2. At year 4, one new asymptomatic, indeterminate bone lesion was discovered that subsequently resolved. Eliglustat may be a therapeutic option for treating the skeletal manifestations of GD1. (orig.)

Summary of the findings of the International Collaboration on Mild Traumatic Brain Injury Prognosis

DEFF Research Database (Denmark)

Donovan, J.; Cancelliere, C.; Cassidy, J. D.

2014-01-01

In 2004, the WHO Collaborating Centre for Neurotrauma, Prevention, Management and Rehabilitation Task Force published the first large systematic review and best evidence synthesis on the clinical course and prognosis for recovery after MTBI. Ten years later, the International Collaboration on Mil...

International collaboration in the history of science of Central Europe

Directory of Open Access Journals (Sweden)

Soňa ŠTRBÁŇOVÁ

2015-12-01

Full Text Available In the last ten years, approximately, we could witness an evolution in informal international collaboration focusing on shared and interconnected history of science in the Habsburg Monarchy and in Central Europe in general. This effort, which includes mainly historians of science from Austria, Czech Republic, Hungary and Poland, has already produced a number of important results and contributed to the thematization of some timeless topics of history of sciences such as, for instance, nationalization and internationalization of science. In the context of this cooperation, the seminar of Jan Surman, a historian of science of Polish descent, held at the Institute of Contemporary History of the Czech Academy of Sciences in Prague in May 2015, concentrated on the formation of national scientific terminologies. It also underlined the necessity and usefulness of international collaboration in achieving a deeper understanding of the “national” histories of science, which cannot be separated from the “international” history.

Evaluation of bone marrow infiltration in non-neuropathic Gaucher disease patients with use of whole-body MRI. A retrospective data analysis

International Nuclear Information System (INIS)

Laudemann, K.; Moos, L.; Lollert, A.; Wagner, D.; Staatz, G.; Mengel, K.E.; Reinke, J.; Brixius-Huth, M.; Dueber, C.

2015-01-01

To evaluate whole-body magnetic resonance imaging (WB-MRI) for the assessment of bone marrow infiltration in patients with confirmed Gaucher disease type 1 under long-term enzyme replacement therapy (ERT). This retrospective data analysis included 38 patients in two subgroups. Group A: 10 females, 9 males, 15-29 years, mean age 22 years and Group B: 11 females, 8 males, 29-77 years, mean age 49 years, all treated with alglucerase or imiglucerase for at least 12.5 years. Whole-body MRI was carried out in all patients using a standard MRI protocol. Two radiologists assessed all MR images retrospectively with the use of three different MRI score systems: The bone marrow burden (BMB) score, the Duesseldorf-Gaucher score (DGS) and the vertebra disc ratio (VDR). As a clinical component, severity score index type 1 (GD-DS3) was determined. In both groups the MR scores showed low to moderate pathologic levels but no statistically significant difference was found between both groups. The median scores in group A/group B were 7.00/9.00 for the BMB score (p=0.07), 4.00/3.00 for the DGS score (p=0.062) and 1.54/1.62 for the VDR score (p=0.267). The GD-DS3 score was statistically significantly different between both groups (1.6/3.9, p=0.000) and osseous Gaucher disease complications were only found in group B. Bone marrow involvement and typical clinical manifestations are reduced to a minimum, when ERT starts immediately after the confirmed diagnosis of Gaucher disease type 1. The applied MR scores are useful markers to control bone marrow infiltration under enzyme replacement therapy in older patients. Pathologic MR scores in young patients may reflect postponed fat conversion of the juvenile bone marrow. This issue has to be examined in further studies.

Evaluation of bone marrow infiltration in non-neuropathic Gaucher disease patients with use of whole-body MRI. A retrospective data analysis

Energy Technology Data Exchange (ETDEWEB)

Laudemann, K.; Moos, L.; Lollert, A.; Wagner, D.; Staatz, G. [University Medical Center of the Johannes Gutenberg University, Mainz (Germany). Section of Pediatric Radiology; Mengel, K.E.; Reinke, J.; Brixius-Huth, M. [University Medical Center of the Johannes Gutenberg University, Mainz (Germany). Clinic for Metabolic Diseases; Dueber, C. [University Medical Center of the Johannes Gutenberg University, Mainz (Germany). Dept. of Diagnostic and Interventional Radiology

2015-12-15

To evaluate whole-body magnetic resonance imaging (WB-MRI) for the assessment of bone marrow infiltration in patients with confirmed Gaucher disease type 1 under long-term enzyme replacement therapy (ERT). This retrospective data analysis included 38 patients in two subgroups. Group A: 10 females, 9 males, 15-29 years, mean age 22 years and Group B: 11 females, 8 males, 29-77 years, mean age 49 years, all treated with alglucerase or imiglucerase for at least 12.5 years. Whole-body MRI was carried out in all patients using a standard MRI protocol. Two radiologists assessed all MR images retrospectively with the use of three different MRI score systems: The bone marrow burden (BMB) score, the Duesseldorf-Gaucher score (DGS) and the vertebra disc ratio (VDR). As a clinical component, severity score index type 1 (GD-DS3) was determined. In both groups the MR scores showed low to moderate pathologic levels but no statistically significant difference was found between both groups. The median scores in group A/group B were 7.00/9.00 for the BMB score (p=0.07), 4.00/3.00 for the DGS score (p=0.062) and 1.54/1.62 for the VDR score (p=0.267). The GD-DS3 score was statistically significantly different between both groups (1.6/3.9, p=0.000) and osseous Gaucher disease complications were only found in group B. Bone marrow involvement and typical clinical manifestations are reduced to a minimum, when ERT starts immediately after the confirmed diagnosis of Gaucher disease type 1. The applied MR scores are useful markers to control bone marrow infiltration under enzyme replacement therapy in older patients. Pathologic MR scores in young patients may reflect postponed fat conversion of the juvenile bone marrow. This issue has to be examined in further studies.

A phase 2 multi-center, open-label, switch-over trial to evaluate the safety and efficacy of Abcertin® in patients with type 1 Gaucher disease.

Science.gov (United States)

Choi, Jin-Ho; Lee, Beom Hee; Ko, Jung Min; Sohn, Young Bae; Lee, Jin-Sung; Kim, Gu-Hwan; Heo, Sun Hee; Park, June-Young; Kim, Yoo-Mi; Kim, Ja-Hye; Yoo, Han-Wook

2015-04-01

Gaucher disease is a lysosomal storage disease for which enzyme replacement therapy has proven to be effective. A switch-over clinical trial was performed to evaluate the efficacy and safety of Abcertin® (ISU Abxis, Seoul, Korea) in subjects with type 1 Gaucher disease who were previously treated with imiglucerase. Five Korean patients with type 1 Gaucher disease were enrolled. Previous doses of imiglucerase ranged from 30 to 55 U/kg every other week. The same dose of Abcertin® was administered to all patients for 24 weeks. Primary efficacy endpoints were changes in hemoglobin levels and platelet counts, and the secondary efficacy endpoints included changes in liver and spleen volumes, serum biomarkers, skeletal status and bone mineral density (BMD). During the study period, no statistically significant changes were observed in all parameters including hemoglobin levels and platelet counts, liver and spleen volumes, skeletal status and BMD. Abcertin® administration was continued in three patients for another 24 weeks as an extension of the study. Hemoglobin levels and platelet counts were maintained in all three patients. In conclusion, the efficacy and safety of Abcertin® are similar to those of imiglucerase, and Abcertin® is an effective therapeutic agent for patients with type 1 Gaucher disease (Clinical Trial Registry No. NCT02053896 at www.clinicaltrials.gov).

Potential efficacy of enzyme replacement and substrate reduction therapy in three siblings with Gaucher disease type III

NARCIS (Netherlands)

Cox-Brinkman, J.; van Breemen, M. J.; van Maldegem, B. T.; Bour, L.; Donker, W. E.; Hollak, C. E. M.; Wijburg, F. A.; Aerts, J. M. F. G.

2008-01-01

We report three siblings with Gaucher disease type III, born between 1992 and 2004. During this period, new developments resulted in different potential therapies, changing clinical practice. The two eldest siblings received enzyme replacement therapy (ERT) from the age of 24 and 5 months

Evolution and results of LCT, international collaboration of superconducting coil development for fusion

International Nuclear Information System (INIS)

Shimamoto, Susumu

1987-01-01

This international collaboration has been promoted centering around the International Energy Agency since ten years ago. This work is that of advancing joint experiments on the equal footing by several countries gathering with large hardwares. As the result, unlike the international collaboration carried out so far, much experiences have been brought in. Now this work is going to be successfully completed. At this time, the realities of the international collaboration experienced through this work are reported while referring to a part of the technical results. Superconductors were found at the end of 1950s, and the technical development of superconducting coils has been advanced mainly for the equipment of high energy physics in foreign countries, while in Japan, for MHD electricity generation and magnetic levitation train. The TFTR (USA), JET (Euratom) and JT-60 (Japan) aiming at the attainment of critical plasma use normal conduction coils, but the agreement on the LCT project was signed in the autumn of 1977, which aims at the development of the superconducting coils for fusion experimental reactors. The development of coil manufacture in respective countries and the experiments in Japan and Euratom, some episode in the negotiation, the experiment on six coils and the results are reported. (Kako, I.)

Imaging characteristics of focal splenic and hepatic lesions in type 1 Gaucher disease.

Science.gov (United States)

Regenboog, Martine; Bohte, Anneloes E; Somers, Inne; van Delden, Otto M; Maas, Mario; Hollak, Carla E M

2016-09-01

In Gaucher disease (GD) imaging of liver and spleen is part of routine follow-up of GD patients. Focal lesions in both liver and spleen are frequently reported at radiological examinations. These lesions often represent benign accumulations of Gaucher cells, so-called "gaucheroma", but malignancies, especially hepatocellular carcinoma, are more frequently found in GD as well. We report the imaging characteristics of all focal lesions in liver and spleen in the Dutch GD cohort. Of the 95 GD1 patients, 40% had focal splenic and/or hepatic lesions, associated with more severe GD. Lesions identified as gaucheroma have variable imaging characteristics: hyper- to hypointense on MRI, hyper- or hypoechoic on US and hypodense on computed tomography (CT). Hepatic lesions were classified as simple cysts or haemangioma based upon imaging characteristics. Focal nodular hyperplasia (FNH), gaucheroma and hepatocellular carcinoma (HCC) could not be distinguished by conventional US, CT or MRI. Growth of these lesions and/or characteristics of HCC on dynamic CT or MRI and pathology was used to identify or rule out HCC. We propose a decision-making algorithm including the use of growth and dynamic CT- or MRI-scanning to characterize lesions. Copyright © 2016 Elsevier Inc. All rights reserved.

Internal and External Collaboration in New Product Development

DEFF Research Database (Denmark)

Timenes Laugen, Bjørge; Lassen, Astrid Heidemann; Middel, Rick

2009-01-01

Industry and academia alike are increasingly becoming aware of the fact that innovation does not take place in isolated cells or functions within the firm. During the last the years the term open innovation has emphasised the importance of internal and external collaboration in order to increase...... strategic priorities influence the degree of external and internal involvement in the NPD process, moderated by contextual factors. Results based on analyses of 584 companies from the International Manufacturing Strategy Survey (IMSS) 2005 indicate that suppliers are heavily involved in the NPD process...... in firms in B2C markets aiming at increasing the innovation volume. For B2B companies the reverse picture emerges. However, when the aim is to increase the radicality of new products, suppliers and customers are heavily involved for firms in B2B markets. Further, market uncertainty, and to some extent...

Key Success Factors and Guidance for International Collaborative Design Projects

Directory of Open Access Journals (Sweden)

Robby Soetanto

2015-11-01

Full Text Available In the built environment (BE sector, the co-creation process of design demands understanding of requirements (as viewed by parties involved, mobilisation of tacit knowledge, negotiation, and complex exchange of information. The need to collaborate over distance has further exacerbated the complexity of the process, and, in itself, represents a significant challenge for BE professionals who are increasingly expected to undertake this process within globally distributed virtual teams. The research aims to identify key success factors and develop guidance for international collaborative design projects, via the implementation of collaborative design courses in UK and Canadian universities over three academic years. Questionnaire surveys, focus groups, observation of online meetings, personal reflections provided data for the analysis. The findings reveal the significance of the perceived risk of collaboration and a difference in preferred communication mode between architects and civil/structural engineers. These findings suggest the impact of training in the subject discipline, and that the opportunity for co-located working has helped the development of trust. The guidance is aimed at BE educators who wish to implement this activity in their courses.

The importance of international collaboration for rare diseases research: a European perspective.

Science.gov (United States)

Julkowska, D; Austin, C P; Cutillo, C M; Gancberg, D; Hager, C; Halftermeyer, J; Jonker, A H; Lau, L P L; Norstedt, I; Rath, A; Schuster, R; Simelyte, E; van Weely, S

2017-09-01

Over the last two decades, important contributions were made at national, European and international levels to foster collaboration into rare diseases research. The European Union (EU) has put much effort into funding rare diseases research, encouraging national funding organizations to collaborate together in the E-Rare program, setting up European Reference Networks for rare diseases and complex conditions, and initiating the International Rare Diseases Research Consortium (IRDiRC) together with the National Institutes of Health in the USA. Co-ordination of the activities of funding agencies, academic researchers, companies, regulatory bodies, and patient advocacy organizations and partnerships with, for example, the European Research Infrastructures maximizes the collective impact of global investments in rare diseases research. This contributes to accelerating progress, for example, in faster diagnosis through enhanced discovery of causative genes, better understanding of natural history of rare diseases through creation of common registries and databases and boosting of innovative therapeutic approaches. Several examples of funded pre-clinical and clinical gene therapy projects show that integration of multinational and multidisciplinary expertize generates new knowledge and can result in multicentre gene therapy trials. International collaboration in rare diseases research is key to improve the life of people living with a rare disease.

Progranulin Recruits HSP70 to ?-Glucocerebrosidase and Is Therapeutic Against Gaucher Disease

OpenAIRE

Jian, Jinlong; Tian, Qing-Yun; Hettinghouse, Aubryanna; Zhao, Shuai; Liu, Helen; Wei, Jianlu; Grunig, Gabriele; Zhang, Wujuan; Setchell, Kenneth D.R.; Sun, Ying; Overkleeft, Herman S.; Chan, Gerald L.; Liu, Chuan-ju

2016-01-01

Highlights ? PGRN is required for lysosomal appearance of GCase and PGRN deficiency causes GCase/LIMP2 aggregation upon stress ? PGRN directly binds to GCase through a two-site mechanism ? PGRN recruits HSP70 to GCase and prevents GCase aggregation in response to stress ? PGRN derivative Pcgin binds to GCase and HSP70 and is therapeutic against Gaucher disease In this study, we demonstrate that PGRN directly binds to GCase and is required for the lysosomal appearance of GCase. In addition, HS...

Brazilian Participations in the International Astronomical Search Collaboration

Science.gov (United States)

Rojas, G. A.; Dalla-Costa, L. J.; Kalmus, A. T.; Kroth, E. C.; Matos, M. F.; Silva, A. L.; Silva, G. G.

2014-10-01

International Astronomical Search Collaboration (IASC) is an international educational project between universities, schools, observatories and research institutions. Its main objective is to enroll high school and college students in the monitoring and discovery of asteroids and Near Earth Objects (NEOs), especially Potentially Hazardous Asteroids. The methodology consists in the analysis of astronomical images obtained in several observatories in North America and Hawaii. The images are distributed throughout the school network and the results must be delivered in a 72-hour timeframe. Since 2010 Brazilian universities and schools have joined IASC, resulting in over a dozen new asteroids found (3 of them NEOs), and hundreds of measurements for already known asteroids. A major event in this collaboration was the All-Brazil Asteroid Search Campaign, which was conducted in September 2012. 2013 marks the fourth year of Brazilian participations in IASC, with one important milestone: the third straight appearance of a Brazilian institution in the Pan-STARRS campaign, which uses the PS1 telescope in Haleakala, Hawaii. We will present a summary of the overall results, as well as the latest news from 2013 campaigns. We will discuss the impact promoted by the past events, such as how the interest in astronomy changed before and after the campaigns, and it has helped the students to choose their future careers.

Intemational collaborative study on the preparation of 1st international standard for rhTSH for bioassay

International Nuclear Information System (INIS)

Huang Ying; Shen Hongzheng; Yu Ting; Xu Ligen

2007-01-01

The history of the international collaborative studies on the preparation of standards of TSH for bioassay and immunoassay was reviewed. The result of collaborative study on the 1st international standard for thyroid-stimulating hormone, recombinant, human, for bioassay was reported in detail in this article. Based on the results of this collaborative study, it is proposed that the candidate standard be established as the international standard for rhTSH for bioassay, and be assigned an activity of 9.5 IU per ampoule. The national standard preparation of TSH for immunoassay was also reassayed, revealing the potency to be 0.557 mIU/ampoule, i.e. 92. 8% of the labelled value of 0.600mIU/ampoule, a reasonable consistency. (authors)

Apparent diffusion coefficient vale of the brain in patients with Gaucher's disease type II and type III

Energy Technology Data Exchange (ETDEWEB)

Abdel Razek, Ahmed Abdel Khalek; Abd El-Gaber, Nahed [Mansoura Faculty of Medicine, Department of Diagnostic Radiology, Mansoura (Egypt); Abdalla, Ahmed; Fathy, Abeer [Mansoura Faculty of Medicine, Department of Pediatric, Mansoura (Egypt); Azab, Ahmed [Mansoura Faculty of Medicine, Department of Neurology, Mansoura (Egypt); Rahman, Ashraf Abdel [Radiology Unit of Pediatric Hospital, Mansoura (Egypt)

2009-11-15

The aim of this work is to assess the usefulness of apparent diffusion coefficient (ADC) value of the brain for diagnosis of patients with Gaucher's disease type II and type III. Prospective study was conducted upon 13 patients (nine boys and four girls aged 8 months-14 years: mean 6.1 years) with Gaucher's disease type II and III and for age-matched control group (n = 13). Diffusion-weighted magnetic resonance imaging using a single-shot echo-planar imaging with a diffusion-weighted factor b of 0, 500, and 1,000 s/mm{sup 2} was done for all patients and volunteers. The ADC value was calculated in ten regions of the brain parenchyma and correlated with genotyping. There was significantly lower ADC value of the cortical frontal (P = 0.003), cortical temporal (P = 0.04), frontal subcortical white matter (P = 0.02), corticospinal tract (P = 0.001), cerebellum (P = 0.001), medulla (P = 0.002), and midbrain (P = 0.02) between patients and volunteers. There was significant difference in the ADC value of the frontal and temporal gray matter (P = 0.04 and 0.05, respectively) between patients with heterozygous and homozygous gene mutation. We concluded that ADC value is a new promising quantitative imaging parameter that can be used for the detection of brain abnormalities in patients with Gaucher's disease type II and type III and has a correlation with genotyping. (orig.)

