bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factor XIII Val34Leu and the risk of venous thromboembolism in factor V Leiden carriers
Authors: Franco Rendrik F. , Middeldorp Saskia , Meinardi Johan R. , Van Pampus Elisabeth C. M. , Reitsma Pieter H. 
Published: July 2010

A mutation in factor XIII (Val34Leu) was reported to protect against venous thromboembolism. We evaluated the effect of Val34Leu on thrombotic risk in 352 factor V Leiden carriers who were first‐degree relatives of 132 thrombotic propositi carrying factor V Leiden. The total observation period was 2594 years in 92 Val34Leu carriers and 7444 years in 260 non‐carriers. The annual incidence of a first episode of venous thromboembolism was 0·31% in Val34Leu carriers and 0·44% in non‐carriers [relative risk (RR) for venous thromboembolism: 0·7, 95% CI 0·3–1·5]. Age‐specific RR for venous thromboembolism were (for Val34Leu carriers and non‐carriers respectively): 1·0 (95% CI 0·3–3·2) in the age group of 15–30 years, 0·4 (95% CI 0·05–3·0) in the age group of 30–45 years, 0·6 (95% CI 0·1–2·9) in the group aged 45–60 years and 0·5 (95% CI 0·06–4·5) in relatives older than 60 years. In conclusion, the impact of FXIII Val34Leu on the venous thromboembolic risk is modest, suggesting that screening for this mutation in factor V Leiden carriers is not justified.
Oxygen tension influences the differentiation, maturation and apoptosis of human megakaryocytes
Authors: Mostafa Sigma S. , Miller William M. , Papoutsakis E. Terry 
Published: July 2010

Megakaryocytes (Mks) mature adjacent to bone marrow (BM) sinus walls and subsequently release platelets within the sinusoidal space or in lung capillaries. As the sites for platelet release have higher levels of oxygen tension (pO2) than the core of the BM where stem and progenitor cells reside, we investigated whether pO2influences Mk maturation. Mks were generated from CD34+cells (from mobilized peripheral blood from cancer patients) under 5% and 20% O2. At day 15, CD41+Mk expansion in 20% and 5% O2cultures was 85‐fold and 31‐fold respectively. Twenty percent O2cultures also had higher levels of high ploidy (≥ 8N, eightfold higher) and proplatelet‐forming (fivefold higher) Mks. At day 21, 20% O2cultures had a fivefold higher number of apoptotic Mks. In contrast, 5% O2promoted Mk colony‐forming unit (CFU‐Mk) generation and maintenance. Similar results were observed in cultures initiated with CD41+Mks, indicating that pO2directly affects Mks. The change from 20% to 5% O2on day 5 and day 7 delayed both maturation and apoptosis, suggesting that these two processes are closely linked. These results were confirmed in CD34+cultures from normal BM samples. These data may provide insights intoin vivoMk maturation, such as an explanation for hypoxia‐induced thrombocytopenia in animals.
Flexible and dynamic organization of bone marrow stromal compartment
Authors: Anjos‐Afonso Fernando , Bonnet Dominique 
Published: July 2010

AbstractThe bone marrow mesenchymal compartment contains putative stem/progenitors of skeletal tissue components such as bone, cartilage, haematopoiesis‐supporting stroma and adipocytes. Previously appreciated as vital to the support of haematopoiesis, these cells have also been recently recognized as having significant immunomodulatory properties with implications for allogeneic haematopoietic cell transplantation. Despite having been studied for more than three decades and currently being used in different clinical settings, their biology remains elusive. The aim of this review is to critically analyse the field of mesenchymal stem/progenitor cell biology, in respect of their relationship with other mesenchymal cell‐types. Several issues concerning lineage commitment and inter‐conversion potential between different mesenchymal cell‐types are reviewed.
Phase I/II clinical trial of sequential subcutaneous and intravenous delivery of dendritic cell vaccination for refractory multiple myeloma using patient‐specific tumour idiotype protein or idiotype (VDJ)‐derived class I‐restricted peptides
Authors: Curti Antonio , Tosi Patrizia , Comoli Patrizia , Terragna Carolina , Ferri Elisa , Cellini Claudia , Massaia Massimo , D’Addio Alessandra , Giudice Valeria , Di Bello Cristiana , Cavo Michele , Conte Roberto , Gugliotta Gabriele , Baccarani Michele , Lemoli Roberto M. 
Published: July 2010

