bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recombinant FVIIa in the management of uncontrolled hemorrhage
Authors: O'Connell Niamh M. , Perry David J. , Hodgson Andrew J. , O'Shaughnessy Denise F. , Laffan Michael A. , Smith Owen P. 
Published: December 2004

BACKGROUND: Recombinant FVIIa (rFVIIa/NovoSeven) is a novel hemostatic agent originally developed to treat patients with hemophilia who had developed inhibitors. Several case reports have suggested that rFVIIa may be effective in treating patients without a pre‐existing bleeding disorder who have uncontrolled bleeding.STUDY DESIGN AND METHODS: Data on the efficacy and safety of rFVIIa in the treatment of massive hemorrhage were obtained retrospectively from the NovoSeven extended‐use data collection system.RESULTS: A total of 40 patients received rFVIIa for uncontrolled bleeding, and in these patients, bleeding stopped or decreased in 32 (80%). Blood product usage was significantly decreased after rFVIIa administration. Thromboembolic events occurred in three patients with additional risk factors for thrombosis. Of 40 patients, 23 (57.5%) died. Bleeding was the direct cause of death in seven cases (all within 24 hr of administration of rFVIIa). The remaining 16 deaths were the result of sepsis, multi‐organ failure, or the underlying disease.CONCLUSIONS: In this retrospective study of data voluntarily submitted to a web‐based drug surveillance program, we present preliminary results on the use of rFVIIa in nonhemophilia patients with bleeding. Although some efficacy is suggested, there was a high mortality rate from nonhemorrhagic causes. Randomized controlled trials are needed to properly assess the role of rFVIIa in the management of hemorrhage.
Similar levels of infectivity in the blood of mice infected with human‐derived vCJD and GSS strains of transmissible spongiform encephalopathy
Authors: Cervenakova Larisa , Yakovleva Oksana , McKenzie Carroll , Kolchinsky Svetlana , McShane Lisa , Drohan William N. , Brown Paul 
Published: December 2004

BACKGROUND: The possible transmission of variant CJD (vCJD) through blood transfusion or use of plasma‐derived products prompted this study comparing infectivity in murine models of vCJD and Gerstmann‐Sträussler‐Scheinker (GSS) disease, a non‐vCJD form of transmissible spongiform encephalopathy (TSE).STUDY DESIGN AND METHODS: RIII/Fa/Dk (RIII) or Swiss‐Webster (Swiss) mice were inoculated intracerebrally (IC) with mouse‐adapted strains of vCJD or GSS (Fukuoka‐1) of similar infectivity. Groups of RIII mice were euthanized 17 weeks after inoculation (during the incubation period), and another 23 weeks after inoculation (when symptomatic). Blood was collected, separated into components, and inoculated into groups of healthy mice; brains and spleens from all mice were harvested and tested for the presence of PrPres by Western blot using 6H4 MoAb.RESULTS: Levels of 20‐30 infectious doses per mL were present in buffy coat and plasma during both the incubation and symptomatic stages of disease; PLT pellet infectivity was lower (10 ID/mL) and RBCs were not infectious. The disease was transmitted more efficiently by IV than IC inoculation of plasma, but there was no difference observed with inoculation of buffy coat. The incubation period was shorter after IC inoculation of GSS‐ than vCJD‐brain inocula. The amount of PrPres in spleens was similar for both TSE agents, but was slightly lower in brains of vCJD than GSS mice.CONCLUSION: Infectivity was detected in blood components of mice infected with a human‐derived strain of vCJD during both the preclinical and clinical phases of disease in a similarly low range of concentrations as in mice infected with a human‐derived nonvariant strain (GSS, Fukuoka‐1). Other measures of virulence, including brain infectivity titers, incubation periods, and the accumulation of PrPres in spleens and brains, were also comparable in both experimental models.
Quantitative real‐time detection of parvovirus B19 DNA in plasma
Authors: Koppelman Marco H.G.M. , Cuypers H. Theo M. , Emrich Thomas , Zaaijer Hans L. 
Published: December 2004

