bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sibling effect on atopy in children of patients with asthma
Authors: Koppelman G. H. , Jansen D. F. , Schouten J. P. , Van Der Heide S. , Bleecker E. R. , Meyers D. A. , Postma D. S. 
Published: March 2003

SummaryBackground Multiple population studies have shown the presence of a sibling effect on atopic disease. However, it is unclear if the sibling effect is also of importance in subjects who are genetically at high risk for the development of atopy.Objective To study the presence of a sibling effect on markers of atopy (serum total IgE, specific IgE, skin tests) and asthma (bronchial hyper‐responsiveness to histamine) in families ascertained through a parent with asthma.Methods First‐degree offspring in 200 asthma families were studied (n = 541). Mixed effects regression models were used to account for the dependence of the observations within a family, and to adjust for possible confounding variables.Results Multiple regression analysis showed that having older siblings was inversely related to atopy, defined as ≥ 2, ≥ 3, ≥ 4, or ≥ 5 skin tests (P = 0.07–0.009). In addition, family size (number of siblings) had a significant protective effect on the presence of specific IgE to common aeroallergens (P = 0.03). Exposure to cigarette smoke in the first 3 years of life significantly increased the risk of having specific IgE to common aeroallergens (P = 0.04). No sibling effect was detected for serum total IgE or bronchial hyper‐responsiveness to histamine.Conclusions This study shows a protective sibling effect on the presence and severity of atopy but not on bronchial hyper‐responsiveness in children who are genetically at risk. The identification of the sibling effect in high‐risk families stresses the need to understand the basis of this effect, in order to design future prevention programmes.
Acquired crateriform hyperkeratotic papules of the lower limbs: an unusual variant of acrokeratoelastoidosis of Costa
Authors: Helbling I. , Tucker S. C. , Chalmers R. J. G. 
Published: March 2003

Abstract
We report a man with a 3-year-history of a striking eruption of small, 2–3 mm diameter keratotic, crateriform papules distributed symmetrically over the lower limbs. Morphologically the individual papules closely resembled those described in acrokeratoelastoidosis (AK) of Costa and in focal acral hyperkeratosis of Dowd (FAH). The case is unusual, however, in that there was dramatic involvement of the legs but the hands and feet were largely spared. Current terms used for these entities are unsatisfactory.
Oxidative stress in physical urticarias
Authors: Briganti S. , Cristaudo A. , D'Argento V. , Cassano N. , Turbino L. , Guarrera M. , Vena G. , Picardo M. 
Published: March 2003

Abstract
The pathogenesis of the physical urticarias has not been completely defined. Indeed, different stimuli can induce similar clinical manifestations, some of which are capable of generating reactive oxygen species. In order to evaluate whether the generation of an oxidative stress response could be a common pathogenetic mechanism of the disease, we have determined the profile of a number of chemical and enzymatic antioxidants in blood samples from a group of patients with physical urticarias. Compared with controls, a systemic imbalance of the antioxidants was detected in the patient group with a decrease of both plasma vitamin E and cellular catalase and glutathione peroxidase activities along with an increase of superoxide dismutase activity. Moreover, an increase in the percentage of plasma polyunsaturated fatty acids, as a target for peroxidative damage, was also observed. These alterations may lead to an increased percentage of peroxidable compounds in skin and to the intracellular generation of reactive oxygen species and could therefore provide one possible explanation for the patients' urticarial response to stimuli. Even if the alteration of the antioxidant status is secondary to changes in cytokine or complement activation, our results suggest a common biochemical profile in patients with different forms of physical urticaria.
Splenic T helper cell type 1 cytokine profile and extramedullary haematopoiesis in severe combined immunodeficient (scid) mice with inflammatory bowel disease (IBD)
Authors: Bregenholt S , Claesson M H 
Published: March 2003

AbstractScid mice develop a severe, chronic, and lethal IBD 3–6 months after engraftment of gut wall from immunocompetent congenic donors, induced by donor-derived CD4+ T cells migrating from the graft [7]. We have investigated intracellular T-helper type 1 (Th1) cytokines in the spleens of gut wall-transplanted scid mice with IBD. Increased fractions of interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α) and IL-2-positive CD4+ T cells were found in the spleens of diseased mice compared with control mice. Moreover, a small but significant population of CD4+ T cells which stained positive for granulocyte-macrophage colony-stimulating factor (GM-CSF) was found in scid mice with IBD but was virtually absent in congenic non-scid control mice. Cloning of granulocyte/macrophage colony-forming cells (G/M-CFC) revealed that both non-transplanted scid mice and scid mice with IBD had an 8–14-fold increase in splenic G/M-CFC compared with control mice. No significant difference in the number of G/M-CFC per total spleen was found between non-transplanted and disease scid mice, although both groups of mice showed a nearly two-fold increase compared with control mice. G/M-CFC were never found in the thymus, liver or lymph nodes of diseased mice. Immunohistochemistry revealed that the multinucleated giant cells observed in the gut wall of diseased mice did not represent haematopoietic foci, but were derived from macrophages. These observations point towards a dominant role for Th1-type CD4+ T cells in the immunopathogenesis of IBD, whereas haematopoiesis does not seem to be affected by the development of the disease.
Evaluation of IgA deficiency in Sardinians indicates a susceptibility gene is encoded within the HLA class III region
Authors: Cucca F , Zhu Z B , Khanna A , Cossu F , Congia M , Badiali M , Lampis R , Frau F , De Virgiliis S , Cao A , Arnone M , Piras P , Campbell R D , Cooper M D , Volanakis J E , Powis S H 
Published: March 2003

