bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk factors for development of a second lymphoid malignancy in patients with chronic lymphocytic leukaemia
Authors: Maddocks‐Christianson Kami , Slager Susan L. , Zent Clive S. , Reinalda Megan , Call Timothy G. , Habermann Thomas M. , Bowen Deborah A. , Hoyer James D. , Schwager Susan , Jelinek Diane F. , Kay Neil E. , Shanafelt Tait D. 
Published: July 2010

SummaryPrevious studies suggested that patients with chronic lymphocytic leukaemia (CLL) are at a three‐ to fivefold increased risk of developing a second lymphoproliferative disorder (LPD). This observational cohort study used the Mayo Clinic CLL Database to identify factors associated with developing a second LPD. A second LPD was identified in 26 (2·7%) of 962 CLL patients during a median follow‐up of 3·3 years. Diffuse large B‐cell lymphoma was the most common subtype of secondary LPD (12 of 26 cases). Patients previously treated for CLL had a trend toward higher prevalence of second LPD (4%) compared with previously untreated patients (2%; P = 0·053). More strikingly, patients treated with purine nucleoside analogues (PNA) had a significantly increased risk of subsequent second LPD (5·2%) compared with patients who had not received PNA (1·9%; P = 0·008). No statistically significant association was observed between risk of second LPD and other CLL characteristics (ZAP‐70, CD38, IgVH mutation status or cytogenetic abnormalities). In this series, prior treatments with PNA or anthracyclines were the only significant factors associated with risk of developing a second LPD in patients with CLL. Physicians should strictly adhere to established criteria to initiate treatment for CLL patients who are not participating in clinical trials.
Influence of human leucocyte antigen disparity and graft lymphocytes on allogeneic engraftment and survival after umbilical cord blood transplant in adults
Authors: Van Heeckeren Willem J. , Fanning Laura R. , Meyerson Howard J. , Fu Pingfu , Lazarus Hillard M. , Cooper Brenda W. , Tse William W. , Kindwall‐Keller Tamila L. , Jaroscak Jennifer , Finney Marcie R. , Fox Robert M. , Solchaga Luis , Forster Margaret , Creger Richard J. , Laughlin Mary J. 
Published: July 2010

SummaryThe dose of graft‐nucleated cells and CD34+ haematopoietic progenitor cells are predictors of allogeneic engraftment and survival in umbilical cord blood (UCB) recipients. In this single institution prospective phase II trial, flow cytometric analyses of CD34+ progenitor and lymphocyte populations in unmodified single unit human leucocyte antigen (HLA)‐disparate UCB grafts infused into 31 consecutive adults (median age 41 years, range 20–64) receiving myeloablative conditioning were compared with clinical outcomes. Median infused UCB graft‐nucleated cells and CD34+ dose was 2·2 × 107/kg and 1·2 × 105/kg respectively. Day to absolute neutrophil count ≥0·5 × 109/l with full donor chimerism averaged 27 d (range 12–41). Univariate analyses demonstrated that UCB graft‐infused cell doses of CD34+ (P = 0·015), CD3+ (P = 0·024) and CD34+HLADR+CD38+ progenitors (P = 0·043) correlated with neutrophil engraftment. This same analysis did not demonstrate a correlation between CD34+ (P = 0·11), CD3+ (P = 0·28) or CD34+HLADR+CD38+ (P = 0·108) cell dose and event‐free survival (EFS). High‐resolution matching for HLA‐class II (DRB1) resulted in improved EFS (P = 0·02) and decreased risk for acute graft‐versus‐host disease (GVHD) (P = 0·004). Early mortality (prior to post‐transplant day +28) occurred in three patients, while 26 patients achieved myeloid engraftment. These results suggest that UCB graft matching at DRB1 is an important risk factor for acute GVHD and survival, while higher UCB graft cell doses of CD34+, committed CD34+ progenitors and CD3+ T cells favourably influence UCB allogeneic engraftment.
Familial myelodysplasia and acute myeloid leukaemia – a review
Authors: Owen Carolyn , Barnett Michael , Fitzgibbon Jude 
Published: July 2010

SummaryFamilial occurrence of myelodysplasia (MDS) and/or acute myeloid leukaemia (AML) is rare but can provide a useful resource for the investigation of predisposing mutations in these myeloid malignancies. To date, examination of families with MDS/AML has lead to the detection of two culprit genes, RUNX1 and CEBPA. Germline mutations in RUNX1 result in familial platelet disorder with propensity to myeloid malignancy and inherited mutations of CEBPA predispose to AML. Unfortunately, the genetic cause remains obscure in most other reported pedigrees. Further insight into the molecular mechanisms of familial MDS/AML will require awareness by clinicians of new patients with relevant family histories.
The influence of prednisolone on the recirculation of peripheral blood lymphocytesin vivo
Authors: BLOEMENA E , WEINREICH S , SCHELLEKENS P T A 
Published: July 2010

