bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vincristine‐induced apoptosis in vivo in peripheral blood mononuclear cells of children with acute lymphoblastic leukaemia (ALL)
Authors: Groninger E. , de Graaf S. S. N. , Meeuwsen‐de Boer G. J. , Sluiter W. J. , Poppema S. 
Published: July 2010

We conducted a study to demonstrate vincristine‐induced apoptosis in vivo in peripheral blood mononuclear cells of children with newly diagnosed acute lymphoblastic leukaemia (ALL). In five children, apoptosis was detected by terminal deoxynucleotide transferase‐mediated dUTP‐digoxigenin nick‐end labelling (TUNEL) assay in blood samples collected during an up‐front window study of vincristine monotherapy. In one patient, we found a striking increase of apoptotic cells from 2% (SEM 0·6) before to 40·7% (SEM 2·9) 3 h after vincristine injection. In the other patients, the maximum increase ranged from 0·8% to 4·3%. Wilcoxon matched pairs analysis of all patients confirmed that vincristine induces apoptosis in vivo in peripheral blood mononuclear cells in childhood ALL (P = 0·043).
Cytokine requirement for the development of T‐lymphoid lineage potential in clonal lymphohaematopoietic progenitors in vitro
Authors: Ma Feng , Yang Feng‐Chun , Kaneko Azusa , Manabe Atsushi , Tanaka Ryuhei , Asano Shigetaka , Nakahata Tatsutoshi , Tsuji Kohichiro 
Published: July 2010

The early process of T‐cell development prior to thymic colonization has been poorly investigated because of the lack of a sensitive assay. We have developed a two‐step in vitro culture system by combining a clonal culture with a fetal thymus organ culture (FTOC) and analysed the early development of T cells from lymphohaematopoietic progenitors. Cells of immature colonies derived from bone marrow cells of 5‐fluorouracil (5FU)‐treated mice using various combinations of early acting cytokines were transferred into a FTOC. All the combinations of stem cell factor (SCF), interleukin (IL)‐3 and IL‐6 capable of inducing colony formation supported T‐cell generation. IL‐11 and the Flt3 ligand possessed T‐lineage promotional effects similar to IL‐6 and SCF respectively. However, there were some quantitative differences in the final T‐cell yield among cytokine combinations. Thus, the commitment towards T lineage in lymphohaematopoietic progenitors may be an event determined intrinsically rather than induced by specific stimuli, but there may be a hierarchy between the activity of cytokines in further development. Furthermore, we examined the T‐lineage potential of individual colonies derived from Lin−c‐Kit+Sca‐1+ cells clone‐sorted from post‐5FU marrow cells. No colonies that contained only myelocytic progenitors showed T‐lineage potential, but 23·3% of colonies with a haematopoietic multipotentiality did. Therefore, the divergence of the T lineage from other lineages such as myeloid potential may occur at an early stage of the hierarchy of haematopoiesis. The proposed method should prove valuable for exploring the molecular and cellular changes that occur during early T‐cell development before thymic colonization.
Combined defect in membrane expression and activation of platelet GPIIb–IIIa complex without primary sequence abnormalities in myeloproliferative disease
Authors: Kaplan Robert , Gabbeta Jagadeesh , Sun Ling , Mao Guang Fen , Rao A. Koneti 
Published: July 2010

Defects in glycoprotein (GP)IIb–IIIa or in its activation may cause abnormal platelet aggregation and a bleeding diathesis. We report studies in a 67‐year‐old man with a myeloproliferative disease and markedly abnormal platelet responses. By flow cytometry, platelet binding of two complex‐specific anti‐GPIIb–IIIa monoclonal antibodies (mAbs), A2A9 and 10E5, was ∼50% of normal. An enzyme‐linked immunosorbent assay (ELISA) using immobilized kistrin showed 18% of normal membrane GPIIb–IIIa complex. By immunoblot analysis, GPIIb and GPIIIa levels in platelet lysates and membranes were near normal. Activation of GPIIb–IIIa, monitored with mAb PAC‐1, was markedly decreased (< 20% of normal) in response to ADP, thrombin and platelet‐activating factor (PAF); expression of ligand‐induced binding sites (LIBS) was ≤ 30% of normal. Signal transduction‐independent LIBS expression, induced by echistatin, was ∼60% of normal, suggesting that the integrin present had intact ligand‐binding capability. Sequence analysis of GPIIb and GPIIIa cDNA, and platelet mRNA levels for both subunits, were normal. These findings document an acquired combined defect in membrane expression (secondary to a defect in post‐translational processing of the complex) and inside‐out signalling‐dependent activation of the GPIIb–IIIa complex.
A comparison of polymorphism in the 3′‐untranslated region of the prothrombin gene between Chinese and Caucasians in Australia
Authors: Chan Daniel K. Y. , Hu Gang , Tao Helen , Owens Daniel , Vun Chee M. , Woo Jean , Chong Beng Hock 
Published: July 2010

