1,721,139 research outputs found
Formazione all’analisi terminologica e variazione interlinguistica: alcune riflessioni sul dominio giuridico
No full textSIDE EFFECTS FROM A DISTANCE AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION IN A PEDIATRIC POPULATION
No full textChildren and adolescents with acute lymphoblastic leukaemia in second remission given allogeneic haematopoietic stem cell transplantation in paediatric institutions have comparable outcome
No full text: IMATINIB MESYLATE INDUCES HIGH COMPLETE CYTOGENETIC AND MAJOR MOLECULAR RESPONSE RATES IN CHILDREN AND ADOLESCENTS WITH PHILADELPHIA CHROMOSOME-POSITIVE CHRONIC MYELOGENOUS LEUKAEMIA IN CHRONIC PHASE
No full textRegulatory T-cells are more resistant to genotoxic agents compared to effector T-cells
No full textBackground: Both host and graft regulatory T cells (Treg) may provide protection from graft-versus-host disease (GVHD) in the mouse system. Findings from a murine model of syngeneic GVHD suggest that host Treg preferentially survive a lethal dose of irradiation and confer protection from disease. In humans, various combinations of genotoxic agents are actually used for myeloablative conditioning. The sensitivity of human Treg to DNA damage induced apoptosis has so far not been investigated. Objective:To evaluate the resistance of Treg to apoptosis induced by genotoxic agents compared to effector T cells (Teff) in vitro.
Materials and methods: PBMC of healthy donors were exposed to either ionizing irradiation or etoposide. After incubation, samples were labelled with annexin V FITC or anti-activated caspase 3 FITC combined with monoclonal antibody conjugates to CD4, CD25 and CD127 or to surface antigen CD4 and transcription factor FoxP3. Propidium iodide or fixable infrared viability dye were included in the staining protocol as dead cell markers. The frequency of apoptotic cells among Treg and effector CD4+ T lymphocytes was determined by flow cytometric analysis at different time points (up to 72h). CD45RA staining was used to analyse the role of differentiation for resistance to apoptosis. Expression of anti-apoptotic proteins bcl-2 and Bcl-xL by Treg and Teff was compared.
Results: Both activation of caspase 3 and exposure of phosphatidylserine following DNA damage in vitro was observed with significantly higher frequency in Treg compared to effector CD4 lymphocytes. This effect was observed in both etoposide treated cultures and those exposed to ionizing irradiation. Similar results were obtained by identifying Treg as CD25highCD127- or as FoxP3+ events. The resistance to DNA damage by Treg could not be explained by their differentiation to a CD45RA negative memory phenotype. When measured as mean fluorescence intensity, anti-apoptotic proteins Bcl-2 and bcl-xL were not more expressed by Treg compared to Teff.
Conclusion: Our observations suggest a higher resistance to DNA damage of regulatory T cells compared to effector T cells in vitro. The higher resistance cannot be explained by differentiation to a memory phenotype or differential expression of anti-apopotic proteins bcl-2 and bcl-xL. The higher resistance to genotoxic agents of Treg could affect the relative size ratio of Treg to effector T cells following conditioning
OUTCOME OF CHILDREN (NON-INFANT) WITH T(4;11) POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA TREATED WITH AIEOP-LLA 2000-R2006 PROTOCOLS
No full textASSESSMENT DAY TESTING FIBRINOLYTICS IN PATIENTS AT RISK OF VOD AFTER TRANSPLANTATION OF HEMATOPOIETIC STEM CELLS: STUDY IN A PEDIATRIC POPULATION
No full textFocal Nodular Hyperplasia in Pediatric Patients With and Without Oncologic History
No full textThe diagnosis of FNH is warranted by the possibility of avoiding unnecessary hepatic resections. The 18 patients of our series, 6 of whom were long-term survivors of malignant, non-hepatic tumors, underwent either a biopsy or a complete excision to obtain the diagnosis. The imaging characteristics could not be considered pathognomonic. The lesion remained stable after the biopsy in 8 patients; no complications were observed in other 10 patients who underwent resection of the mass. The outcome of all our patients with or without previous oncological disease was benign
Inside and outside the liver: hepatitis-associated aplastic anaemia (haaa) in three paediatric cases.