SUMMARYIn humans and in laboratory animals, administration of a single dose of glucocorticosteroids induces a rapid and transient decrease in the numbers of peripheral blood lymphocytes through a redistribution of circulating lymphocytes. This lymphocytopenic effect is an important factor in the immunosuppressive capacity of corticosteroids. We have investigated whether the redistribution is due to an increased influx of circulating lymphocytes from the blood into the lymphoid organs or to a decreased efflux from the organs. Fluoresceinated lymphocytes were injected intravenously in unrestrained normal and prednisolone-treated rabbits and the distribution curves in the peripheral blood were analysed on the basis of a two-compartment model (known from pharmacokinetic studies). In this way. it is shown that the rapid fall in peripheral blood lymphocyte numbers induced by prednisolone is due to a decreased efflux of circulating lymphocytes from the lymphoid organs. In addition, it is demonstrated that prolonged infusion of prednisolone leads to an altered distribution pattern of the circulating lymphocytes among the organs.
Haemorrhage produces depressions in alloantigen-specific immune responses in the mouse through activation of suppressor T cells
Authors: CHANG Y H , JAGELS M , ABRAHAM E 
Published: July 2010

SUMMARYThe development of cell-mediated and humoral immune responses in BALB/c mice (H-2d) directed toward El4 cells (H-2b) was suppressed (cell-mediated cytotoxicity, 40–50% of control; antibody titres 127±17 versus 287±17 in controls) following haemorrhage of 30% total blood volume. This haemorrhage-induced depression of immune response can be transferred to normal recipients with T cells (3 × 107) from haemorrhaged syngeneic donors. Flow microfluorimetry (FMF) analysis showed no shift in CD8:CD4 ratios following haemorrhage. These results suggest that haemorrhage suppresses immune response through activation of suppressor T cells.
T activation marker evaluation in ARC patients treated with AZT. Comparison with CD4+ lymphocyte count in non-progressors and progressors towards AIDS
Authors: LEVACHER M , TALLET S , DAZZA M C , DOURNON E , ROUVEIX B , POCIDALO J J 
Published: July 2010

SUMMARYReductions in the percentage and absolute number of CD4+ lymphocytes, as well as abnormally high levels of activated peripheral T lymphocytes (CD3+ HLA-DR+ phenotype) and an increased proportion of CD8+ cells coexpressing the CD57 surface antigen (involved in natural killer activity) have been reported in HIV infection and associated with disease progression. We prospectively measured these subsets of lymphocytes in 34 patients with advanced AIDS-related complex (ARC) treated with azidothymidine (AZT). Peripheral blood lymphocyte phenotyping was performed before treatment, then at weeks 12 and 24. A striking fall in the proportion of activated T lymphocytes from baseline was observed (P &lt; 0.001) at week 24. In contrast, the percentage of CD4+ cells showed a slight and transient rise at week 12 (P&lt;0.05). No modification in levels of CD8+ or CD8+ CD57+ cells was detected during the study. Of the 34 patients, 11 developed AIDS, and 23 remained AIDS-free during 51 weeks of follow-up. Similar patterns of change in CD4+ and HLA-DR+ CD3+ lymphocytes were found in the AIDS progressors and nonprogressors. Likewise, HIV p24 antigenaemia showed parallel decreases in both groups of patients. Although changes in CD4+ cells, p24 antigenaemia and HLA-DR-reactive T lymphocytes were not predictive of clinical outcome, large differences existed between the two groups prior to the initiation of therapy. The short-term onset of AIDS was associated with lower CD4+ cell numbers, higher levels of serum p24 antigen and a greater proportion of activated T lymphocytes. Our results suggest that the possible interest of T lymphocyte activation markers, in conjunction with conventional phenotyping, should be investigated further.
Antibody binding and inhibition of pyruvate dehydrogenase (PDH) in sera from patients with primary biliary cirrhosis
Authors: SUNDIN U 
Published: July 2010