Complexity in graduate medical education: a collaborative education agenda for internal medicine and geriatric medicine.

Science.gov (United States)

Chang, Anna; Fernandez, Helen; Cayea, Danelle; Chheda, Shobhina; Paniagua, Miguel; Eckstrom, Elizabeth; Day, Hollis

2014-06-01

Internal medicine residents today face significant challenges in caring for an increasingly complex patient population within ever-changing education and health care environments. As a result, medical educators, health care system leaders, payers, and patients are demanding change and accountability in graduate medical education (GME). A 2012 Society of General Internal Medicine (SGIM) retreat identified medical education as an area for collaboration between internal medicine and geriatric medicine. The authors first determined a short-term research agenda for resident education by mapping selected internal medicine reporting milestones to geriatrics competencies, and listing available sample learner assessment tools. Next, the authors proposed a strategy for long-term collaboration in three priority areas in clinical medicine that are challenging for residents today: (1) team-based care, (2) transitions and readmissions, and (3) multi-morbidity. The short-term agenda focuses on learner assessment, while the long-term agenda allows for program evaluation and improvement. This model of collaboration in medical education combines the resources and expertise of internal medicine and geriatric medicine educators with the goal of increasing innovation and improving outcomes in GME targeting the needs of our residents and their patients.

Scintigraphic findings on 99mTc-MDP, 99mTc-sestamibi and 99mTc-HMPAO images in Gaucher's disease

International Nuclear Information System (INIS)

Mariani, G.; Molea, N.; La Civita, L.; Porciello, G.; Lazzeri, E.; Ferri, C.

1996-01-01

We report here on the use of the lipophilic cationic complex technetium-99m sestamibi ( 99m Tc-MIBI), employed as an indicator of increased cellular density and metabolic activity, to evaluate Gaucher cell infiltrates in the bone marrow; 99m Tc-hexametazime ( 99m Tc-HMPAO) was also employed, as a pure indicator of lipidic infiltration in the bone marrow. A 67-year-old patient with known type 1 Gaucher's disease presented with a painful left hip and knee and difficulty in gait subsequent to traumatic fracture of the left femoral neck that had required implant of a fixation screw-plaque. Bone scan with 99m Tc-methylene diphosphonate revealed reduced uptake at the distal metaphyseal-epiphyseal femoral region. In addition, whole-body maps and spot-view acquisitions of the thighs and legs were recorded at both 30 min and 2.5 h after the injection of 99m Tc-MIBI: the scintigraphic pattern clearly showed increased uptake at several sites involved by Gaucher deposits in the bone marrow (both knees, with variable intensity in different areas), matching the bone changes detected by conventional x-ray. The target to non-target ratios slowly decreased with time, from an average value of 2.25 in the early scan to an average value of 2 in the delayed scan. The lipid-soluble agent 99m Tc-HMPAO exhibited a superimposable scintigraphic pattern of accumulation at the involved sites, though with lower target to non-target ratios (1.27-1.48). The results obtained in this patient suggest a potential role of 99m Tc-MIBI in the scintigraphic evaluation of Gaucher's lipid deposits in the bone marrow. If the results are confirmed in other patients, this radiopharmaceutical would offer clear advantages over 133 Xe because of its wider availability and greater practicality (i.v. administration of 99m Tc-MIBI versus inhalation of 133 Xe, and use of a single gamma camera instead of two as with 133 Xe). (orig.). With 3 figs

Selective chaperone effect of aminocyclitol derivatives on G202R and other mutant glucocerebrosidases causing Gaucher disease.

Science.gov (United States)

Serra-Vinardell, Jenny; Díaz, Lucía; Gutiérrez-de Terán, Hugo; Sánchez-Ollé, Gessamí; Bujons, Jordi; Michelakakis, Helen; Mavridou, Irene; Aerts, Johannes M F G; Delgado, Antonio; Grinberg, Daniel; Vilageliu, Lluïsa; Casas, Josefina

2014-09-01

Gaucher disease is an autosomal recessive lysosomal disorder characterized by the accumulation of glucosylceramide as a result of a deficiency of the enzyme glucocerebrosidase. Several competitive glucocerebrosidase inhibitors are able to act as pharmacological chaperones for an efficient rescue of the mutated, misfolded forms of the enzyme. Along this line, we report in this work on the ability of several aminocyclitols to increase the residual glucocerebrosidase activity in patient fibroblasts with different genotypes. Some of the compounds were slightly active on fibroblasts bearing some mutations, including the highly prevalent N370S mutation. All compounds were highly active as enzyme activity enhancers on fibroblasts from Gaucher disease patients containing the G202R mutation. Moreover, using the novel tagged sphingolipid ω-azidosphingosine, a reduction in the tagged glucosylceramide accumulation was also observed for selected aminocyclitols. Attempts to explain the activity impairment observed in glucocerebrosidase bearing the G202R mutation by comparative molecular dynamic studies on wild type and the G202R mutated proteins (free and isofagomine-bound, in both cases) were unsuccessful. Under the simulation conditions used, no clear effect of the G202R mutation neither over the global structure of the protein nor on the loops that constitute the glucocerebrosidase active site was observed. Since the G202R residue is located on the protein surface, altered protein-membrane or protein-protein interactions could account for the observed differences. In conclusion, we have tested novel compounds that have shown some chaperone effect on particular glucocerebrosidase mutant enzymes, supporting the enhancement therapy as an alternative approach for Gaucher disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

A Study on intensifying efficiency for international collaborative development of Advanced Nuclear Energy Technology

Energy Technology Data Exchange (ETDEWEB)

Chang, Moon Hee; Kim, H. R.; Kim, H. J.; Chang, J. H.; Hahn, D. H.; Bae, Y. Y.; Kim, W. W.; Jeong, I.; Lee, D. S.; Lee, J. H. [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2008-06-15

Generation IV International Forum(GIF), where 13 countries including Korea collaborate to develop future nuclear energy systems, put into force 'Generation IV International Forum Project Arrangement' in 2007 for the international research and development of Gen IV Systems, following the entry into force of Framework Agreement in 2005. The International Nuclear Research Initiative(I-NERI) between Korea and United States and the International Project on Innovative Nuclear Energy Systems and Fuel Cycles(INPRO) of IAEA are continued in this year, produced lots of visible outcomes. These international activities have a common goal of the collaborative development of advanced nuclear system technologies but differ in the main focusing areas and aspects, so Korea needs to establish the integrated strategy based on the distinguished and complementary approach for the participation of each international programs, as examples the GIF for the advanced system technology development, INPRO for the set-up of institution and infra-structure, and I-NERI for the access of the core technologies and acquisition of the transparency of nuclear R and D.

A Study on intensifying efficiency for international collaborative development of Advanced Nuclear Energy Technology

International Nuclear Information System (INIS)

Chang, Moon Hee; Kim, H. R.; Kim, H. J.; Chang, J. H.; Hahn, D. H.; Bae, Y. Y.; Kim, W. W.; Jeong, I.; Lee, D. S.; Lee, J. H.

2008-06-01

Generation IV International Forum(GIF), where 13 countries including Korea collaborate to develop future nuclear energy systems, put into force 'Generation IV International Forum Project Arrangement' in 2007 for the international research and development of Gen IV Systems, following the entry into force of Framework Agreement in 2005. The International Nuclear Research Initiative(I-NERI) between Korea and United States and the International Project on Innovative Nuclear Energy Systems and Fuel Cycles(INPRO) of IAEA are continued in this year, produced lots of visible outcomes. These international activities have a common goal of the collaborative development of advanced nuclear system technologies but differ in the main focusing areas and aspects, so Korea needs to establish the integrated strategy based on the distinguished and complementary approach for the participation of each international programs, as examples the GIF for the advanced system technology development, INPRO for the set-up of institution and infra-structure, and I-NERI for the access of the core technologies and acquisition of the transparency of nuclear R and D

19th International Conference on Interactive Collaborative Learning

CERN Document Server

Guralnick, David; Uhomoibhi, James

2017-01-01

This book presents the proceedings of the 19th International Conference on Interactive Collaborative Learning, held 21-23 September 2016 at Clayton Hotel in Belfast, UK. We are currently witnessing a significant transformation in the development of education. The impact of globalisation on all areas of human life, the exponential acceleration of developments in both technology and the global markets, and the growing need for flexibility and agility are essential and challenging elements of this process that have to be addressed in general, but especially in the context of engineering education. To face these topical and very real challenges, higher education is called upon to find innovative responses. Since being founded in 1998, this conference has consistently been devoted to finding new approaches to learning, with a focus on collaborative learning. Today the ICL conferences have established themselves as a vital forum for the exchange of information on key trends and findings, and of practical lessons le...

Productive international collaboration in the large coil task

International Nuclear Information System (INIS)

Haubenreich, P.N.; Komarek, P.; Shimamoto, S.; Vecsey, G.

1987-01-01

The Large Coil Task (LCT), initiated in 1977, has been very productive of useful technical information about superconducting toroidal field (TF) coil design and manufacture. Moreover, it has demonstrated close international collaboration in fusion technology development, including integration of large components built in four different countries. Each of six 40-t test coils was designed and produced by a major industrial team, with government laboratory guidance, to a common set of specifications. The six were assembled into a toroidal array for testing in the International Fusion Superconducting Magnet Test Facility (IFSMTF) at Oak Ridge. Testing was done by a team of representatives of EURATOM, Japan, Switzerland, and the United States, with each participant having full access to all data. Coils were thoroughly instrumented, enabling penetrating analysis of behavior

Overweight, insulin resistance and type II diabetes in type I Gaucher disease patients in relation to enzyme replacement therapy

NARCIS (Netherlands)

Langeveld, M.; de Fost, M.; Aerts, J. M. F. G.; Sauerwein, H. P.; Hollak, C. E. M.

2008-01-01

Type I Gaucher disease, a lysosomal storage disorder is associated with metabolic abnormalities such as high resting energy expenditure, low circulating adiponectin and peripheral insulin resistance. Treatment with enzyme replacement therapy (enzyme therapy) leads to a decrease in resting energy

Good collaborative practice: reforming capacity building governance of international health research partnerships.

Science.gov (United States)

Ward, Claire Leonie; Shaw, David; Sprumont, Dominique; Sankoh, Osman; Tanner, Marcel; Elger, Bernice

2018-01-08

In line with the policy objectives of the United Nations Sustainable Development Goals, this commentary seeks to examine the extent to which provisions of international health research guidance promote capacity building and equitable partnerships in global health research. Our evaluation finds that governance of collaborative research partnerships, and in particular capacity building, in resource-constrained settings is limited but has improved with the implementation guidance of the International Ethical Guidelines for Health-related Research Involving Humans by The Council for International Organizations of Medical Sciences (CIOMS) (2016). However, more clarity is needed in national legislation, industry and ethics guidelines, and regulatory provisions to address the structural inequities and power imbalances inherent in international health research partnerships. Most notably, ethical partnership governance is not supported by the principal industry ethics guidelines - the International Conference on Harmonization Technical Requirements for Registration of Pharmaceutical for Human Use (ICH) Good Clinical Practice (ICH-GCP). Given the strategic value of ICH-GCP guidelines in defining the role and responsibility of global health research partners, we conclude that such governance should stipulate the minimal requirements for creating an equitable environment of inclusion, mutual learning, transparency and accountability. Procedurally, this can be supported by i) shared research agenda setting with local leadership, ii) capacity assessments, and iii) construction of a memorandum of understanding (MoU). Moreover, the requirement of capacity building needs to be coordinated amongst partners to support good collaborative practice and deliver on the public health goals of the research enterprise; improving local conditions of health and reducing global health inequality. In this respect, and in order to develop consistency between sources of research governance, ICH

Imiglucerase in the treatment of Gaucher disease: a history and perspective

Science.gov (United States)

Deegan, Patrick B; Cox, Timothy M

2012-01-01

The scientific and therapeutic development of imiglucerase (Cerezyme®) by the Genzyme Corporation is a paradigm case for a critical examination of current trends in biotechnology. In this article the authors argue that contemporary interest in treatments for rare diseases by major pharmaceutical companies stems in large part from an exception among rarities: the astonishing commercial success of Cerezyme. The fortunes of the Genzyme Corporation, latterly acquired by global giant Sanofi SA, were founded on the evolution of a blockbuster therapy for a single but, as it turns out, propitious ultra-orphan disorder: Gaucher disease. PMID:22563238

Successful therapy for protein-losing enteropathy caused by chronic neuronopathic Gaucher disease

Directory of Open Access Journals (Sweden)

A.A. Mhanni

2016-03-01

Full Text Available Gaucher disease (OMIM #230800 is caused by β-glucosidase deficiency and primarily involves the mononuclear phagocyte system (also called Reticuloendothelial System or Macrophage System. The disease is classified into three main phenotypes based on the presence or absence of neurological manifestations: non-neuronopathic (type 1, acute neuronopathic (type 2 and chronic neuronopathic (type 3. Typical manifestations include hepatosplenomegaly, skeletal deformities, hematological abnormalities, interstitial lung fibrosis and neurodegeneration in neuronopathic cases. Mesenteric lymphadenopathy with resultant protein losing enteropathy (PLE has only been rarely described. Mesenteric lymphadenopathy may lead to intestinal lymphatic obstruction and secondary lymphangiectasia resulting in chronic diarrhea, abdominal pain and weight loss. Fecal protein loss with secondary hypoalbuminemia can be significant. We report a male with Chronic Neuronopathic Gaucher disease (GD (homozygous for c.1448T>C (NM_000157.3 GBA mutation who at 16 years of age developed intractable abdominal pain, diarrhea and weight loss. This was caused by PLE secondary to intestinal lymphangiectasia caused by calcified mesenteric lymphadenopathy despite prior long term enzyme replacement therapy (ERT and/or substrate reduction therapy (SRT. His older similarly affected sister who had been receiving treatment with ERT and/or SRT remains stable on these treatments with no evidence of mesenteric lymphadenopathy. Medical management with total parenteral nutrition, daily medium chain triglyceride-oil (MCT supplementation, low dose oral budesonide, continued oral SRT and an increased dose of parenteral ERT has stabilized his condition with resolution of the gastrointestinal symptoms and appropriate weight gain.

Eliglustat tartrate for the treatment of adults with type 1 Gaucher disease

Directory of Open Access Journals (Sweden)

Bennett LL

2015-08-01

Full Text Available Lunawati L Bennett, Kelsey TurcotteSchool of Pharmacy, Union University, Jackson, TN, USA Abstract: The purpose of this article is to review eliglustat tartrate, a substrate reduction therapy, for the treatment of Gaucher disease type 1 (GD1. GD is an rare inborn error of metabolism caused by accumulation of lipid substrates such as glucosylceramide within the monocyte-macrophage system that affects the body by causing enlargement of the spleen and liver, destruction of bone, and abnormalities of the lungs and blood, such as anemia, thrombocytopenia, and leukopenia. GD is classified into three types: GD1, a chronic and non-neuronopathic disease accounting for 95% of GD cases; and types 2 and 3 (GD2 GD3 which are more progressive diseases with no approved drugs available at this time. Treatment options for GD1 include enzyme replacement therapy and substrate reduction therapy. Eliglustat works by inhibiting UDP-glucosylceramide synthase, the first enzyme that catalyzes the biosynthesis of glycosphingolipids, thus reducing the load of glucosylceramide influx into the lysosome. Eliglustat was approved by the US Food and Drug Administration after three Phase I, two Phase II, and two Phase III clinical trials. The dose of eliglustat is 84 mg twice a day or once daily depending on the cytochrome P450 2D6 genotype of the patient. Keywords: Gaucher disease, glucocerebrosidase, glucosylceramide synthase, eliglustat tartrate, substrate reduction therapy

Changing the face of cyber warfare with international cyber defense collaboration

CSIR Research Space (South Africa)

Grobler, M

2011-03-01

Full Text Available . The result is that many countries are not properly prepared, nor adequately protected by legislation, in the event of a cyber attack on a national level. This article will address the international cyber defense collaboration problem by looking at the impact...

International funding opportunities for ideas of collaboration projects in OOHP

Directory of Open Access Journals (Sweden)

Ilin, Corina

2012-04-01

Full Text Available The present paper is presenting the exploratory workshop organized by the OOHP Master team in December 2011, which opened paths for theoretical knowledge and for collaboration with researchers having international prestige. Also, the paper presents funding opportunities available in national grants, and the strategy chosen by the team to prepare a two-step access to funds.

International Combined Orthopaedic Research Societies: A model for international collaboration to promote orthopaedic and musculoskeletal research

Directory of Open Access Journals (Sweden)

Theodore Miclau

2014-10-01

Full Text Available In October 2013, the International Combined Orthopaedic Research Societies (ICORS; http://i-cors.org was founded with inaugural member organisations from the previous Combined Orthopaedic Research Society, which had sponsored combined meetings for more than 2 decades. The ICORS is dedicated to the stimulation of orthopaedic and musculoskeletal research in fields such as biomedical engineering, biology, chemistry, and veterinary and human clinical research. The ICORS seeks to facilitate communication with member organisations to enhance international research collaborations and to promote the development of new international orthopaedic and musculoskeletal research organisations. Through new categories of membership, the ICORS represents the broadest coalition of orthopaedic research organisations globally.

Spotlight on taliglucerase alfa in the treatment of pediatric patients with type 1 Gaucher disease

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Gupta P

2017-06-01

Full Text Available Punita Gupta,1 Gregory M Pastores2 1Division of Genetics, Department of Pediatrics, St. Joseph’s Children’s Hospital, Paterson, New Jersey, USA; 2National Center for Inherited Metabolic Disorders, Mater Misericordiae University Hospital, University College Dublin, Dublin, Ireland Abstract: Gaucher disease (GD is a heritable storage disorder caused by functional defects of the lysosomal acid β-glucosidase and the accumulation of glucosylceramide within macrophages, resulting in multiple organ dysfunction. There are three commercially available enzyme replacement therapy (ERT products for the treatment of GD type 1 (GD1: imiglucerase, velaglucerase alfa, and taliglucerase alfa. Imiglucerase and velaglucerase alfa are produced in different mammalian cell systems; imiglucerase requires postproduction deglycosylation to expose terminal α-mannose residues, which are required for mannose receptor-mediated uptake by target macrophages. These steps are critical to the success of ERT for the treatment of visceral and hematologic manifestations of GD. Taliglucerase alfa is the first US Food and Drug Administration-approved plant-cell-expressed recombinant human protein, using carrot root cell cultures. Furthermore, it does not require postproduction glycosidic modifications. It is indicated for treatment of adults with GD1 in the US, Israel, Australia, Canada, Chile, Brazil, and other countries, and it is additionally approved for the treatment of pediatric patients in the US, Australia, and Canada and for the treatment of hematologic manifestations in pediatric patients with Type 3 GD in Canada and other countries. Our review focuses on the role of taliglucerase alfa in the pediatric population. A literature search through PubMed (from 1995 up till November 2016 of English language articles was performed with the following terms: Gaucher disease, lysosomal storage disease, taliglucerase. Secondary and tertiary references were obtained by reviewing

New Directions in Gaucher Disease.