BACKGROUND:  As of 2004, the European Pharmacopoeia demands that plasma pools for production of anti‐D immunoglobulin should not contain more than 104 IU per mL of parvovirus B19 (B19V) DNA. Hence, before pooling, highly viremic donations have to be identified, and after pooling the level of B19V DNA must be determined. The performance of a new real‐time B19V DNA PCR test (Roche, Mannheim, Germany) was studied, using a DNA extractor (NucliSens, bioMerieux, Boxtel, the Netherlands) for isolation of nucleic acid, and using a DNA quantification test (LightCycler apparatus, Roche, Mannheim, Germany) for amplification and detection.STUDY DESIGN AND METHODS:  Dilutions of the international B19V DNA standard and reference preparations were tested to determine the precision, linear range, and accuracy of the assay and to calculate the factor for conversion of B19V DNA copies to IUs. The internal control signals, invalid test results, and the effect of cryo‐poor plasma were studied as a measure for robustness. Routine performance was assessed by testing 164 manufacturing pools (not screened for B19V) and 1048 test pools of 480 donations each.RESULTS:  The copies‐to‐IU conversion factor was calculated to be 3.34 (95% CI, 3.07‐3.63). The assay appears linear between 103 and 107 IU per mL. Between 103 and 105 IU per mL, the test can discriminate samples differing a factor two in B19V DNA content. Overall, 0.78 percent of the test results were invalid. Of 127 B19V DNA negative control plasma samples, 7 were contaminated with low levels of B19V DNA. Of 164 nonscreened manufacturing plasma pools, 92 contained B19V DNA (56%); 13 contained more than 104 IU per mL. Of 503,040 donations, 29 contained more than 5 × 106 IU per mL B19V DNA (1:17,346).CONCLUSION:  The B19V DNA quantification test (LightCycler, Roche ) is suitable for quantitative, routine, in‐process measurement of B19V DNA levels in plasma pools, using the DNA extractor (NucliSens, bioMerieux) for nucleic acid isolation.
Cord blood units collected at a remote site: a collaborative endeavor to collect umbilical cord blood through the Hawaii Cord Blood Bank and store the units at the Puget Sound Blood Center
Authors: Wada Randal K. , Bradford Andrea , Moogk Margery , Yim Robyn , Strong D. Michael , Drachman Jonathan , Reems Jo Anna 
Published: December 2004

BACKGROUND:  Umbilical cord blood is a useful source of hematopoietic stem cells, especially because compared to equivalent HLA‐matched stem cells from unrelated adult donors. A network of community collection sites targeted at particular ethnic groups and serviced by a central processing and storage facility can maximize the genetic diversity of banked cord blood units (CBUs) in a cost‐effective fashion.STUDY DESIGN AND METHODS:  The present study compared CBUs collected near the Puget Sound Blood Center in Seattle, WA, with those collected in Honolulu, HI, and processed in Seattle. Evaluated variables include collection volume, total nucleated cell count, cellular viability, CD34+ cell count, clonogenic activity, and donor race for a total of 1646 CBUs received from July 1998 through November 2002.RESULTS:  CBUs from the two sites did not differ with regard to volume or total nucleated cells. Those from Hawaii had significantly longer transit times (p < 0.001) and lower whole cord blood cell viability. However, the numbers of CFU and viable CD34+ cells were not affected by remote collection. CBUs screened from Seattle were largely from Caucasian donors, whereas over 85 percent of those from Honolulu were from donors of Asian‐Pacific Islander or mixed ethnicity.CONCLUSION:  These studies demonstrate the feasibility of long‐distance umbilical cord blood banking. Arrange‐ments such as those described here could be used to help target cost‐effective collection from minority popula‐tions and increase the HLA and ethnic diversity for CBUs.
Expression of Transforming Growth Factor‐β Isoforms and Their Receptors in Lepromatous and Tuberculoid Leprosy
Authors: Kiszewski C. A. , Becerril E. , Baquera J. , Aguilar L. D. , Hernández‐Pando R. 
Published: December 2004

