bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spontaneous regression of congenital leukaemia with an 8;16 translocation
Authors: Weintraub Michael , Kaplinsky Chaim , Amariglio Ninette , Rosner Esther , Brok‐Simoni Frieda , Rechavi Gideon 
Published: July 2010

Congenital leukaemia (CL) is a rare disorder that presents with extramedullary infiltrates and a myeloid phenotype. CL can progress rapidly without adequate treatment, but, paradoxically, may also remit spontaneously. Because of the significant toxicity involved in delivering chemotherapy to newborns, it is important to identify those newborns who may not require treatment. We describe an infant who presented at 1 week of age with congenital myeloid leukaemia. Cytogenetic analysis revealed a t(8;16)(q11;p13) translocation. The infant's leukaemia underwent a spontaneous regression. This case further confirms the possibility of spontaneous remission in congenital leukaemia. Moreover, it suggests that the presence of a clonal cytogenetic aberration does not preclude the possibility of a spontaneous regression in CL.
Cyclosporin A response and dependence in children with acquired aplastic anaemia: a multicentre retrospective study with long‐term observation follow‐up
Authors: Saracco Paola , Quarello Paola , Iori Anna Paola , Zecca Marco , Longoni Daniela , Svahn Johanna , Varotto Stefania , Del Vecchio Gian Carlo , Dufour Carlo , Ramenghi Ugo , Bacigalupo Andrea , Locasciulli Anna ,   on behalf of the Bone Marrow Failure Study Group of the AIEOP (Italian Association of Paediatric Haematology Oncology)
Published: July 2010

SummaryImmunosuppressive therapy (IST) with antithymocyte globulin and cyclosporin A (CyA) is the standard treatment for children with acquired aplastic anaemia (AAA) lacking a matched donor. Survival rates of more than 80% at 5 years are achieved, but the response is drug‐dependent in 15–25% of cases. This study, of 42 consecutive children with AAA treated with IST, assessed the incidence of CyA‐dependence, CyA and granulocyte colony‐stimulating factor (G‐CSF) tapering schedules and the impact of drug accumulation on progression to myelodysplasia/acute myeloid leukaemia (MDS/AML). Overall survival was 83% at 10 years. CyA‐dependence without a predictive marker was observed in 18% of responders. Probability of discontinuing CyA was 60·5% at 10 years; a slow CyA tapering schedule was performed in 84% of patients; the cumulative incidence of relapse was 16% at 10 years. Relapse risk was significantly associated with rapid CyA discontinuation: 60% compared to 7·6% in the slow tapering group (P = 0·001). Cumulative incidence of MDS/AML was 8% at 10 years, with a significant correlation with both G‐CSF cumulative dose and second IST. This long‐term follow‐up of children with AAA shows that IST with a slow CyA tapering course is an effective treatment with a low‐relapse rate in these cases.
Considerations in the approach to invasive fungal infection in patients with haematological malignancies
Authors: Bow Eric J. 
Published: July 2010

SummaryInvasive infections because of opportunistic yeasts and moulds have contributed significantly to the morbidity and mortality associated with potentially curative treatment for haematological malignancies. Many risk factors have been identified that permit the clinician to predict the likelihood of these infections. The diagnostic process involves maintaining a high index of suspicion based upon an understanding of the clinical circumstances under which invasive fungal infections occur, of the spectrum of fungal syndromes, and of the advantages and limitations of diagnostic testing strategies now available. Treatment strategies may be categorized as prophylactic, pre‐emptive, empiric, or directed based upon the circumstances. The therapeutic options have increased in recent years but are not applicable to all clinical circumstances. These considerations are discussed.
Genetic variation and susceptibility to infection: the red cell and malaria
Authors: Weatherall D. J. 
Published: July 2010

SummaryThere is now convincing evidence that the extremely high frequencies of certain genetic disorders of the red cell involving haemoglobin, the red‐cell membrane, or its metabolic pathways reflect relative resistance to malaria over thousands of years. At least some progress has been made towards an understanding of the cellular mechanisms involved, although much remains to be learnt. As well as the extremely valuable information that this field is providing about how exposure to infection has moulded the current structure of the human genome, recent research in this field is starting to provide some valuable new approaches to the better control of parasitic and other infections that remain a major global health problem.
An introduction to induced pluripotent stem cells
Authors: Hanley Joanna , Rastegarlari Ghasem , Nathwani Amit C. 
Published: July 2010

