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Age- and sex-specific incidence of childhood leukemia by immunophenotype in the Nordic countries.

https://arctichealth.org/en/permalink/ahliterature18160
Source
J Natl Cancer Inst. 2003 Oct 15;95(20):1539-44
Publication Type
Article
Date
Oct-15-2003
Author
Lisa Lyngsie Hjalgrim
Klaus Rostgaard
Kjeld Schmiegelow
Stefan Söderhäll
Svein Kolmannskog
Kim Vettenranta
Jon Kristinsson
Niels Clausen
Mads Melbye
Henrik Hjalgrim
Göran Gustafsson
Author Affiliation
Department of Epidemiology Research, Danish Epidemiology Science Centre, Statens Serum Institut, Copenhagen, Denmark. lih@ssi.dk
Source
J Natl Cancer Inst. 2003 Oct 15;95(20):1539-44
Date
Oct-15-2003
Language
English
Publication Type
Article
Keywords
Adolescent
Age Distribution
Child
Child, Preschool
Female
Finland - epidemiology
Humans
Iceland - epidemiology
Immunophenotyping
Incidence
Infant
Infant, Newborn
Leukemia, Lymphocytic, Acute, L1 - epidemiology - genetics
Leukemia, Myelocytic, Acute - epidemiology - genetics
Male
Poisson Distribution
Research Support, Non-U.S. Gov't
Scandinavia - epidemiology
Sex Distribution
Abstract
BACKGROUND: Studies from various countries have found an increasing incidence of childhood leukemia in recent decades. To characterize time trends in the age- and sex-specific incidence of childhood acute leukemia during the last 20 years in the Nordic countries, we analyzed a large set of population-based data from the Nordic Society of Paediatric Haematology and Oncology (NOPHO) in their acute leukemia database covering a population of approximately 5 million children aged 0-14 years. METHODS: Temporal trends in acute myeloid leukemia and acute lymphoblastic leukemia incidence rates overall and for acute lymphoblastic leukemia immunophenotypes and for specific age groups were analyzed by Poisson regression adjusting for age, sex, and country. All statistical tests were two-sided. RESULTS: We identified 1595 girls and 1859 boys diagnosed with acute lymphoblastic leukemia between January 1, 1982, and December 31, 2001, and 260 girls and 224 boys diagnosed with de novo acute myeloid leukemia between January 1, 1985, and December 31, 2001. No statistically significant change was seen in the overall incidence rate for acute lymphoblastic leukemia during the 20-year study (annual change = 0.22%, 95% confidence interval [CI] = -0.36% to 0.80%). The incidence rate of B-precursor acute lymphoblastic leukemia remained unchanged (annual change = 0.30%, 95% CI = -0.57% to 1.18%) from January 1, 1986, through December 31, 2001. A somewhat lower incidence in the first years of the study period indicated an early increasing incidence of B-precursor acute lymphoblastic leukemia that corresponded to a simultaneous decreasing incidence of unclassified acute lymphoblastic leukemia. Incidences of T-cell acute lymphoblastic leukemia (annual change = 1.55%, 95% CI = -1.14% to 4.31%) and acute myeloid leukemia (annual change = 0.58%, 95% CI = -1.24% to 2.44%) were stable during the study period. CONCLUSION: Incidences of acute myeloid leukemia overall, acute lymphoblastic leukemia overall, and specific acute lymphoblastic leukemia immunophenotypes have been stable in the Nordic countries over the past two decades.
PubMed ID
14559876 View in PubMed
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Ag-specific recognition, activation, and effector function of T cells in the conjunctiva with experimental immune-mediated blepharoconjunctivitis.

