bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of the CD33‐related Siglec receptor, Siglec‐5 (CD170), as a useful marker in both normal myelopoiesis and acute myeloid leukaemias
Authors: Virgo Paul , Denning‐Kendall Patricia A. , Erickson‐Miller Connie L. , Singha Sakon , Evely Roger , Hows Jill M. , Freeman Sylvie D. 
Published: October 2003

Summary. Sialic acid‐binding immunoglobulin‐like lectin (Siglec)‐5 or CD170 is a CD33‐related receptor, containing cytoplasmic immune receptor‐based tyrosine signalling motifs, that has previously been reported to be myeloid‐specific like CD33 and thus may be useful in the characterization of both normal and malignant haemopoiesis. This study showed that Siglec‐5 had a distinct expression pattern to CD33 both on normal myeloid cells and in acute myeloid leukaemia (AML). In normal bone marrow and cord blood, myeloid cells predominantly expressed Siglec‐5 at the later stages of granulocytic differentiation. Siglec‐5 was not expressed at significant levels by CD34+ progenitors either from bone marrow or mobilized peripheral blood. During in vitro myeloid differentiation of cord blood purified CD34+ cells, Siglec‐5 was upregulated later than CD33. Siglec‐5 expression remained absent or very low on cultured CD34+ cells, unlike CD33, which was present on almost all CD34+ cells by day 4. However, analysis of blasts from 23 patients with AML revealed aberrant expression of Siglec‐5 with CD34 in 50% (seven of 14) of patients with CD34+ AML; 61% (14 of 23) of AML cases were positive for Siglec‐5 with an increased frequency in the French–American–British subtypes M3‐5 (80%) compared with M0‐2 (25%). All 13 acute lymphoblastic leukaemic (ALL) samples tested, including a CD33+ ALL, were Siglec‐5 negative. These results support the further evaluation of Siglec‐5 antibodies in the diagnosis and monitoring of AML.
Progenitor cell involvement is predictive of response to induction chemotherapy in paediatric acute myeloid leukaemia
Authors: Johnston Donna L. , Meshinchi Soheil , Opheim Kent E. , Pallavicini Maria G. , Feusner James , Woods William G. , Lange Beverly J. , Radich Jerald P. , Bernstein Irwin D. 
Published: October 2003

Summary. In acute myeloid leukaemia (AML), involvement of early progenitor cells may predict poor response to induction chemotherapy. We evaluated the involvement of early progenitor cells in two AML subtypes with a favourable prognosis [t(8;21) and t(15;17)], and a subtype with poor prognosis (monosomy 7). CD34+CD33− cells were isolated by fluorescence‐activated cell sorting, grown in liquid medium followed by culture in semi‐solid medium, and the colonies that were formed were analysed for the identifiable genetic markers. Two of 136 colonies from six t(8;21) AML patients expressed the AML1‐ETO transcript, and all six patients achieved remission after induction. None of 192 colonies from five t(15;17) AML patients expressed the RARα‐PML transcript and all achieved remission. In contrast, in three of 10 cases of monosomy 7 AML, colonies were positive for monosomy 7, and all three patients failed to enter remission. However, five of six evaluable patients with colonies negative for monosomy 7 entered remission. These data support the hypothesis that leukaemic involvement of early progenitor cells affects the response to induction chemotherapy.
Lymphoproliferative disease in antibody deficiency: a multi-centre study
Authors:   ASSOCIATED STUDY GROUP, GOMPELS M M , HODGES E , LOCK R J , ANGUS B , WHITE H , LARKIN A , CHAPEL H M , SPICKETT G P , MISBAH S A , SMITH J L 
Published: October 2003