Science.gov (United States)

Horowitz, Mia; Elstein, Deborah; Zimran, Ari; Goker-Alpan, Ozlem

2016-11-01

In Gaucher disease (GD), mutant lysosomal acid β-glucocerebrosidase fails to properly hydrolyze its substrate, glucosylceramide, which accumulates in the lysosomes. Due to its phenotypic heterogeneity, GD has been classified into type 1, non-neuronopathic, and types 2 and 3, the neuronopathic forms, based on the primary involvement of the central nervous system. Neuroinflammation and necroptotic death may appear in the neuronopathic forms of GD, whereas type 1 GD patients may develop Parkinson disease (PD), a prototype of protein misfolding disorders of the nervous system. PD is significantly more prevalent among GD carriers and patients than among the non-GD populations. It is apparent that the amount of mutant enzyme present in lysosomes depends on the amount of mutant enzyme recognized as correctly folded in the endoplasmic reticulum (ER) for physiologically correct transport through the Golgi apparatus to the lysosome. Mutant enzyme recognized as misfolded is retained in the ER, inducing the Unfolded Protein Response. In the current review, we present three discrete areas of interest: molecular and cellular mechanisms underlying the association between GD and PD; the clinical and genetic associations between GD and PD; and treatment options for GD. We also discuss the relevance of induced pleuripotent stem cells to the above associations. © 2016 WILEY PERIODICALS, INC.

Supply chain process collaboration and Internet utilization: an international perspective of business to business relationships

Directory of Open Access Journals (Sweden)

Marcos Paulo Valadares de Oliveira

2015-01-01

Full Text Available This paper compiles the findings of an international study which primary objective was to investigate the relationships between Internet utilization in business-to-business relationships, collaborative efforts and their impact over supplier and customer-oriented processes performance. It highlights the Internet as an important enhancer of collaboration in supply chains and addresses the effects of such efforts on companies’ overall performance. As a conclusive-descriptive and quantitative study, data from a survey of 788 companies from the USA, China, Canada, United Kingdom, and Brazil were analyzed with the use of descriptive statistics, reliability evaluation of the research model’s internal scales, path analysis and structural equation modeling to evaluate supply chain processes collaboration, both up- and down-stream. Internet utilization in supplier and customer-oriented processes was found positively related to collaborative practices in business-to-business relationships. Collaborative practices in supplier and customer-oriented processes, in turn, showed potential effects on performance. Also, supplier-oriented processes performance was found positively associated with customer-oriented process performance. Both internet use and collaborative practices are even more important in a high-context country like Brazil. The paper helps clarify the impact of internet use on business-to-business collaborative relationships. In this sense, practitioners can take this impact to redraw the organizational landscape and business processes amongst supply chain participants.

Social Network Analysis of 50 Years of International Collaboration in the Research of Educational Technology

Science.gov (United States)

Guo, Shesen; Zhang, Ganzhou; Guo, Yufei

2016-01-01

The definition of the field of educational technology has evolved over 50 years. New inventions and economic globalization increasingly facilitate people's communication for exchange of ideas and collaboration. This work attempts to describe international research collaboration in educational technology for the past 50 years. This article intends…

International collaboration on used fuel disposition crystalline rocks

Energy Technology Data Exchange (ETDEWEB)

Wang, Yifeng [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Gardner, Payton [Univ. of Montana, Missoula, MT (United States); Kim, Geon-Young [Korean Atomic Energy Research Inst. Daejeon (Korea); Ji, Sung-Hoon [Korean Atomic Energy Research Inst., Daejeon (Korea)

2016-08-01

Active participation in international R&D is crucial for achieving the UFD long-term goals of conducting “experiments to fill data needs and confirm advanced modeling approaches” (by 2015) and of having a “robust modeling and experimental basis for evaluation of multiple disposal system options” (by 2020). DOE’s Office of Nuclear Energy (NE) and its Office of Used Fuel Disposition Research and Development (UFD) have developed a strategic plan to advance cooperation with international partners. The international collaboration on the evaluation of crystalline disposal media at Sandia National Laboratories (SNL) in FY16 focused on the following four activities: (1) thermal-hydrologic-mechanical-chemical modeling single fracture evolution; (2) simulations of flow and transport in Bedrichov Tunnel, Czech Republic, (3) completion of streaming potential testing at Korean Atomic Energy Research Institute (KAERI), and (4) technical data exchange with KAERI on thermal-hydrologic-mechanical (THM) properties and specifications of bentonite buffer materials. The first two activities are part of the Development of Coupled Models and their Validation against Experiments (DECOVALEX-2015) project.

In the Wake of Japan’s Triple Disaster: Rebuilding Capacity through International Collaboration

Directory of Open Access Journals (Sweden)

Eric Anthony Des Marais

2012-08-01

Full Text Available Natural disasters occur when the destructive forces of natural events, such as earthquakes, flood, and volcanoes, overwhelm the capacities of communities. In the winter of 2011, Japan, a model for disaster-preparedness, was shaken by one of the largest earthquakes on record, a ten-story tsunami, and a nuclear emergency on par with Chernobyl. In the acute stages of the disaster, the Japanese government officially asked for help from a number of countries. During this time period, international collaboration played a key role in providing help to survivors in the form of medical assistance, food aid, and psychosocial support. As provision of aid evolved into capacity building, national and local Japanese government agencies, in partnership with local grassroots non-profits, assumed most responsibilities, and international organizations transitioned into new roles. This paper will present a study of the collaboration facilitated by a global non-profit humanitarian organization between international faculty and local partners in Japan.

Plasma level of the macrophage-derived soluble CD163 is increased and positively correlates with severity in Gaucher's disease

DEFF Research Database (Denmark)

Møller, Holger Jon; de Fost, Maaike; Aerts, Hans

2004-01-01

Recently, soluble CD163 (sCD163) has been identified as a macrophage/monocyte-specific plasma protein and increased concentrations have been measured in patients with infection and myeloid leukaemia. In the present study we investigated the levels of sCD163 in patients with Gaucher's disease...

Role of pH in determining the cell-type-specific residual activity of glucocerebrosidase in type 1 Gaucher disease

NARCIS (Netherlands)

van Weely, S.; van den Berg, M.; Barranger, J. A.; Sa Miranda, M. C.; Tager, J. M.; Aerts, J. M.

1993-01-01

The properties of control and 370Asn-->Ser glucocerebrosidase, the frequently encountered mutated form of the enzyme in type 1 Gaucher disease, were studied in vitro as well as in situ. The catalytic properties of purified 370Asn-->Ser glucocerebrosidase were highly dependent on the assay

Organizational approaches to collaboration in vocational rehabilitation − An international literature review

Directory of Open Access Journals (Sweden)

Johanna Andersson

2011-11-01

Full Text Available Introduction: Collaboration between welfare organizations is an important strategy for integrating different health and welfare services. This article reports a review of the international literature on vocational rehabilitation, focusing on different organizational models of collaboration as well as different barriers and facilitating factors. Methods: The review was based on an extensive search in scientific journals from 1995 to 2010, which generated more than 13 000 articles. The number of articles was reduced in different steps through a group procedure based on the abstracts. Finally, 205 articles were read in full text and 62 were included for content analysis. Results: Seven basic models of collaboration were identified in the literature. They had different degrees of complexity, intensity and formalization. They could also be combined in different ways.  Several barriers and facilitators of collaboration were also identified. Most of these were related to factors as communication, trust and commitment.Conclusion: There is no optimal model of collaboration to be applied everywhere, but one model could be more appropriate than others in a certain context. More research is needed to compare different models and to see whether they are applicable also in other fields of collaboration inside or outside the welfare system.

Organizational approaches to collaboration in vocational rehabilitation − An international literature review

Directory of Open Access Journals (Sweden)

Johanna Andersson

2011-11-01

Full Text Available Introduction: Collaboration between welfare organizations is an important strategy for integrating different health and welfare services. This article reports a review of the international literature on vocational rehabilitation, focusing on different organizational models of collaboration as well as different barriers and facilitating factors.  Methods: The review was based on an extensive search in scientific journals from 1995 to 2010, which generated more than 13 000 articles. The number of articles was reduced in different steps through a group procedure based on the abstracts. Finally, 205 articles were read in full text and 62 were included for content analysis. Results: Seven basic models of collaboration were identified in the literature. They had different degrees of complexity, intensity and formalization. They could also be combined in different ways.  Several barriers and facilitators of collaboration were also identified. Most of these were related to factors as communication, trust and commitment. Conclusion: There is no optimal model of collaboration to be applied everywhere, but one model could be more appropriate than others in a certain context. More research is needed to compare different models and to see whether they are applicable also in other fields of collaboration inside or outside the welfare system.

Magnetic resonance imaging of bone marrow changes in Gaucher disease during enzyme replacement therapy: first German long-term results

International Nuclear Information System (INIS)

Poll, L.W.; Koch, J.A.; Scherer, A.; Boerner, D.; Moedder, U.; Dahl, S. vom; Niederau, C.; Haeussinger, D.; Willers, R.

2001-01-01

Objective:. Since 1991, enzyme replacement therapy (ERT) has been available for patients with Gaucher disease in Germany. The aim of this study was to analyse the MR pattern of bone marrow involvement and response to ERT in Gaucher disease type I. Patients and design:. Thirty patients with Gaucher disease type I had MRI examinations prior to initiation of ERT with alglucerase/imiglucerase and during follow-up. Median MR follow-up and duration of ERT were 36 months. Coronal T1- and T2-weighted spin-echo images of the lower extremities were obtained to evaluate changes in the appearance of yellow marrow. MR images were categorized as having either a homogeneous (type A) or non-homogeneous patchy (type B) appearance of bone involvement and response to ERT was assessed by two radiologists. Results:. Overall, 19 of 30 patients (63%) showed an increased signal intensity on T1- and T2-weighted images after 36 months of ERT, consistent with partial reconversion of fatty marrow during treatment. Focal bone lesions surrounded by a low signal intensity (SI) rim did not respond to ERT, suggesting bone infarcts. Of the 11 patients with bone infarcts (low SI rim lesion), 82% had the non-homogeneous type B pattern (P=0.0021). In 86% of patients with splenectomy, bone infarcts were seen (P<0.05). Conclusions:. MRI using T1- and T2-weighted spin-echo sequences is a valuable, non-invasive method for monitoring bone marrow response in patients receiving ERT. A non- homogeneous patchy signal intensity of bone marrow involvement correlates with the presence of bone infarcts (P=0.0021). (orig.)

Magnetic resonance imaging of bone marrow changes in Gaucher disease during enzyme replacement therapy: first German long-term results

Energy Technology Data Exchange (ETDEWEB)

Poll, L.W.; Koch, J.A.; Scherer, A.; Boerner, D.; Moedder, U. [Duesseldorf Univ. (Germany). Inst. fuer Diagnostische Radiologie; Dahl, S. vom; Niederau, C.; Haeussinger, D. [Duesseldorf Univ. (Germany). Medizinische Fakultaet; Willers, R. [Duesseldorf Univ. (Germany). Rechenzentrum

2001-09-01

Objective:. Since 1991, enzyme replacement therapy (ERT) has been available for patients with Gaucher disease in Germany. The aim of this study was to analyse the MR pattern of bone marrow involvement and response to ERT in Gaucher disease type I. Patients and design:. Thirty patients with Gaucher disease type I had MRI examinations prior to initiation of ERT with alglucerase/imiglucerase and during follow-up. Median MR follow-up and duration of ERT were 36 months. Coronal T1- and T2-weighted spin-echo images of the lower extremities were obtained to evaluate changes in the appearance of yellow marrow. MR images were categorized as having either a homogeneous (type A) or non-homogeneous patchy (type B) appearance of bone involvement and response to ERT was assessed by two radiologists. Results:. Overall, 19 of 30 patients (63%) showed an increased signal intensity on T1- and T2-weighted images after 36 months of ERT, consistent with partial reconversion of fatty marrow during treatment. Focal bone lesions surrounded by a low signal intensity (SI) rim did not respond to ERT, suggesting bone infarcts. Of the 11 patients with bone infarcts (low SI rim lesion), 82% had the non-homogeneous type B pattern (P=0.0021). In 86% of patients with splenectomy, bone infarcts were seen (P<0.05). Conclusions:. MRI using T1- and T2-weighted spin-echo sequences is a valuable, non-invasive method for monitoring bone marrow response in patients receiving ERT. A non- homogeneous patchy signal intensity of bone marrow involvement correlates with the presence of bone infarcts (P=0.0021). (orig.)

International collaboration including patients is essential to develop new therapies for patients with myositis.

Science.gov (United States)

Lundberg, Ingrid E; Vencovsky, Jiri

2017-05-01

To discuss the needs for international collaborations between investigators in different disciplines working with myositis and with patients with myositis. Recent advances in detection of several myositis-specific autoantibodies that are associated with distinct clinical phenotypes, will enable studies in new well defined clinically homogenous subgroups of myositis This is likely to lead to development of new information on molecular pathogenesis that might be different in different myositis subgroups. Subgrouping patients according to autoantibody profile may also be important to assess outcome, to identify prognostic biomarkers and in clinical trials. As these are rare disorders international collaboration is essential to enrol large enough cohorts of the subgroups. To facilitate such collaboration we have developed a web-based international myositis register, www.euromyositis.eu, which includes validated outcome measures and patient reported outcome measures. This register is to support research but also to support decision-making in the clinic. We welcome investigators to join the Euromyositis register. Myositis is a heterogeneous disorder with varying treatment response and outcome. There is a high unmet need for new therapies which can only be achieved by increased knowledge on molecular disease mechanisms. Subgrouping patients according to autoantibody profile may be a new way forward to get a better understanding on disease mechanisms and to develop novel therapies.

A Complexity Approach to Evaluating National Scientific Systems through International Scientific Collaborations

Science.gov (United States)

Zelnio, Ryan J.

2013-01-01

This dissertation seeks to contribute to a fuller understanding of how international scientific collaboration has affected national scientific systems. It does this by developing three methodological approaches grounded in social complexity theory and applying them to the evaluation of national scientific systems. The first methodology identifies…

Scintigraphic and magnetic resonance studies in a patient with Gaucher's disease

International Nuclear Information System (INIS)

Zanzi, I.; Taylor, S.; Gould, E.; Allen, S.L.; Kroop, S.; Asnis, S.; Margouleff, D.

1988-01-01

In-111 chloride imaging was used in the evaluation of a patient with Type I Gaucher's disease before splenectomy for pancytopenia. This case is the first report of its use in this clinical setting. The image demonstrated the presence of adequate marrow reserve, thereby suggesting that the pancytopenia was due to hypersplenism rather than marrow replacement. Normalization of blood counts after splenectomy confirmed this interpretation. Eight months later, the patient had acute pain in the left knee. Bone imaging suggested a left lateral tibial plateau fracture that was not seen on plain radiographs or magnetic resonance imaging, but was confirmed by x-ray tomography. The significance and implications of these findings are discussed

ELENA’s International Collaboration is born

CERN Multimedia

Antonella Del Rosso

2012-01-01

On 13 June, ten institutes signed a Memorandum of Understanding (MoU) for the construction of the Extra Low ENergy Antiproton ring (ELENA). Allowing the further deceleration of antiprotons from the Antimatter Decelerator, ELENA will significantly increase the number of particles trapped downstream in the experimental set-ups. This will give an important boost to antimatter research in the years to come.   Electrostatic triplet lenses - a device that will transport antiprotons from ELENA to the experiments. The electrostatic device was successfully tested with the ASACUSA experiment two weeks ago. ELENA - an upgrade of the existing Antiproton Decelerator (AD) - was approved by the CERN Council last year under the condition that external user institutions would contribute to its construction. On 13 June, the foundation stone of the new international collaboration was laid with the signature of the MoU. ELENA is a small magnetic decelerator ring 30 m in circumference that will fit inside the ...

Proinflammatory and proosteoclastogenic potential of peripheral blood mononuclear cells from Gaucher patients: Implication for bone pathology.

Science.gov (United States)

Mucci, J M; Cuello, M F; Kisinovsky, I; Larroude, M; Delpino, M V; Rozenfeld, P A

2015-08-01

Gaucher disease (GD) is caused by mutations in the GBA gene that confer a deficient level of activity of glucocerebrosidase (GCase). This deficiency leads to the accumulation of the glycolipid glucocerebroside in the lysosomes of cells of monocyte/macrophage system. Bone compromise in Gaucher disease patients is the most disabling aspect of the disease. However, pathophysiological aspects of skeletal alterations are still poorly understood. On the other hand it is well known that inflammation is a key player in GD pathology. In this work, we revealed increased levels of the proinflammatory CD14(+)CD16(+) monocyte subset and increased inflammatory cytokine production by monocytes and T cells in the circulation of GD patients. We showed increased levels of osteoclast precursors in PBMC from patients and a higher expression of RANKL in the surface of T cells. PBMC from patients presented higher osteoclast differentiation compared to healthy controls when cultured in the presence of M-CSF alone or in combination with RANKL. In vitro treatment with Velaglucerase reduced osteoclast levels to control levels. On the other hand THP-1 derived osteoclast precursors cultured in the presence of conditioned media from PBMC of GD patients presented higher differentiation to active osteoclasts. This induction involved TNF-α and RANKL. Copyright © 2015 Elsevier Inc. All rights reserved.

MR imaging in adults with Gaucher disease type I: evulation of marrow involvement and disease activity

Energy Technology Data Exchange (ETDEWEB)

Hermann, G. (Dept. of Radiology, Mount Sinai Medical Center, City Univ. of New York, NY (United States)); Shaprio, R.S. (Dept. of Radiology, Mount Sinai Medical Center, City Univ. of New York, NY (United States)); Abdelwahab, I.F. (Dept. of Radiology, Mount Sinai Medical Center, City Univ. of New York, NY (United States)); Grabowski, G. (Dept. of Pediatrics, Mount Sinai Medical Center, City Univ. of New York, NY (United States))

1993-05-01

An investigation was conducted to determine the usefulness of magnetic resonance imaging (MRI) in the evaluation of bone marrow involvement in patients with Gaucher disease type I. T1- and T2-weighted images were obtained of the lower extremities of 29 adult patients. Patients were classified into one of three groups based on marrow signal patterns on T1- and T2-weighted images as well as change in signal intensity from T1- to T2-weighted images. An increase in signal intensity from T1- to T2-weighted images was the criterion for an 'active process' within the bone marrow. Classification of the 29 patients produced the following results: Group A: Normal, 4 patients; group B: Marrow infiltration, 16 patients; group C: Marrow infiltration plus active marrow process, 9 patients. Correlation with clinical findings revealed that all nine patients with evidence of an active marrow process on MRI (group C) had acute bone pain. Conversely, only one of the remaining 20 patients (groups A and B) had bone pain. There was no correlation between disease activity and findings on conventional radiographs. We conclude the MRI provides an excellent noninvasive assessment of the extent and activity of marrow involvement in type I Gaucher disease. (orig.)