https://arctichealth.org/en/permalink/ahliterature50675
Source
Invest Ophthalmol Vis Sci. 2003 Oct;44(10):4366-74
Publication Type
Article
Date
Oct-2003
Author
Atsuki Fukushima
Akemi Ozaki
Kazuyo Fukata
Waka Ishida
Hisayuki Ueno
Author Affiliation
Department of Ophthalmology, Kochi Medical School, Nankoku City, Japan. fukusima@kochi-ms.ac.jp
Source
Invest Ophthalmol Vis Sci. 2003 Oct;44(10):4366-74
Date
Oct-2003
Language
English
Publication Type
Article
Keywords
Animals
Blepharitis - immunology
Blotting, Western
Chemokines - metabolism
Conjunctiva - immunology
Conjunctivitis - immunology
Cytokines - metabolism
Epitopes - immunology
Flow Cytometry
Fluoresceins
Immunoenzyme Techniques
Immunophenotyping
Lymphocyte Activation - physiology
Male
Mice
Mice, Inbred BALB C
Ovalbumin - immunology
Rats
Rats, Inbred BN
Receptors, Chemokine - metabolism
Research Support, Non-U.S. Gov't
Reverse Transcriptase Polymerase Chain Reaction
Succinimides
T-Lymphocytes - physiology
Abstract
PURPOSE. To investigate antigen (Ag) specificity, activation, and effector function of the Ag-specific T cells involved in the development of experimental immune-mediated blepharoconjunctivitis (EC), an experimental conjunctivitis. METHODS. EC was induced in Brown Norway rats by injection of ovalbumin (OVA)-specific T cells followed by OVA challenge with eye drops. Eyes, including the conjunctivas, were harvested at different time points after challenge. The dependence of EC onset on the challenging Ag was assessed by challenge with an irrelevant Ag or stimulatory OVA peptides. To show the infiltration of transferred T cells into the conjunctiva, T cells were labeled with 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester (CFSE) before transfer. The activation of T cells in the conjunctiva was assessed by measuring phosphorylation of Lck-associated molecules by Western blot analysis. Conjunctivas were also examined by immunohistochemistry and used for reverse transcription-polymerase chain reaction to determine the phenotype of the infiltrating cells and cytokine, chemokine, and chemokine receptor expression. To investigate infiltration of non Ag-specific T cells into the conjunctiva, ragweed (RW)-primed lymphocytes were transferred into OVA-specific T-cell receptor transgenic (DO11.10) mice. The mice were then challenged with RW and the conjunctivas were harvested for immunohistochemistry to detect T cells derived from DO11.10 mice. RESULTS. EC was induced only when challenged with OVA protein or stimulatory OVA peptides, and CFSE-labeled transferred cells were found in the conjunctiva. Phosphorylation of Lck and an 85-kDa Lck-associated molecule were observed in the conjunctiva 6 hours after challenge. Many cytokines and chemokines began to be expressed at 6 hours, and individual expression patterns over time correlated well with the infiltration patterns of different inflammatory cells. In DO11.10 mice that received RW-primed lymphocytes, T cells derived from the recipient mice infiltrated the conjunctiva after RW challenge. CONCLUSIONS. Ag-specific T cells initiate EC by first infiltrating the conjunctiva, where they become activated by the specific Ag in the conjunctiva.
PubMed ID
14507881 View in PubMed
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Analysis of Ag-presenting cells in the conjunctiva during the development of experimental immune-mediated blepharoconjunctivitis.

https://arctichealth.org/en/permalink/ahliterature50604
Source
Curr Eye Res. 2004 Oct-Nov;29(4-5):277-86
Publication Type
Article
Author
Akemi Ozaki
Atsuki Fukushima
Waka Ishida
Olga Zinchuk
Kazuyo Fukata
Yoshihiro Hayashi
Hideaki Enzan
Masaru Takata
Hideo Yagita
Hisayuki Ueno
Author Affiliation
Department of Ophthalmology, Kochi Medical School, Kohasu, Oko-cho, Nankoku City 783-8505, Japan.