AbstractLeprosy is an infectious disease with two polar forms, tuberculoid leprosy (TT) and lepromatous leprosy (LL), that are characterized by strong cell‐mediated immunity (CMI) and CMI anergy, respectively. Transforming growth factor‐β (TGF‐β) belongs to a family of pleiotropic cytokines (TGF‐β1, TGF‐β2 and TGF‐β3) that participate in the control of cell differentiation and proliferation, as well as tissue repair. This cytokine family is unique because it suppresses CMI. In this study, we compared the expression of the three TGF‐β isoforms and their receptors in skin biopsies from LL and TT patients (LL = 20; TT = 20) using immunohistochemistry and automated morphometry. The percentage of cells immunostained for the three TGF‐β isoforms and cells positive for the three TGF‐β receptors in the inflammatory infiltrate located in the papillary dermis, reticular dermis and periadnexal tissue were significantly higher in LL than that in TT, with macrophages being the most common and strongest immunoreactive cells. Some lymphocytes, fibroblasts, keratinocytes and epithelial cells from sweat glands and hair roots were also positive. In situ reverse‐transcription polymerase chain reaction corroborated the capacity of these cells to synthesize TGF‐β1 and TGF‐β receptor 2. This high expression of TGF‐β isoforms and their receptors could contribute to CMI anergy and other clinical characteristic features of leprosy, like skin atrophy.
Cellular Profile of Cytokine Production in a Patient with Visceral Leishmaniasis: γδ+ T Cells Express Both Type 1 Cytokines and Interleukin‐10
Authors: Lagler H. , Willheim M. , Traunmüller F. , Wahl K. , Winkler H. , Ramharter M. , Graninger W. , Winkler S. 
Published: December 2004

AbstractThe cytokine profile of CD4+, CD8+ T cells, γδ+ T cells and natural killer (NK) cells (CD94+CD3–) was studied in a patient with visceral leishmaniasis (VL). The otherwise healthy, human immunodeficiency virus‐negative patient acquired the disease in Tuscany, Italy. Diagnosis was made by demonstration of high concentrations of antibodies against Leishmania antigens in serum. Flow cytometry for the detection of intracellular interferon‐γ (IFN‐γ), interleukin (IL)‐2, IL‐4, IL‐6, IL‐10, IL‐13 and tumour necrosis factor (TNF)‐α expression in peripheral blood mononuclear cells stimulated with phorbol 12‐myristate 13‐acetate and ionomycin was performed, followed by treatment with liposomal amphotericin B. CD4+ cells were identified as major cytokine‐expressing cells, capable of producing both type 1 and type 2 cytokines. A high frequency of IL‐4‐ and IL‐13‐expressing CD8+ cells was noted. NK cells and γδ+ T cells, thought to be involved in innate host defences against Leishmania, expressed IFN‐γ and TNF‐α. Ten per cent of γδ+ T cells expressed IL‐10, predominantly together with IFN‐γ, suggesting additional immune‐regulatory roles for this T‐cell subset in VL.
Pretransplant Xenogeneic Blood Transfusions Reduce the Humoral Response in a Mouse‐to‐Rat Heart Transplantation Model
Authors: Bersztel A. , Johnsson C. , Björkland A. , Tufveson G. 
Published: December 2004