SUMMARYAutoantibodies reactive against mitochondria which are present in sera from patients with primary biliary cirrhosis (PBC) have been shown to bind to the lipoamidc acctyltransferase moiety (E2) of the pyruvate dehydrogenase enzyme complex (PDH). This newly described antigen has been shown to be identical to M2, a 70-kD antigen of the inner mitochondrial membrane. Sera from 10 patients with PBC, 11 patients with chronic active hepatitis (CAH), 20 healthy controls and patients with thyroiditis and systemic lupus erythematosus (SLE) were tested by ELISA for the presence of antibodies (IgG and IgM classes and IgG subclasses) reactive against PDH. The effect of serum and separated IgG and IgM on the PDH enzyme activity was measured spectrophotometrically. Nine out of 10 PBC sera were positive by immunofluorescence for mitochondria (M2 pattern). These nine sera reacted strongly with both IgG and IgM to PDH in the ELISA and also inhibited the enzyme activity by 80% (s.d. 25%). This was significantly different compared with the controls (4 ± 6%: P&lt;0.001). Enzyme inhibition was mainly caused by IgG. Of all control sera (from healthy and patient individuals) only one patient with CAH reacted significantly in the tests. This CAH patient had a high antibody titre against mitochondria as measured by immunofluorescence.
Anti-cardiolipin antibodies and HIV infection
Authors: MACLEAN C , FLEGG P J , KILPATRICK D C 
Published: July 2010

SUMMARY
Anti-cardiolipin antibodies of IgG class were found in 48% of intravenous drug users, 38% of homosexuals and 14% of heterosexuals (with no other risk factor) infected with HIV. Anti-cardiolipin antibodies were not increased in HIV-negative heterosexual partners of HIV-infected patients, but mildly elevated levels were detected in HIV-negative drug users, relative to healthy controls unselected for HIV status. Among HIV infected drug users, anti-cardiolipin antibodies were more common in men (P=0.01). Anti-cardiolipin antibodies were not associated with thrombocytopenia, Pneumocystis carinii pneumonia, disease progression or clinical stage. Anti-cardiolipin antibodies appear to be another non-specific marker of HIV infection which may be particularly common in male intravenous drug users infected with the virus.
Immune activation and T cell subset abnormalities in circulation of patients with recently diagnosed type I diabetes mellitus
Authors: AL-KASSAB A S , RAZIUDDIN S 
Published: July 2010

SUMMARYThe peripheral blood lymphocytes from patients with insulin-dependent diabetes mellitus (IDDM) and healthy controls were analysed for the HLA-DR+, interleukin-2 receptor-positive (IL-2R+) activating antigens, and for CD45R+ and CDw29+ subsets from the purified CD4+ and CD8+ T cell populations. Patients with IDDM had an increased percentage of HLA-DR+ and IL-2R+ cells in both CD4+ and CD8+ T cells. However, the percentage of CD4+CD45R+ suppressor/inducer T cells were decreased and CD4+CDw29+ helper/inducer T cells increased in all patients with IDDM, compared with healthy controls. Thus, IDDM patients exhibit a deficiency in the CD4+CD45R+ suppressor/inducer T cell subsets, which is probably related to the autoimmune phenomenon in this disease. In contrast, the percentage of CD8+CD45R+ and CD8+CDw29+ T cell subsets showed no major differences between patients with IDDM and controls. An alteration in the CD4+CD45R+ and CD4+CDw29+ T cell subsets appears to be a characteristic feature, and may relate to the impaired cell-mediated immunity in IDDM. These data provide new evidence for T cell dysregulation in IDDM.
Characterization of the binucleated giant cells generated in the autologous mixed leucocyte reaction from patients with rheumatoid arthritis
Authors: GOTO M , TSAI V , ZVAIFLER N J 
Published: July 2010

SUMMARYBinucleated giant cells several limes larger than lymphocytes or monocytes were generated in an autologous mixed leucocyte reaction (AMLR) independent of DNA synthesis in patients with rheumatoid arthritis (RA). The AMLR giant cells with multiple cytoplasmic granules were nonspecific esterase-staining positive, phagocytic, non-adherent, HLA-DR+, CD11b+, CD14+, 4F2+, CDW29+, and anti-transferrin receptor positive, but negative for T, B or NK markers. RA patients aged less than 60 years form more giant cells: 12.6 ± 13.5% (n= 33) as compared with 0.4±1.5% in age- and sex-matched normals (n= 38) (P&lt;0.001). More giant cells were seen over age 60 in both groups: RA 20.1 ± 15.5% (n=5) and healthy controls 3.0 ±3.2% (n= 8) (P&lt;0.01). Neither disease activity nor treatment appear to influence the result in RA. The giant cells that are probably derived from monocytcs in AMLR may explain the formation of the giant cells in rheumatoid granulation tissues.
Detection of transforming growth factor-beta in rheumatoid arthritis synovial tissue: lack of effect on spontaneous cytokine production in joint cell cultures
Authors: BRENNAN F M , CHANTRY D , TURNER M , FOXWELL B , MAINI R , FELDMANN M 
Published: July 2010

