bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heparin‐induced thrombocytopenia and thrombosis: a prospective analysis of the incidence in patients with heart and cerebrovascular diseases
Authors: Kappers‐Klunne M. C. , Boon D. M. S. , Hop W. C. J. , Michiels J. J. , Stibbe J. , Van Der Zwaan C. , Koudstaal P. J. , Van Vliet H. H. D. M. 
Published: November 2003

Heparin‐induced thrombocytopenia and/or thrombosis (HITT) are serious complications of heparin treatment. The incidence, as previously reported, varies widely and, in consequence, is not precisely known. Moreover, most reports only concern clinically defined heparin‐induced thrombocytopenia. Therefore we carried out a prospective study of the incidence of serologically confirmed HITT.All patients admitted to the Departments of Cardiology and Neurology of our institution with an indication for treatment with therapeutic‐dose intravenous unfractionated heparin were enrolled in the study. The patients were examined daily for the occurrence of thromboembolic complications. Regular platelet counts and tests for the presence of heparin‐dependent antibodies were carried out using two different tests: a quantitative platelet factor 4/heparin (PF4/hep) Elisa, and a functional test, the heparin‐induced platelet activation assay (HIPAA). HITT was defined as a rapidly occurring (within 5 d) decrease of the platelet count from normal values of >120 ×109 l to <60 ×109 l or to <100 ×109 l if there was a rapid fall of >50% of starting value or >30% with concomitant acute thrombosis.The observed incidence of HITT was 1/358 patients (0.3%, 95% confidence limits 0.01–1.5%). However, Elisa PF4/hep specific IgG antibodes were demonstrated in nine (2.5%) and IgM antibodies in seven (2.0%) of 358 patients. 30/358 patients (8.4%) had platelet activating antibodies in the HIPAA.We conclude that the incidence of serologically confirmed HITT in this study is very low (0.3%) in patients with cardiac and neurologic diseases treated with intravenous unfractionated heparin. The frequency of heparin‐dependent antibodies without concomitant occurrence of thrombocytopenia is much higher.
Two subsets of peripheral blood plasma cells defined by differential expression of CD45 antigen
Authors: Schneider Ulrike , Lessen Antje van , Huhn Dieter , Serke Stefan 
Published: November 2003

The purpose of this study was to optimize the flow cytometric determination of circulating normal and malignant plasma cells (PC). We investigated peripheral blood (PB) samples of 65 patients with multiple myeloma or monoclonal gammopathy of unknown significance and 47 control subjects using CD38, CD45, B‐B4, CD56, VLA‐4, VLA‐5 and CD19 monoclonal antibodies (MoAbs). Mono‐ or polyclonality was determined by staining of intracellular kappa and lambda light chains. Two subpopulations of PBPC were distinguished by differential expression of CD45. CD45 positive (CD45+) PC showed a more immature morphology and were detected in all groups. They were polyclonal in the control subjects and either poly‐ or monoclonal in the myeloma patients. In contrast, CD45 negative (CD45−) PBPC only occurred in myeloma patients and were consistently monoclonal, their presence being significantly associated with high disease activity (P<0.001). Although detection of CD45− PBPC using CD38 or B‐B4 MoAbs lead to similar results, CD45+ PBPC often were recognized to a lesser extent by B‐B4 than by CD38 MoAbs.In conclusion, normal and malignant circulating PC can reliably be identified using CD38 and CD45 MoAbs. CD45 expression separates PBPC into two subsets of which the CD45− one only occurs in myeloma patients.
In situ hybridization analysis of ICAM‐1 (CD54) mRNA on conjunctival epithelium during allergic inflammation
Authors: BAGNASCO M. , PESCE G. , FIORINO N. , RICCIO A. M. , CIPRANDI G. , BUSCAGLIA S. , CANONICA G. W. 
Published: November 2003