SummaryFifteen multiple myeloma (MM) patients who had failed maintenance therapy after tandem autologous stem cell transplantation underwent anti‐idiotype (Id) vaccination with dendritic cells (DCs). CD14+‐derived DCs were loaded with the autologous Id as whole protein (=6) or Id‐derived class I‐restricted peptides (=9) and keyhole limpet hemocyanin (KLH). Vaccination consisted of three subcutaneous (sc) and two intravenous injections of increasing DC doses at 2 weeks interval. DC therapy was well tolerated. Most patients developed both humoral and T‐cell responses to KLH, suggesting immunocompetence. Eight of 15 patients developed an Id‐specific T‐cell proliferative response, 8/15 increased interferon‐γ‐secreting T cells and 4/15 showed an Id‐positive delayed‐type hypersensitivity test. Anti‐Id cytotoxic T‐lymphocyte precursors increased after DC vaccination in 2/2 evaluable patients. A more robust T‐cell response was observed after sc DC injections and increased Id‐specific T‐cell proliferation was found up to 1 year after vaccination. VDJ‐derived peptides were as effective as the whole protein in stimulating T‐cell responses. Clinically, 7/15 patients have stable disease after a median follow‐up of 26 months, one patient achieved durable partial remission after 40 months, and seven patients progressed. In conclusion, sc injections of cryopreserved Id‐pulsed DCs were safe and, in contrast with intravenous administrations, induced anti‐MM T‐cell responses.
Increased elastase secretion by peripheral blood monocytes in cystic fibrosis patients
Authors: JONES M M , SEILHEIMER D K , PIER G B , ROSSEN R D 
Published: July 2010

SUMMARYMorbidity and mortality in cystic fibrosis (CF) is predominantly due to destruction of pulmonary tissue. The host immune response may, in part, play a pathogenic role in pulmonary destruction in these patients. To further understand host immune response in CF, we examined the state of activation of peripheral blood monocyles in CF. Baseline elastase activity was 2.2-fold greater in the CF monocytes than in controls. Pseudomonas aeruginosa mucoid exopolysaccharide (MEP) and high molecular weight polysaccharide (HMP) increased elastase activity in both control and CF monocytes, with a greater absolute increase in the CF monocytes. There was no difference in baseline or MEP-stimulated secretion of interleukin-1 (IL-1) or interleukin-6 (IL-6) between CF and control monocytes. Ibuprofen enhanced both MEP and HMP-stimulated elastase activity, whereas dexamethasone suppressed both baseline and stimulated elastase activity &gt; 20% in both CF and control monocytes. These results suggest that circulating monocytes in CF are stimulated in vivo, resulting in a remarkably elevated elastase activity in vitro. Elevated elastase release by peripheral blood monocytes as they enter the lung in response to chemotactic stimuli may contribute to lung destruction in CF.
Antibody responses reveal differences in oral tolerance to wheatand maize grain protein fractions
Authors: JOHNSON R B , LABROOY J T , SKERRITT J H 
Published: July 2010

SUMMARYThe influence of diet on humoral immune responses to gluten- and maize-derived proteins wasexamined using ELISA and protein blotting techniques. Mice raised on the maize-based (gluten-free)diet responded well to parenteral immunization with each of six gluten-derived protein preparations(whole gliadin, two omega-gliadin fractions, wheat salt-soluble proteins, a peptic-tryptic digest and asubtilisin digest of gluten), as serum antibody levels increased at least 300-fold in each case. Incontrast, mice raised on the wheat-based diet responded poorly to immunization with either wholegliadin or omega-gliadin and were virtually non-responsive to enzymic digest of gluten. Diet had littleeffect on the magnitude of the antibody response to wheat salt-soluble proteins, with both groupsshowing a 300-fold increase in titre. Similarly, tolerance to alpha-zeins, the alcohol-soluble proteinsof maize, did not occur on either diet. However, some oral tolerance was observed to maize glutelin. The specificity of the various antibody responses was then analysed by immunoblotting. Followingimmunization with gluten proteins or digests, antibodies from the maize-fed mice bound more or lessequally to each of the main gliadin bands and to the glutenins while the mice on the wheat-based diethad antibody specific for omega-gliadin proteins. Serum antibodies from the maize-fed mice, immunized with cither alpha-zein or maize glutelin, showed even labelling of the major maizeendosperm proteins while antibodies from mice on the wheat diet showed strong labelling of the M,27000 and 58000 bands. These results show that diet influenced the specificity, as well as themagnitude of serum antibody responses to cereal proteins. In addition, oral tolerance appeared toaffect the humoral response to some cereal proteins more than others. Both of these findings haveimportant implications for our understanding of coeliac disease.
Autoreactive cytotoxicity in HIV-infected individuals
Authors: ISRAËL-BIET D , VENET A , BELDJORD K , ANDRIEU J M , EVEN P 
Published: July 2010