Source
Curr Eye Res. 2004 Oct-Nov;29(4-5):277-86
Language
English
Publication Type
Article
Keywords
Animals
Antigen-Presenting Cells - immunology
Antigens, CD - metabolism
Antigens, CD86
Blepharitis - immunology
Blotting, Western
Cell Count
Conjunctiva - immunology
Conjunctivitis, Allergic - immunology
Extracellular Signal-Regulated MAP Kinases - metabolism
Flow Cytometry
Histocompatibility Antigens Class II - metabolism
Immunoenzyme Techniques
Immunophenotyping
Lymphocyte Activation
Macrophages - immunology
Male
Membrane Glycoproteins - metabolism
Microscopy, Confocal
Models, Theoretical
Ovalbumin - immunology
Phosphorylation
Rats
Rats, Inbred BN
T-Lymphocytes - immunology
Abstract
PURPOSE: The aim of this study was to investigate the phenotypes of antigen (Ag) presenting cells (APCs) in the conjunctiva during the development of experimental immune-mediated blepharoconjunctivitis (EC), which serves as a model for investigation of severe types of human allergic conjunctivitis. METHODS: Brown Norway rats treated by ovalbumin (OVA) were used in this study. To confirm the restriction of MHC class II by OVA-specific T cells, monoclonal Abs against MHC class II were added to the conventional proliferation assay. To evaluate the MHC class II expression in the conjunctiva during the development of EC, an immunohistochemical analysis, either as the single or double staining, was performed. Conjunctival fibroblast cell lines were established from naive rats and the MHC class II expression was evaluated by flow cytometric analysis. To examine the roles of costimulatory molecules, OVA-specific T cells were stimulated with anti-TcR Ab and anti-CD28 Ab and then subjected for Western blotting to evaluate the ERK phosphorylation. Finally, in vivo expression of B7 molecules was examined immunohistochemically. RESULTS: OVA-specific T cells recognized OVA in the context of MHC class II. MHC class II was expressed in conjunctival macrophages but not in fibroblasts. EC induction was accompanied by abundant infiltration of macrophages positive for MHC class II. MHC class II was also expressed in conjunctival epithelial cells by EC induction. Stimulation from CD28 was necessary for ERK phosphorylation. B7-2, but not B7-1, was expressed in the conjunctiva. CONCLUSION: Conjunctival macrophages may represent a major source of APCs for the induction of EC in the conjunctiva.
PubMed ID
15590473 View in PubMed
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Analysis of blood lymphocyte subsets in children living around Chernobyl exposed long-term to low doses of cesium-137 and various doses of iodine-131.

https://arctichealth.org/en/permalink/ahliterature32778
Source
Radiat Res. 2000 Jun;153(6):760-72
Publication Type
Article
Date
Jun-2000
Author
E V Vykhovanets
V P Chernyshov
I I Slukvin
Y G Antipkin
A. Vasyuk
V. Colos
Author Affiliation
Laboratory of Immunology, Institute Pediatrics, Obstetrics and Gynecology, Academy of Medical Science of Ukraine, Kiev, Ukraine.
Source
Radiat Res. 2000 Jun;153(6):760-72
Date
Jun-2000
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Adolescent
Cesium radioisotopes
Child
Dose-Response Relationship, Drug
Humans
Immunophenotyping
Iodine Radioisotopes
Lymphocyte Subsets - immunology - radiation effects
Power Plants
Thyroid Gland - radiation effects
Ukraine
Abstract
Epidemiological studies have found that children living around Chernobyl have rates of respiratory tract illness that are higher than those seen in the area before the Chernobyl accident. The present study investigates the possible effects of radiation exposure on the composition of peripheral blood lymphocyte subsets in children living around Chernobyl. Two hundred nineteen healthy children and children suffering from recurrent respiratory diseases aged 6-14 years who received both low doses of radiation to the whole body from (137)Cs and various doses of radiation to the thyroid from (131)I as fallout from the accident were assessed 5 (1991) and 8-10 years (1994-1996) after the accident. A total of 148 healthy children and children suffering from recurrent respiratory diseases living in noncontaminated areas were also evaluated as controls. Children with recurrent respiratory diseases who lived around Chernobyl had a significantly lower percentage of T cells and a higher percentage of NK cells compared to control children with recurrent respiratory diseases during the study period. In contrast to the findings in 1991, a significant decrease in the percentage of helper-inducer cells was observed in children with recurrent respiratory diseases in 1994-1996. In contrast to 1991, there is a positive correlation between the percentage of helper-inducer cells, the helper-inducer/cytotoxic-suppressor cell ratio, and the dose of radiation to the thyroid of healthy children from (131)I in 1994-1996. There was a positive correlation between the dose of radiation to the thyroid from (131)I and the percentage of helper-inducer cells in children with recurrent respiratory diseases 5 years (1991) after the accident. Further, the dose of radiation to the thyroid from (131)I correlated negatively with the percentage of T and B cells and positively with the percentage of NK cells in children with recurrent respiratory diseases 8-10 years (1994-1996) after the accident. These results raise the possibility that long-term exposure to low doses of (137)Cs may have altered the composition of the T-cell subsets and NK cells in children with recurrent respiratory diseases. The differences in the composition of the peripheral blood lymphocyte subsets between healthy children and those with recurrent respiratory diseases may be attributed to long-term low-dose exposure of the whole body to radiation from (137)Cs and exposure of the thyroid to radiation from (131)I subsequent to the Chernobyl accident.