SUMMARY
We have undertaken a retrospective study of antibody deficient patients, with and without lymphoma, and assessed the ability of specific polymerase chain reaction (PCR) primers to determine if the detection of clonal lymphocyte populations correlates with clinical and immunohistochemical diagnosis of lymphoma. We identified 158 cases with antibody deficiency presenting during the past 20 years. Paraffin-embedded biopsy specimens or slides were available for analysis in a cohort of 34 patients. Of these patients, 29 had common variable immunodeficiency, one X-linked agammaglobulinaemia, one X-linked immunoglobulin deficiency of uncertain cause and three isolated IgG subclass deficiency. We have confirmed that lymphoma in antibody deficiency is predominantly B cell in origin. Clonal lymphocyte populations were demonstrated in biopsies irrespective of histology (16/19 with lymphoma and 11/15 without). Isolated evidence of clonality in biopsy material is therefore an insufficient diagnostic criterion to determine malignancy. Furthermore, our data suggest that clonal expansions are rarely the result of Epstein–Barr virus-driven disease.
Evidence for increased expression of regulatory cytokine receptors interleukin-12R and interleukin-18R in common variable immunodeficiency
Authors: McQUAID A , TORMEY V J , TRAFFORD B , WEBSTER A D , BOFILL M 
Published: October 2003

SUMMARYWe investigated the expression of T helper (Th)1/Th2 regulatory cytokine receptors on lymphocytes from patients with common variable immunodeficiency (CVID), a disorder associated with raised Th1 cytokine production, comparing the results with those from healthy individuals and atopic asthmatics, the latter generally considered to have a Th2-driven disease. We proposed that alterations in some of the relevant receptors might be related to the observed imbalances in Th1/Th2 cytokines. Cells from CVID patients showed an increase in the percentages of CD212 [interleukin (IL)-12Rβ1] cells within the CD4+ CD45RA+ and CD8+ CD45RA+ subsets (24% and 41%, respectively), as compared to CD4+ CD45RA+ and CD8+ CD45RA+ in healthy subjects (6% and 23%, respectivey). Approximately 21% of the CD4+ CD45RA+ naïve cells expressed IL-18Rα, compared with 11% in healthy subjects. In contrast, the cytokine-receptor expression in asthmatics was similar to that of controls. In spite of the above differences, after 72 h of stimulation with anti-CD3 and anti-CD28, cytokine receptor up-regulation was similar in all three groups, with up to 80% of both CD45RA+ and CD45RO+ lymphocytes expressing CD212 (IL-12Rβ1) and IL-18Rα. Approximately 50% of the ‘naïve’, and 25% of the ‘memory’ subpopulations up-regulated IL-12Rβ2. These findings provide further evidence of a polarization towards a Th1 immune response in CVID, the mechanism possibly involving up-regulation of IL-12-mediated pathways.
Interferon-γ and skin test responses of schoolchildren in southeast England to purified protein derivatives fromMycobacterium tuberculosisand other species of mycobacteria
Authors: WEIR R E , FINE P E M , NAZARETH B , FLOYD S , BLACK G F , KING E , STANLEY C , BLISS L , BRANSON K , DOCKRELL H M 
Published: October 2003

SUMMARYThe immune responses of schoolchildren in southeast England to Mycobacterium tuberculosis and other species of mycobacteria were studied prior to vaccination with bacille Calmette-Guérin (BCG). Data are presented for tuberculin (Heaf) skin test and interferon-γ (IFN-γ) responses to M. tuberculosis purified protein derivative (PPD), and IFN-γ responses to PPDs from eight other environmental mycobacteria, measured in 424 schoolchildren (13–15 years of age). Responses to M. tuberculosis PPD were detected in 27% of schoolchildren by in vitro IFN-γ response and in 20% by the Heaf test. IFN-γ responses were more prevalent to PPDs from species of mycobacteria other than M. tuberculosis, predominantly those of the MAIS complex and M. marinum (45–60% responders). Heaf test and IFN-γ responses were associated (P &lt; 0·001) for M. tuberculosis, MAIS and M. marinum. These findings have implications for appropriate implementation of vaccination against tuberculosis.
Significant elevation of serum levels of eotaxin-3/CCL26, but not of eotaxin-2/CCL24, in patients with atopic dermatitis: serum eotaxin-3/CCL26 levels reflect the disease activity of atopic dermatitis
Authors: KAGAMI S , KAKINUMA T , SAEKI H , TSUNEMI Y , FUJITA H , NAKAMURA K , TAKEKOSHI T , KISHIMOTO M , MITSUI H , TORII H , KOMINE M , ASAHINA A , TAMAKI K 
Published: October 2003

SUMMARYAtopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease characterized by the predominant infiltration of T cells, eosinophils and macrophages in lesional skin. Recently, eotaxin-2/CCL24 and eotaxin-3/CCL26 were identified as CC chemokines that signal exclusively via the CCR3 receptor and have eosinophil-selective chemoattractant activity, as does eotaxin/CCL11. We previously reported that serum levels of thymus and activation-regulated chemokine (TARC)/CCL17 and macrophage-derived chemokine (MDC)/CCL22 were correlated with the severity of AD. In this report, we investigated the participation of eotaxin-2/CCL24 and eotaxin-3/CCL26 in AD, first measuring the serum levels of eotaxin-2/CCL24 and eotaxin-3/CCL26 in 30 patients with AD, 20 patients with psoriasis vulgaris and 20 healthy controls. The serum levels of eotaxin-3/CCL26 (but not eotaxin-2/CCL24) were significantly higher in patients with AD than in either healthy controls or patients with psoriasis vulgaris; furthermore, the eotaxin-3/CCL26 levels in patients with moderate and severe AD were significantly higher than eotaxin-3/CCL26 levels in patients with mild AD. The serum eotaxin-3/CCL26 levels tended to decrease after treatment, but there was no significant difference between groups. Moreover, the serum eotaxin-3/CCL26 levels were significantly correlated with the serum TARC/CCL17 and MDC/CCL22 levels, eosinophil numbers in peripheral blood and the scoring AD (SCORAD) index. Our study strongly suggests that serum levels of eotaxin-3/CCL26, but not of eotaxin-2/CCL24, have a notable correlation with disease activity of AD and that eotaxin-3/CCL26, as well as TARC/CCL17 and MDC/CCL22, may be involved in the pathogenesis of AD.
Autoantibodies against mannose-binding lectin in systemic lupus erythematosus
Authors: SEELEN M A , TROUW L A , VAN DER HOORN J W A , FALLAUX-VAN DEN HOUTEN F C , HUIZINGA T W J , DAHA M R , ROOS A 
Published: October 2003

SUMMARYIn systemic lupus erythematosus (SLE), autoantibodies directed against complement components of the classical pathway, especially against C1q, are associated with severe disease and are of prognostic value for flares of lupus nephritis. Mannose-binding lectin (MBL), the recognition unit of the MBL pathway of complement activation, has structural similarities to C1q. Deficiencies of MBL have been shown to predispose to the development of SLE and to influence the course of the disease. We hypothesized that the presence of autoantibodies to MBL, analogous to autoantibodies to C1q in patients with SLE, may contribute to disease development. The occurrence of anti-MBL autoantibodies was assessed by enzyme-linked immunosorbent assay (ELISA) of 68 serum samples from 20 patients with SLE and in serum from 70 healthy controls. Levels of antibodies directed against MBL were significantly higher in patients with SLE compared to healthy subjects. No significant difference was found between patients with active disease compared to those with inactive disease. While the occurrence of anti-C1q autoantibodies was associated with renal involvement, no such relationship was found for anti-MBL autoantibodies. A significant correlation was found between anti-MBL and anti-C1q antibody levels. The level of anti-MBL antibodies was negatively correlated with MBL–complex activity of circulating MBL. Anti-MBL autoantibodies were of the immunoglobulin G (IgG) isotype and the binding site of IgG anti-MBL was located in the F(ab′)2 portion. We conclude that anti-MBL are present in sera from SLE patients and influence the functional activity of MBL.
Langerhans’ cells in the murine oral mucosa in the inductive phase of delayed type hypersensitivity with 1-chloro-2, 4-dinitrobenzene
Authors: OKAMURA T , MORIMOTO M , YAMANE G , TAKAHASHI S 
Published: October 2003