AbstractA mouse heart transplanted to a rat is rejected promptly 3 days after transplantation, independent of whether cyclosporin A (CyA) is used as an immunosuppressant or not. Adding a short course of deoxyspergualin (DSG) initially, in addition to continuous CyA treatment, results in long‐term graft survival and permits retransplantation during CyA monotherapy. In this paper, we have explored the possibility of substituting the initial heart transplant with blood transfusions.Lymphocyte‐enriched blood transfusions combined with CyA and an initial course of DSG proved to lower or eliminate the haemagglutinating antibody titre normally seen in acute vascular xenorejection. The therapy, however, did not prolong the mean survival of the cardiac xenograft, but the same treatment protocol could result in either hyperacute rejection or prolonged survival of up to 11 days.In conclusion, this and earlier studies propose that a humoral unresponsiveness can be induced if the recipient vascular circulation is exposed to a xenoantigen in a mouse‐to‐rat combination.
Antigen‐Specific T‐Cell Downregulation by Human Dendritic Cells Following Blockade of NF‐κB
Authors: Calder V. L. , Bondeson J. , Brennan F. M. , Foxwell B. M. J. , Feldmann M. 
Published: December 2004

AbstractDendritic cells (DCs) are important for presenting antigen to T cells, especially naïve T cells. It has recently been shown that blocking the transcription factor, nuclear factor kappa B (NF‐κB) in human DCs inhibited the mixed leukocyte reaction. The aim of this study was to investigate the effect of blocking NF‐κB in DCs during presentation of antigen to memory T cells in vitro. Peripheral blood monocytes were differentiated into immature DCs with interleukin‐4 (IL‐4) and granulocyte‐macrophage colony‐stimulating factor, and pulsed with an immunogenic tetanus toxoid peptide. Upon maturation, the antigen‐pulsed DCs were highly effective in presenting antigen to autologous T cells. However, stimulation with antigen‐pulsed DCs overexpressing ΙκΒα, the endogenous inhibitor of NF‐κB, led to a significant reduction in T‐cell proliferation, and decreased production of interferon‐γ, IL‐4 and IL‐10, whereas transforming growth factor‐β production was low throughout. There was a significant increase in apoptosis of antigen‐specific T cells, even in the presence of IL‐2, which was not found in resting T cells. Similar findings were observed using a proteasome inhibitor to block NF‐κB. The effective downregulation of antigen‐specific T‐cell responses following blockade of NF‐κB in DCs could be a useful approach for immunomodulating inflammatory T‐cell responses.
Individual and Common Antigen‐Recognition Sites of Liver‐Derived T Cells in Patients with Autoimmune Hepatitis
Authors: Löhr H. F. , Pingel S. , Weyer S. , Fritz T. , Galle P. R. 
Published: December 2004

AbstractAutoimmune hepatitis (AIH) is characterized by dense T‐cell infiltrations in the liver tissue, but little is known how T cells influence the pathogenesis. To address this question, the distribution of T‐cell receptor variable β‐chain (TCR Vβ) transcripts of peripheral blood and liver‐infiltrating T cells from previously untreated patients with newly diagnosed acute exacerbated AIH was investigated. Furthermore, the lengths and sequences of complementary‐determining region 3 (CDR3) were studied. Reverse transcriptase‐polymerase chain reaction (RT‐PCR) analysis and CDR3 spectratyping revealed multiple clonal expansions of liver‐infiltrating T cells but not peripheral T cells within various TCR Vβ families. Further analysis of overexpressed TCR Vβ transcripts using TCR β‐chain‐joining element (TCR Jβ)‐specific primers in a nested PCR showed characteristic Vβ/Jβ combinations. Subsequent sequencing of CDR3 regions from PCR products confirmed the clonality of T‐cell expansions and the usage of common and individual CDR3 motifs. In conclusion, the clonality of expanded T cells within the liver tissue during early clinical manifestation of untreated AIH indicated that autoantigen‐specific T cells accumulate at the inflammation site. Individual and common CDR3 motifs argued for predominant epitopes that were recognized by liver‐infiltrating T cells in AIH patients.
Monocyte‐Derived CD1a+ Dendritic Cells Generated in Two Different Culture Systems: Immunophenotypic and Functional Comparison
Authors: Xia C.‐Q. , Kao K. J. 
Published: December 2004