MR imaging in adults with Gaucher disease type I: evulation of marrow involvement and disease activity

International Nuclear Information System (INIS)

Hermann, G.; Shaprio, R.S.; Abdelwahab, I.F.; Grabowski, G.

1993-01-01

An investigation was conducted to determine the usefulness of magnetic resonance imaging (MRI) in the evaluation of bone marrow involvement in patients with Gaucher disease type I. T1- and T2-weighted images were obtained of the lower extremities of 29 adult patients. Patients were classified into one of three groups based on marrow signal patterns on T1- and T2-weighted images as well as change in signal intensity from T1- to T2-weighted images. An increase in signal intensity from T1- to T2-weighted images was the criterion for an 'active process' within the bone marrow. Classification of the 29 patients produced the following results: Group A: Normal, 4 patients; group B: Marrow infiltration, 16 patients; group C: Marrow infiltration plus active marrow process, 9 patients. Correlation with clinical findings revealed that all nine patients with evidence of an active marrow process on MRI (group C) had acute bone pain. Conversely, only one of the remaining 20 patients (groups A and B) had bone pain. There was no correlation between disease activity and findings on conventional radiographs. We conclude the MRI provides an excellent noninvasive assessment of the extent and activity of marrow involvement in type I Gaucher disease. (orig.)

Collaborative innovation: Internal and external involvement in new product development

DEFF Research Database (Denmark)

Timenes Laugen, Bjørge; Lassen, Astrid Heidemann

2011-01-01

Industry and academia alike are increasingly becoming aware of the fact that innovation does not take place in isolated cells or functions within the firm. During the last the years the term open innovation has emphasized the importance of internal and external collaboration in order to increase...... strategic priorities influence the degree of external and internal involvement in the NPD process, moderated by contextual factors. Results based on analyses of 584 companies from the International Manufacturing Strategy Survey (IMSS) 2005 indicate that suppliers are heavily involved in the NPD process...... in firms in B2C markets aiming at increasing the innovation volume. For B2B companies the reverse picture emerges. However, when the aim is to increase the radicality of new products, suppliers and customers are heavily involved for firms in B2B markets. Further, market uncertainty, and to some extent...

International collaboration and comparative research on ocean top predators under CLIOTOP

Science.gov (United States)

Hobday, Alistair J.; Arrizabalaga, Haritz; Evans, Karen; Scales, Kylie L.; Senina, Inna; Weng, Kevin C.

2017-06-01

Oceanic top predators have ecological, social and economic value of global significance. These wide-ranging marine species, which include sharks, tunas and billfishes, marine mammals, turtles and seabirds, are the focus of international research attention under the Climate Impacts on Oceanic Top Predators (CLIOTOP) science programme, one of the Integrated Marine Biosphere Research (IMBeR) projects. Over more than a decade, research conducted under CLIOTOP has involved scientists from more than 30 countries, with international collaboration increasing markedly over time, and comparative analyses resulting in new knowledge and understanding of oceanic top predators. This special issue presents 27 papers arising from the 3rd CLIOTOP symposium, held in San Sebastián, Spain in September 2015, spanning topics such as conservation biology, trophic ecology, fisheries science, climate change, and adaptive management. The maturation and synthesis of CLIOTOP's collaborative research is now resulting in real-world management applications and improving understanding of potential ecological and socio-economic impacts of climate change in oceanic systems. The ultimate CLIOTOP goal of preparing both climate-sensitive predator populations and the human societies dependent on them for the impending impacts of climate change is now within reach.

The identification of type 1 Gaucher disease patients, asymptomatic cases and carriers in The Netherlands using urine samples: an evaluation

NARCIS (Netherlands)

Aerts, J. M.; Sa Miranda, M. C.; Wanzeller de Lacerda, L.; van Weely, S.; Donker-Koopman, W.; Brouwer-Kelder, B.; Jansen, D. C.; van Leeuwen, M.; Schram, A. W.; Tsiapara, A.

1991-01-01

The feasibility of using urine samples for the identification of patients with Gaucher disease and carriers has been investigated. It was found that the pH of a urine sample should be pH 6.0 or lower to ensure stability of lysosomal hydrolases. Two parameters of glucocerebrosidase, which is

International energy technology collaboration and climate change mitigation. Case study 2. Cooperation in Agriculture. R and D on High-Yielding Crop Varieties

Energy Technology Data Exchange (ETDEWEB)

Gagnon-Lebrun, F. [Global and Structural Policies Division, Organisation for Economic Co-operation and Development OECD, Paris (France)

2004-07-01

Mitigating climate change and achieving stabilisation of greenhouse gas atmospheric concentrations will require deep reductions in global emissions of energy-related carbon dioxide emissions. Developing and disseminating new, low-carbon energy technology will thus be needed. Two previous AIXG papers have focused on possible drivers for such a profound technological change: Technology Innovation, Development and Diffusion, released in June 2003, and International Energy Technology Collaboration and Climate Change Mitigation, released in June 2004. The first of these papers assesses a broad range of technical options for reducing energy-related CO2 emissions. It examines how technologies evolve and the role of research and development efforts, alternative policies, and short-term investment decisions in making long-term options available. It considers various policy tools that may induce technological change, some very specific, and others with broader expected effects. Its overall conclusion is that policies specifically designed to promote technical change, or 'technology push', could play a critical role in making available and affordable new energy technologies. However, such policies would not be sufficient to achieve the Convention's objective in the absence of broader policies. First, because there is a large potential for cuts that could be achieved in the short run with existing technologies; and second, the development of new technologies requires a market pull as much as a technology push. The second paper considers the potential advantages and disadvantages of international energy technology collaboration and transfer for promoting technological change. Advantages of collaboration may consist of lowering R and D costs and stimulating other countries to invest in R and D; disadvantage may include free-riding and the inefficiency of reaching agreement between many actors. This paper sets the context for further discussion on the role of

Technological learning through international collaboration: Lessons from the field

Science.gov (United States)

Wood, Danielle; Weigel, Annalisa

2013-02-01

Countries on every continent are making new or renewed commitments to domestic satellite programs. These programs have the potential to address national needs by enhancing access to information, improving infrastructure and providing inspiration to the public. How do countries without local expertise in space technology begin a new satellite program? What is the role of international collaboration in supporting the efforts of a new space fairing country? This paper explores such questions by highlighting outputs from intensive field work in Africa and Asia. Specifically, the study explores case studies of early space activity in these countries to search for lessons about the management of a young space program. The observations from field work are compared to ideas from scholarly literature on technological learning. The findings are organized using principles from systems architecture. The paper presents a model that captures many of the influences and strategic decision areas for a collaborative satellite development project. The paper also highlights the growth of capability among African countries in the area of satellite technology.

The ANTOSTRAT legacy: Science collaboration and international transparency in potential marine mineral resource exploitation of Antarctica

Science.gov (United States)

Cooper, Alan; Barker, Peter; Barrett, Peter; Behrendt, John; Brancolini, Giuliano; Childs, Jonathan R.; Escutia, Carlota; Jokat, Wilfried; Kristoffersen, Yngve; Leitchenkov, German; Stagg, Howard; Tanahashi, Manabu; Wardell, Nigel; Webb, Peter

2009-01-01

The Antarctic Offshore Stratigraphy project (ANTOSTRAT; 1989–2002) was an extremely successful collaboration in international marine geological science that also lifted the perceived “veil of secrecy” from studies of potential exploitation of Antarctic marine mineral resources. The project laid the groundwork for circum-Antarctic seismic, drilling, and rock coring programs designed to decipher Antarctica’s tectonic, stratigraphic, and climate histories. In 2002, ANTOSTRAT evolved into the equally successful and currently active Antarctic Climate Evolution research program. The need for, and evolution of, ANTOSTRAT was based on two simple tenets within SCAR and the Antarctic Treaty: international science collaboration and open access to data. The ANTOSTRAT project may be a helpful analog for other regions of strong international science and geopolitical interests, such as the Arctic. This is the ANTOSTRAT story.

Improving Collaborative Planning and Reflection Practices at International Baccalaureate Diploma Schools in Amman

Science.gov (United States)

Saa'd AlDin, Kawther

2014-01-01

In 2010, the International Baccalaureate (IB) Organization mandated that all its schools, including Diploma (DP) schools, adhere to the collaborative planning and reflection requirements, which emphasized the importance of integrating its theory of knowledge (TOK) core component into all disciplines. Many schools officials and educations in Amman…

Disposal R&D in the Used Fuel Disposition Campaign: A Discussion of Opportunities for Active International Collaboration

Energy Technology Data Exchange (ETDEWEB)

Birkholzer, J.T.

2011-06-01

For DOE's Used Fuel Disposition Campaign (UFDC), international collaboration is a beneficial and cost-effective strategy for advancing disposal science with regards to multiple disposal options and different geologic environments. While the United States disposal program focused solely on Yucca Mountain tuff as host rock over the past decades, several international programs have made significant progress in the characterization and performance evaluation of other geologic repository options, most of which are very different from the Yucca Mountain site in design and host rock characteristics. Because Yucca Mountain was so unique (e.g., no backfill, unsaturated densely fractured tuff), areas of direct collaboration with international disposal programs were quite limited during that time. The decision by the U.S. Department of Energy to no longer pursue the disposal of high-level radioactive waste and spent fuel at Yucca Mountain has shifted UFDC's interest to disposal options and geologic environments similar to those being investigated by disposal programs in other nations. Much can be gained by close collaboration with these programs, including access to valuable experience and data collected over recent decades. Such collaboration can help to efficiently achieve UFDC's long-term goals of conducting 'experiments to fill data needs and confirm advanced modeling approaches' (by 2015) and of having a 'robust modeling and experimental basis for evaluation of multiple disposal system options' (by 2020). This report discusses selected opportunities of active international collaboration, with focus on both Natural Barrier System (NBS) and Engineered Barrier System (EBS) aspects and those opportunities that provide access to field data (and respective interpretation/modeling) or allow participation in ongoing field experiments. This discussion serves as a basis for the DOE/NE-53 and UFDC planning process for FY12 and beyond.

Collaboration under the International Partnership for the Hydrogen Economy (IPHE) and the Carbon Sequestration Leadership Forum (CSLF)

Energy Technology Data Exchange (ETDEWEB)

Neff, H.J. [Forschungszentrum Juelich (Germany)

2005-06-01

The objectives and achievements of the International Partnership for the Hydrogen Economy (IPHE) and the Carbon Sequestration Leadership Forum (CSLF) will be described. Both are agreements between governments and aim at identifying and promoting potential areas of bilateral and multilateral collaboration on new and advanced energy technologies. The IPHE has analysed priorities for international collaboration in research, development, demonstration and utilisation of hydrogen equipment in five areas: hydrogen production, fuel cells, hydrogen storage, codes and standards, socio-economic research. A report on such options is available and a series of IPHE conferences and workshops will pave the way to concrete collaboration projects. The CSLF is focused on development of improved cost-effective technologies for the cost-efficient capture and safe, long-term storage of carbon dioxide (CO{sub 2}) for fossil power plants. The mission of the CSLF is to facilitate the development and deployment of such technologies via collaborative efforts that address key technical issues, as well as economic, and environmental challenges. The CSLF also promotes awareness and champion legal, regulatory, financial, and institutional environments conducive to such technologies. The CSLF has worked out a Technology Roadmap as a guide for the CSLF and its Members that describes possible routes to future CO2 capture, transport and storage needs. Included are modules on the current status of these technologies, ongoing activities in CO{sub 2} capture, transport and storage, and identification of technology gaps and non-technology needs that should be addressed over the next decade. The Technology Roadmap indicates areas where the CSLF can add value through international collaborative effort. Both, hydrogen technologies and CO2 sequestration, are closely connected and will serve an overall strategic framework with clean fossil fuels as a key element of a sustainable energy portfolio

WDS/DSA Certification - International collaboration for a trustworthy research data infrastructure

Science.gov (United States)

Mokrane, Mustapha; Hugo, Wim; Harrison, Sandy

2016-04-01

Today's research is international, transdisciplinary, and data-enabled, which requires scrupulous data stewardship, full and open access to data, and efficient collaboration and coordination. New expectations on researchers based on policies from governments and funders to share data fully, openly, and in a timely manner present significant challenges but are also opportunities to improve the quality and efficiency of research and its accountability to society. Researchers should be able to archive and disseminate data as required by many institutions or funders, and civil society to scrutinize datasets underlying public policies. Thus, the trustworthiness of data services must be verifiable. In addition, the need to integrate large and complex datasets across disciplines and domains with variable levels of maturity calls for greater coordination to achieve sufficient interoperability and sustainability. The World Data System (WDS) of the International Council for Science (ICSU) promotes long-term stewardship of, and universal and equitable access to, quality-assured scientific data and services across a range of disciplines in the natural and social sciences. WDS aims at coordinating and supporting trusted scientific data services for the provision, use, and preservation of relevant datasets to facilitate scientific research, in particular under the ICSU umbrella, while strengthening their links with the research community. WDS certifies its Members, holders and providers of data or data products, using internationally recognized standards. Certification of scientific data services is essential to ensure trustworthiness of the global research data infrastructure. It contributes to building a searchable, distributed, interoperable and sustainable research data infrastructure. Several certification standards have been developed over the last decade, such as the Network of Expertise in long-term Storage and Accessibility of Digital Resources in Germany (NESTOR) seal

The outcome of clinical parameters in adults with severe Type I Gaucher disease using very low dose enzyme replacement therapy.

Science.gov (United States)

Wilson, Callum; Spearing, Ruth; Teague, Lochie; Robertson, Patsy; Blacklock, Hilary

2007-01-01

Enzyme replacement therapy is now well established as the treatment of choice in Type I Gaucher disease. Historically higher dosage regimens have been used in preference to lower doses despite the little clinical evidence in the way of large controlled clinical trials to support this. Moreover, the extraordinary cost of therapy means that not all eligible patients are able to be treated at the higher dose. Twelve type I adult patients with relatively severe disease were commenced on a very low dose of 7.5U of alglucerase/imiglucerase per kg every two weeks (initially given thrice weekly and later weekly). Follow-up 5 year data reveal a good visceral and haematological response with outcomes consistent with recently published treatment guidelines. Satisfactory clinical and radiological skeletal improvement was also demonstrated in most patients. Three patients had an inadequate overall skeletal response to therapy. Biomarkers also steadily improved although perhaps not quite at the same rate as that seen in higher doses. Very low dose enzyme replacement therapy may be appropriate for adult type I Gaucher patients with mild-moderate skeletal disease.

Gaucher's disease. Plain radiography, US, CT and MR diagnosis of lungs, bone and liver lesions

Energy Technology Data Exchange (ETDEWEB)

Hainaux, B.; Christophe, C.; Hanquinet, S.; Perlmutter, N. (Free Univ. of Brussels (Belgium). Dept. of Pediatric Radiology)

1992-04-01

We report our observations made by conventional radiography, ultrasound, computerized tomography (CT), and magnetic resonance imaging (MRI) on a 3 1/2-year-old girl with Gaucher's disease. The interest of the case consists in the exceptional lungs involvement, the demonstration by MRI of the bone marrow involvement and the necrosis and fibrosis of the liver, as shown by CT. This liver complication has been previously reported only once. (orig.).

International collaborative study for the calibration of proposed International Standards for thromboplastin, rabbit, plain and for thromboplastin, recombinant, human, plain

DEFF Research Database (Denmark)

van den Besselaar, A M H P; Chantarangkul, V; Angeloni, F

2018-01-01

BACKGROUND: The availability of International Standards for thromboplastin is essential for the calibration of routine reagents and hence the calculation of the International Normalized Ratio (INR). Stocks of the current 4(th) International Standards are running low. Candidate replacement materia......) international standard (rTF/09). The candidate materials have been accepted by WHO as the 5(th) International Standards for thromboplastin, rabbit plain, and thromboplastin, recombinant, human, plain. This article is protected by copyright. All rights reserved.......BACKGROUND: The availability of International Standards for thromboplastin is essential for the calibration of routine reagents and hence the calculation of the International Normalized Ratio (INR). Stocks of the current 4(th) International Standards are running low. Candidate replacement materials...... have been prepared. This report describes the calibration of the proposed 5(th) International Standards for thromboplastin, rabbit, plain (coded RBT/16) and for thromboplastin, recombinant, human, plain (coded rTF/16). METHODS: An international collaborative study was carried out for the assignment...

The United Kingdom Hydrogen Association Forms with International Collaboration in Mind

International Nuclear Information System (INIS)

Karen Hall; John Carolin; Ian Williamson

2006-01-01

In April 2006, the United Kingdom Hydrogen Association was launched. This paper will describe the context under which the need was established, and address the challenges and opportunities faced in creating the association. A UK Hydrogen Association can encourage information sharing among regional hydrogen efforts, and provide a mechanism for a larger, single voice on the national level. In addition, a UK Hydrogen Association can serve as a focal point for UK participation in EU activities such as the European Hydrogen and Fuel Cell Technology Platform (HFP), and other international activities such as IPHE and IEA. The results of the stakeholder briefing and progress of a UK Hydrogen Association will be presented, with a focus on international collaboration. (authors)

NASA's Solar System Exploration Research Virtual Institute: Building Collaboration Through International Partnerships

Science.gov (United States)

Gibbs, K. E.; Schmidt, G. K.

2017-01-01

The NASA Solar System Exploration Research Virtual Institute (SSERVI) is a virtual institute focused on re-search at the intersection of science and exploration, training the next generation of lunar scientists, and community development. As part of the SSERVI mission, we act as a hub for opportunities that engage the larger scientific and exploration communities in order to form new interdisciplinary, research-focused collaborations. This talk will describe the international partner re-search efforts and how we are engaging the international science and exploration communities through workshops, conferences, online seminars and classes, student exchange programs and internships.