SummaryBackground
The intercellular adhesion molecule ICAM‐1 has been detected by immunohistochemical methods on epithelial cells of the conjunctiva and nose during allergic inflammation.Objective
The aim of the present study was to evaluate whether ICAM‐1 expression on conjunctival epithelium derives from endogenous synthesis or is merely due to passive uptake of soluble ICAM‐1 released from inflammatory cells.Methods
In situ hybridization was performed using a 3’end dygoxygenin‐labelled specific DNA oligonucleotide probe on fixed conjunctival smears from allergic subjects challenged with, or naturally exposed to the allergen, and from healthy subjects. Immunocytochemistry for ICAM‐1 was performed by alkaline phosphatase antialkaline phosphatase.Results
Results In allergic patients, both naturally exposed to the allergen and after specific challenge, a clear hybridization pattern on epithelial cells was apparent. Out of allergen exposure, some symptomfree pollinosic subjects, as well as a few healthy volunteers showed mild ICAM‐1 mRNA cytoplasmic staining in the absence of immunohistochemically detectable ICAM‐1. This finding may explain the very early appearance of ICAM‐1 on conjunctival epithelium following specific challenge in allergic individuals.Conclusions
These results indicate that the presence of ICAM‐1 on conjunctival epithelium during allergic inflammation derives from endogenous synthesis and not from uptake of soluble ICAM‐l.
Specific induction of interleukin‐4‐producing cells in response to in vitro allergen stimulation in atopic individuals
Authors: GABRIELSSON S. , PAULIE S. , RAK S. , LAGGING E. , VAN HAGE‐HAMSTEN M. , HARFAST B. , TROYE‐BLOMBERG M. 
Published: November 2003

SummaryBackground and Objective
CD4+ T cells can be divided into two major subsets. T helper (TH)1 and TH2 cells. Interleukin‐4 (IL‐4) is produced by TH2 cells and induces switching of immunoglobulin (Ig) M/lgG to IgE. Interferon‐γ (IFNγ) produced by TH1 cells counteracts the IgE‐promoting effects of IL‐4. In this study we wanted to investigate whether the number of IL4‐producing cells could be a direct measurement of allergen exposure in vitro, and whether this was correlated to the elevated serum IgE‐levels seen in atopic persons.Methods
We compared the number of IL‐4‐ and IFNγ‐producing cells using an enzyme‐linked immunospot assay (ELISPOT) in response to allergens from birch and cat in peripheral mononuclear cells from atopic and healthy individuals.Results
In the two sensitized groups there was an increase in the number of lL‐4producing cells in response to the specific allergen which was not seen in the healthy group (1/20000 cells and 1/200 000 cells, respectively, P < 0.001 for birch). In criss‐cross experiments where birch‐sensitized individuals were stimulated with cat allergen, no lL‐4‐producing cells were seen, indicating a high degree of specificity. In individual subjects, the elevated numbers of IL‐4‐producing cells were significantly correlated with their allergen‐specific serum IgE levels. When allergen was combined with a suboptimal dose of PHA, there was a synergistic increase in the number of allergen‐induced IL‐4‐producing cells (1/4000 cells) in the atopic donors, which was not seen with the number of IFNγ‐producing cells.Conclusions
Allergen‐specific IL‐4 producing cells in a peripheral blood mononuclear cell (PBMC) culture can be detected by ELISPOT and the response can synergistically be enhanced by suboptimal concentrations of PHA.
Reduction of exposure to laboratory animal allergens in the workplace
Authors: GORDON S. , WALLACE J. , COOK A. , TEE R. D. , TAYLOR A. J. NEWMAN 
Published: November 2003

SummaryObjectives
Evidence is now accumulating that the prevalence of allergy to laboratory animals is related to the intensity of exposure to animal allergens. Whilst airborne animal allergen concentrations may be influenced by the litter type, cage design and stock density, the effectiveness of methods to reduce personal exposure has not been objectively assessed. Methods Air samples were collected at 2 L/min and 180L/min onto polytetrafluoroethylene (PTFE) filters and the rat urinary aeroallergen (RUA) and mouse urinary aeroallergen (MUA) concentrations were measured by radioallergosorbent test (RAST) inhibition.Results
When 545 mice (11.1 mice/m3) were housed in ventilated cages (Thoren Maximiser cage system) operated at positive pressure to the environment, the static MUA concentration (n= 24. median = 0.10μg/m3) was reduced sevenfold when compared with conventional cage systems (n= 12, median = 0.67μ/g/m3, P < 0.001). MUA could be further reduced if the ventilated cage system was operated at lower pressure: static samples (n= 1) collected at 180 L/min at negative, ambient and positive pressure registered < 0.003, 0.02 and 0.28 μg/m3, respectively. During cleaning out, the intensity of personal exposure to RUA was apparently reduced twofold when soiled litter was removed by vacuum (n= 17, median = 22.87 μg/m3) when compared with tipping (n=18, median = 38.l.5μg/m3), P= 0.002) although the task took twice as long to perform. The RUA exposure associated with handling rats was reduced 25‐fold when performed in a ventilated cabinet (n= 21, median = 2.67 μg/m3) compared with handling of rats on an open bench (n= 17, medians 54.39 μg/m3, P= 0.0001).Conclusions
Effective reduction of exposure to animal allergens can now be achieved by the use of ventilated systems both for housing and handling rats and mice providing safety equipment is used correctly. The vacuum removal of soiled litter during the task of cleaning out was less efficient and additional respiratory protection is therefore recommended for this procedure.
Detection, isolation and complete amino acid sequence of an aeroallergenic protein from rapeseed flour
Authors: MONSALVE R. I. , DE LA PEÑA M. A. GONZÁLEZ , LÓPEZOTÍÍN C. , FIANDOR A. , FERNÁNDEZ C. , VILLALBA M. , RODRÍGUEZ R. 
Published: November 2003