AbstractPrevious studies demonstrated that CD1a+ dendritic cells (DCs) could not be prepared ex vivo without using fetal calf serum (FCS). Recently, we developed a method of using heparin to induce differentiation of human monocytes into CD1a+ DCs without using FCS. In order to determine the potential clinical applicability of heparin‐induced CD1a+ DCs, we conducted this study to compare both types of CD1a+ DCs, immunophenotypically and functionally. Our results showed that the expression of CD1a on heparin‐DCs was lower than that on FCS‐DCs. Both types of DCs expressed similar levels of CD11c, HLA‐DR, CD40, CD83, CD80 and CD86 before and after lipopolysaccharide stimulation. Immature heparin‐DCs and FCS‐DCs had similar phagocytic activities. Heparin‐DCs consistently secreted higher interleukin‐10 (IL‐10) and lesser IL‐12 than FCS‐DCs after activation. Mature heparin‐DCs were slightly more active than mature FCS‐DCs in stimulating the proliferation of allogeneic CD4+ T cells. Both types of mature CD1a+ DCs primed the naïve CD4+ T cells to produce large amount of interferon‐γ (IFN‐γ). However, naïve CD4+ T cells stimulated with FCS‐DCs produced more IFN‐γ, while the naïve CD4+ T cells stimulated with heparin‐DCs produced more IL‐5. The results indicate that both types of CD1a+ DCs do not have identical function in the priming of CD4+ T cells and have minor difference in immunophenotypes.
Potent Influence of Bovine Serum Proteins in Experimental Dendritic Cell‐Based Vaccination Protocols
Authors: Toldbod H. E. , Agger R. , Bolund L. , Hokland M. 
Published: December 2004

AbstractTypically autologous dendritic cells (DCs) intended for vaccination are generated from bone marrow derived stem cells or blood monocytes, loaded with antigen and introduced into the organism. However, addition of serum to DC culture medium is often necessary. Thus, serum proteins will be taken up and presented by the DCs together with other antigens. If heterologous serum is used, some of the serum proteins might be antigenic and thus induce a strong immune response when introduced in the recipient. We used the murine model of malignant melanoma, B16, to investigate the consequences of addition of fetal calf serum (FCS) to the medium for culturing murine DCs. The results showed that vaccination of mice with DCs cultured in vitro in the presence of FCS but in the absence of extraneous tumour antigens, protected the mice from challenge with B16 tumour cells similarly cultured in FCS. This protection could not be elicited by vaccination with FCS alone. Interestingly, the protective effect of DC vaccination was abolished when the challenging B16 tumour cells were free of serum proteins. Thus, these results show that DCs grown in the presence of FCS are able to induce immunity, which may be mistaken to be tumour immunity.
γδ T Cells and Interleukin‐6 Levels Could Provide Information Regarding the Progression of Human Renal Allograft
Authors: Borel I. Malan , Racca A. , Garcia M. I. , Bailat A. , Quiroga F. , Soutullo A. , Gaite L. 
Published: December 2004

AbstractWe have determined the percentage of αβ and γδ T cells by flow cytometry as well as serum interleukin‐6 (IL‐6) and soluble interleukin‐6 receptor (sIL‐6R) levels by enzyme‐linked immunosorbent assay in kidney allograft recipients with acute, chronic or stable graft evolution. The percentage of CD4 and CD8 T cells in transplanted patients was lower than in the control group (P < 0.001) with the exception of CD8 γδ T cells from patients with stable evolution (P > 0.05). The serum levels of IL‐6 and sIL‐6R in acute and chronic rejection were higher than in the controls (P < 0.05). No differences in IL‐6 levels were observed between the stable evolution and the control groups (P > 0.05). The levels of sIL‐6R were higher in stable evolution patients than in the controls (P < 0.05) and no differences were observed between the chronic and stable evolution patients (P > 0.05). IL‐6 decreased in patients with a favourable evolution, increased in those with an increased renal dysfunction and was maintained when the renal dysfunction was not modified. These results suggest that γδ T cells could participate in renal allograft maintenance and that IL‐6 but not sIL‐6R serum levels may provide a prognostic marker for measuring the evolution of kidney allograft.
The Interaction Defect of Accessory Molecules is Responsible for the Poor Ex Vivo Response to Human Antigens of Mouse T Helper Cells
Authors: Sun Y. , Langnas A. N. , Zhao Y. 
Published: December 2004