The 20210G→A mutation in the 3′‐untranslated (UT) region of the prothrombin gene is extremely rare or absent in the Chinese population (0 in 449 subjects, 140 with a history of thromboembolism). This is in contrast to the results from 302 Caucasians from Australia in our study (4·6% in 153 patients with a thromboembolic history and 1·3% in 149 patients with no history). This rarity implies that the variant of the prothrombin gene is probably not the main cause of venous thromboembolism in the Chinese population. Even among Caucasians this mutation accounts for only a minor percentage of all patients with thromboembolism. The relatively low incidence of venous thromboembolism in the Chinese population compared with Caucasians is probably as a result of the low prevalence of factor V Leiden or other environmental or genetic factors.
Natural killer activity and antibody-dependent cellular cytotoxicity in progressive systemic sclerosis
Authors: CIFONE M GRAZIA , GIACOMELLI R , FAMULARO G , PAOLINI R , DANESE C , NAPOLITANO T , PROCOPIO A , PEREGO A M , SANTONI A , TONIETTI G 
Published: July 2010

SUMMARYEnhanced natural killer (NK) activity and normal lymphocyte antibody-dependent cellular cytotoxicity (ADCC) were observed in 16 patients with a diagnosis of progressive systemic sclerosis (PSS). Higher NK activity levels were observed against NK-sensitive K562 target cells, while the NK-resistant P815, Daudi and Raji cell lines were not lysed. Cytofluorimetric studies and morphological analysis of peripheral blood lymphocytes (PBL) showed an increased number of CD16 positive cells and large granular lymphocytes (LGL), indicating that the enhancement observed was probably attributable to an increase in the number of circulating NK cells.
Analysis of immunoglobulins secreted by hybridomas derived from rheumatoid synovia
Authors: BROWN C M S , PLATER-ZYBERK C , MAGEED R A , JEFFERIS R , MAINI R N 
Published: July 2010

SUMMARYTwenty-six IgG-secreting and eight IgM-secreting hybridomas were derived from the synovia of two patients with rheumatoid arthritis (RA). Hybridomas were obtained by fusing a heteromyeloma cell line, SPAZ-4 with synovial mononuclear cells that were not deliberately stimulated in vitro. Over 96% of the IgG-secreting hybridomas produced antibodies which belonged to the IgGl subclass and showed lambda light chain predominance; the latter was not seen in IgM antibodies, where kappa light chains dominated by 3:1. All IgG antibodies were cationic. Synovial B cells were not exposed to extrinsic stimuli prior to fusion, therefore these results reflect the state of B cell activation and differentiation in vivo. Our results indicate that IgG-secreting B cells in the RA joint are under a selective influence which is, as yet, unidentified. One out of eight IgM-secreting and two out of 26 IgG-secreting hybridomas produced rheumatoid factors (RF). The IgM-RF specificity for IgG heavy chain subclasses was determined and showed that the monoclonal bound to IgG1, IgG2 and IgG4 but not IgG3 with exception of IgG3 Goe of the G3m (st) allotype, a profile typical of specificity for the Ga epitope. This monoclonal also distinguished a determinant in the Fc region of human IgG which was not present in rabbit IgG. The overall frequency of RF-secreting hybridomas we observed indicates that B cells committed to RF production in the synovium of a seropositive and a seronegative RA patient is below 10%.
B cells expressing CD5 are increased in cerebrospinal fluidof patients with multiple sclerosis
Authors: MIX E , OLSSON T , CORREALE J , BAIG S , KOSTULAS V , OLSSON O , LINK H 
Published: July 2010