SUMMARY
We created a murine model of delayed-type hypersensitivity (DTH) to 1-chloro-2, 4-dinitrobenzene (DNCB). Using this murine model, we compared oral mucosal sensitization and skin sensitization for the difference in reaction during the elicitation phase. Evaluation of sensitizability, using the mouse ear swelling test (MEST) after oral mucosal or skin sensitization, showed that the ear swelling response peaked 24 h after challenge. The optimal induction concentration was 1·0% in both oral mucosal and skin sensitization, resulting in a positive reaction rate of 100%. However, the ear swelling response 24 h after challenge with the optimal concentration of DNCB (1·0%) was significantly lower in oral mucosal than in skin sensitization. We compared the oral mucosal and skin sensitization sites for the number of Langerhans’ cells (LC) and the antigen-presenting capability in the induction phase. The numbers of F4/80+ major histocompatibility complex (MHC) class II+ LC before induction did not differ significantly between the oral mucosa and the skin. After induction, F4/80+ MHC class II+ LC increased in number, but the increase was significantly smaller in the oral mucosa than in the skin. MEST on anti-CD86 antibody-administered mice showed that ear swelling was similarly suppressed after oral mucosal or skin sensitization. In murine models of DTH after oral mucosal sensitization, the number of F4/80+CD86+ LC increased after induction, but the increase was significantly smaller than that in murine models of DTH after skin sensitization. This study showed that, in murine models of DTH, oral mucosal sensitization elicited a weaker reaction than skin sensitization. This was presumably because oral mucosal sensitization induced fewer LC, resulting in lower antigen-presenting capability.
Clinical course and immune response of a renal cell carcinoma patient to adoptive transfer of autologous cytotoxic T lymphocytes
Authors: KAWAI K , SAIJO K , OIKAWA T , MORISHITA Y , NOGUCHI M , OHNO T , AKAZA H 
Published: October 2003

SUMMARY
The cytotoxic T lymphocyte (CTL) is a promising candidate for an effector cell in adoptive immunotherapy for renal cell carcinoma (RCC). Here we report the clinical course and in vivo immune responses of a RCC patient with bulky retroperitoneal lymph node (RPLN) metastases who received adoptive autologous CTL therapy. A 56-year-old woman diagnosed with RCC with multiple RPLN metastases underwent unilateral nephrectomy. Autologous RCC cells were primary-cultured from surgical specimens. Before addition of peripheral blood mononuclear cells (PBMC) for CTL induction, subconfluent RCC cells were irradiated with 50 Gy. The PBMCs were then cultured on RCC cells in the induction medium supplemented with four kinds of interleukins. The induced CTLs showed the potent killing activity against autologous RCC cells in a typical MHC-class I-restricted manner. The patient received three courses of CTL therapy with a total of 10·2 × 109 cells, and the RPLN mass decreased markedly in size after the second course. Eosinophilia and enhanced CTL inducibility from peripheral blood were observed after CTL administrations. The patient was progression free without further treatment; however, she developed rapidly progressive glomerulonephritis more than 1 year after the last treatment. The patient died of newly developed metastases 27 months after the start of CTL therapy. At autopsy, viable RCC cells were found in multiple metastatic sites. However, only diffuse fibrous tissue was observed in the responding RPLN mass. Apparent histological divergence was observed between primary and metastatic sites.
Involvement of Fcγ receptors andβ2 integrins in neutrophil activation by anti-proteinase-3 or anti-myeloperoxidase antibodies
Authors: Reumaux D , Kuijpers T W , Hordijk P L , Duthilleul P , Roos D 
Published: October 2003