SummaryRecent landmark studies show that it is now possible to convert somatic cells, such as skin fibroblasts and B lymphocytes, into pluripotent stem cells that closely resemble embryonic stem cells. These induced pluripotent stem (iPS) cells can be generated without using human embryos or oocytes, thus bypassing some of the ethical issues that have limited the use of human embryonic stems (hES) cells. Additionally, they can be derived from the patient to be treated, thereby overcoming problems of immunological rejection associated with the use of allogeneic hES cell derived progenitors. Whilst these patient‐specific iPS cells have great clinical potential, their immediate utility is likely to be in drug screening and for understanding the disease process. This review discusses the promise of iPS cells as well as the challenges to their use in the clinic.
Suppression of experimental allergic encephalomyelitis by intraventricular administration of interferon-gamma in Lewis rats
Authors: VOORTHUIS J A C , UITDEHAAG B M J , DE GROOT C J A , GOEDE P H , MEIDE P H VAN DER , DIJKSTRA C D 
Published: July 2010

SUMMARYExperimental allergic encephalomyelitis (EAE) is an autoimmune inflammatory disease of the central nervous system (CNS) which causes paralysis. Several studies have reported the involvement of Ia antigen-expressing cells in the pathogenesis of EAE. Interferon-gamma (IFN-γ) can induce Ia antigen expression on a wide range of cells. We examined the effect of IFN-γ on EAE in Lewis rats. Systemically administered IFN-γ did not change the disease course of EAE, whereas IFN-γ applied locally into the ventricular system of the CNS resulted in complete suppression of clinical signs. Furthermore, we found that systemic administration of anti-IFN-γ just prior to the onset of clinical symptoms resulted in a more severe disease course. We conclude that IFN-γ is capable of exerting a suppressive action in EAE, possibly through induction of Ia antigen expression or through the induction of suppressive mechanisms locally in the CNS.
Autoantibodies to mitochondrial and centromere antigens in primary biliary cirrhosis and systemic sclerosis
Authors: MCHUGH N J , JAMES I E , FAIRBURN K , MADDISON P J 
Published: July 2010

SUMMARYHigh levels of IgG antibodies to the multi-enzyme complex bovine pyruvate dehydrogenase (PDHC) were detected by a sensitive ELISA in all patients with histologically proven primary biliary cirrhosis (PBC), in a minority of patients with systemic sclerosis without overt PBC or with chronic liver diseases of another cause and in no rheumatoid arthritis or normal controls. Most (15/21) but not all of these positive patients recognized a 70-kD (E2) component of PDHC on immunoblotting. Additional recognition of a centromere-associated 140-kD polypeptide was associated with the presence of scleroderma-like features (Raynaud's phenomenon and sclerodactyly) in PBC, further emphasizing the serological and clinical overlap between these two conditions.
Recognition of synthetic peptides of Sm-D autoantigen by lupus sera
Authors: BARAKAT S , BRIAND J-P , WEBER J-C , VAN REGENMORTEL M H V , MULLER S 
Published: July 2010

SUMMARYThe reactivity of autoantibodies present in the serum of patients with systemic lupus erythematosus (SLE) was investigated by ELISA using seven overlapping synthetic peptides representing the entire sequence of the polypeptide D component of ‘Sm antigen’. Of the 165 SLE sera tested, 59% were found to contain IgG antibodies able to bind to peptide 1–20, while 37% of the sera reacted with peptide 44–67. All sera reacting with peptide 44–67 also reacted with peptide 1–20. These two peptides were only seldom recognized by the sera of 187 patients with other rheumatic autoimmune diseases or by 53 sera of normal individuals. In a parallel study using sera that reacted with the D band in immunoblotting, most of the sera recognized peptides 44–67 (89%) and 1–20 (67%), while 33% of them reacted with peptide 97–119. The use of these synthetic peptides in ELISA may be of considerable help for detecting anti Sm autoantibodies.
Cross-reactive idiotypes in sera from patients with leprosy, lupus and Lyme disease and from healthy individuals
Authors: MACKWORTH-YOUNG C G 
Published: July 2010