SUMMARYA possible role for autoimmunity in the pathogenesis of HIV infection has been suggested, based upon the certain degree of homology shared by HIV gp41 and MHC class II molecules. A number of humoral markers of autoimmunity have since been found in seropositive subjects. We have evaluated the cellular autoreactive response in HI V-infected individuals. Our study demonstrates the existence of a cytolytic activity, present in seropositive but not in seronegative subjects. This activity is mediated by CD3 T cells, which only occasionally express the CD8 or the CD4 surface markers. Effector cells do not appear to exert their activity in a MHC-restricted fashion, since allogeneic target cells could also be killed, recovered from allogeneic seropositive as well as from seronegative subjects. Several types of target cells were lysed: T cell blasts and Epstein-Barr virus (EBV) transformed B cells, suggesting that the target antigen is common to at least these two cell types. The fact that cells from seronegative individuals were lysed argues against the recognition of an HIV-specific antigen. The nature of the target determinants and the identity of the effector cells are discussed.
Multiple infusions of human intravenous immunoglobulin in chimpanzees do not lead to immune elimination
Authors: LEIBL H , WOLF H M , EDER G , MANNHALTER J W , EIBL M M 
Published: July 2010

SUMMARYAdministration of human i.v. immunoglobulins was shown to lead to a permanent increase in IgGl and IgG2 levels in chimpanzees. Half-lives of human IgG1 and IgG2 in chimpanzees were comparable to those found in humans, and no signs of immune elimination were observed. Furthermore, long-term treatment of chimpanzees had no effect on the percentage of immunoregulatory T cells (CD2+, CD4+ and CD8+ T cells) as determined by FACS analysis. In addition, serum IgM levels in chimpanzees were found to be comparable to those in humans, whereas the chimpanzees' IgG levels are slightly elevated due to higher concentrations of IgG2 and, in particular, IgG4.
Effects of FK506 on rat thymus: time-course analysis by immunoperoxidase technique and flow cytofluorometry
Authors: TAKAI K , JOJIMA K , SAKATOKU J , FUKUMOTO T 
Published: July 2010

SummaryThe effect of administration of FK506 at 1 mg/kg body weight for 14 days on rat lymphoid tissues, especially the thymus, and recovery after discontinuation of treatment, were investigated by the immunoperoxidase technique and flow cytofluorometry using monoclonal antibodies OX6, OX7, OX8, OX18 and W3/25, reactive with rat lymphocytes. Marked reduction of the thymic medulla upon treatment was clearly demonstrated by staining with OX18 and OX6. Changes produced by FK506 were also observed in the cortical area of the thymus, and were especially marked in the subcapsular area and around blood vessels. Eventually, the thymic cortex appeared patchy, this change being maximal 14 days after the start of administration. Obvious restitution of the thymic medulla was evident about 14 days after withdrawal of FK506. Flow cylometric analysis of the thymus showed that the percentages of cells labelled positively with OX7, OX8 and W3/25 were increased with FK506 treatment, and recovered to the normal levels soon after withdrawal. Furthermore, the peak of fluorescence intensity of OX7+, OX8+ and W3/25+ cells showed a temporary shift to the right during FK506 treatment; however, the peak of fluorescence intensity of OX18+ cells showed a temporary shift to the left. Treatment with FK506 also produced a significant change in 3H-thymidine uptake by thymocyte. These results suggest that FK506 may inhibit the proliferation, maturation and differentiation of thymocytes. However, thymocytes prepared from FK506-treated rats and labelled with FITC behaved similarly to rat thymocytes in normal recipient rats. This suggests that during FK506 treatment thymocytes may retain their potential for peripheral mobilization.
The effect of gold sodium thiomalate and auranofin on lipopolysaccharide-induced interleukin-1 production by blood monocytesin vitro:variation in healthy subjects and patients with arthritis
Authors: DANIS V A , KULESZ A J , NELSON D S , BROOKS P M 
Published: July 2010