SUMMARYWe previously described the requirement of tumour necrosis factor-alpha (TNF-α) and the role of β2 integrins in the Fc-gamma receptor IIa (FcγRIIa)-mediated mechanism of neutrophil activation by antiproteinase-3 (anti-PR3) or anti-myeloperoxidase (anti-MPO) antibodies. In the present study, we assessed the involvement of FcγRIIIb by studying the respiratory burst activation of completely FcγRIIIb-deficient neutrophils primed by TNF-αand exposed to anti-PR3 or anti-MPO. Activation of the NADPH oxidase occurred normally in these neutrophils, which indicates that engagement of FcγRIIIb is not essential in our model. Experiments performed with neutrophils from severe leucocyte adhesion deficiency (LAD) patients confirmed that β2 integrins play a pivotal role in this activation. We next studied whether adhesion per se, β2-integrin-mediated adhesion, or β2-integrin ligation without adhesion is necessary or sufficient for this activation. Anti-PR3 or anti-MPO induced an FcγRIIa-dependent burst in TNF-primed neutrophils incubated in wells coated with poly-l-lysine, known to induce β2-integrin-independent adhesion, but this reaction was still inhibited by blocking CD18 antibodies. In a system with granulocyte-macrophage colony-stimulating factor (GM-CSF)-primed neutrophils, which did not enhance adhesion, we measured a similar activation by anti-PR3 or anti-MPO and inhibition by CD18. We also noticed that treatment with the β2-integrin-activating CD18 MoAb KIM185 per se is insufficient for neutrophil activation by anti-PR3 or anti-MPO. We therefore conclude that ligation of β2 integrins rather than adherence per se is essential for this activation, and that TNF-α or GM-CSF is needed for priming but not for adherence.
A recombinant fragment of human SP-D reduces allergic responses in mice sensitized to house dust mite allergens
Authors: STRONG P , TOWNSEND P , MACKAY R , REID K B M , CLARK H W 
Published: October 2003

SUMMARYC57Bl6 mice sensitized to Dermatophagoides pteronyssinus and challenged with D. pteronyssinus allergen extract given intranasally followed by treatment with intranasal applications of a 60-kDa truncated, trimeric recombinant form of human SP-D (rfhSP-D) showed a significant reduction in serum IgE, IgG1, peripheral blood eosinophilia and airway hyperresponsiveness compared to saline or bovine serum albumin-treated controls. Intracellular cytokine staining of lung and spleen homogenates showed increases in interleukin (IL)-12 production in lung tissue and normalization of IL-12 and interferon (IFN)-γ in spleen tissue. In previous studies we demonstrated the effectiveness of native SP-D and rfhSP-D in down-regulating allergic responses to allergens of Aspergillus fumigatus. The results reported here indicate that rfhSP-D can suppress the development of allergic symptoms in sensitized mice challenged with allergens of the common house dust mite.
Anti-annexin V antibodies in Takayasu's arteritis: prevalence and relationship with disease activity
Authors: TRIPATHY N K , SINHA N , NITYANAND S 
Published: October 2003

SUMMARYAnnexin V has an important role in the regulation of apoptosis and antibodies directed against it have been shown to lead to apoptosis of vascular endothelial cells. To evaluate the role of anti-annexin V antibodies (AA5A) in Takayasu's arteritis (TA), we investigated these antibodies in the sera of 66 TA patients, 50 healthy controls and in the follow-up sera of 12 active TA patients by enzyme-linked immunosorbent assay. The AA5A-positive patients were analysed further for the presence of anti-endothelial cell antibodies (AECA) and anticardiolipin antibodies (ACLA) to determine the relationship of AA5A with these autoantibodies. AA5A were observed in 36% (24/66) of the patients versus 6% (3/50) of the controls (P &lt; 0·001) and in 53% (19/36) of patients with active TA versus 17% (5/30) of those with inactive disease (P &lt; 0·01). Levels of AA5A were also observed to be significantly higher in patients with TA compared to controls (0·557 ± 0·362 versus 0·259 ± 0·069; P &lt; 0·0001) and in patients with active disease compared to those with inactive disease (0·700 ± 0·403 versus 0·385 ± 0·205; P &lt; 0·0001). In the follow-up study, 6/12 patients who became inactive during follow-up also showed normalization of AA5A levels. AECA and ACLA were detected in 54% (13/24) and 12% (3/24) of the AA5A-positive patients, respectively. Our results show that a significant proportion of TA patients have AA5A, which exhibit an association with AECA and because they have a correlation with disease activity thus appear to be involved in the disease pathogenesis.
Modulation of the expression of M150 on macrophages by Th1/Th2 cytokines and co-stimulatory molecules CD40, B7-1, B7-2 and ICAM-1
Authors: SUVAS S , VOHRA H , AGREWALA J N 
Published: October 2003