SummaryBackground
Seed proteins have been found to cause hypersensitivity by ingestion or inhalation. Rapeseed fiour was responsible for allergic symptoms in a patient, who develops into allergy to mustard spice.Objective
To determine the presence of allergenic proteins in rapeseed fiour, and analyse the structure of the main component and its crossreactivity with the mustard allergeti.Methods
SDS‐PAGE (sodium dodecyl sulfate‐polyacrylamide gel electrophoresis) and subsequent immunoblotting with a serum from a rapeseed allergic patient were performed to detect IgE‐binding proteins. Proteolytic digestiotis and high performance liquid chromatography were used to obtain the peptides from the allergenic BnIII napin from rapeseed flour. Automatic Edman degradations were carried out to determine their amino acid sequences, which were compared with other sequences in nucleotide and amino acid sequence databases. Crossreactivity assays were carried out by ELISA inhibition using sera from a rapeseed allergic patient and from patients allergic to mustard.Results
The 2S albumins of rapeseed were recognized by the serum from a patient allergic to this seed. The most abundant isoform of the allergenic napins, Bnlll, was used for structural and immunological analysis. The protein consists of two different chains of 9.5 and 4,5 kDa. Their complete amino acid sequences were determined. The protein exhibited structural relationships with other napin‐like storage proteins from seeds. IgE and IgG crossreactivity between rapeseed and mustard allergens was also demonstrated. Considering the structural and immunological data, certain polypeptide regions are suggested to be involved in the allergenicity of these proteins.Conclusions
Rapeseed contains 2S storage proteins which may cause allergy in hypersensitive individuals. These proteins exhibit great sequence similarity with 2S albumins from different seeds. Crossreactivity between mustard and rapeseed flours can be explained by sequetice homology.
Intranasal capsaicin is efficacious in non‐allergic, non‐infectious perennial rhinitis. A placebo‐controlled study
Authors: BLOM H. M. , VAN RIJSWUK J. B. , GARRELDS I. M. , MULDER P. G. H. , TIMMERMANS T. , VAN WIJK R. GERTH 
Published: November 2003

SummaryBackground
Several authors described capsaicin, the pungent substance in red pepper, as an efficacious therapy for non‐allergic non‐infectious perennial rhinitis (NANIPER). Repeated capsaicin application induces peptide depletion and specific degeneration of the unmyelinated sensory C‐fibres in the nasal mucosa.Methods
We performed a placebo‐controlled (NaCl 0.9%) study with 25 NANIPER patients. Daily record charts and visual analogue scales (VAS) were used for clinical evaluation. Nasal lavages were obtained before, during, and after treatment.Results
There was a significant and long‐term reduction in the VAS scores in the capsaicin group. No significant difference was found between the placebo and capsaicin treated groups for the mean group concentrations of leukotriene (LT) C4/D4/E4, prostaglandin D2 (PGD2). and tryptase. The levels of mast cell mediators, tryptase and PGD2. and leukotrienes, mediators derived from a variety of inflammatory cells, were low at baseline and comparable with levels observed in nasal lavages obtained from normals.Conclusion
As involvement of inflammation could not be demonstrated, it is not surprising that capsaicin has no effect on inflammatory mediators. This suggests that inflammatory cells do not play a major part in the pathogenesis of NANIPER.
Selective type IV phosphodiesterase inhibitors prevent IL‐4‐induced IgE production by human peripheral blood mononuclear cells
Authors: COQUERET O. , BOICHOT E. , LAGENTE V. 
Published: November 2003