SUMMARYThe presence of transforming growth factor-beta (TGF-β) in inflammatory joint disease was investigated. Synovial fluid from patients with rheumatoid arthritis (RA) and patients with other non-autoimmune inflammatory joint diseases contained high levels of both active and latent TGF-β. Levels of active TGF-β did not correlate with drug regimen in either patient group or with the recovery period in the individuals with non-RA joint disease. Freshly isolated synovial cells from individuals with RA were shown by Northern blotting to express the mRNA for TGF-β1 and to secrete latent TGF-β protein which could be neutralized by antibodies to TGF-β1 and TGF-β2. Lipopolysaccharide-stimulated peripheral blood mononuclear cells from normal donors produced interleukin-l (IL-1) and tumour necrosis factor-alpha (TNF-α) which was inhibited by pretreatment of these cells with recombinant TGF-β. Cytokine production was not inhibited if the addition of TGF-β was used after the inducing stimulus, suggesting that in activated cells cytokine production cannot be inhibited. This was confirmed by the observation that neither TGF-β1 or TGF-β2 inhibited spontaneous IL-1 or TNF-α production by rheumatoid synovial mononuclear cells in culture. These findings show that despite the presence of active TGF-β in RA synovial joints and the spontaneous production of latent (potentially active) TGF-β by RA cells in culture, additional TGF-β did not inhibit ongoing cytokine synthesis in vitro. This suggests that TGF-β may not inhibit cytokine production in the rheumatoid joint although it cannot be ruled out that in rivo TGF-β already has an immunosuppressive effect which cannot be further increased in vitro by exogenous protein.
A primed state exists in vivo following histological regression of amyloidosis
Authors: HAWKINS P N , PEPYS M B 
Published: July 2010

SUMMARY
Using a sensitive, quantitative, and non-invasive in vivo method, based on the specific binding of serum amyloid P component to amyloid fibrils, we have directly documented the spontaneous resolution of AA amyloid deposits in mice, and the prolonged existence thereafter of a primed state of enhanced susceptibility to further amyloid deposition. These results may have important implications for understanding and management of amyloidosis in humans.
Sequential measurement of the murine acute-phase protein serum amyloid P component (SAP) as an indicator of graft-versus-host disease following allogeneic bone marrow transplantation in mice
Authors: BAYSTON K F , HUBY R , COHEN J 
Published: July 2010

SUMMARYMurine models of bone marrow transplantation (BMT) are used commonly for studies of the pathogenesis and treatment of graft-versus-host disease (GVHD). We report here that the sequential measurement of the mouse acute-phase protein SAP can be used to provide a sensitive, quantitative index of the severity of GVHD. Thirty mice underwent allogeneic, and a further 30 syngeneic BMT. GVHD w as assessed in vivo by clinical appearances and weight change, and post mortem by histology and calculation of splenic indices. Blood was obtained twice/week for SAP measurement and blood culture. In all mice an initial rise in SAP levels due to irradiation was followed by a return to baseline. Thereafter in syngeneic marrow recipients levels remained low. In contrast, after allogeneic BMT SAP levels rose progressively as mice developed GVHD, reaching a peak of 135 μg ml prior to death, from a nadir at day 20 of 15 μg ml. Mice with high splenic indices and histological evidence of severe GVHD had significantly higher SAP levels than mice with mild GVHD (P=0.002). Elevation in SAP levels occurred independently of bacteraemia. We conclude that in murine BMT sequential measurement of SAP provides an objective means of assessing GVHD in tiro.
Graft-versus-host reactions in the rat mimic toxin-induced autoimmunity
Authors: TOURNADE H , PELLETIER L , PASQUIER R , VIAL M C , MANDET C , DRUET P 
Published: July 2010

SUMMARYGold salts, d-penicillamine or mercurials induce autoimmunity in Brown Norway (BN) rats and provoke an immunosuppression in Lewis (LEW) rats. It has been suggested that immunologically mediated manifestations induced by drugs could result from graft-verves-host (GVH) like reactions. We show that BN spleen cells transferred into (LEW × BN)FI hybrids induce a chronic GVH reaction (GVHR). This reaction led to an autoimmune disease quite similar to that induced by drugs in BN rats. In both situations, a common part of the B cell repertoire is triggered. In contrast. LEW spleen cells transferred into (LEW × BN)FI hybrids provoke a lethal GVHR. This is to be compared with the CD8-mediated immunosuppression observed in LEW rats injected with HgCI2. These findings are in agreement with the prediction that immune dysregulation induced by drugs leads to GVH-like reactions either stimulatory or suppressive depending upon the strain tested.
Monocyte disorder causing cellular immunodeficiency: a family study
Authors: PRIETO J , SUBIRÁ M L , CASTILLA A , CIVEIRA M P , SERRANO M 
Published: July 2010