SUMMARYM150 is an 150-kDa protein associated with the surface of macrophages and is responsible chiefly for the activation of Th1 cells. It is a unique subset of the lysosome-associated membrane protein-1 glycoprotein and its co-stimulatory activity depends on its post-translational modification, which has a distinct glycosylation pattern restricted to macrophages. In the present study, we have observed that M150 is expressed constitutively on peritoneal but not splenic macrophages isolated from mice of different genetic backgrounds: Balb/c, C57BL/6 and C3He. However, M150 was expressed not only on peritoneal but also on splenic macrophages of non-obese diabetic (NOD) mice. Expression on splenic macrophages was induced by culture with lipopolysaccharide (LPS). Expression could also be significantly up-regulated by interferon (IFN)-γ and granulocyte-macrophage colony stimulating factor (GM-CSF) but was inhibited by interleukin (IL)-10; IL-4 exhibited no effect. Further, cross-linking of B7-2, CD40, ICAM-1 but not B7-1 enhanced the level of M150 significantly. IFN-γ and GM-CSF acted synergistically with CD40. The significance of these findings is that cytokines IFN-γ, GM-CSF and IL-10 and the co-stimulatory molecules B7-2, CD40 and ICAM-1 can regulate the expression of M150 on macrophages.
No strong relationship between mannan binding lectin or plasma ficolins and chemotherapy-related infections
Authors: KILPATRICK D C , MCLINTOCK L A , ALLAN E K , COPLAND M , FUJITA T , JORDANIDES N E , KOCH C , MATSUSHITA M , SHIRAKI H , STEWART K , TSUJIMURA M , TURNER M L , FRANKLIN I M , HOLYOAKE T L 
Published: October 2003

SUMMARY
Chemotherapy causes neutropenia and an increased susceptibility to infection. Recent reports indicate that mannan-binding lectin (MBL) insufficiency is associated with an increased duration of febrile neutropenia and incidence of serious infections following chemotherapy for haematological malignancies. We aimed to confirm or refute this finding and to extend the investigation to the plasma ficolins, P35 (L-ficolin) and the Hakata antigen (H-ficolin). MBL, L-ficolin and H-ficolin were measured in 128 patients with haematological malignancies treated by chemotherapy alone or combined with bone marrow transplantation. Protein concentrations were related to clinical data retrieved from medical records. MBL concentrations were elevated compared with healthy controls in patients who received chemotherapy, while L-ficolin concentrations were decreased and H-ficolin levels were unchanged. There was no correlation between MBL, L-ficolin or H-ficolin concentration and febrile neutropenia expressed as the proportion of neutropenic periods in which patients experienced fever, and there was no relation between abnormally low (deficiency) levels of MBL, L-ficolin or H-ficolin and febrile neutropenia so expressed. Patients with MBL ≤ 0·1 µg/ml had significantly more major infections than no infections within the follow-up period (P &lt; 0·05), but overall most patients had signs or symptoms of minor infections irrespective of MBL concentration. Neither L-ficolin nor H-ficolin deficiencies were associated with infections individually, in combination or in combination with MBL deficiency. MBL, L-ficolin and H-ficolin, independently or in combination, did not have a major influence on susceptibility to infection in these patients rendered neutropenic by chemotherapy. These results cast doubt on the potential value of MBL replacement therapy in this clinical context.