SUMMARYMonoclonal IgM autoantibodies have previously been generated from a patient with lepromatous leprosy. Polyclonal anti-idiotypes raised against two of these monoclonal antibodies (8E7 and TH9) were used in an immunoassay to detect the presence of idiotype in human serum. The anti-idiotypes recognize different but overlapping sets of idiotypic determinants, some of which are present on antibodies which bind to Mycobacterium leprae. Sera were tested from 16 individuals with leprosy. 45 with systemic lupus erythematosus. 20 with Lyme disease, and 80 healthy subjects. Positive sera were detected in all groups (seven, two, three, and four, respectively). In most cases the serum bound to both anti-idiotypes, the idiotype being present in the IgM and/or IgG fraction. Levels of the two idiotypes varied independently of total serum IgG concentration and, in serial serum samples from one patient, independently of each other. The results indicate that 8E7 and TH9 may be representative of serum antibodies which are commonly expressed in leprosy, but may also be expressed in other diseases and in health; and they suggest that such scrum antibodies are encoded by a widely shared set of variable region genes.
Stimulation of the respiratory burst and promotion of bacterial killing in human granulocytes by intravenous immunoglobulin preparations
Authors: MARÓDI L , KALMÁR A , KARMAZSIN L 
Published: July 2010

SUMMARY
We have examined the effect of two i.v. immunoglobulin preparations on the metabolic and functional activities of neutrophil granulocytes from the peripheral blood. Production of superoxide anion (O2) by granulocytes was measured through superoxide dismutase inhibitable reduction of ferricytochrome C after incubation of cells for various times together with immunoglobulin (concentration ranging from 0.25 to 5.0 mg/ml). The results showed dose-dependent response of O2 production independent of the incubation time. Granulocytes containing ingested Staphylococcus aureus released a significantly (P &lt; 0.001) larger amount of O2 and killed a higher number (P &lt; 0.001) of viable bacteria in the presence of 5 mg/ml immunoglobulin than did cells incubated in the absence of extracellular i.v. immunoglobulin. These data raise the possibility that immunoglobulin concentrates for i.v. use may enhance the anti-bacterial activities of phagocytic cells through direct stimulation of the respiratory burst. Inflammatory reactions observed during i.v. immunoglobulin infusion in hypo- or agammaglobulinaemic patients may also be related to phagocytic cell activation.
Synovial fluid antigen-presenting cells unmask peripheral blood T cell responses to bacterial antigens in inflammatory arthritis
Authors: LIFE P F , VINER N J , BACON P A , GASTON J S H 
Published: July 2010

SUMMARYWe and others have previously shown that synovial fluid (SF) mononuclear cells (MC) from patients with both reactive arthritis and other inflammatory arthritides proliferate in vitro in response to bacteria clinically associated with the triggering of reactive arthritis. In all cases, such SFMC responses are greater than the corresponding peripheral blood (PB) MC responses, often markedly so, and the mechanism for this is unclear. We have investigated this phenomenon by comparing the relative abilities of irradiated non-T cells derived from PB and SF to support autologous T cell responses to ReA-associated bacteria. Seven patients whose SFMC had been shown previously to respond to bacteria were studied. We demonstrate antigen-specific responses of PB T cells to bacteria in the presence of SF non-T cells which are in marked contrast to the minimal responses of either unfractionated PBMC or PB T cells reconstituted with PB non-T cells. We also show that PB, but not SF T cells respond strongly to autologous SF non-T cells in the absence of antigen or mitogen. These findings demonstrate that SF antigen-presenting cells (APC) are potent activators of PB T cells. We conclude that the contrasting responses of SFMC and PBMC to bacterial antigens may be accounted for at least in part by an enhanced ability of SF APC to support T cell proliferative responses.
Repeated exposure to bacterial lipopolysaccharide interferes with disposal of pathogenic immune complexes in mice
Authors: CAVALLO T , GRANHOLM N A 
Published: July 2010