Review of the Strategic Plan for International Collaboration on Fusion Science and Technology Research. Fusion Energy Sciences Advisory Committee (FESAC)

International Nuclear Information System (INIS)

1998-01-01

The United States Government has employed international collaborations in magnetic fusion energy research since the program was declassified in 1958. These collaborations have been successful not only in producing high quality scientific results that have contributed to the advancement of fusion science and technology, they have also allowed us to highly leverage our funding. Thus, in the 1980s, when the funding situation made it necessary to reduce the technical breadth of the U.S. domestic program, these highly leveraged collaborations became key strategic elements of the U.S. program, allowing us to maintain some degree of technical breadth. With the recent, nearly complete declassification of inertial confinement fusion, the use of some international collaboration is expected to be introduced in the related inertial fusion energy research activities as well. The United States has been a leader in establishing and fostering collaborations that have involved scientific and technological exchanges, joint planning, and joint work at fusion facilities in the U.S. and worldwide. These collaborative efforts have proven mutually beneficial to the United States and our partners. International collaborations are a tool that allows us to meet fusion program goals in the most effective way possible. Working with highly qualified people from other countries and other cultures provides the collaborators with an opportunity to see problems from new and different perspectives, allows solutions to arise from the diversity of the participants, and promotes both collaboration and friendly competition. In short, it provides an exciting and stimulating environment resulting in a synergistic effect that is good for science and good for the people of the world.

Crop improvement in the CGIAR as a global success story of open access and international collaboration

Directory of Open Access Journals (Sweden)

Derek Byerlee

2009-12-01

Full Text Available International agricultural research has historically been an example par excellence of open source approach to biological research. Beginning in the 1950s and especially in the 1960s, a looming global food crisis led to the development of a group of international agricultural research centers with a specific mandate to foster international exchange and crop improvement relevant to many countries. This formalization of a global biological commons in genetic resources was implemented through an elaborate system of international nurseries with a breeding hub, free sharing of germplasm, collaboration in information collection, the development of human resources, and an international collaborative network. This paper traces the history of the international wheat program with particular attention to how this truly open source system operated in practice and the impacts that it had on world poverty and hunger. The paper also highlights the challenges of maintaining and evolving such a system over the long term, both in terms of financing, as well the changing ‘rules of the game’ resulting from international agreements on intellectual property rights and biodiversity. Yet the open source approach is just as relevant today, as witnessed by current crises in food prices and looming crop diseases problem of global significance.

Establishing and maintaining international collaborative research teams: an autobiographical insight

Directory of Open Access Journals (Sweden)

T J Carr

2013-07-01

Full Text Available Despite the growing impetus for international collaborative research teams (ICRT, there are relatively few resources available to guide and support researchers through the processes of establishing and maintaining ICRTs. In particular, no articles were found that provided researchers’ firsthand accounts of being a member of such a team. Having access to such personal accounts can help both experienced and novice researchers learn more directly about what to expect, as well as the benefits, challenges, pitfalls, and success strategies for establishing and maintaining ICRTs. The authors used phenomenological autobiographical reflective journaling to capture their experiences as members of ICRTs. In this article we provide an overview of key themes that emerged from the analysis of our reflections as members of ICRTs. These themes include: benefits, challenges, and strategies for success. Our aim is to share our first-hand experiences of what it is like to establish and participate in ICRT. It is not our intention to provide readers with prescriptive guidelines on how to set up and maintain ICRTs. Every ICRT is unique and some of these ideas may or may not apply in every case. Instead, we are describing what worked for us, hoping that others may benefit from our experience. Consequently, we suggest that the focus of ICRT should be on the benefits thereof which promote and encourage interaction between disciplines, transfer of knowledge and techniques and personal and professional development. Keywords: international, collaborative, research, teams, interdisciplinary

Educational Technology Research Journals: "International Journal of Computer-Supported Collaborative Learning," 2006-2014

Science.gov (United States)

Howland, Shiloh M. J.; Martin, M. Troy; Bodily, Robert; Faulconer, Christian; West, Richard E.

2015-01-01

The authors analyzed all research articles from the first issue of the "International Journal of Computer-Supported Collaborative Learning" in 2006 until the second issue of 2014. They determined the research methodologies, most frequently used author-supplied keywords as well as two- and three-word phrases, and most frequently published…

Simultaneous and Comparable Numerical Indicators of International, National and Local Collaboration Practices in English-Medium Astrophysics Research Papers

Science.gov (United States)

Méndez, David I.; Alcaraz, M. Ángeles

2016-01-01

Introduction: We report an investigation on collaboration practices in research papers published in the most prestigious English-medium astrophysics journals. Method: We propose an evaluation method based on three numerical indicators to study and compare, in absolute terms, three different types of collaboration (international, national and…

Unbalanced international collaboration affects adversely the usefulness of countries' scientific output as well as their technological and social impact.

Science.gov (United States)

Zanotto, Sonia R; Haeffner, Cristina; Guimarães, Jorge A

The unbalanced international scientific collaboration as cause of misleading information on the country's contribution to the scientific world output was analyzed. ESI Data Base (Thomson Reuters' InCites), covering the scientific production of 217 active countries in the period 2010-2014 was used. International collaboration implicates in a high percentage (33.1 %) of double-counted world articles, thus impacting qualitative data as citations, impact and impact relative to word. The countries were divided into three groups, according to their individual contribution to the world publications: Group I (24 countries, at least 1 %) representing 83.9 % of the total double-counted world articles. Group II (40 countries, 0.1-0.99 % each). Group III, 153 countries (70.5 %) with international collaboration were: Group I, 43.0 %; Group II, 55.8 % and Group III, 85.2 %. We concluded that very high and unbalanced international collaboration, as presented by many countries, misrepresent the importance of their scientific production, technological and social outputs. Furthermore, it jeopardizes qualitative outputs of the countries themselves, artificially increasing their scientific impact, affecting all fields and therefore, the whole world. The data confirm that when dealing with the qualitative contribution of countries, it is necessary to take in consideration the level of international cooperation because, as seen here, it can and in fact it does create false impression of the real contribution of countries.

Eliglustat, an investigational oral therapy for Gaucher disease type 1: Phase 2 trial results after 4 years of treatment.

Science.gov (United States)

Lukina, Elena; Watman, Nora; Dragosky, Marta; Pastores, Gregory M; Arreguin, Elsa Avila; Rosenbaum, Hanna; Zimran, Ari; Angell, Jennifer; Ross, Leorah; Puga, Ana Cristina; Peterschmitt, Judith M

2014-12-01

Eliglustat is an investigational, oral substrate reduction therapy for Gaucher disease type 1 (GD1). Nineteen treatment-naïve patients have now completed 4years of an open-label study (NCT00358150). Mean hemoglobin level and platelet count increased by 2.3±1.5g/dL (baseline: 11.3±1.5g/dL) and 95% (baseline: 68,700±21,200/mm(3)), respectively. Mean spleen and liver volumes (multiples of normal, MN) decreased by 63% (baseline: 17.3±9.5 MN) and 28% (baseline: 1.7±0.4 MN), respectively. Median chitotriosidase and CCL-18 each decreased by 82%; plasma glucosylceramide and GM3 normalized. Mean bone mineral density T-score for the lumbar spine increased by 0.8 (60%) (baseline: -1.6±1.1). Femur dark marrow, a reflection of Gaucher cell infiltration into bone marrow, was reduced or stable in 17/18 patients. There were no bone crises. Most adverse events were mild and unrelated to treatment. These results extend the safety and efficacy of eliglustat reported at 1 and 2 years to 4 years. Copyright © 2014. Published by Elsevier Inc.

Imiglucerase in the treatment of Gaucher disease: a history and perspective

Directory of Open Access Journals (Sweden)

Deegan PB

2012-04-01

Full Text Available Patrick B Deegan, Timothy M CoxDepartment of Medicine, University of Cambridge, Lysosomal Disorders Unit, Addenbrooke's NHS Foundation Hospitals Trust, Cambridge, UKAbstract: The scientific and therapeutic development of imiglucerase (Cerezyme® by the Genzyme Corporation is a paradigm case for a critical examination of current trends in biotechnology. In this article the authors argue that contemporary interest in treatments for rare diseases by major pharmaceutical companies stems in large part from an exception among rarities: the astonishing commercial success of Cerezyme. The fortunes of the Genzyme Corporation, latterly acquired by global giant Sanofi SA, were founded on the evolution of a blockbuster therapy for a single but, as it turns out, propitious ultra-orphan disorder: Gaucher disease.Keywords: enzyme therapy, ultra-orphan, macrophage targeting, lysosomal disease, mannose lectin, biopharmaceutical

International collaboration

International Nuclear Information System (INIS)

Anon.

1994-01-01

In the wake of the demise of the US Superconducting Supercollider (SSC) project last year which empoverished both US and world science, some rapid scene shifting is going on. The SSC may be dead, but the underlying physics quest lives on. In the US, the 'future vision' subpanel of the High Energy Physics Advisory Board (HEPAP) is at work formulating its recommendations. On the international front, the International Committee for Future Accelerators (ICFA) at a special meeting in Vancouver in January drafted a statement

Preparation of IHY-2007 in Indonesia: Local Observational Facilities, International Collaborations, and the Use of International Data

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Djamaluddin, T.

2006-11-01

t_djamal@hotmail.com Since 1980, the National Institute of Aeronautics and Space (LAPAN) has been carrying out integrated observations of solar activities, geomagnetic disturbance, and ionospheric parameters, as well as other solar-terrestrial relationship research. International collaboration, especially with Japan in the field of solar physics, geomagnetism and equatorial atmosphere and with Australia in the field of ionosphere and upper atmosphere, help us in increasing national capacity building. The international data available on the Internet also helps us in comparing our local data with the global one or in fulfilling our needs of data due to lack of facilities, ground based or space based data. Some results will be reviewed. Preparation for IHY-2007 will also be discussed.

International collaboration on inherently safe nuclear reactors

International Nuclear Information System (INIS)

Barkenbus, J.N.

1989-01-01

Science and technology transcend economic and political ideologies, providing a means of communications and approach common to both the United States and the Soviet Union. This paper suggests that the field of nuclear fission is a logical and productive area for superpower and broader collaboration, but that the kind of collaboration characteristic of past and present activity is less than it optimally could be. The case for cost sharing is compelling with budget constraints and mounting concerns over global warming. The case for collaboration is based on economic, psychological, and political grounds. A collaborative effort in nuclear fission is presented as a near term effort by building and testing of a prototype reactor in the 1990s

Hyperferritinemia and iron metabolism in Gaucher disease: Potential pathophysiological implications.

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Regenboog, Martine; van Kuilenburg, André B P; Verheij, Joanne; Swinkels, Dorine W; Hollak, Carla E M

2016-11-01

Gaucher disease (GD) is characterized by large amounts of lipid-storing macrophages and is associated with accumulation of iron. High levels of ferritin are a hallmark of the disease. The precise mechanism underlying the changes in iron metabolism has not been elucidated. A systematic search was conducted to summarize available evidence from the literature on iron metabolism in GD and its potential pathophysiological implications. We conclude that in GD, a chronic low grade inflammation state can lead to high ferritin levels and increased hepcidin transcription with subsequent trapping of ferritin in macrophages. Extensive GD manifestations with severe anemia or extreme splenomegaly can lead to a situation of iron-overload resembling hemochromatosis. We hypothesize that specifically this latter situation carries a risk for the occurrence of associated conditions such as the increased cancer risk, metabolic syndrome and neurodegeneration. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bone turnover markers in patients with type 1 Gaucher disease

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Gaetano Giuffrida

2012-11-01

Full Text Available Bone complications occur frequently in Gaucher disease (GD and reduce the quality of life of these patients. Skeletal involvement is an important indication for treatment to ameliorate symptoms and reduce the risk of irreversible and debilitating disease. Bone biomarkers have been used to assess disease status and the response to therapy in a number of bone disorders. Here, we examine the literature for evidence of abnormalities in bone turnover markers in patients with type 1 GD to assess whether they might be useful for the assessment of bone involvement in GD. We have found that bone biomarkers in GD show highly variable results which do not currently support their routine use for clinical assessment of bone status, as an indication for therapy initiation, or for monitoring the response to therapy. A greater understanding of bone markers and their relation to the bone manifestations of GD is required.

Ethical challenges for international collaborative research partnerships in the context of the Zika outbreak in the Dominican Republic: a qualitative case study.

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Canario Guzmán, Julio Arturo; Espinal, Roberto; Báez, Jeannette; Melgen, Ricardo Elias; Rosario, Patricia Antonia Pérez; Mendoza, Eddys Rafael

2017-09-25

The establishment of international collaborative research partnerships in times of infectious disease outbreaks of international importance has been considered an ethical imperative. Frail health research systems in low- and middle-income countries can be an obstacle to achieve the goal of knowledge generation and the search for health equity before, during and after infectious disease outbreaks. A qualitative case study was conducted to identify the challenges and opportunities facing the Dominican Republic with regards to developing international collaborative research partnerships in the context of the Zika outbreak and its ethical implications. Researchers conducted 34 interviews (n = 30 individual; n = 4 group) with 39 participants (n = 23 males; n = 16 females) representing the government, universities, international donor agencies, non-governmental organisations, community-based organisations and medical societies, in two metropolitan cities. Five international collaborative research projects related to the Zika virus were identified. Major ethical challenges were linked to the governance of health research, training of human resources, the institutionalisation of scientific activity, access to research funds and cultural aspects. Capacity-building was not necessarily a component of some partnership agreements. With few exceptions, local researchers were merely participating in data collection and less on defining the problem. Opportunities for collaborative work included the possibility of participation in international research consortiums through calls for proposals. The Dominican government and research stakeholders can contribute to the international response to the Zika virus through active participation in international collaborative research partnerships; however, public recognition of the need to embrace health research as part of public policy efforts is warranted. A working group led by the government and formed by national and

Disposal R and D in the Used Fuel Disposition Campaign: A Discussion of Opportunities for Active International Collaboration

International Nuclear Information System (INIS)

Birkholzer, J.T.

2011-01-01

For DOE's Used Fuel Disposition Campaign (UFDC), international collaboration is a beneficial and cost-effective strategy for advancing disposal science with regards to multiple disposal options and different geologic environments. While the United States disposal program focused solely on Yucca Mountain tuff as host rock over the past decades, several international programs have made significant progress in the characterization and performance evaluation of other geologic repository options, most of which are very different from the Yucca Mountain site in design and host rock characteristics. Because Yucca Mountain was so unique (e.g., no backfill, unsaturated densely fractured tuff), areas of direct collaboration with international disposal programs were quite limited during that time. The decision by the U.S. Department of Energy to no longer pursue the disposal of high-level radioactive waste and spent fuel at Yucca Mountain has shifted UFDC's interest to disposal options and geologic environments similar to those being investigated by disposal programs in other nations. Much can be gained by close collaboration with these programs, including access to valuable experience and data collected over recent decades. Such collaboration can help to efficiently achieve UFDC's long-term goals of conducting 'experiments to fill data needs and confirm advanced modeling approaches' (by 2015) and of having a 'robust modeling and experimental basis for evaluation of multiple disposal system options' (by 2020). This report discusses selected opportunities of active international collaboration, with focus on both Natural Barrier System (NBS) and Engineered Barrier System (EBS) aspects and those opportunities that provide access to field data (and respective interpretation/modeling) or allow participation in ongoing field experiments. This discussion serves as a basis for the DOE/NE-53 and UFDC planning process for FY12 and beyond.

Complex Collaborations: India and International Agendas on Girls' and Women's Education, 1947-1990

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Vaughan, Rosie Peppin

2013-01-01

This article explores the dynamics of global campaigns for education through a study of the movement for girls' and women's education in India since independence in 1947. In particular, it uses the trajectory of ideas within India to theorise about international collaboration on educational goals, with UNESCO and the World Bank being two of the…

A Study on intensifying efficiency for international collaborative development of Advanced Nuclear Energy Technology

International Nuclear Information System (INIS)

Chang, Moon Hee; Kim, H. R.; Kim, H. J.

2009-08-01

The objective of the study was to participate the GIF for the efficient propulsion of future nuclear system development. For achieving the objective of this study, the followings were carried out. · Investigation and analysis of the international and domestic trends related to future nuclear system · To maximize the national interests by the strategic participation of GIF meeting - To participate of GIF meeting and to support of relative work - To investigate the System R and D Arrangement and to inform its progress situation · To maximize the propulsion results of Korea/U.S nuclear energy joint research(I-NERI) - To support a delegation by the review of agenda in aspect of the technical/legal point - To participate of BINERIC meeting and to support of relative work · Streamline the nuclear energy R and D due to the effective connection between domestic R and D and international collaboration The result of this study may be used for 1) contribution to establishing the effective foundation and broadening the cooperation activities between the advanced countries and Korea and 2) contribution effective management of Gen IV international collaboration by technical/legal supporting

The United Kingdom Hydrogen Association Forms with International Collaboration in Mind

International Nuclear Information System (INIS)

Karen Hall; John Carolin; Ian Williamson

2006-01-01

In April 2006, the United Kingdom Hydrogen Association was launched. This paper will describe the context under which the need was established, and address the challenges and opportunities faced in creating the association. A UK Hydrogen Association can encourage information sharing among regional hydrogen efforts, and provide a mechanism for a larger, single voice on the national level. In addition, a UK Hydrogen Association can serve as a focal point for UK participation in EU activities such as the European Hydrogen and Fuel Cell Technology Platform (HFP), and other international activities such as IPHE and IEA. The results of the stake holder briefing and progress of a UK Hydrogen Association will be presented, with a focus on international collaboration. (authors)

Academic performance and personal experience of local, international, and collaborative exchange students enrolled in an Australian pharmacy program.

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Davey, Andrew K; Grant, Gary D; Anoopkumar-Dukie, Shailendra

2013-09-12

To assess the academic performance and experiences of local, international, and collaborative exchange students enrolled in a 4-year Australian bachelor of pharmacy degree program. Survey instruments exploring the demographics, background, and academic and cultural experiences of students during the program were administered in 2005 to students in all 4 years. Additionally, grades from each semester of the program for students (406 local, 70 international, 155 exchange) who graduated between 2002 and 2006 were analyzed retrospectively. The main differences found in the survey responses among the 3 groups were in students' motivations for choosing the degree program and school, with international and collaborative exchange students having put more thought into these decisions than local students. The average grades over the duration of the program were similar in all 3 demographic groups. However, local students slightly outperformed international students, particularly at the start of the year, whereas collaborative exchange students' grades mirrored those of local students during the 2 years prior to leaving their home country of Malaysia but more closely mirrored those of international students in the final 2 years after arriving on campus in Australia. Despite differences in academic backgrounds and culture, international and exchange students can perform well compared to local students in a bachelor of pharmacy program and were actually more satisfied than local students with the overall experience. Studying in a foreign country can negatively influence academic grades to a small extent and this is probably related to adjusting to the new environment.

Substrate compositional variation with tissue/region and Gba1 mutations in mouse models--implications for Gaucher disease.