SUMMARYBy two-colour flow cytometric analysis, we found increased numbers of B cells co-expressing the pan-T cell marker CD5 and the B cell marker CD19 in cerebrospinal fluid (CSF) of 21 patients withmultiple sclerosis (MS), compared with 17 control subjects with muscular tension headache. Only onepatient with MS, but nine controls lacked CD5+ B cells in CSF. This difference was not observed inperipheral blood. Numbers of CD5+19+ B cells were increased in CSF compared with blood in MS, but not in the controls. In both groups, CD5+19+ B cells were not restricted to small restinglymphocytes, but were also found among larger-sized lymphocytes. The relative density of CD5molecules and of CD19 molecules was lower in CD5+ 19+ thaninCD5- 19+ B cells and CD5+ 19- Tcells. CD5+ B cells are assumed to be responsible for auloanlibody production, and our resultssuggest a palhogenetic role of such cells, predominantly within the central nervous system, in MS.
Cross-reactive rheumatoid factors inrheumatoid arthritis with extra-articular disease
Authors: KINOSHITA M , AOTSUKA S , YOKOHARI R 
Published: July 2010

SUMMARYRheumatoid factors (RF) have been shown to have considerable heterogeneity and bind with IgG aswell as with a variety of substances such as nuclear histone, non-histone nuclear protein, nitrophenylgroups or ssDNA. We describe evidence that polyclonal RF cross-reactive with ssDNA (CRRF) arewidely distributed in a variety of rheumatic diseases, and that their serum level is significantly higherin rheumatoid arthritis (RA) with extra-articular disease. Although the mechanism of the cross-reactivity is not clear, the presence of CRRF could be a serological feature of a clinical subset of RA.The high prevalence rale of CRRF in RA with extra-articular disease also suggests its pathogeneticrole in the extra-articular manifestation of this disease.
Defective interleukin-2 induction of lymphokine-activatedkiller (LAK) activity in peripheral blood T lymphocytesof patients with monoclonal gammopathies
Authors: MASSAIA M , BIANCHI A , DIANZANI U , CAMPONI A , ATTISANO C , BOCCADORO M , PILERI A 
Published: July 2010

SUMMARYThe recombinant interleukin-2 (rIL-2) generation of lymphokine-activated killer (LAK) cells wasinvestigated in peripheral blood T lymphocytes (PBT) of 16 patients with monoclonal gammopathyof undetermined significance (MGUS) and 32 patients with multiple myeloma (MM). LAK activitywas significantly decreased in MM. but not in MGUS patients, and was partially recovered in MM inthe remission phase. This finding was unexpected, because CD8+ CD11b+ cells, which contain LAKprecursors, are significantly increased in MM. LAK activity was investigated in purifiedCD8+ CD11b+ lymphocytes to discriminate between an intrinsic defect or a defective regulation byother T cell subsets. These cells were intrinsically unable to generate LAK activity fully followingrIL-2 stimulation. MM showed the more pronounced LAK deficiency, while MGUS patients showedintermediate values. Phenotyping revealed significantly increased proportions of Leu7+ and HLA-DR+ cells in MM patients. These data reveal another dysregulation of T cell effector functions inpatients with monoclonal gammopathies and offer further evidence of the impairment of their cell-mediated immunity.
Rapidly proliferative arteriopathy in cyclosporin-induced permanently surviving rat cardiac allografts simulating chronic vascular rejection
Authors: FELLSTRÖM B , DIMÉNY E , LARSSON E , CLAESSON K , TUFVESON G 
Published: July 2010

SUMMARY
In an attempt to create a model of chronic rejection in rat, cardiac allograft transplantation was performed of hearts from PVG rats to DA rats treated with cyclosporin, 20 mg/kg body weight per day for 14 days and thereafter no immunosuppressive therapy. Experiments were made in 83 rats fed on a normal diet and in 24 rats fed on a diet containing an additional 0·5% cholesterol. Rats on the normal diet showed moderate signs of acute rejection during the first 20–40 days and grafts were lost in acute rejection during this period of time. However, after 2–3 months no signs of acute rejection were present. On the contrary, excessive proliferative changes of the vascular intima and endocardium along with fibrosis and fibrin deposition appeared and was progressive until 6 months post-transplantation. These morphological changes are similar to those found in chronically rejected organs like heart and kidney. In rats fed on a cholesterol diet after cessation of cyclosporin, development of the vascular and endocardial proliferative changes appeared three to four times as fast and were on average fully developed within 4–6 weeks post cessation of cyclosporin treatment. The recipients’ own hearts showed no signs of vascular or endocardial damage. It is thus concluded that two models of vascular and endocardial proliferative changes in cardiac allografts have been developed showing distinct similarities to chronic vascular rejections seen in the clinical transplantation and with apparent similarities to severe arteriosclerosis. The models could be useful in the investigation of pathogenesis and therapeutical means for preventing chronic vascular damage in transplanted organs and arteriosclerosis.
In vitroIgG rheumatoid factor production by CD5-negative murine B cells in response to immune complexes of lipopolysaccharide
Authors: TAGUCHI H , KANOH M , TAKUBO N , KADOTA S , KANAZAWA K , SHIBATA T , UTSUMI S 
Published: July 2010