SUMMARYWe report a familial type of monocyte dysfunction not recognized previously. This disorder was observed in a young adult man with a long clinical history of recurrent, sell-limited episodes of cryptogenic fever accompanied by digestive and respiratory symptoms and repeated oral and skin infections. Lectin-induced lymphocyte transformation was reduced and skin tests revealed anergy to tuberculin and candidin. Monocytes from this patient exhibited markedly diminished expression of cytoskeletal vimentin intermediate filaments. HLA-DR antigens and immunological receptors for IgG Fc and C3b. These abnormal monocytes demonstrated impaired phagocytosis and reduced accessory cell function on PHA-mediated lymphoeyte activation. Release of soluble lymphocyte-activating factors by these cells was found to be defective. Lymphocytes from the patient responded appropriately to lectin in the presence of normal monocytes. Two family members of the proband presented similar monocyte defects although they only manifested minor clinical symptoms. This syndrome underlines the interest of testing monocyte markers and function in subjects with clinical manifestations of immunodeficiency.
Effect of human intestinal macrophages on immunoglobulin production by human intestinal mononuclear cells isolated from patients with inflammatory bowel disease
Authors: WU K C , MAHIDA Y R , PRIDDLE J D , JEWELL D P 
Published: July 2010

SUMMARYThe effect of macrophages on spontaneous immunoglobulin production by isolated human intestinal mononuclear cells (MNC) is unknown. Depietion of macrophages by adherence to fibronectin or by panning with macrophage-specific monoclonal antibody 3C10 lead to a significant reduction in IgA, IgG and lgM production by intestinal MNC from both normal (n= 10) and inflammatory bowel disease (IBD) (n= 13) mucosa. The reduction in immunoglobulin produced by macrophage-depleted intestinal MNC was greater in IBD patients than in normal controls. There was a significant correlation (r=0·816, P&lt;0·001) between the percentage of macrophages depleted by panning with 3C10 and the reduction in IgG produced by macrophage-depleted intestinal MNC. Addition of either fibronectin-adherent cells or the supernatant from these macrophage-enriched cells enhanced immunoglobulin production in a dose-dependent fashion. A greater increase in IgG production by macrophage-depleted cells was seen when cultured with supernatant from inflamed IBD mucosal cells, compared with that from normal mucosal cells. The soluble factor(s) responsible in the supernatant was acid and heat susceptible but was not affected by freezing and thawing. Addition of recombinant human interleukin-1β or human interferon-gamma to cell cultures did not influence immunoglobulin production. Thus, human intestinal macrophages enhance spontaneous immunoglobulin production by isolated intestinal MNC by secreting soluble factor(s) which remain to be fully characterized.
Immunoregulatory CD4+ CD45R+ suppressor/inducer T lymphocyte subsetsand impaired cell-mediated immunity in patients with Down's syndrome
Authors: RAZIUDDIN S , ELAWAD M E 
Published: July 2010

SUMMARYThe monoclonal antibodies 2H4 and 4B4 allow CD4+ and CD8+ T lymphocytes to be subdividedinto CD45R+ and CDW29+ functional subpopulations. The CD4+ CD45R+ lymphocytes aredesignated as suppressor/inducer and CD4+ CDW29+ as helper/inducer subsets. Peripheral bloodlymphocytes from 19 patients with Down's syndrome and 19 age- and sex-matched normal controlswere analysed for the CD45R+ and CDW29+ subsets from the CD4+ and CD8+ T lymphocytes. Thepercentage of CD4+ CD45R+ cells (suppressor inducer) was markedly increased and of CD4+CDW29+ cells (helper/inducer) decreased in all patients with Down's syndrome. In contract, thepercentage of CD8+ CD45R+ and CD8+ CDW29+ subsets showed no major differences betweenpatients with Down's syndrome and normal controls. Moreover, an alteration in the CD4+ andCD45R+ and CD4+ CDW29+ T cell subsets was accompanied by a markedly reduced proliferativeresponse to phytohaemagglutinin and concanavalin A stimulation of the CD4+ T lymphocytes. Thus, a deficiency exists in patients with Down's syndrome in the CD4+ CDW29+ helper/inducerT cell subset which may contribute to their impaired cell-mediated immunity.