Directory of Open Access Journals (Sweden)

Ying Sun

Full Text Available Gaucher disease results from GBA1 mutations that lead to defective acid β-glucosidase (GCase mediated cleavage of glucosylceramide (GC and glucosylsphingosine as well as heterogeneous manifestations in the viscera and CNS. The mutation, tissue, and age-dependent accumulations of different GC species were characterized in mice with Gba1 missense mutations alone or in combination with isolated saposin C deficiency (C*. Gba1 heteroallelism for D409V and null alleles (9V/null led to GC excesses primarily in the visceral tissues with preferential accumulations of lung GC24∶0, but not in liver, spleen, or brain. Age-dependent increases of different GC species were observed. The combined saposin C deficiency (C* with V394L homozygosity (4L;C* showed major GC18:0 degradation defects in the brain, whereas the analogous mice with D409H homozygosity and C* (9H;C* led to all GC species accumulating in visceral tissues. Glucosylsphingosine was poorly degraded in brain by V394L and D409H GCases and in visceral tissues by D409V GCase. The neonatal lethal N370S/N370S genotype had insignificant substrate accumulations in any tissue. These results demonstrate age, organ, and mutation-specific quantitative differences in GC species and glucosylsphingosine accumulations that can have influence in the tissue/regional expression of Gaucher disease phenotypes.

Ethics of international clinical research collaboration - the experience of AlloStem.

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Chaplin, C

2006-02-01

This paper examines the ethics of international clinical collaboration in stem cell research by focusing on the AlloStem project. AlloStem is an international research programme, financed by the European Union under the Sixth Framework Programme, with the aim of advancing the use of stem cells in treating leukaemia and other haematological diseases. Several areas of ethical importance are explored. Research justification and the need to consider both deontological and teleological aspects are examined. Ethical sensitivity in research and the requirement to respond to areas of ethical concern identified by the European Commission, such as the involvement of human beings, the use of human tissue, and the use of animals are also explored. Ethical issues around project structure and management, such as ethical standardization in international research, and achieving set targets are discussed. The ethical importance of dissemination of findings and teaching in clinical research is also considered. Finally, the distribution of benefits is addressed and the importance of distributive justice is emphasized.

Early manifestations of type 1 Gaucher disease in presymptomatic children diagnosed after parental carrier screening.

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Yang, Amy C; Bier, Louise; Overbey, Jessica R; Cohen-Pfeffer, Jessica; Desai, Khyati; Desnick, Robert J; Balwani, Manisha

2017-06-01

The overall published experience with pediatric type 1 Gaucher disease (GD1) has been based on ascertainment through clinical presentation of the disease. We describe the longitudinal follow-up in a presymptomatic pediatric cohort. The cohort includes children diagnosed with GD1, either prenatally or postnatally by molecular genetic testing, and followed for clinical care at our center from 1998 to 2016. All patients' parents were GBA mutation carriers identified through carrier screening programs. Longitudinal clinical, laboratory, and imaging data were obtained through chart review. Thirty-eight patients aged 1-18 years (mean at last visit 6.9 ± 4.1 years) were followed, including 32 p.N409S homozygotes and 6 p.N409S/p.R535H compound heterozygotes. At the last evaluation, a minority had hematological (5%), bone (15%), or linear growth (19%) issues. Only 12% had splenomegaly and 74% had moderate hepatomegaly. Chitotriosidase activity varied widely (6-5,640 nmol/hour/ml) and generally increased with age. Pediatric Gaucher severity scores (GSS) remained stable and within the mild-disease range for most (95%). Treatment for progressive disease during this period was recommended for four children. Most children with the p.N409S/p.N409S and p.N409S/p.R535H GD1 genotypes have minimal disease manifestations and progression during childhood and can be monitored using limited assessments. Those with other mutations may require additional monitoring. These data are valuable for newborn screening and counseling.Genet Med advance online publication 13 October 2016.

Protective effect of catechin in type I Gaucher disease cells by reducing endoplasmic reticulum stress

International Nuclear Information System (INIS)

Lee, Yea-Jin; Kim, Sung-Jo; Heo, Tae-Hwe

2011-01-01

Highlights: → Catechin reduces the expression level of ER stress marker protein in type I Gaucher disease cells. → Catechin induces the proliferation rate of GD cells similar levels to normal cells. → Catechin improves wound healing activity. → Catechin-mediated reductions in ER stress may be associated with enhanced cell survival. → We identified catechin as a protective agent against ER stress in GD cells. -- Abstract: Gaucher disease (GD) is the most common lysosomal storage disorder (LSD) and is divided into three phenotypes, I, II, and III. Type I is the most prevalent form and has its onset in adulthood. The degree of endoplasmic reticulum (ER) stress is one of the factors that determine GD severity. It has recently been reported that antioxidants reduce ER stress and apoptosis by scavenging the oxidants that cause oxidative stress. For this report, we investigated the possibility that catechin can act on type I GD patient cells to alleviate the pathogenic conditions of GD. We treated GD cells with catechin and examined the expression level of GRP78/BiP (an ER stress marker) by western blots and fluorescence microscopy, the proliferation rate of GD cells, and scratch-induced wound healing activity. Our results show that catechin reduces the expression level of GRP78/BiP, leads to cell proliferation rates of GD cells similar levels to normal cells, and improves wound healing activity. We conclude that catechin protects against ER stress in GD cells and catechin-mediated reductions in ER stress may be associated with enhanced cell survival.

Protective effect of catechin in type I Gaucher disease cells by reducing endoplasmic reticulum stress

Energy Technology Data Exchange (ETDEWEB)

Lee, Yea-Jin [Department of Biotechnology, Hoseo University, Baebang, Asan, Chungnam, 336-795 (Korea, Republic of); Kim, Sung-Jo, E-mail: sungjo@hoseo.edu [Department of Biotechnology, Hoseo University, Baebang, Asan, Chungnam, 336-795 (Korea, Republic of); Heo, Tae-Hwe, E-mail: thhur92@catholic.ac.kr [College of Pharmacy, The Catholic University of Korea, Bucheon 420-743 (Korea, Republic of)

2011-09-23

Highlights: {yields} Catechin reduces the expression level of ER stress marker protein in type I Gaucher disease cells. {yields} Catechin induces the proliferation rate of GD cells similar levels to normal cells. {yields} Catechin improves wound healing activity. {yields} Catechin-mediated reductions in ER stress may be associated with enhanced cell survival. {yields} We identified catechin as a protective agent against ER stress in GD cells. -- Abstract: Gaucher disease (GD) is the most common lysosomal storage disorder (LSD) and is divided into three phenotypes, I, II, and III. Type I is the most prevalent form and has its onset in adulthood. The degree of endoplasmic reticulum (ER) stress is one of the factors that determine GD severity. It has recently been reported that antioxidants reduce ER stress and apoptosis by scavenging the oxidants that cause oxidative stress. For this report, we investigated the possibility that catechin can act on type I GD patient cells to alleviate the pathogenic conditions of GD. We treated GD cells with catechin and examined the expression level of GRP78/BiP (an ER stress marker) by western blots and fluorescence microscopy, the proliferation rate of GD cells, and scratch-induced wound healing activity. Our results show that catechin reduces the expression level of GRP78/BiP, leads to cell proliferation rates of GD cells similar levels to normal cells, and improves wound healing activity. We conclude that catechin protects against ER stress in GD cells and catechin-mediated reductions in ER stress may be associated with enhanced cell survival.

Outcomes after 18 months of eliglustat therapy in treatment-naïve adults with Gaucher disease type 1: The phase 3 ENGAGE trial.

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Mistry, Pramod K; Lukina, Elena; Ben Turkia, Hadhami; Shankar, Suma P; Baris, Hagit; Ghosn, Marwan; Mehta, Atul; Packman, Seymour; Pastores, Gregory; Petakov, Milan; Assouline, Sarit; Balwani, Manisha; Danda, Sumita; Hadjiev, Evgueniy; Ortega, Andres; Gaemers, Sebastiaan J M; Tayag, Regina; Peterschmitt, M Judith

2017-11-01

Eliglustat, an oral substrate reduction therapy, is a first-line treatment for adults with Gaucher disease type 1 (GD1) who are poor, intermediate, or extensive CYP2D6 metabolizers (>90% of patients). In the primary analysis of the Phase 3 ENGAGE trial (NCT00891202), eliglustat treatment for 9 months resulted in significant reductions in spleen and liver volumes and increases in hemoglobin concentration and platelet count compared with placebo. We report 18-month outcomes of patients who entered the trial extension period, in which all patients received eliglustat. Of 40 trial patients, 39 entered the extension period, and 38 completed 18 months. Absolute values and percent change over time were determined for spleen and liver volume, hemoglobin concentration, platelet count, bone mineral density, bone marrow burden, and Gaucher disease biomarkers. For patients randomized to eliglustat in the double-blind period, continuing treatment with eliglustat for 9 more months resulted in incremental improvement of all disease parameters. For patients randomized to placebo in the double-blind period, eliglustat treatment during the 9-month, open-label period resulted in significant decrease of spleen and liver volumes and significant increase of hemoglobin and platelets, with a similar rate of change to patients who had received eliglustat in the double-blind period. Eliglustat treatment was also associated with improvement in bone marrow burden score, bone mineral density, and established biomarkers of Gaucher disease, including reduction of the bioactive lipid, glucosylsphingosine. These findings underscore the efficacy of eliglustat in treatment-naïve patients. Eliglustat was well-tolerated, and there were no new safety concerns with longer-term exposure. © 2017 The Authors American Journal of Hematology Published by Wiley Periodicals, Inc.

International Collaboration on Air Pollution and Pregnancy Outcomes (ICAPPO)

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Woodruff, Tracey J.; Parker, Jennifer D.; Adams, Kate; Bell, Michelle L.; Gehring, Ulrike; Glinianaia, Svetlana; Ha, Eun-Hee; Jalaludin, Bin; Slama, Rémy

2010-01-01

Reviews find a likely adverse effect of air pollution on perinatal outcomes, but variation of findings hinders the ability to incorporate the research into policy. The International Collaboration on Air Pollution and Pregnancy Outcomes (ICAPPO) was formed to better understand relationships between air pollution and adverse birth outcomes through standardized parallel analyses in datasets from different countries. A planning group with 10 members from 6 countries was formed to coordinate the project. Collaboration participants have datasets with air pollution values and birth outcomes. Eighteen research groups with data for approximately 20 locations in Asia, Australia, Europe, North America, and South America are participating, with most participating in an initial pilot study. Datasets generally cover the 1990s. Number of births is generally in the hundreds of thousands, but ranges from around 1,000 to about one million. Almost all participants have some measure of particulate matter, and most have ozone, nitrogen dioxide, sulfur dioxide and carbon monoxide. Strong enthusiasm for participating and a geographically-diverse range of participants should lead to understanding uncertainties about the role of air pollution in perinatal outcomes and provide decision-makers with better tools to account for pregnancy outcomes in air pollution policies. PMID:20644693

Gaucher disease in children: radiology of non-central nervous system manifestations

International Nuclear Information System (INIS)

McHugh, K.; Olsen, Oe.E.; Vellodi, A.

2004-01-01

The radiological findings in paediatric Gaucher disease (GD) are reviewed and future challenges for radiology are discussed. This overview is based on a literature review and our experience of children with GD in one of two national institutions for paediatric GD in the UK. GD is known to progress more rapidly in childhood. Current imaging is mainly suitable for ascertaining the complications of GD. The UK recommendations for routine radiological surveillance are discussed. With enzyme replacement therapy (ERT), which dramatically modifies the course of the disorder, the challenge for radiology in the future is likely to be assessing treatment efficacy rather than the detection of disease complications. Disease manifestations are likely to change in those on ERT and the most notable recent alteration in the disease profile in childhood is the virtual disappearance of the acute bone crisis in this population

Gaucher disease in children: radiology of non-central nervous system manifestations

Energy Technology Data Exchange (ETDEWEB)

McHugh, K. E-mail: kmchugh@gosh.nhs.uk; Olsen, Oe.E.; Vellodi, A

2004-02-01

The radiological findings in paediatric Gaucher disease (GD) are reviewed and future challenges for radiology are discussed. This overview is based on a literature review and our experience of children with GD in one of two national institutions for paediatric GD in the UK. GD is known to progress more rapidly in childhood. Current imaging is mainly suitable for ascertaining the complications of GD. The UK recommendations for routine radiological surveillance are discussed. With enzyme replacement therapy (ERT), which dramatically modifies the course of the disorder, the challenge for radiology in the future is likely to be assessing treatment efficacy rather than the detection of disease complications. Disease manifestations are likely to change in those on ERT and the most notable recent alteration in the disease profile in childhood is the virtual disappearance of the acute bone crisis in this population.

Altered lysosome distribution is an early neuropathological event in neurological forms of Gaucher disease.

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Zigdon, Hila; Meshcheriakova, Anna; Farfel-Becker, Tamar; Volpert, Giora; Sabanay, Helena; Futerman, Anthony H

2017-03-01

In the lysosomal storage disorder Gaucher disease (GD), glucosylceramide (GlcCer) accumulates due to the defective activity of glucocerebrosidase. A subset of GD patients develops neuropathology. We now show mislocalization of Limp2-positive puncta and a large reduction in the number of Lamp1-positive puncta, which are associated with impaired tubulin. These changes occur at an early stage in animal models of GD, prior to development of overt symptoms and considerably earlier than neuronal loss. Altered lysosomal localization and cytoskeleton disruption precede the neuroinflammatory pathways, axonal dystrophy and neuronal loss previously characterized in neuronal forms of GD. © 2017 Federation of European Biochemical Societies.

Research and collaboration overview of Institut Pasteur International Network: a bibliometric approach toward research funding decisions.

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Mostafavi, Ehsan; Bazrafshan, Azam

2014-01-01

Institut Pasteur International Network (IPIN), which includes 32 research institutes around the world, is a network of research and expertise to fight against infectious diseases. A scientometric approach was applied to describe research and collaboration activities of IPIN. Publications were identified using a manual search of IPIN member addresses in Science Citation Index Expanded (SCIE) between 2006 and 2011. Total publications were then subcategorized by geographic regions. Several scientometric indicators and the H-index were employed to estimate the scientific production of each IPIN member. Subject and geographical overlay maps were also applied to visualize the network activities of the IPIN members. A total number of 12667 publications originated from IPIN members. Each author produced an average number of 2.18 papers and each publication received an average of 13.40 citations. European Pasteur Institutes had the largest amount of publications, authored papers, and H-index values. Biochemistry and molecular biology, microbiology, immunology and infectious diseases were the most important research topics, respectively. Geographic mapping of IPIN publications showed wide international collaboration among IPIN members around the world. IPIN has strong ties with national and international authorities and organizations to investigate the current and future health issues. It is recommended to use scientometric and collaboration indicators as measures of research performance in IPIN future policies and investment decisions.

Research and Collaboration Overview of Institut Pasteur International Network: A Bibliometric Approach toward Research Funding Decisions

Directory of Open Access Journals (Sweden)

Ehsan Mostafavi

2014-01-01

Full Text Available Background Institut Pasteur International Network (IPIN, which includes 32 research institutes around the world, is a network of research and expertise to fight against infectious diseases. A scientometric approach was applied to describe research and collaboration activities of IPIN. Methods Publications were identified using a manual search of IPIN member addresses in Science Citation Index Expanded (SCIE between 2006 and 2011. Total publications were then subcategorized by geographic regions. Several scientometric indicators and the H-index were employed to estimate the scientific production of each IPIN member. Subject and geographical overlay maps were also applied to visualize the network activities of the IPIN members. Results A total number of 12667 publications originated from IPIN members. Each author produced an average number of 2.18 papers and each publication received an average of 13.40 citations. European Pasteur Institutes had the largest amount of publications, authored papers, and H-index values. Biochemistry and molecular biology, microbiology, immunology and infectious diseases were the most important research topics, respectively. Geographic mapping of IPIN publications showed wide international collaboration among IPIN members around the world. Conclusion IPIN has strong ties with national and international authorities and organizations to investigate the current and future health issues. It is recommended to use scientometric and collaboration indicators as measures of research performance in IPIN future policies and investment decisions.

International workshop: islet transplantation without borders enabling islet transplantation in Greece with international collaboration and innovative technology.

Science.gov (United States)

Papas, Klearchos K; Karatzas, Theodore; Berney, Thierry; Minor, Thomas; Pappas, Paris; Pattou, François; Shaw, James; Toso, Christian; Schuurman, Henk-Jan

2013-01-01

Recently, initiatives have been undertaken to establish an islet transplantation program in Athens, Greece. A major hurdle is the high cost associated with the establishment and maintenance of a clinical-grade islet manufacturing center. A collaboration was established with the University Hospitals of Geneva, Switzerland, to enable remote islet cell manufacturing with an established and validated fully operational team. However, remote islet manufacturing requires shipment of the pancreas from the procurement to the islet manufacturing site (in this case from anywhere in Greece to Geneva) and then shipment of the islets from the manufacturing site to the transplant site (from Geneva to Athens). To address challenges related to cold ischemia time of the pancreas and shipment time of islets, a collaboration was initiated with the University of Arizona, Tucson, USA. An international workshop was held in Athens, December 2011, to mark the start of this collaborative project. Experts in the field presented in three main sessions: (i) islet transplantation: state-of-the-art and the "network approach"; (ii) technical aspects of clinical islet transplantation and outcomes; and (iii) islet manufacturing - from the donated pancreas to the islet product. This manuscript presents a summary of the workshop. © 2013 John Wiley & Sons A/S.

International collaboration between nuclear research centres and the role of research reactors

International Nuclear Information System (INIS)

Dodd, B.

2001-01-01

A research reactor is a core facility in many nuclear research centres (NRCs) of Member States and it is logical that it should be the focus of any international collaboration between such centres. There are several large and sophisticated research reactors in operation in both developed and developing Member States, such as Belgium, China, Egypt, France, Hungary, Indonesia, India, Japan, ROK, Netherlands, South Africa and the USA. There are also several new, large reactors under construction or being planned such as those in Australia, Canada, China, France, Germany, and Thailand. It is felt that the utilization of these reactors can be enhanced by international co-operation to achieve common goals in research and applications. (author)

Validation of the Impact of Health Information Technology (I-HIT) Scale: an international collaborative.

Science.gov (United States)

Dykes, Patricia C; Hurley, Ann C; Brown, Suzanne; Carr, Robyn; Cashen, Margaret; Collins, Rita; Cook, Robyn; Currie, Leanne; Docherty, Charles; Ensio, Anneli; Foster, Joanne; Hardiker, Nicholas R; Honey, Michelle L L; Killalea, Rosaleen; Murphy, Judy; Saranto, Kaija; Sensmeier, Joyce; Weaver, Charlotte

2009-01-01

In 2005, the Healthcare Information Management Systems Society (HIMSS) Nursing Informatics Community developed a survey to measure the impact of health information technology (HIT), the I-HIT Scale, on the role of nurses and interdisciplinary communication in hospital settings. In 2007, nursing informatics colleagues from Australia, England, Finland, Ireland, New Zealand, Scotland and the United States formed a research collaborative to validate the I-HIT across countries. All teams have completed construct and face validation in their countries. Five out of six teams have initiated reliability testing by practicing nurses. This paper reports the international collaborative's validation of the I-HIT Scale completed to date.