SUMMARYPatients with systemic lupus erythematosus (SLE) experience clinical flares in association with superimposed bacterial infection. To investigate whether heightened immune phenomena during the course of bacterial infections were related to abnormal disposal of immune complexes, we administered bacterial lipopolysaccharide (LPS) to C57BL/6 mice for 5 weeks. Control mice received vehicle only. We then challenged the mice with a subsaturating dose of radiolabelled immune complexes intravenously and determined the localization of immune complexes in liver, spleen and kidney. In comparison to control mice, mice exposed to LPS developed features of polyclonal B cell activation, autoimmune phenomena, delayed removal of immune complexes from the circulation, diminished liver uptake of immune complexes, and enhanced localization of immune complexes in the kidneys. The findings could not be attributed to biological processes dependent on complement concentration. Instead, interferences with Fc receptor function, or with endocytosis of immune complexes may represent likely possibilities. Thus, clinical flares in patients with SLE, in the presence of a superimposed infection, may result from enhanced localization of immune complexes in organs due to altered mechanisms of their disposal.
Experimental studies of immunologically mediated enteropathy. V. Destructive enteropathy during an acute graft-versus-host reaction in adult BDF1 mice
Authors: MOWAT A McI , FELSTEIN M V 
Published: July 2010

SUMMARYAs a means of investigating further the pathogenesis of intestinal immunopathology, we have attempted to produce a destructive enteropathy by inducing an acute graft-versus-host reaction (GVHR) in mature, immunocompetent mice. Adult (C57B1/10 × DBA/2)F1 (BDF1) mice given C57B1/10 (B10) spleen cells develop a severe GVHR which is associated with marked weight loss and high mortality. In the intestine an initial phase of enteropathy characterized by intense crypt hyperplasia is replaced by more severe intestinal damage which includes villus atrophy and loss of intra-epithelial lymphocytes. These pathological alterations are paralleled by the generation of anti-host cytotoxic T lymphocytes (CTL). marked immunosuppression and the loss of natural killer (NK) cells. In contrast to these findings, adult BDF1 mice given DBA/2 donor cells do not develop an acute systemic GVHR and have no CTL or intestinal pathology, despite prolonged splenomegaly and enhanced NK cell activity. Thus, destructive enteropathy can be induced during a GVHR in intact hosts and our results confirm that this enteropathy has a biphasic pattern, with villus atrophy representing the progression of initial crypt hyperplasia in severe forms of disease associated with weight loss and specific CTL.
Human monoclonal IgM with autoantibody activity against two gangliosides (GM1 and GDlb) in a patient with motor neuron syndrome
Authors: JAUBERTEAU M O , GUALDE N , PREUD'HOMME J L , RIGAUD M , GIL R , VALLAT J M , BAUMANN N 
Published: July 2010

SUMMARYSmall amounts of oligoclonal immunoglobulins were detected by Western blotting in the serum from a patient with motor neuron syndrome. The prominent one. a monoclonal IgMλ, reacted strongly with the gangliosides GM1 and GDlb and more weakly with asialo GM1, as shown by immunoenzymatic staining of thin-layer chromatograms of gangliosides, ELISA on purified glycolipid coats and immunoadsorption with purified GM1. Affinity-chromatography with purified GMI resulted in the purification of monoclonal IgMλ. This purified IgM and its Fab fragments showed the same pattern of reactivity with gangliosides as that observed with whole serum. Such monoclonal IgM could be responsible for motor neuron diseases in some patients with overt or barely detectable monoclonal gammopathies.
Aberrant IgG subclass distribution to measles in healthy seropositive individuals, in patients with SSPE and in immunoglobulin-deficient patients
Authors: MATHIESEN T , HAMMARSTRÖM L , FRIDELL E , LINDE A , WIRSEN G , SMITH C I E , NORRBY E , WAHREN B 
Published: July 2010

SUMMARYSera from healthy seropositive donors, patients with acute measles, subacute sclerosing panencephalitis, common variable immunodeficiency, and CH gene deletions were analysed for anti-measles IgG1–4. Compared with other anti-viral immune responses of IgGl and IgG3, an unusual predominance of specific IgGl prevailed; only four out of a total of 68 patients showed anti-measles IgG3. Of the 17 healthy, measles seropositive serum donors, all showed specific IgGl, none showed IgG3 and six had IgG4. Eight out of 10 patients with SSPE showed an anti-measles IgGl and IgG4 response while IgG3 was not seen. The IgGl and IgG4 subclass patterns had some exceptions. Antimeasles IgG3 was found in five out of five patients with deletion of the γ-1 encoding gene segments and in four out of 15 patients with recent measles antigen stimulation. The subclass pattern was suggested to reflect the immunological compromise associated with measles infections.
Echinococcus granulosus: the potential use of specific radiolabelled antibodies in diagnosis by immunoscintigraphy
Authors: ROGAN M T , MORRIS D L , PRITCHARD D I , PERKINS A C 
Published: July 2010