SummaryBackground
Selective type IV phosphodiesterase (PDE) inhibitors elicit anti‐inflammatory and bronchodilatory activities in vitro and in vivo which suggest that these drugs could provide a new therapeutic approach for asthma treatment.Objective
Regarding the role of IgE production in allergic and inflammatory reactions of the airways, we investigated the effect of selective PDE inhibitors on IL‐4‐driven IgE production by peripheral blood mononuclear cells (PBMC) or by purified B lymphocytes.Methods
PBMC or purified B lymphocytes from non‐allergic donors were stimulated for 13 days with IL‐4 (100U/mL) in the presence or in the absence of selective PDE inhibitors. IgE production is evaluated by an ELISA technique.Results
The selective PDE IV inhibitors, rolipram and Ro 20–1724 (10μM), inhibit lL‐4‐induced IgE production by PBMC. but not by purified B lymphocytes. No modification of the IgE production was noted with the selective PDE III inhibitors, milrinone and SK&F94‐836, or the selective PDE V inhibitor, SK&F 96–231 (10 μM). Flow cytometry experiments showed that the effect of Rolipram could not be explained by the inhibition of the cell surface expression of the IL‐4 receptor. Similarly, no significant effect of PDE IV inhibitors was observed on PHA‐induced cell proliferation. The incubation of monocytes only with rolipram was sufficient to achieve a significant reduction of IgE production induced by IL‐4.Conclusion
Taken together, these results indicate that PDE IV inhibitors reduce lL‐4‐induced IgE production by PBMC and suggest that the inhibition of IgE production could be explained by a failure of monocytes to provide the necessary costimulatory signals.
Thunderstorm‐related asthma – the epidemic of 24/25 June 1994
Authors: VENABLES K. M. , ALLITT U. , COLLIER C. G. , EMBERLIN J. , GREIG J. B. , HARDAKER P. J. , HIGHHAM J. H. , LATNG‐MORTON T. , MAYNARD R. L. , MURRAY V. , STRACHAN D. , TEE R. D. 
Published: November 2003

SummaryBackground
A large epidemic of asthma occurred following a thunderstorm in southern and central England on 24/25 June 1994. A collaborative study group was formed.Objectives
To describe the epidemic and the meteorological, aerobiological and other environmental characteristics associated with it.Methods
Collation of data from the Meteorological Office, the Pollen Research Unit, the Department of the Environtnent's Automatic Urban Network, from health surveillance by the Department of Health and the National Poisons Unit, from clinical experience in general practice and hospitals, and from an immunological study of some of the affected cases from north east London.Results
The thunderstorm was a Mesoscale Convective System, an unusual and large form of storm with several centres and severe wind gusts. It occurred shortly after the peak grass pollen concentration in the London area. A sudden and extensive epidemic occurred within about an hour affecting possibly several thousand patients. Emergency services were stretched but the epidemic did not last long. Cases had high serum levels of IgE antibody to mixed grass pollen.Conclusion
This study supports the view that patients with specific IgE to grass pollen are at risk of thunderstorm‐related asthma. The details of the causal pathway from storm to asthma attack are not clear. Case‐control and time series studies are being carried out.
Defective antigen processing associated with familial disseminated mycobacteriosis
Authors: D’Souza S , Levin M , Faith A , Yssel H , Bennett B , Lake R A , Brown I N , Lamb J R 
Published: November 2003

SUMMARY
To gain insights into a possible immune defect predisposing to disseminated mycobacteria infection, we studied three of six surviving children with disseminated Mycobacterium avium complex infection, who had no recognized form of immunodeficiency. We used mycobacteria isolated from the patients and diphtheria, tetanus and pertussis vaccine (DTP) to study antigen-specific T lymphocyte responses. We observed that interferon-gamma (IFN-γ) production by T cells in response to antigens (both mycobacteria and DTP) in these patients with disseminated infection was greatly impaired. This defect did not seem to be the result of T cell unresponsiveness, as phytohaemagglutinin (PHA) stimulation was able to induce high levels of IFN-γ comparable to those seen in control patients with localized infection. Further experiments showed that peripheral blood mononuclear cells (PBMC) from patients with disseminated infection were able to present influenza haemagglutinin (HA) peptides to specific T cell clones. However, this ability was lost when the whole HA protein was used as source of antigen. Taken together, these observations support the notion that the primary immune defect in these patients with disseminated mycobacterial infection rests in the antigen-processing functions of their antigen-presenting cells (APC). These findings may provide clues to the wider problem of susceptibility to mycobacteria and other intracellular pathogens and have implications in designing therapy for these patients.
Cytotoxic T lymphocytes specific for murine type II collagen do not trigger arthritis in B10 mice
Authors: Gao X-M , Mcmichael A J 
Published: November 2003