PubMed ID
10825751 View in PubMed
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Antimyeloperoxidase-associated proliferative glomerulonephritis: an animal model.

https://arctichealth.org/en/permalink/ahliterature57724
Source
J Exp Med. 1993 Apr 1;177(4):905-14
Publication Type
Article
Date
Apr-1-1993
Author
E. Brouwer
M G Huitema
P A Klok
H. de Weerd
J W Tervaert
J J Weening
C G Kallenberg
Author Affiliation
Department of Clinical Immunology, University Hospital, Groningen, The Netherlands.
Source
J Exp Med. 1993 Apr 1;177(4):905-14
Date
Apr-1-1993
Language
English
Publication Type
Article
Keywords
Animals
Antibodies - immunology
Basement Membrane - immunology
Disease Models, Animal
Fluorescent Antibody Technique
Glomerulonephritis - enzymology - immunology
Humans
Hydrogen Peroxide - metabolism
Immunophenotyping
Kidney - enzymology - immunology - metabolism
Microscopy, Electron
Perfusion
Peroxidase - immunology - metabolism
Precipitin Tests
Rats
Research Support, Non-U.S. Gov't
T-Lymphocytes - immunology
Abstract
To develop an animal model for antimyeloperoxidase (MPO)-associated necrotizing crescentic glomerulonephritis (NCGN), we immunized Brown Norway rats with MPO and localized a neutrophil lysosomal enzyme extract, primarily consisting of MPO and elastinolytic enzymes, plus H2O2, the substrate of MPO, to the glomerular basement membrane (GBM). Upon immunization rats developed antibodies and positive skin tests to MPO. After unilateral perfusion of the left kidney with the lysosomal enzyme extract and H2O2, MPO and immunoglobulin (Ig)G localized transiently along the GMB. At the time of maximal inflammation, at 4 and 10 d after perfusion, MPO, IgG, and C3 could not be detected anymore. MPO-immunized rats perfused with the lysosomal enzyme extract and H2O2, in contrast to control-immunized and/or control-perfused rats, developed a proliferative GN characterized by intra- and extracapillary cell proliferation, ruptured Bowman's capsule, periglomerular granulomatous inflammation, and formation of giant cells. Monocytes, polymorphonuclear leukocytes (PMN), and to a far lesser extent T cells were found in the glomeruli. Interstitial infiltrates consisted of monocytes, PMN, and T cells. Granulomatous vasculitis of small vessels was found at 10 d after perfusion. The proliferative NCGN in this rat model closely resembles human anti-MPO-associated pauci-immune NCGN, and enables the study of the pathophysiology of anti-MPO-associated NCGN.
PubMed ID
8384653 View in PubMed
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Assessment of an efficient xeno-free culture system of human periodontal ligament stem cells.