SUMMARYWe studied the in vitro production of rheumatoid factor (RF) by spleen cells of normal adult mice. IgG RF cross-reactive with rabbit IgG was produced in response to immune complexes of TNP-lipopolysaccharide (LPS) with murine IgG anti-TNP antibody in an Fc-specific manner, but not to a mixture or IgG and LPS. Antibody-uncomplexed LPS induced little IgG RF production, but suppressed the subsequent IgG RF response to antibody-complexed LPS, whereas IgM RF was induced by either LPS or antibody-complexed LPS. The IgG RF production followed as rapid a time course as IgM RF production; the rate of IgG RF production reached its maximum soon after a lag period of l day and declined after S days. Treatment of splenic B cells from BALBJc mice with anti-Ly-1.2 antibody and rabbit complement resulted in a selective reduction of IgM RF production by 90%, with little effect on IgG RF production. These result suggest that IgG RF is derived primarily from CDS memory B cells which have been developed in normal mice by an unknown mechanism. Unlike the CT)5+ precursor cells for IgM RF, these memory cells arc unresponsive to polyclonal stimulation by LPS but are activated by simultaneous stimulation by aggregated He epilopes and the mitogenic stimulus from LPS.
Cytolytic activity in T cell clones derived from human synovial rheumatoid membrane: inhibition by synovial fluid
Authors: MILTENBURG A M M , VAN LAAR J M , DE KUIPER P , DAHA M R , BREEDVELD F C 
Published: July 2010

SummaryA panel of T cell clones was derived from the synovial membrane of a patient with rheumatoid arthritis (RA). We investigated whether T cell clones with cytolytic properties were present and whether T cell cytotoxicity was influenced by the presence of synovial fluid. These issues were studied using anti-CD3 and lectin-induced cytotoxicity assays. The majority of the T cell clones derived from the synovial membrane showed cytotoxic properties although non-cytotoxic clones were also found. Three clones (N11, N6 and N15) showed strong cytotoxicity (more than 40% lysis at an effector-to-target cell ratio of 10:1) whereas three clones (N16, N4 and N14) were non-cytotoxic (less than 20% lysis at an effector-to-target cell ratio of 10:1). The induction of cytotoxicity in the anti-CD3-driven system was shown to be dependent on the dose of anti-CD3 present. When synovial fluid was added to these assays a strong inhibition of cytotoxicity was found. This inhibition of cytotoxicity was found with synovial fluid samples of RA patients, as well as with non-RA synovial fluids. Both anti-CD3 and lectin-dependent cytotoxicity assays were strongly inhibited. In conclusion, T cell clones with cytotoxic activity can be isolated from rheumatoid synovial membrane. In the presence of synovial fluid these cytotoxic cells are inhibited to exert their cytotoxic function.
Cytokine regulation of HLA on thyroid epithelial cells
Authors: MIGITA K , EGUCHI K , OTSUBO T , KAWAKAMI A , NAKAO H , UEKI Y , SHIMOMURA C , KURATA A , FUKUDA T , MATSUNAGA M , ISHIKAWA N , ITO K , NAGATAKI S 
Published: July 2010

SummaryThe regulation of class I and class II HLA expression in human thyroid follicular cells was studied in vitro. Tumour necrosis factor-alpha (TNF-α) enhanced the expression of class I antigen on thyrocytes, but these cytokines had little effect on the expression of class II antigen. Interleukin-lβ (IL- lβ) and interleukin-6(IL-6) did not affect class I and class II antigen expression. The combination of interferon-gamma (IFN-γ) with TNF-α or IL-1β enhanced the induction of class I and class II antigens, compared with the effect of IFN-β alone. Neither class I nor class II expression was induced by lL-6 alone or in combination with IFN-γ. These findings suggest that TNF-α and IL-1β may have an important role in inappropriate expression of HLA antigens on thyrocytes in thyroid gland.
Normal and sarcoid alveolar macrophages differ in their ability to present antigen and to cluster with autologous lymphocytes
Authors: GANT V A , SHAKOOR Z , BARBOSA I L , HAMBLIN A S 
Published: July 2010