SUMMARY
To investigate the role of cytotoxic T lymphocytes (CTL) in arthritis, we set out to induce CTL specific for murine type II collagen (mCII) in a mouse model. The primary protein sequence of the murine pro-α1(II) was screened for fragments bearing H-2 Db or Kb binding motifs. Six fragments were identified and the corresponding peptides synthesized. One of these peptides, peptide P201 (amino acid 199–208 in the C-propeptide of the murine pro-α1(II)), was found to be a strong binder to H-2 Db. When used to treat RMA-S cells at 26°C, peptide P201 induced a four-fold increase of surface expression of H-2 Db. Administration of the P201-treated RMA-S cells into B10 mice (H-2b) induced strong CTL responses against the immunizing collagen peptide. Despite the high frequencies of mCII-specific CTL precursors in the periphery, however, the immunized mice showed no sign of arthritis up to 16 weeks after immunization. Implications of these data for autoimmunity and arthritis are discussed.
Production of neutralizing granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies in carcinoma patients following GM-CSF combination therapy
Authors: Wadhwa M , Bird C , Fagerberg J , Gaines-Das R , Ragnhammar P , Mellstedt H , Thorpe R 
Published: November 2003

SUMMARY
In this study, the development of neutralizing and non-neutralizing GM-CSF antibodies and the clinical consequences related to the induction of these antibodies were analysed in 20 patients with metastatic colorectal carcinoma receiving a combination therapy of Escherichia coli-derived GM-CSF and a colon carcinoma-reactive MoAb in the absence of any concomitant chemotherapy. The recombinant human GM-CSF was administered subcutaneously for 10 days every month for 4 months. Following the first cycle of treatment, no GM-CSF antibodies were detected, but during subsequent therapy, 19 of the 20 patients studied developed GM-CSF binding antibodies. However, only a proportion (40%) of the 19 antibody-positive patients developed antibodies that neutralized the biological activity of GM-CSF in an in vitro bioassay. The presence of GM-CSF neutralizing antibodies was associated with a significant reduction in GM-CSF-induced expansion of leucocytes, neutrophils and eosinophils. Such clinical effects were not apparent in patients with non-neutralizing antibodies. Further characterization of sera from patients with neutralizing antibodies showed that, in most cases, the antibodies neutralized the biological activity of GM-CSF preparations derived using different expression systems (chinese hamster ovary cells and yeast), suggesting that these antibodies may have the potential to cross-react with endogenously produced GM-CSF. These effects should be considered before therapeutic use of cytokines, particularly in patients who are not immunosuppressed, and therefore capable of mounting an effective immune response. Our results indicate that assessment of production of neutralizing antibodies induced during cytokine therapy can be used to predict diminished clinical response to further therapy.
Autoantibodies to the collagenous region of C1q occur in three strains of lupus-prone mice
Authors: Hogarth M B , Norsworthy P J , Allen P J , Trinder P K E , Loos M , Morley B J , Walport M J , Davies K A 
Published: November 2003

SUMMARY
We have developed an ELISA to measure murine autoantibodies to the collagenous region (CLR) of C1q, using the whole human C1q molecule as the solid-phase ligand, in the presence of 1 m NaCl. The assay was validated by testing positive sera from 20 mice using purified mouse C1q, and from 10 mice using purified human C1q-CLR, as the solid-phase ligands. There were highly significant correlations between results obtained with human C1q (whole molecule) and: (i) mouse C1q (rSp = 0.73, P &lt; 0.001), and (ii) human C1q-CLR alone (rSp = 0.86, P = 0.001). Antibodies to C1q were measured in 53 MRL/lpr, 17 BXSB and 25 NZB/W lupus-prone mice. Median (range) anti-C1q (CLR) antibody levels in MRL/lpr, BXSB, and NZB/W autoimmune mice aged 3 months were 22 (16–66), 21 (17–39) and 19 (15–27) EU, respectively. The median anti-C1q antibody level in MRL/lpr mice aged 5 months was 76 (35–142) EU, significantly higher than that at 3 months (U = 558, P &lt; 0.0005). Median anti-C1q antibody level in NZB/W mice at 8 months was 37 (13–74) EU and in BXSB mice at 11 months was 62 (31–231) EU, significantly higher than corresponding values at 3 months (U = 326, and U = 4, P &lt; 0.001, respectively). This is the first demonstration of anti-C1q (CLR) antibodies in NZB/W and BXSB mice. The pathologic significance and the potential utility of these antibodies for monitoring disease in lupus-prone mice are under evaluation.