Bone marrow involvement in Gaucher disease at MRI: what long-term evolution can we expect under enzyme replacement therapy?

International Nuclear Information System (INIS)

Fedida, Benjamin; Touraine, Sebastien; Laredo, Jean-Denis; Stirnemann, Jerome; Belmatoug, Nadia; Petrover, David

2015-01-01

To study the long-term evolution of the bone marrow burden (BMB) score at MRI in patients with Gaucher disease (GD) under enzyme replacement therapy (ERT). Forty patients treated for GD were retrospectively studied in a referral centre. BMB scores were assessed on spine and femur MR examinations performed between January 2003 and June 2014. The long-term evolution of the BMB scores was analyzed using a linear mixed model. A total of 121 MRI examinations were performed during the study period with a mean follow-up of 7.1 years ± 5.6, an average rate of 3.1 MR examinations ± 1.7 per patient and an interval of 2.3 years ± 1.1 between examinations. Patients had received ERT during 12 years on average ± 6.7. The trend of BMB scores with time decreased significantly by 15 % (P = 0.008) during the total study period and 39 % (P = 0.01) during the first 5 years of treatment. No changes in BMB scores were observed after five years of treatment. In Gaucher patients, the trend of MRI BMB scores with time decreased significantly under ERT the first 5 years of treatment before a long-term stabilization. (orig.)

High throughput screening for small molecule therapy for Gaucher disease using patient tissue as the source of mutant glucocerebrosidase.

Directory of Open Access Journals (Sweden)

Ehud Goldin

Full Text Available Gaucher disease (GD, the most common lysosomal storage disorder, results from the inherited deficiency of the lysosomal enzyme glucocerebrosidase (GCase. Previously, wildtype GCase was used for high throughput screening (HTS of large collections of compounds to identify small molecule chaperones that could be developed as new therapies for GD. However, the compounds identified from HTS usually showed reduced potency later in confirmatory cell-based assays. An alternate strategy is to perform HTS on mutant enzyme to identify different lead compounds, including those enhancing mutant enzyme activities. We developed a new screening assay using enzyme extract prepared from the spleen of a patient with Gaucher disease with genotype N370S/N370S. In tissue extracts, GCase is in a more native physiological environment, and is present with the native activator saposin C and other potential cofactors. Using this assay, we screened a library of 250,000 compounds and identified novel modulators of mutant GCase including 14 new lead inhibitors and 30 lead activators. The activities of some of the primary hits were confirmed in subsequent cell-based assays using patient-derived fibroblasts. These results suggest that primary screening assays using enzyme extracted from tissues is an alternative approach to identify high quality, physiologically relevant lead compounds for drug development.

Bone marrow involvement in Gaucher disease at MRI: what long-term evolution can we expect under enzyme replacement therapy?

Energy Technology Data Exchange (ETDEWEB)

Fedida, Benjamin; Touraine, Sebastien; Laredo, Jean-Denis [Hopital Lariboisiere, AP-HP, Department of Musculoskeletal Imaging, Paris (France); Stirnemann, Jerome [Universite Paris-Diderot Hopital Bichat, AP-HP, Department of Biostatistics and Medical Data Processing, INSERM UMR 738, Paris (France); Geneva University Hospital, Division of General Internal Medicine, Faculty of Medicine, Geneva (Switzerland); Belmatoug, Nadia [Hopital Beaujon, AP-HP, Referral Center for Lysosomal Diseases (RCLD), Clichy (France); Hopital Beaujon, AP-HP, Department of Internal Medicine, Clichy (France); Petrover, David [Hopital Lariboisiere, AP-HP, Department of Musculoskeletal Imaging, Paris (France); Hopital Beaujon, AP-HP, Referral Center for Lysosomal Diseases (RCLD), Clichy (France)

2015-10-15

To study the long-term evolution of the bone marrow burden (BMB) score at MRI in patients with Gaucher disease (GD) under enzyme replacement therapy (ERT). Forty patients treated for GD were retrospectively studied in a referral centre. BMB scores were assessed on spine and femur MR examinations performed between January 2003 and June 2014. The long-term evolution of the BMB scores was analyzed using a linear mixed model. A total of 121 MRI examinations were performed during the study period with a mean follow-up of 7.1 years ± 5.6, an average rate of 3.1 MR examinations ± 1.7 per patient and an interval of 2.3 years ± 1.1 between examinations. Patients had received ERT during 12 years on average ± 6.7. The trend of BMB scores with time decreased significantly by 15 % (P = 0.008) during the total study period and 39 % (P = 0.01) during the first 5 years of treatment. No changes in BMB scores were observed after five years of treatment. In Gaucher patients, the trend of MRI BMB scores with time decreased significantly under ERT the first 5 years of treatment before a long-term stabilization. (orig.)

International Collaboration in the field of GNSS-Meteorology and Climate Monitoring

Science.gov (United States)

Jones, J.; Guerova, G.; Dousa, J.; Bock, O.; Elgered, G.; Vedel, H.; Pottiaux, E.; de Haan, S.; Pacione, R.; Dick, G.; Wang, J.; Gutman, S. I.; Wickert, J.; Rannat, K.; Liu, G.; Braun, J. J.; Shoji, Y.

2012-12-01

International collaboration in the field of GNSS-meteorology and climate monitoring is essential, as severe weather and climate change have no respect for national boundaries. The use of Global Navigation Satellite Systems (GNSS) for meteorological purposes is an established atmospheric observing technique, which can accurately sense water vapour, the most abundant greenhouse gas, accounting for 60-70% of atmospheric warming. Severe weather forecasting is challenging, in part due to the high temporal and spatial variation of atmospheric water vapour. Water vapour is currently under-sampled and obtaining and exploiting more high-quality humidity observations is essential to severe weather forecasting and climate monitoring. A proposed EU COST Action (http://www.cost.eu) will address new and improved capabilities from concurrent developments in both GNSS and atmospheric communities to improve (short-range) weather forecasts and climate projections. For the first time, the synergy of the three GNSS systems, GPS, GLONASS and Galileo, will be used to develop new, advanced tropospheric products, stimulating the full potential exploitation of multi-GNSS water vapour estimates on a wide range of temporal and spatial scales, from real-time severe weather monitoring and forecasting to climate research. The Action will work in close collaboration with the Global Climate Observing System (GCOS) Reference Upper Air Network (GRUAN), GNSS Precipitable Water Task Team (TT). GRUAN is a global reference observing network, designed to meet climate requirements and to fill a major void in the current global observing system. GRUAN observations will provide long-term, high-quality data to determine climatic trends and to constrain and validate data from space-based remote sensors. Ground-based GNSS PW was identified as a Priority 1 measurement for GRUAN, and the GNSS-PW TT's goal is to develop explicit guidance on hardware, software and data management practices to obtain GNSS PW

Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus

DEFF Research Database (Denmark)

Petri, Michelle; Orbai, Ana-Maria; Alarcón, Graciela S

2012-01-01

The Systemic Lupus International Collaborating Clinics (SLICC) group revised and validated the American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria in order to improve clinical relevance, meet stringent methodology requirements, and incorporate new...

Mobility and International Collaboration: Case of the Mexican Scientific Diaspora.

Directory of Open Access Journals (Sweden)

Rafael Marmolejo-Leyva

Full Text Available We use a data set of Mexican researchers working abroad that are included in the Mexican National System of Researchers (SNI. Our diaspora sample includes 479 researchers, most of them holding postdoctoral positions in mainly seven countries: USA, Great Britain, Germany, France, Spain, Canada and Brazil. Their research output and impact is explored in order to determine their patterns of production, mobility and scientific collaboration as compared with previous studies of the SNI researchers in the periods 1991-2001 and 2003-2009. Our findings confirm that mobility has a strong impact on their international scientific collaboration. We found no substantial influence among the researchers that got their PhD degrees abroad from those trained in Mexican universities. There are significant differences among the areas of knowledge studied: biological sciences, physics and engineering have better production and impact rates than mathematics, geosciences, medicine, agrosciences, chemistry, social sciences and humanities. We found a slight gender difference in research production but Mexican female scientists are underrepresented in our diaspora sample. These findings would have policy implications for the recently established program that will open new academic positions for young Mexican scientists.

Mobility and International Collaboration: Case of the Mexican Scientific Diaspora.

Science.gov (United States)

Marmolejo-Leyva, Rafael; Perez-Angon, Miguel Angel; Russell, Jane M

2015-01-01

We use a data set of Mexican researchers working abroad that are included in the Mexican National System of Researchers (SNI). Our diaspora sample includes 479 researchers, most of them holding postdoctoral positions in mainly seven countries: USA, Great Britain, Germany, France, Spain, Canada and Brazil. Their research output and impact is explored in order to determine their patterns of production, mobility and scientific collaboration as compared with previous studies of the SNI researchers in the periods 1991-2001 and 2003-2009. Our findings confirm that mobility has a strong impact on their international scientific collaboration. We found no substantial influence among the researchers that got their PhD degrees abroad from those trained in Mexican universities. There are significant differences among the areas of knowledge studied: biological sciences, physics and engineering have better production and impact rates than mathematics, geosciences, medicine, agrosciences, chemistry, social sciences and humanities. We found a slight gender difference in research production but Mexican female scientists are underrepresented in our diaspora sample. These findings would have policy implications for the recently established program that will open new academic positions for young Mexican scientists.

Estudo da doença de Gaucher em Santa Catarina Study of Gaucher disease in Santa Catarina

Directory of Open Access Journals (Sweden)

Jovino S. Ferreira

2008-02-01

Full Text Available A doença de Gaucher (DG foi a primeira doença de armazenamento lisossomal descrita e a mais encontrada. Caracteriza-se pela deficiência hereditária da atividade da enzima lisossomal glucocerebrosidase, que bloqueia o metabolismo do glicocerebrosídeo. A proposta deste trabalho foi estudar as características clínicas, laboratoriais e radiológicas, as principais mutações encontradas, relacionando-as com as formas clínicas e avaliar a resposta à terapia de reposição enzimática (TRE nos pacientes com DG em Santa Catarina. Foram estudados dez pacientes com DG no Hospital Universitário, no período entre 1998 e 2003, após confirmação diagnóstica da doença pela dosagem da enzima beta-glicosidase em leucócitos. Pesquisa das mutações foi realizada em amostras de sangue e de mucosa oral. A média de idade ao diagnóstico foi de 19,6 anos. A DG tipo 1 foi diagnosticada em 80% dos casos, e a tipo 2 em 20%. Quatro pacientes tiveram história familiar de DG. Hepatoesplenomegalia foi a manifestação clínica mais comum. Anemia e trombocitopenia ocorreram em 100% dos casos. Dores ósseas foram relatadas por 75% dos pacientes. Os alelos mutantes encontrados foram N370S e L444P. Houve elevação dos níveis de hemoglobina em todos os pacientes com DG tipo 1. Concluímos que a DG tipo 1 é a forma clínica mais comum. Anemia, trombocitopenia, hepatoesplenomegalia e osteopenia são as características mais freqüentes dos pacientes com DG. O alelo N370S é o mais freqüente, estando relacionado com o tipo 1. O alelo L444P em homozigose sugere letalidade precoce. A TRE é segura e efetiva para a DG tipo 1.Gaucher Disease (GD was the first described and is the most common lysosomal deposit disease. It is characterized byahereditary deficiency of glucocerebrosidase lysosomal enzyme activity which blocks the metabolism of glucocerebrosideo. The aim of this work was to study the clinical, laboratorial and radiological characteristics, the main

Nuclear safety research collaborations between the US and Russian Federation international nuclear safety centers

International Nuclear Information System (INIS)

Hill, D.J; Braun, J.C; Klickman, A.E.; Bugaenko, S.E; Kabanov, L.P; Kraev, A.G.

2000-01-01

The Russian Federation Ministry for Atomic Energy (MINATOM) and the U.S. Department of Energy (USDOE) have formed International Nuclear Safety Centers to collaborate on nuclear safety research. USDOE established the U. S. Center at Argonne National Laboratory in October 1995. MINATOM established the Russian Center at the Research and Development Institute of Power Engineering in Moscow in July 1996. In April 1998 the Russian center became an independent, autonomous organization under MINATOM. The goals of the centers are to: cooperate in the development of technologies associated with nuclear safety in nuclear power engineering. be international centers for the collection of information important for safety and technical improvements in nuclear power engineering. maintain a base for fundamental knowledge needed to design nuclear reactors.The strategic approach that is being used to accomplish these goals is for the two centers to work together to use the resources and the talents of the scientists associated with the US Center and the Russian Center to do collaborative research to improve the safety of Russian-designed nuclear reactors

Is There a Relationship between the Usage of Active and Collaborative Learning Techniques and International Students' Study Anxiety?

Science.gov (United States)

Khoshlessan, Rezvan

2013-01-01

This study was designed to explore the relationships between the international students' perception of professors' instructional practices (the usage of active and collaborative learning techniques in class) and the international students' study anxiety. The dominant goal of this research was to investigate whether the professors' usage of active…

CMS Collaboration

International Nuclear Information System (INIS)

Faridah Mohammad Idris; Wan Ahmad Tajuddin Wan Abdullah; Zainol Abidin Ibrahim

2013-01-01

Full-text: CMS Collaboration is an international scientific collaboration located at European Organization for Nuclear Research (CERN), Switzerland, dedicated in carried out research on experimental particle physics. Consisting of 179 institutions from 41 countries from all around the word, CMS Collaboration host a general purpose detector for example the Compact Muon Solenoid (CMS) for members in CMS Collaboration to conduct experiment from the collision of two proton beams accelerated to a speed of 8 TeV in the LHC ring. In this paper, we described how the CMS detector is used by the scientist in CMS Collaboration to reconstruct the most basic building of matter. (author)

Polymorphisms in the glucocerebrosidase gene and pseudogene urge caution in clinical analysis of Gaucher disease allele c.1448T>C (L444P

Directory of Open Access Journals (Sweden)

Lahey Cora

2006-08-01

Full Text Available Abstract Background Gaucher disease is a potentially severe lysosomal storage disorder caused by mutations in the human glucocerebrosidase gene (GBA. We have developed a multiplexed genetic assay for eight diseases prevalent in the Ashkenazi population: Tay-Sachs, Gaucher type I, Niemann-Pick types A and B, mucolipidosis type IV, familial dysautonomia, Canavan, Bloom syndrome, and Fanconi anemia type C. This assay includes an allelic determination for GBA allele c.1448T>C (L444P. The goal of this study was to clinically evaluate this assay. Methods Biotinylated, multiplex PCR products were directly hybridized to capture probes immobilized on fluorescently addressed microspheres. After incubation with streptavidin-conjugated fluorophore, the reactions were analyzed by Luminex IS100. Clinical evaluations were conducted using de-identified patient DNA samples. Results We evaluated a multiplexed suspension array assay that includes wild-type and mutant genetic determinations for Gaucher disease allele c.1448T>C. Two percent of samples reported to be wild-type by conventional methods were observed to be c.1448T>C heterozygous using our assay. Sequence analysis suggested that this phenomenon was due to co-amplification of the functional gene and a paralogous pseudogene (ΨGBA due to a polymorphism in the primer-binding site of the latter. Primers for the amplification of this allele were then repositioned to span an upstream deletion in the pseudogene, yielding a much longer amplicon. Although it is widely reported that long amplicons negatively impact amplification or detection efficiency in recently adopted multiplex techniques, this assay design functioned properly and resolved the occurrence of false heterozygosity. Conclusion Although previously available sequence information suggested GBA gene/pseudogene discrimination capabilities with a short amplified product, we identified common single-nucleotide polymorphisms in the pseudogene that

PRINCESS: Privacy-protecting Rare disease International Network Collaboration via Encryption through Software guard extensionS.

Science.gov (United States)

Chen, Feng; Wang, Shuang; Jiang, Xiaoqian; Ding, Sijie; Lu, Yao; Kim, Jihoon; Sahinalp, S Cenk; Shimizu, Chisato; Burns, Jane C; Wright, Victoria J; Png, Eileen; Hibberd, Martin L; Lloyd, David D; Yang, Hai; Telenti, Amalio; Bloss, Cinnamon S; Fox, Dov; Lauter, Kristin; Ohno-Machado, Lucila

2017-03-15

We introduce PRINCESS, a privacy-preserving international collaboration framework for analyzing rare disease genetic data that are distributed across different continents. PRINCESS leverages Software Guard Extensions (SGX) and hardware for trustworthy computation. Unlike a traditional international collaboration model, where individual-level patient DNA are physically centralized at a single site, PRINCESS performs a secure and distributed computation over encrypted data, fulfilling institutional policies and regulations for protected health information. To demonstrate PRINCESS' performance and feasibility, we conducted a family-based allelic association study for Kawasaki Disease, with data hosted in three different continents. The experimental results show that PRINCESS provides secure and accurate analyses much faster than alternative solutions, such as homomorphic encryption and garbled circuits (over 40 000× faster). https://github.com/achenfengb/PRINCESS_opensource. shw070@ucsd.edu. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Phebus FP: organisation of the project and international collaboration

International Nuclear Information System (INIS)

Tattegrain, A.; Hardt, P. von der

1992-01-01

PHEBUS Fission Product (FP) Research Programme developed from the initial French design study into a European project, and further into an international programme by agreements with overseas partners during the past two years. The programme is supervised by a Steering Committee which reviews the technical-scientific options and the results. The executive body under the Committee, the Project Group, includes a Commissariat a l'Energie Atomique (CEA) and Commission of the European Communities (CEC) manager as well as three (CEA) project leaders for design and manufacture, experiment operation, and interpretation of test results. The Steering Committee can request expertise from the two working groups the Analytical Group (SAWG) (elaborating test objectives, carrying out reactor calculations and test precalculations) and the Technical Group (TG) (assessing the designs proposed and the results obtained by the Project Group). A third group looks into financial aspects of the CEA-CEC contract only. The two working groups, SAWG and TG, play an important role in the exchange of information and of expertise between all partners. The paper reviews the internal Project organisation and the collaboration network, inside the European Community and through CEA overseas. (author)

Management goals for type 1 Gaucher disease: An expert consensus document from the European working group on Gaucher disease.