https://arctichealth.org/en/permalink/ahliterature266376
Source
Tissue Eng Part C Methods. 2015 Jan;21(1):52-64
Publication Type
Article
Date
Jan-2015
Author
Oriana Trubiani
Adriano Piattelli
Valentina Gatta
Marco Marchisio
Francesca Diomede
Marco D'Aurora
Ilaria Merciaro
Laura Pierdomenico
Nadir Mario Maraldi
Nicoletta Zini
Source
Tissue Eng Part C Methods. 2015 Jan;21(1):52-64
Date
Jan-2015
Language
English
Publication Type
Article
Keywords
Adult
Cell Culture Techniques - methods
Cell Differentiation
Cell Proliferation
Cell Shape
Cells, Cultured
Flow Cytometry
Gene Expression Regulation
Humans
Immunophenotyping
Karyotyping
Multipotent Stem Cells - cytology
Osteogenesis - genetics
Periodontal Ligament - cytology
Stem Cells - cytology - ultrastructure
Young Adult
Abstract
The possibility of transplanting adult stem cells into damaged organs has opened new prospects for the treatment of several human pathologies. The purpose of this study was to develop a culture system for the expansion and production of human Periodontal Ligament Stem Cells (hPDLSCs) using a new xeno-free media formulation and ensuring the maintenance of the stem cells features comprising the multiple passage expansion, mesengenic lineage differentiation, cellular phenotype, and genomic stability, essential elements for conforming to translation to cell therapy. Somatic stem cells were isolated from the human periodontium using a minimally invasive periodontal access flap surgery in healthy donors. Expanded hPDLSCs in a xeno-free culture showed the morphological features of stem cells, expressed the markers associated with pluripotency, and a normal karyotype. Under appropriate culture conditions, hPDLSCs presented adipogenic and osteogenic potential; indeed, a very high accumulation of lipid droplets was evident in the cytoplasm of adipogenic-induced cells, and indisputable evidence of osteogenic differentiation, investigated by transmission electron microscopy, and analyzed for gene expression analysis has been shown. Based on these data, the novel xeno-free culture method might provide the basis for Good Manufacturing Procedure culture of autologous stem cells, readily accessible from human periodontium, and can be a resource to facilitate their use in human clinical studies for potential therapeutic regeneration.
Notes
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PubMed ID
24787358 View in PubMed
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Autoimmune phenomena in non-Hodgkin's lymphoma.

https://arctichealth.org/en/permalink/ahliterature23154
Source
Leuk Lymphoma. 1995 Jul;18(3-4):311-6
Publication Type
Article
Date
Jul-1995
Author
K. Grønbaek
F. D'Amore
K. Schmidt
Author Affiliation
Department of Haematology, Odense University Hospital, Denmark.
Source
Leuk Lymphoma. 1995 Jul;18(3-4):311-6
Date
Jul-1995
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Aged, 80 and over
Autoimmune Diseases - etiology - mortality
Denmark
Female
Humans
Immunophenotyping
Lymphoma, Non-Hodgkin - immunology - mortality
Male
Middle Aged
Prognosis
Registries
Reproducibility of Results
Retrospective Studies
Survival Rate
Abstract
In order to obtain valid data on the pattern, frequency and prognostic significance of autoimmune derangements in non-Hodgkin's lymphoma (NHL) we studied 626 consecutive adult NHL patients participating in a population-based lymphoma registry. A total of 86 patients, corresponding to 13.7%, showed autoimmune phenomena (AP). Of these, 7.8% exhibited clinical autoimmune phenomena (CAP), and 5.9% showed immunohaematological phenomena (IHP). The distribution of histological subgroups of NHL in the AP and non-AP patients was similar. The same holds true for the CAP and IHP patients. A slight, non-significant overrepresentation of NHL, T-cell phenotype was found in patients with AP. CAP preceded the diagnosis of NHL in most patients, whereas IHP was associated with active lymphoma disease. AP as a whole did not predict for time to complete response, time to relapse or for survival. The finding that IHP patients relapsed earlier than CAP patients was not reflected in a significant difference in survival.