SUMMARYThe anti-rheumatic gold compounds gold sodium thiomalate (GST) and auranofin (AF) have variable and often unpredictable effects in patients treated for arthritis As inhibition of interleukin-1 (IL-1) production may be an important effect of these drugs, we investigated their effect on IL-1 production by lipopolysaccharide (LPS) stimulated monocytes in a serum-free. non-adherent culture system. A bi-modal effect was observed: low concentrations (GST 10–250 ng/ml and AF 1–100 ng/ml) potentiated IL-1 production, and higher concentrations (GST 200–1000 ng/ml and AF10–500 ng/ml) inhibited This bi-modal effect was observed for both secreted and cell-associated IL-1 activity with the exception that GST failed to inhibit cell-associated IL-1 generation. The potentiating effect was dependent on the continuous presence of gold for at least the first few hours after LPS stimulation. The inhibitory effect of GST was dependent on its presence after LPS Stimulation while that of AF was evident even if cells were pretreated with AF and washed before exposure to LPS. There was considerable individual variation in IL-1 production in response to LPS as well as in the effects of gold on cells from both healthy individuals and patients with arthritis. There was also some overlap in the range of concentrations of gold that potentiated and inhibited IL-1 production, and there was relative insensitivity to the inhibitory effects of gold in certain individuals. These results may explain some of the variability in the response of patients to chrysotherapy and support further studies to see if these in vitro effects might predict clinical response to gold.
Differential augmentation ofin vivonatural killer cytotoxicity in normal primates with recombinant human interleukin-1 and granulocyte-macrophage colony-stimulating factor
Authors: DAVIS T A , MONROY R L , SKELLY R R , DONAHUE R E , MACVITTIE T J 
Published: July 2010

SUMMARYThe effect of recombinant human interleukin-1 (IL-1) alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), and combined factor therapy (CFT) on Rhesus monkey peripheral blood natural killer (NK) activity in vivo was compared. During a 14-day treatment period, IL-1-treated animals demonstrated a 170% increase in NK activity against K562 target cells by day 4, reaching maximal levels (300%) at day 16, and returning to baseline by day 30. NK activity of GM-CSF-treated monkeys increased slightly (60–100%) during days 4–12. as did saline-treated monkeys, but returned to baseline values by day 16. A delayed increase in NK activity resulted after GM-CSF treatment, reaching a peak (260%) on day 23 and remaining elevated through day 39. CFT resulted in a bimodal response pattern, with two peaks of NK activity, one at day 16 and a second at day 39, The first peak of activity (223%) was significantly less than the activity attained with IL-1 alone; the second peak (300%) was of greater duration and occurred later than the peak observed in GM-CSF-treated monkeys. Unlike IL-1, GM-CSF treatment did not lead to a immediate stimulation of NK activity; augmentation was delayed by more than 7 days post treatment. CFT results suggest that GM-CSF reduced the direct NK response to IL-1; while IL-1 led to an enhanced delayed NK response. Therefore, IL-1 and GM-CSF augment NK activity through different but interrelated pathways.
Urinary excretion of CD23 antigen in normal individuals and patients with chronic lymphocytic leukaemia (CLL)
Authors: LING N R , STEVENSON F K , BROWN B 
Published: July 2010

SUMMARY
A soluble form of CD23 (sCD23) was found in the urine from 12 normal individuals but was not present in 20 normal sera, suggesting that sCD23 produced by cells in tissues is eliminated in the urine. The sCD23 from urine differed in physicochemical properties from the sCD23 found in supernales from B-lymphoblastoid cell lines (B-LCL) and in the sera of patients with B type chronic lymphocytic leukaemia (B-CLL). On SDS-PAGE analysis under reducing conditions urinary sCD23 showed two bands corresponding to molecular weights of 45 60 kD and 2S 35 kD indicating that sCD23may be excreted in combination with another molecule. When subjected to gel filtration in its native state, sCD23 from urine showed a major peak at approximately 150 kD and a minor peak (probably a breakdown product) at 21 kD. Urinary sCD23 was more strongly held by DEAE-cellulose and required 0–5 m buffer pH 8·0 for elution, suggesting that it is more anionic than sCD23 from culture supernates. Five MoAbs recognizing different epitopes on sCD23 from B-LCL supernates were tested on urinary sCD23. Four of the MoAbs were reactive but one (EBVCS-1) was not. Urinary sCD23 did not bind to IgE. The level of sCD23 found in normal urine (approximately 0·02–0·05 μg/ml) was exceeded in 17 of 24 cases of B-CLL. In one case with a high cell count and a serum concentration of 10 μg/ml. the urine contained 80 μg/ml sCD23. In another case a high serum sCD23 was not matched by a high urinary level. In this case the gel filtration pattern was closer to that found with urine sCD23 rather than the B-LCL pattern found with sera of other B-CLL patients.
Anti-human thyroid peroxidase and anti-human thyroglobulin antibodies present no cross-reactivity on recombinant peptides
Authors: HENRY M , ZANELLI E , MALTHIERY Y 
Published: July 2010