Science.gov (United States)

Biegstraaten, M; Cox, T M; Belmatoug, N; Berger, M G; Collin-Histed, T; Vom Dahl, S; Di Rocco, M; Fraga, C; Giona, F; Giraldo, P; Hasanhodzic, M; Hughes, D A; Iversen, P O; Kiewiet, A I; Lukina, E; Machaczka, M; Marinakis, T; Mengel, E; Pastores, G M; Plöckinger, U; Rosenbaum, H; Serratrice, C; Symeonidis, A; Szer, J; Timmerman, J; Tylki-Szymańska, A; Weisz Hubshman, M; Zafeiriou, D I; Zimran, A; Hollak, C E M

2018-02-01

Gaucher Disease type 1 (GD1) is a lysosomal disorder that affects many systems. Therapy improves the principal manifestations of the condition and, as a consequence, many patients show a modified phenotype which reflects manifestations of their disease that are refractory to treatment. More generally, it is increasingly recognised that information as to how a patient feels and functions [obtained by patient- reported outcome measurements (PROMs)] is critical to any comprehensive evaluation of treatment. A new set of management goals for GD1 in which both trends are reflected is needed. To this end, a modified Delphi procedure among 25 experts was performed. Based on a literature review and with input from patients, 65 potential goals were formulated as statements. Consensus was considered to be reached when ≥75% of the participants agreed to include that specific statement in the management goals. There was agreement on 42 statements. In addition to the traditional goals concerning haematological, visceral and bone manifestations, improvement in quality of life, fatigue and social participation, as well as early detection of long-term complications or associated diseases were included. When applying this set of goals in medical practice, the clinical status of the individual patient should be taken into account. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The influence of genetic variability and proinflammatory status on the development of bone disease in patients with Gaucher disease.

Directory of Open Access Journals (Sweden)

Javier Gervas-Arruga

Full Text Available Gaucher disease, the most common lysosomal storage disorder, is caused by β-glucocerebrosidase deficiency. Bone complications are the major cause of morbidity in patients with type 1 Gaucher disease (GD1. Genetic components strongly influence bone remodelling. In addition, chronic inflammation produced by Gaucher cells induces the production of several cytokines, which leads to direct changes in the bone remodelling process and can also affect the process indirectly through other immune cells. In this study, we analysed the association between bone mineral density (BMD, bone marrow burden score, and relevant genetic polymorphisms related to bone metabolism, as well as profiles of proinflammatory cytokines in a GD1 cohort. This study included 83 patients distributed according to bone status. BMD was measured with DXA and broadband ultrasound attenuation; bone marrow involvement was evaluated using MRI. We also analysed 26 SNPs located in 14 genes related to bone metabolism. To assess proinflammatory status, we analysed IL-4, IL-6, IL-7, IL-10, IL-13, MIP-1α, MIP-1β, and TNFα in plasma samples from 71 control participants and GD1 patients. SNP genotype proportions and BMD differed significantly between ESRI c.453-397T>C and VDR c.1024+283G>A variants. We also observed significant associations between GD1 genotypes and bone affectation. When patients were stratified by spleen status, we observed significant correlations between non-/splenectomized groups and Spanish MRI (S-MRI score. Across genotype proportions of non-/splenectomized patients and S-MRI, we observed significant differences in ESRI c.453-397T>C, VDR c.-83-25988G>A, and TNFRSF11B c.9C>G polymorphisms. We observed different significant proinflammatory profiles between control participants, treatment-naïve patients, and patients on enzyme replacement therapy (ERT; between non-/splenectomized patients (between untreated and ERT-treated patients and among those with differing GBA

Sustaining a Global Geoscience Workforce-The Case for International Collaboration

Science.gov (United States)

Leahy, P. P.; Keane, C. M.

2013-05-01

Maintaining an adequate global supply of qualified geoscientists is a major challenge facing the profession. With global population expected to exceed 9 billion by midcentury, the demand for geoscience expertise is expected to dramatically increase if we are to provide to society the resource base, environmental quality, and resiliency to natural hazards that is required to meet future global demands. The American Geoscience Institute (AGI) has for the past 50 years tracked the supply of geoscientists and their various areas of specialty for the US. However, this is only part of the necessary workforce analysis, the demand side must also be determined. For the past several years, AGI has worked to acquire estimates for workforce demand in the United States. The analysis suggests that by 2021 there will be between 145,000 to 202,000 unfilled jobs in the US. This demand can be partially filled with an increase in graduates (which is occurring at an insufficient pace in the US to meet full demand), increased migration of geoscientists internationally to the US (a challenge since demands are increasing globally), and more career placement of bachelor degree recipients. To understand the global workforce dynamic, it is critical that accurate estimates of global geoscience supply, demand and retirement be available. Although, AGI has focused on the US situation, it has developed international collaborations to acquire workforce data. Among the organizations that have contributed are UNESCO, the International Union of Geological Sciences (IUGS), the Young Earth-Scientists Network, and the Geological Society of Africa. Among the areas of international collaboration, the IUGS Task Group on Global Geoscience Workforce enables the IUGS to take a leadership role in raising the quality of understanding of workforce across the world. During the course of the taskforce's efforts, several key understandings have emerged. First, the general supply of geoscientists is quantifiable

1-Deoxynojirimycins with dansyl capped N-substituents as probes for Morbus Gaucher affected cell lines.

Science.gov (United States)

Fröhlich, Richard F G; Furneaux, Richard H; Mahuran, Don J; Rigat, Brigitte A; Stütz, Arnold E; Tropak, Michael B; Wicki, Jacqueline; Withers, Stephen G; Wrodnigg, Tanja M

2010-07-02

Cyclization by double reductive amination of d-xylo-hexos-5-ulose with methyl 6-aminohexanoate gave (methoxycarbonyl)pentyl-1-deoxynojirimycin. Reaction of the terminal carboxylic acid with N-dansyl-1,6-diaminohexane provided the corresponding chain-extended fluorescent derivative. By reaction with bis(6-dansylaminohexyl)amine, the corresponding branched di-N-dansyl compound was obtained. Both compounds are strong inhibitors of d-glucosidases and could also be shown to distinctly improve, at sub-inhibitory concentrations, the activity of beta-glucocerebrosidase in a Gaucher fibroblast (N370S) cell-line through chaperoning of the enzyme to the lysosome. Copyright 2010 Elsevier Ltd. All rights reserved.

International Collaboration: the Virtuous Cycle of Low Carbon Innovation and Diffusion. An Analysis of Solar Photovoltaic, Concentrating Solar Power and Carbon Capture and Storage

International Nuclear Information System (INIS)

Dominique, Katheen

2010-01-01

International collaboration can be leveraged to accelerate the innovation and diffusion of low carbon technologies required to realize the shift to a low carbon trajectory. A collaborative approach to innovation has the potential to capture several benefits, including: pooling risks and achieving scale; knowledge sharing that accommodates competition and cooperation; the creation of a global market; facilitation of policy learning and exchange; and the alignment of technology, finance and policy. International Collaboration: the Virtuous Cycle of Low Carbon Innovation and Diffusion An Analysis of Solar Photovoltaic, Concentrating Solar Power and Carbon Capture and Storage A range of obstacles to the diffusion of low carbon technologies provides ample opportunity for international collaboration in global market creation and capacity building, expanding beyond conventional modes of technology transfer. Current collaborative efforts for carbon capture and storage, solar photovoltaic and concentrating solar power technologies are active in all stages of innovation and diffusion and involve a wide range of actors. Yet, current efforts are not sufficient to achieve the necessary level of emission mitigation at the pace required to avoid catastrophic levels of atmospheric destabilization. This analysis sets forth recommendation to scale up current endeavors and create new ones. The analysis begins by describing the fundamental characteristics of innovation and diffusion processes that create opportunities for international collaboration. It then illustrates a broad array of on-going collaborative activities, depicting how these efforts contribute to innovation and diffusion. Finally, highlighting the gap between the current level of collaborative activities and technology targets deemed critical for emission mitigation, the report sets forth several recommendations to build on current efforts and construct new endeavors

Assessment of precision and concordance of quantitative mitochondrial DNA assays: a collaborative international quality assurance study

NARCIS (Netherlands)

Hammond, Emma L.; Sayer, David; Nolan, David; Walker, Ulrich A.; Ronde, Anthony de; Montaner, Julio S. G.; Cote, Helene C. F.; Gahan, Michelle E.; Cherry, Catherine L.; Wesselingh, Steven L.; Reiss, Peter; Mallal, Simon

2003-01-01

Background: A number of international research groups have developed DNA quantitation assays in order to investigate the role of mitochondrial DNA depletion in anti-retroviral therapy-induced toxicities. Objectives: A collaborative study was undertaken to evaluate intra-assay precision and between

A study on intensifying efficiency for international collaborative development of advanced nuclear energy technology

Energy Technology Data Exchange (ETDEWEB)

Lee, J. H.; Hahn, D. H.; Song, K. C.; Chang, J. H.; Kim, H. J.; Kim, H. J.; Lim, C. Y.; Lee, D. S.; Lee, Y. J. [KAERI, Daejeon (Korea, Republic of)

2011-03-15

The objective of the study was to participate the GIF for the efficient propulsion of future nuclear system development. For achieving the objective of this study, the followings were carried out. {Omicron} Analyze the international/domestic trends in the future nuclear energy system {Omicron} Analyze the domestic long-term R and D program for the future nuclear system and assist its implementation - Review the agenda of the executive committee, the technical committee, and sub-technical committee - Assist the committee meetings and workshops related to the future nuclear energy system {Omicron} Develop the participation strategy for the collaborative development of Gen-IV technology and conducting the international cooperation activities - Support the delegation by reviewing the agenda of GIF meetings in the technical and legal perspective - Research the system R and D arrangement and report its progress - Participate in the SFR SIA PA negotiation meeting and report its progress {Omicron} Support the activities related to I-NERI between Korea and U.S. - Support a delegation by reviewing the agenda in the technical/legal point of view - Participate in the BINERIC meetings and Support the related activities The result of this study may be used for 1) contribution to establishing the effective foundation and broadening the cooperation activities between the advanced countries and Korea and 2) contribution effective management of Gen IV international collaboration by technical/legal supporting

A study on intensifying efficiency for international collaborative development of advanced nuclear energy technology

International Nuclear Information System (INIS)

Lee, J. H.; Hahn, D. H.; Song, K. C.; Chang, J. H.; Kim, H. J.; Kim, H. J.; Lim, C. Y.; Lee, D. S.; Lee, Y. J.

2011-03-01

The objective of the study was to participate the GIF for the efficient propulsion of future nuclear system development. For achieving the objective of this study, the followings were carried out. Ο Analyze the international/domestic trends in the future nuclear energy system Ο Analyze the domestic long-term R and D program for the future nuclear system and assist its implementation - Review the agenda of the executive committee, the technical committee, and sub-technical committee - Assist the committee meetings and workshops related to the future nuclear energy system Ο Develop the participation strategy for the collaborative development of Gen-IV technology and conducting the international cooperation activities - Support the delegation by reviewing the agenda of GIF meetings in the technical and legal perspective - Research the system R and D arrangement and report its progress - Participate in the SFR SIA PA negotiation meeting and report its progress Ο Support the activities related to I-NERI between Korea and U.S. - Support a delegation by reviewing the agenda in the technical/legal point of view - Participate in the BINERIC meetings and Support the related activities The result of this study may be used for 1) contribution to establishing the effective foundation and broadening the cooperation activities between the advanced countries and Korea and 2) contribution effective management of Gen IV international collaboration by technical/legal supporting

Building an International Collaboration for GeoInformatics

Science.gov (United States)

Snyder, W. S.; Lehnert, K.; Klump, J.

2005-12-01

Geoinformatics (cyberinfrastructure for the geosciences) is being developed as a linked system of sites that provide to the Earth science community a library of research data research-grade tools to manipulate, mine, analyze and model interdisciplinary data, and mechanisms to provide the necessary computational resources for these activities. Our science is global in scope and hence, geoinformatics (GI) must be an international effort. How do we build this international GI? What are the main challenges presented by the political, cultural, organizational, and technical diversity of the global science community that we need to address to achieve a truly global cyberinfrastructure for the Geosciences? GI needs to be developed in an internet-like fashion establishing connections among independent globally distributed sites (`nodes') that will share, link, and integrate their data holdings and services. Independence of the GI pieces with respect to goals, scope, and approaches is critical to sustain commitment from people to build a GI node for which they feel ownership and get credit. This should not be fought by funding agencies - and certainly not by state and federal agencies. Communication, coordination, and collaboration are the core efforts to build the connections, but incentives and resources are required to advance and support them. Part of the coordination effort is development and maintenance of standards. Who should set these standards and govern their modification? Do we need an official international body to do so, and should this be a "governing body" or an "advisory body"? What role should international commissions and bodies such as CODATA/ICSU or IUGS-CGI, international societies and unions, the national geological surveys and other federal agencies play? Guidance from the science community is key to construct a system that geo-researchers will want to use, and that meets their needs. Only when the community endorses GI as a fundamental platform to

Committee for international collaborative research of medical and welfare apparatus; Iryo fukushi kiki kokusai kyodo kenkyu jigyo

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-03-01

The paper summarized activities for an investigational study on the international collaborative research project on the medical and welfare apparatus implemented in fiscal 1995. As investigation activities, the second meeting of information exchanges with E.U. and three north European countries was held following the meeting in fiscal 1994, and at the same time, information exchanges were made with organizations/institutions of industry/government/university in Germany, France and Canada. The study made it clear that Europe is also taking a direction of low-degree action diagnosis/care as Japan is. Further, concrete exchanges of information advanced and an awareness of the common issues was made clear such as the necessity of developing apparatus which meets the apparatus market and users` needs. As international collaborative activities, new methods of information exchanges were adopted such as the satellite meeting of the International MR Society, meetings with researchers who visited Japan. The satellite meeting of the International MR Society was favorably accepted by participants, and it was pointed out that it is important to continue the meeting in view of the materialization of themes, etc. 4 refs., 32 figs., 5 tabs.

Establishment of the international collaboration and licensing preparation planning for the specific design of a prototype SFR

International Nuclear Information System (INIS)

Kim, Y. G.; Joo, H. K.; Cho, C. H.; Yoo, J. W.; Lee, D. U.; Ahn, K. S.; Hwang, Y. S.

2013-05-01

The conceptual design of prototype of Gen IV SFR (PGSFR) will be early determined through the review of the international experts. After this, the technology demonstration plan and validation of fuel design will be determined in more detail. The project will be accomplished efficiently by introducing the proven technology already validated from the international collaboration. The conceptual design and its requirements of PGSFR will be reviewed by ANL, who has a lot of design experiences in the metal fueled SFR development. The collaboration with ANL has been done through Work For Others (WFO) contract, and the MOU was signed between SFRA and Terra Power(USA), and SFRA and IGCAR. The licensing issues raised during PFBR and FBTR licensing in India will be discussed and reflected into the PGSFR design by inviting the high level expert from India, for example Dr. Chetal in IGCAR. The specific design, technology validation plan and fuel development plan will be established in more detail through the annual International Technical Review Meeting (ITRM) and experimental facilities available from the international institute and companies, which will be the basis for shortening the project period and to reduce the development cost

Propionibacterium endocarditis: a case series from the International Collaboration on Endocarditis Merged Database and Prospective Cohort Study

NARCIS (Netherlands)

Lalani, Tahaniyat; Person, Anna K.; Hedayati, Susan S.; Moore, Laura; Murdoch, David R.; Hoen, Bruno; Peterson, Gail; Shahbaz, Hasan; Raoult, Didier; Miro, Jose M.; Olaison, Lars; Snygg-Martino, Ulrika; Suter, Fredy; Spelman, Dennis; Eykyn, Susannah; Strahilevitz, Jacob; van der Meer, Jan T.; Verhagen, Dominique; Baloch, Khaula; Abrutyn, Elias; Cabell, Christopher H.

2007-01-01

Propionibacterium species are occasionally associated with serious systemic infections such as infective endocarditis. In this study, we examined the clinical features, complications and outcome of 15 patients with Propionibacterium endocarditis using the International Collaboration on Endocarditis

Reducing selection bias in case-control studies from rare disease registries.

Science.gov (United States)

Cole, J Alexander; Taylor, John S; Hangartner, Thomas N; Weinreb, Neal J; Mistry, Pramod K; Khan, Aneal

2011-09-12

In clinical research of rare diseases, where small patient numbers and disease heterogeneity limit study design options, registries are a valuable resource for demographic and outcome information. However, in contrast to prospective, randomized clinical trials, the observational design of registries is prone to introduce selection bias and negatively impact the validity of data analyses. The objective of the study was to demonstrate the utility of case-control matching and the risk-set method in order to control bias in data from a rare disease registry. Data from the International Collaborative Gaucher Group (ICGG) Gaucher Registry were used as an example. A case-control matching analysis using the risk-set method was conducted to identify two groups of patients with type 1 Gaucher disease in the ICGG Gaucher Registry: patients with avascular osteonecrosis (AVN) and those without AVN. The frequency distributions of gender, decade of birth, treatment status, and splenectomy status were presented for cases and controls before and after matching. Odds ratios (and 95% confidence intervals) were calculated for each variable before and after matching. The application of case-control matching methodology results in cohorts of cases (i.e., patients with AVN) and controls (i.e., patients without AVN) who have comparable distributions for four common parameters used in subject selection: gender, year of birth (age), treatment status, and splenectomy status. Matching resulted in odds ratios of approximately 1.00, indicating no bias. We demonstrated bias in case-control selection in subjects from a prototype rare disease registry and used case-control matching to minimize this bias. Therefore, this approach appears useful to study cohorts of heterogeneous patients in rare disease registries.

NanoJapan: international research experience for undergraduates program: fostering U.S.-Japan research collaborations in terahertz science and technology of nanostructures

Science.gov (United States)

Phillips, Sarah R.; Matherly, Cheryl A.; Kono, Junichiro

2014-09-01

The international nature of science and engineering research demands that students have the skillsets necessary to collaborate internationally. However, limited options exist for science and engineering undergraduates who want to pursue research abroad. The NanoJapan International Research Experience for Undergraduates Program is an innovative response to this need. Developed to foster research and international engagement among young undergraduate students, it is funded by a National Science Foundation Partnerships for International Research and Education (PIRE) grant. Each summer, NanoJapan sends 12 U.S. students to Japan to conduct research internships with world leaders in terahertz (THz) spectroscopy, nanophotonics, and ultrafast optics. The students participate in cutting-edge research projects managed within the framework of the U.S-Japan NSF-PIRE collaboration. One of our focus topics is THz science and technology of nanosystems (or `TeraNano'), which investigates the physics and applications of THz dynamics of carriers and phonons in nanostructures and nanomaterials. In this article, we will introduce the program model, with specific emphasis on designing high-quality international student research experiences. We will specifically address the program curriculum that introduces students to THz research, Japanese language, and intercultural communications, in preparation for work in their labs. Ultimately, the program aims to increase the number of U.S. students who choose to pursue graduate study in this field, while cultivating a generation of globally aware engineers and scientists who are prepared for international research collaboration.