AbstractMouse T cells fail to respond to xenogeneic pig and human antigens using the direct antigen‐presenting pathway. The poor response by mouse CD8 cells is because of multiple defects in the molecular interactions between mouse CD8 cells and xenogeneic antigen‐presenting cells (APCs). Using human CD4/DR3+, mouse CD4−/major histocompatibility complex (MHC) class II − mice, we investigated the defects in molecular interaction responsible for the poor response to xenogeneic antigens by naïve mouse CD4+ cells. Mouse CD4 cells failed to respond to human leucocyte antigen (HLA)‐DR3 expressed on mouse APCs but developed a strong response to alloantigens, indicating a defect in the interaction between mouse CD4 and HLA‐DR3 molecules. Human CD4+/mouse CD4– mouse T cells respond poorly to human and pig APCs but not allogeneic APCs, indicating that accessory molecular interactions are deficient across highly separated species. Adding mouse interleukin‐2 (IL‐2) to the mixed lymphocyte reaction system did not improve the poor response to human or pig antigens by mouse or human CD4+/mouse CD4– mouse T cells. Therefore, multiple molecular interactions deficient between mouse CD4 cells and human or pig APCs may lead to the poor response to xenogeneic antigens by naïve mouse CD4 cells.
Circumgranular bassanite in a gypsum crust from eastern Algeria – a potential palaeosurface indicator
Authors: Mees Florias , Stoops Georges 
Published: December 2004

AbstractDetrital sand grains are surrounded by thin bassanite coatings in the upper part of a coarse‐crystalline gypsum crust from the Algerian Sahara. The bassanite developed by topotactic replacement of the surrounding gypsum in the absence of a liquid phase. Heating experiments using a gypsum crystal with sand inclusions produced similar patterns and textures. In one experiment, bassanite developed around quartz and carbonate grains but not along the sides of the heated gypsum crystal. This is the result of differences in heat capacity between gypsum, quartz and calcite. Bassanite formation in the crust from Algeria was not controlled by differences in thermal properties. Instead, the bassanite apparently formed under conditions of thermal equilibrium. The occurrence of bassanite as circumgranular coatings in the crust is interpreted as being related to the availability of submicroscopic space along the contact between the gypsum cement and the enclosed sand grains. The presence of coatings of this type, or derived relict features, is a potential criterion for the recognition of palaeosurfaces.
Effects of temperature and humidity upon the transport of sedimentary particles by wind
Authors: Neuman Cheryl McKenna 
Published: December 2004

AbstractWind tunnel simulations of aeolian transport carried out over a range in mean temperature between 32 °C and −9 °C suggest that cold airflows support higher mass transport rates (Q) than very warm air. The magnitude of this increase is larger than expected, so that analytical and semi‐empirical models underestimate Q. Extrapolation of the results suggests that, at −40 °C, as for example in the dry valleys of Antarctica in winter, Q may be as much as 70% higher than for the equivalent wind speed in hot deserts at air temperatures of 40 °C. Temperature‐dependent changes in air density and turbulence contribute to this result. The decreased tension of water adsorbed onto particle surfaces at low temperatures is postulated to reduce interparticle cohesion and, thus, to increase the elasticity of particle impacts on cold beds. Definition of the roles that temperature and humidity play in aeolian transport is relevant to studies of palaeoenvironmental reconstruction and extraterrestrial (or planetary) geology. Investigation of present‐day, cold climate features and of climate change effects also requires knowledge of these fundamental relations.