PubMed ID
8535198 View in PubMed
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B-cell lineage confers a favorable outcome among children and adolescents with large-cell lymphoma: a Pediatric Oncology Group study.

https://arctichealth.org/en/permalink/ahliterature214620
Source
J Clin Oncol. 1995 Aug;13(8):2023-32
Publication Type
Article
Date
Aug-1995
Author
R E Hutchison
C W Berard
J J Shuster
M P Link
T E Pick
S B Murphy
Author Affiliation
State University of New York Health Science Center, Syracuse, USA.
Source
J Clin Oncol. 1995 Aug;13(8):2023-32
Date
Aug-1995
Language
English
Publication Type
Article
Keywords
Adolescent
Antigens, CD30 - metabolism
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Canada
Chi-Square Distribution
Child
Disease-Free Survival
Female
Humans
Immunophenotyping
Lymphoma, B-Cell - drug therapy - immunology - mortality
Lymphoma, Large B-Cell, Diffuse - drug therapy - immunology - mortality
Lymphoma, T-Cell - immunology - mortality - therapy
Male
Prognosis
Risk factors
United States
Abstract
The goal of this study was to assess the immunophenotype of uniformly treated cases of pediatric large-cell non-Hodgkin's lymphoma (NHL) to determine the prognostic importance of B-cell and T-cell lineages and of CD30 positivity.
Sixty-nine patients were analyzed by immunochemistry. All patients were classified histologically, staged in a uniform manner, and treated according to one of two protocols for localized (stage I and II) NHL or advanced (stage III and IV) large-cell NHL. Antibodies included anti-CD45, CD20, CD45Ra, MB-2 (not clustered), CD3, CD45Ro, CD43, CD15, CD30, and CD68. Statistical analysis used the exact conditional chi 2 and Kruskall-Wallace tests for clinical features and the log-rank test to evaluate event-free survival (EFS).
Immunophenotypic results demonstrated 25 B-cell, 23 T-cell, and 21 indeterminate lineage. Twenty-seven patients expressed CD30 (17 T-cell and 10 indeterminate lineage), and of these, 22 showed histology of anaplastic large-cell lymphoma (ALCL). B-cell patients were older (P = .018) and showed more favorable survival than patients with T-cell or indeterminate lineage (96% EFS at 3 years, 96% v 67% and 74%, B v T and indeterminate lineage [P = .027]). B-cell lineage was seen more frequently in limited-stage patients, but was also associated with favorable survival when stratified for stage (P = .036). CD30 expression (P = .96) and ALCL histology (P = .90) did not show significant associations with survival.
We conclude that among pediatric large-cell lymphomas, B-cell lineage is proportionately less frequent than in adults and CD30 antigen-expressing lymphomas are frequent among patients with T-cell and indeterminate lineage. B-cell phenotype tends to occur in older children and is associated with superior survival.