SUMMARYDiagnosis of hydatid disease in man is frequently dependent on the imaging of cysts in situ by techniques such as ultrasonography and CAT scans. Such methods are useful but are not specific and can lead to errors in diagnosis. The present work reports preliminary experiments on the development of a specific imaging technique for hydatid cysts using radiolabelled antibodies. A purified preparation of antigen B of hydatid fluid was used to raise polyclonal antisera in rabbits and the resulting affinity-purified IgG labelled with 131I. Gerbils with an established Echinococcus granulosus infection were injected intraperitoneally with the labelled antibody and imaged 48 h later with a gamma camera. Hydatid cysts could be identified within the peritoneal cavity and post-mortem assessment of activity showed the cysts to contain approximately four times as much activity as the surrounding organs thereby indicating successful targeting of the antibody to the cysts.
A phenotypic study of B lymphocyte subpopulations in human bone marrow
Authors: CHAPPLE M R , MACLENNAN I C M , JOHNSON G D 
Published: July 2010

SUMMARYThe regulatory mechanisms that monitor the size of the peripheral B cell pool and determine cell death or survival are poorly understood. In rodents B lymphopoiesis is maintained at a high rate throughout adult life, and under resting conditions there is little recruitment into the long-lived peripheral pool; it therefore follows that most newly formed B lymphocytes have a very short life-span. The maturation stages of B lymphopoiesis in humans and in experimental mammals appear to be similar. We have determined the phenotype of sIgM- and sIgD-expressing cells from normal adult human bone-marrow and peripheral blood by dual immunofluorescence with an extensive panel of monoclonal antibodies representative of major B cell clusters, in order to identify antigenic differences that may play a regulatory role. Antibodies of the CD21, CD22 and CD9 clusters, the unclustered restricted B antibody 7-F-7 and anti-IgD were reactive with different proportions of sIgM+ cells in blood and bone marrow; 29·5% (range 5·60%) of sIgM+ cells in marrow were sIgD−and most of these cells were also CD21− and CD22−, thus defining a unique marrow population. However, newly formed and mature re-circulating cells comprising the sIgM+ sIgD+ population could not be distinguished by the panel of antibodies.
Lymphocyte activation markers in idiopathic myositis: changes with disease activity and differences among clinical and autoantibody subgroups
Authors: MILLER F W , LOVE L A , BARBIERI S A , BALOW J E , PLOTZ P H 
Published: July 2010

SUMMARYWe studied the immunologic correlates of disease activity and differences among subgroups of patients with idiopathic inflammatory myopathy by analysing phenotypic and activation marker expression on peripheral blood mononuclear cells (PBMC). Compared with controls, myositis patients with clinically active disease (n = 51) had significantly lower proportions of CD8- cells and higher proportions of PBMC that expressed DR. CD3- DR, CD14- DR, interlcukin-2 receptors. and the late T cell activation markers CD26 and TLiSA1. TLiSA1 expression, a marker for cytotoxic differentiation, correlated significantly with both clinical activity indices and serum levels of muscle-associated enzymes. In serial studies of seven patients, the proportion of PBMC expressing MHC class II antigen and late T cell activation markers decreased as myositis disease activity decreased, independent of type of therapy. Among the clinical subgroups, polymyositis (n= 21) and inclusion body myositis (n=21) were virtually indistinguishable; dcrmatomyositis patients (n= 19) showed decreased proportions of CD3+DR+ and TLiSA1+ cells, and increased proportions of CD20+ and CD20+ DR+ cells compared with the other two groups. Patients with autoantibodies to histidyl-tRNA synthctasc (Jo-1 antigen. n= 11) had significantly lower proportions of CD3+ andCD4+ cells, lower CD4/CD8 ratios, and higher proportions of DR+ cells expressing CD20, compared with patients without anti-Jo-1 antibodies. These findings support the concept that activated lymphocytes, especially cells undergoing anamnestic responses and cytotoxic differentiation, are important in the pathogenesis of idiopathic myositis. Moreover, taken together with other studies, these data suggest that groups of patients segregated by clinical or autoantibody status have different mechanisms of systemic immune activation and immunopathology.