No full textBackground: Hepatitis-associated aplastic anemia (HAAA) is a
variant of aplastic anemia (AA) in which pancytopenia appears two
to three months after an acute hepatitis [1]. The etiology of this
syndrome is still uncompletely clarified: a role of various hepatitis and
non hepatitis viruses (i.e. CMV, EBV and Parvovirus B19) has been
detected; genetic predisposition and immune-mediated mechanisms
(including imbalance of the T cell immune system and the response
to immunosuppressive therapy) are also considered to have a pivotal
role.
Specific aim:We report three paediatric cases with HAAA who where
successfully treated with haematopoietic stem cell transplantation
(HSCT) or with administration of anti-lymphocyte globulins.
Case serie: (1) A formerly healthy 9 year old boy was admitted to
our Unit of Paediatric Gastroenterology and Hepatology for detection
of elevated transaminases and GGT at blood tests prescribed for
sudden appearance of hecchymoses and petechiae at his limbs,
feet and face. No trauma had occurred. In the previous two
months, asthenia had been referred. Blood tests showed pancytopenia
and repeated transfusions of immunoglobulines and platelets were
required. CRP-DNA for Parvovirus B19 was positive both on blood
and on bone marrow aspirate. Bone marrow aspirate and bone
biopsy confirmed AA. Given the absence of any recovery of the
medullar function within one month of follow-up, a HSCT was
successfully performed thank to the HLA compatibility of one sibling.
(2) A 12 year old boy was evaluated at our Unit for jaundice with
acute onset. A diagnosis of Type 1 Autoimmune Hepatitis (AIH 1)
was based on both serologic profile and liver biopsy. The genetic
screening for thiopurine methyltransferase excluded mutations, so a
treatment with azathioprine was began to withdrawal corticosteroids.
Pancytopenia was detected after two weeks of therapy. The CRPDNA
for Parvovirus B19, initially negative at the time of AIH
1 diagnosis, turned out to be positive on both peripheral blood
Oral Communications / Digestive and Liver Disease 44 Suppl. 4 (2012) S241–S257 S251
and bone marrow. Pancytopenia persisted with a worsening trend
until the appearance of clinical signs (major epistaxis, ecchymoses)
and repeated administrations of immunoglobulins, platelets and
erythrocytes were needed. A bone biopsy evidenced AA. HSCT
was finally required, and the existence of a HLA compatible twin
made it feasible. (3) A 3 year old boy was admitted at our Unit for
acute jaundice and detection of leucopenia, thrombocytopenia and
elevated transaminases. Infusions of platelets and erythrocytes were
required, given a progressive worsening of the bone marrow function.
A bone biopsy evidenced AA. An immunosuppressive treatment
with anti-lymphocyte globulins, cyclosporine, methylprednisolone
was administered, together with G-CSF. No infective causes were
detected. The bone marrow and liver function increased significantly
until a final recovery, so that no bone marrow transplantation was
needed.
Discussion: Diagnosis of HAAA includes clinical manifestations,
blood profiling, viral testing, immune functioning and bone marrow
examination. Patients presenting the features of HAAA are mostly
treated with HSCT from HLA matched donor. Immunosuppressive
therapy has a minor efficacy, as far as it is currently demonstrated.
Table
Pts Clinical onset AST/
ALT
(U/L)
GGT
(U/L)
Parvovirus
B19 DNA
PCR on
blood
and bone
marrow
Ig adm.
and blood
component
transfusions
Anti-lymphocyte
globulins and/or
G-CSF Adm.
Allogeneic
HSCT
Follow-up
since
diagnosis
Current
clinical
and
haemat.
outcome
Pt 1 Hecchymoses
and petechiae
at limbs,
feet and face
Asthenia
1284/
2949
111 Positive Yes No Yes 1 year Good
Pt 2 Jaundice
major
epistaxis
ecchymoses at
limbs
540/
780
94 Positive Yes No Yes 5 months Good
Pt 3 Jaundice 1357/
2322
230 No Yes Yes No 10 years Good
Pt: Patient, Adm.: Administration, Ig: Immunoglobulines, Transpl: Transplantation, Haemat.: Haematological,
HSCT: Haematopoietic Stem Cell Transplantation.
Reference(s)
[1] Rauff B, Idrees M, Shah SA, Butt S, Butt AM, Ali L, Hussain A, Irshad-
Ur-Rehman, Ali M. Hepatitis associated aplastic anemia: a review. Virol
J. 2011 Feb 28;8: 87
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