SUMMARYHuman bronchoalveolar macrophages from normal individuals function poorly as accessory cells for the presentation of common recall antigens. In sarcoidosis, alveolar macrophages (AM) are reported to be effective accessory cells for the presentation of such antigens. In this study normal and sarcoid AM were compared with blood monocytes for their ability to act as accessory cells in presenting tuberculin purified protein derivative (PPD) and streptokinase-streptodornase (SKSD) to autologous T lymphocytes, or to form spontaneous, antigen- or mitogen-induced clusters with the T cells. When compared to autologous monocytes, normal AM failed to present the two recall antigens effectively. Likewise normal AM formed very few clusters with T lymphocytes when compared to monocytes, even in the presence of antigens or the mitogen phytohaemagglutinin (PHA). In contrast, sarcoid AM presented both antigens as effectively, and were equally effective as monocytes in forming clusters with T lymphocytes, spontaneously and in further response to antigen or mitogen. The results suggest that in sarcoidosis enhanced accessory cell function and enhanced cluster formation may be related features of bronchoalveolar macrophage populations.
The control of class II expression on T cells is independent of the regulation of Tac and the induction of proliferation
Authors: SALVADORI S , PIZZIMENTI A , COHEN S , ZIER K S 
Published: July 2010

SUMMARYIn order to define the association between class II expression and other markers of T cell activation we tested the ability of various modes of stimulation to induce the expression of class II, Tac, and to stimulate proliferation. Stimulation of T cells with phytohaemagglutinin (PHA) in the presence of accessory cells strongly induced proliferation, Tac and the class II antigen DR. When purified T cells without accessory cells were stimulated with the phorbol ester, PdB, and the calcium ionophore, ionomycin. strong proliferation and Tac expression were induced, but only low levels of surface class II were observed. In contrast, stimulation of the same cells with PHA resulted in weak proliferation, strong Tac, but again low class II levels. The addition of PdB to the PHA increased the proliferative response, but did not affect Tac expression, which remained high, or class II expression, which remained low. Subsequent culture in conditioned medium of purified T cells which had been activated with either PdB and ionomycin or with PHA resulted in increased surface class II levels in both cases. Additional experiments suggested that neither IL-2, IL-4, nor interferon-gamma (IFN-γ) alone was responsible. These results demonstrate that class II expression can be separated from the induction of proliferation and the upregulation of Tac and that the mode of T cell stimulation influences the resulting activation pathway. Furthermore, they suggest that the control of class II expression on T cells is more tightly regulated than it is on other cells.
Hepatitis B surface antigen induces an early-type hypersensitivity
Authors: LEI H Y , WANG J Y , CHANG T T , WANG C C 
Published: July 2010

SUMMARYIn addition to the delayed-type hypersensitivity (DTH), a unique type of hypersensitivity could be induced at a late stage of the immune responses after hepatitis B surface antigen (HBsAg) immunization. This antigen-specific ear swelling that develops within 1 h after antigen challenge has been referred to as the early-type hypersensitivity (ETH) in contrast to the 24-h DTH. Although expression of ETH was earlier than DTH, the induction of the former needed 3 days longer than that of the latter. In ETH, the plasma protein leaked into the tissue and the vasopermeability increased within 15 min, causing the oedema of ETH. The observation that cyproheptadine, not dexamethasone, inhibited ETH suggests that it is mediated through the release of histamine and/or serotonin. Furthermore, ETH could be transferred by immune sera. Heat treatment (56°C for 4 h) did not destroy the transfer, suggesting that it was not mediated by IgE. The human anti-HBs sera from either hepatitis B virus infection or HBsAg vaccinee also contained the activity to transfer the ETH in mice
Antigen DNA isolated from immune complexes in plasma of patients with systemic lupus erythematosus hybridizes with theEscherichia colilac Z gene
Authors: TERADA K , OKUHARA E , KAWARADA Y 
Published: July 2010

SUMMARYAntigen DNA was isolated from immune complexes in plasma of three patients with active systemic lupus erythematosus (SLE) using affinity column. The antigen DNA thus obtained was subjected to hybridization experiments in order to investigate its origin. Unexpectedly, plasmid pUC18s used as a probe was found to hybridize with the antigen DNA. pUC18 was then cleaved into three fragments with the restriction enzyme Haell. A 445-bp fragment containing lac Z DNA hybridized with the antigen DNA. Finally, the lac Z DNA itself was found to hybridize with the antigen DNA. These data strongly suggest that the antigen DNA obtained from three patients is of bacterial origin.