PubMed ID
7636544 View in PubMed
Less detail
Source
Int J Cancer. 1997 Jan 6;70(1):1-8
Publication Type
Article
Date
Jan-6-1997
Author
J. Avila-Cariño
N. Lewin
Y. Tomita
A. Szeles
A. Sandlund
S. Mosolits
H. Mellstedt
G. Klein
E. Klein
Author Affiliation
Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden. Javier.Avila-Carino@mtc.ki.se
Source
Int J Cancer. 1997 Jan 6;70(1):1-8
Date
Jan-6-1997
Language
English
Publication Type
Article
Keywords
Aged
Antigens, CD - metabolism
Cell Survival
Cell Transformation, Viral - physiology
Chromosomes, Human, Pair 18 - genetics
Chromosomes, Human, Pair 22 - genetics
Herpesvirus 4, Human - classification - immunology
Humans
Immunophenotyping
Leukemia, Lymphocytic, Chronic, B-Cell - genetics - immunology - pathology - virology
Male
Phenotype
T-Lymphocytes - immunology
T-Lymphocytes, Cytotoxic - immunology
Translocation, Genetic
Tumor Cells, Cultured
Tumor Markers, Biological - metabolism
Tumor Virus Infections - immunology
Viral Proteins - analysis
Abstract
In studies concerning the interaction of B-CLL cells and Epstein-Barr virus (EBV), we encountered one patient whose cells had several unusual properties. In addition to the B-cell markers, the CLL cells expressed the exclusive T-cell markers CD3 and CD8 and carried a translocation t(18,22)(q21;q11), involving the bcl-2 and Ig lambda loci. The patient represents the 4th reported CLL case with this translocation. The CLL cells could be infected and immortalized by the indigenous and by the prototype B958 virus in vitro. The T-cell markers were not detectable on the established lines. In all experiments the immortalized lines originated from the CLL cells. Their preferential emergence over virus-infected normal B cells may be coupled to the high expression of the bcl-2 gene due to the translocation. In spite of the sensitivity of CLL cells to EBV infection in vitro, no EBNA-positive cells were detected in the ex vivo population. In vitro, we could generate cytotoxic function in T-lymphocyte cultures which acted on autologous EBV-infected CLL cells. Therefore we assume that if such cells emerged in vivo they were eliminated by the T-cell response.
PubMed ID
8985083 View in PubMed
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Bone marrow transplantation for T-B- severe combined immunodeficiency disease in Athabascan-speaking native Americans.

https://arctichealth.org/en/permalink/ahliterature32178
Source
Bone Marrow Transplant. 2001 Apr;27(7):703-9
Publication Type
Article
Date
Apr-2001
Author
A S O'Marcaigh
K. DeSantes
D. Hu
H. Pabst
B. Horn
L. Li
M J Cowan
Author Affiliation
Department of Pediatrics Bone Marrow Transplant Division, University of California San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143-1278, USA.
Source
Bone Marrow Transplant. 2001 Apr;27(7):703-9
Date
Apr-2001
Language
English
Publication Type
Article
Keywords
B-Lymphocytes
Bone Marrow Transplantation - immunology - methods
Canada
Child, Preschool
Female
Follow-Up Studies
Haplotypes
Histocompatibility
Humans
Immunophenotyping
Indians, North American - genetics
Infant
Infant, Newborn
Lymphocyte Depletion
Male
Nuclear Family
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Severe Combined Immunodeficiency - complications - therapy
T-Lymphocytes
Tissue Donors
Treatment Outcome
United States
Abstract
A distinct form of autosomal recessive T-B- severe combined immunodeficiency disease occurs with a high frequency among Athabascan-speaking Native Americans (SCIDA), including Navajo and Apache Indians from the southwestern US and Dene Indians from the Canadian Northwest Territories. The SCIDA gene has been linked to markers on chromosome 10p although its identity and role in the pathogenesis of this disease are unknown. We report our experience in treating 18 Navajo and Dene children with SCIDA between 1984 and 1999; 16 underwent bone marrow transplants (BMT). All children were symptomatic within 2 months of birth, had the T-B- NK(+)SCID phenotype and 67% presented with oral and/or genital ulcers. Three children had evidence of maternal engraftment prior to transplant. Two children died shortly after diagnosis. Three children required more than one BMT and 12 are alive with T cell reconstitution at a median follow-up of 7 years. Three children developed normal B cell immunity, two of whom received ablative conditioning therapy with either radiation or busulfan. Three of the four children who died received therapy with either radiation or busulfan and two of eight long-term survivors who were also recipients of cytotoxic chemotherapy have failed to develop secondary teeth. These results demonstrate the efficacy of BMT in treating infants with this distinct form of SCID, although B cell reconstitution remains a problem even with HLA-matched donors. Without conditioning, T cell engraftment is likely when closely HLA-matched donors are used. With T cell depletion of haplocompatible marrow, conditioning with immunosuppressive therapy may be necessary; however, children with SCIDA who were treated with intensive immunosuppressive and myeloablative therapy had a poor outcome.
PubMed ID
11360109 View in PubMed
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