SUMMARYThyroglobulin (Tg) and thyroid peroxidase (TPO) are two antigens largely recognized by the sera from patients with autoimmune thyroid disease (AITD). Recently, the complete mapping of both antigens was established with rabbit polyclonal antibodies by the use of recombinant proteins expressed in prokaryotic vector. Several investigators have argued for the existence of a crossreactivity of some hetero- and autologous antibodies versus these two proteins. In the present study, using rabbit polyclonal antibody, mouse polyclonal antibody and autoimmune antibody (aAb). we observed no common epitope on human Tg (hTg) and human TPO (hTPO).
Evidence that X-linked severe combined immunodeficiency is not a differentiation defect of T lymphocytes
Authors: GOODSHIP J , MALCOLM S , LEVINSKY R J 
Published: July 2010

SUMMARY
In order to gain information about the nature of the defect in X-linked severe combined immunodeficiency (XSCID). we investigated gene expression in different lymphoid and haematopoietic cells of female carriers by looking for non-random X chromosome usage. We have shown non-random X chromosome usage in T lymphocyte enriched (E+) fraction in all carriers. E cells and monocytes showed non-random X chromosome usage in three carriers tested. In the B cell series one carrier showed non-random inactivation in all EBV lines tested (10) and the same X chromosome was shown to be active in all cells, In other carriers there was a preference for use of the normal X chromosome but some B cell lines used the mutant X as well as the normal X. Similar results were found with granulocytes. In two female carriers DNA made directly from whole blood showed a non-random pattern of X chromosome usage. In fibroblast cultures from two female carriers more cells had the normal gene on the active X chromosome than had the defective gene on the active X chromosome. Within families there was heterogeneous expression of the gene. The gene that is defective in XSCID is expressed in all the cell types studied and. therefore, is not a T lymphocyte differentiation gene. The results are consistent with the gene being in a metabolic pathway as in certain autosomal recessive forms of SCID i.e. adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency.
Asbestos fibres inhibit thein vitroactivity of ymphokine-activated killer (LAK) cells from healthy individualsand patients with malignant mesothelioma
Authors: MANNING L S , DAVIS M R , ROBINSON B W S 
Published: July 2010

SUMMARYAsbestos exposure is associated with an increased incidence of several malignances. including malignant mesothelioma (MM). This study evaluates the relationship between asbestos exposure and the in vitro generation and function of LAK cells, an immune effector cell population with powerful lytic activity against MM cells. Both serpentine (chrysotile) and amphibole (amosite and crocidolilc) forms of asbestos fibres suppress LAK cell generation, viability (by 5–11%, P &lt; 0.02) and cell recovery (by 13.15%, P &lt; 0.02). However, the LAK cells generated in the presence of the amphiboles were as effective as unexposed cells in lysing both standard tumour cell targets (K562, 56.4% lysis versus 61.5%. respectively, P &gt; 0.5; NS; Daudi. 60.5% lysis versus 64.5%P &gt; 0.5; NS). and MM tumour cell targets (mean of three MM cell lines 48.3%versus 46.3%. P &gt; 0.5; NS), whereas the function of LAK cells generated in the presence of chrysotile was significantly reduced against three out of the five tumour cell targets tested (P &lt; 0.03). In the presence of asbestos fibres, LAK cell function was reduced against all five tumour cell targets (P &lt; 0.0l). irrespective of whether the cell donors were healthy individuals or patients with MM. NK cell activity was also suppressed (P &lt; 0.0l). The serpentine form of asbestos, chrysotile, was significantly more suppressive of both effector cell functions than either of the amphiboles (P &lt; 001). These findings suggest that asbestos exposure may suppress the function and in some instances the generation of immune effector cell mechanisms, thereby increasing the risk of disease and malignancy.