Abstract
IgA deficiency (IgA-D) has been associated with the HLA region, in particular with the North European haplotype HLA-A1, -B8, -DR3, but the exact location of the susceptibility gene(s) is unknown. Some reports suggest that a susceptibility gene is encoded in the class II region, while others implicate the class III region. We exploited differences between the common Sardinian and North European HLA-DR3 haplotypes to help localize the IgA-D susceptibility gene(s). With the knowledge that approximately 13% of HLA-DR3 homozygous individuals of North European origin are IgA-D, we examined 43 HLA-DR3 homozygous Sardinians to find that all had normal serum IgA, IgG and IgM levels. A detailed analysis of their MHC haplotypes indicated a common Sardinian HLA-DR3 haplotype TAP1A, TAP2A, HLA-DQB1*0201, -DQA1*0501, -DRB1*0301, LH1-(Z  +  2), D3A-(Z  +  2), C4B-0, C4A-L, G11-15, Bf-0.4, C2-a, HSP70-7.5, 9N3-(Z  +  10), 82I-(Z  −  2), TNFα-9, 62-(Z  −  20), HLA-B18, -Cw5, -A30 which diverges from the common North European HLA-DR3 haplotype telomeric to the HLA-DR region. In parallel studies of five Sardinians with IgA-D, two of the 10 HLA haplotypes (20%) contained HLA-DR3, a frequency similar to that observed in the background population. One of these was the HLA-DR3- B8 North European haplotype, which occurs rarely in Sardinia. Our data favour the hypothesis that a class III region allele, present on the common North European but not on the Sardinian HLA-DR3 haplotype, confers susceptibility to IgA-D.
Effect of annexin-1 on experimental autoimmune encephalomyelitis (EAE) in the rat
Authors: Huitinga I , Bauer J , Strijbos P J L M , Rothwell N J , Dijkstra C D , Tilders F J H 
Published: March 2003

AbstractAnnexin-1, a calcium-dependent phospholipid binding protein, has been shown to act as an endogenous central neuroprotectant, notably against cerebral ischaemic damage. In the present study we extend these findings to an animal model of multiple sclerosis, EAE, and report that endogenous annexin-1 is expressed in ED1+ macrophages and resident astrocytes localized within the lesions in the central nervous system (CNS). Intracerebroventricular (icv) administration of an NH2-terminal fragment spanning amino acids 1–188 of annexin-1 after the onset of the clinical symptoms significantly reduced both the neurological severity as well as weight loss of mild EAE. Immunoneutralization of endogenous brain annexin-1 failed to exacerbate the clinical features of EAE. Thus, although the role of endogenous annexin-1 in the pathogenesis of EAE remains to be determined, our findings suggest that annexin-1 may be of therapeutic benefit to the treatment of multiple sclerosis.
Detection of complement C3 and factor B gene expression in normal colorectal mucosa, adenomas and carcinomas
Authors: Andoh A , Fujiyama Y , Sakumoto H , Uchihara H , Kimura T , Koyama S , Bamba T 
Published: March 2003

SUMMARYLocal secretion of complement components in the human intestine has been previously reported. However, the cellular source has not been identified. In this study, we demonstrate complement C3 and factor B mRNA expression in the normal colonic mucosa by in situ hybridization analysis. C3 and factor B genes were found to be expressed at high levels in the epithelial cells of the lower parts of the crypts in colonic mucosa, and this expression decreased gradually from the crypt base to the luminal surface. At the upper crypt and the luminal surface, these genes almost disappeared. C3 and factor B genes were expressed in all crypts at the same level. Furthermore, C3 and factor B gene expression was also identified in adenomas and carcinomas. In these neoplastic tissues, C3 and factor B genes were expressed uniformly, and the polarized distribution observed in the normal crypts was not detected. It is likely that complement components are locally synthesized in the intestine, and that these complement components may actively participate in normal immune and inflammatory responses over the enormous surface area of the intestinal mucosa.
Anti-mitochondrial antibodies in patients with dilated cardiomyopathy (anti-M7) are directed against flavoenzymes with covalently bound FAD
Authors: Otto A , Stähle I , Klein R , Berg P A , Pankuweit S , Brandsch R 
Published: March 2003

SUMMARY
Anti-mitochondrial antibodies (anti-M7) in sera from patients with dilated cardiomyopathy and myocarditis recognize, besides mitochondrial antigens, bacterial sarcosine dehydrogenase. The common target antigen was identified as the covalently bound FAD of mitochondrial and bacterial flavoenzymes. Thus, anti-M7-positive serum reacted on Western blots exclusively with covalently flavinylated enzymes. The antigenic specificity of anti-M7 sera was reproduced by an antiserum raised in rabbits with 6-hydroxy-d-nicotine oxidase. The heart mitochondrial membrane antigen recognized by anti-M7 serum was identified as the flavoprotein subunit of succinate dehydrogenase, the antigens in rat liver mitochondrial matrix as the flavoenzymes dimethylglycine dehydrogenase and sarcosine dehydrogenase. Anti-M7 serum contained a specific anti-flavoenzyme antibody fraction. Nanomolar concentrations of FAD and riboflavin inhibited the immune reaction on Western blots and in ELISA, and incubation with FAD-agarose depleted the anti-M7 activity of the serum. N-terminally deleted dimethylglycine dehydrogenase proteins were only immunoprecipitated by anti-M7 sera when the FAD was covalently incorporated. An affinity constant (KD) of 10−8 m was established for the anti-flavoenzyme antibodies by competitive ELISA. Of patients with cardiomyopathy and myocarditis, 36% and 25%, respectively, were anti-flavoenzyme-positive by Western blot and ELISA, but only two of 15 patients with other heart diseases and none of 50 healthy controls.
A tumour necrosis factor-alpha (TNF-α) promoter polymorphism is associated with chronic hepatitis B infection
Authors: Höhler T , Kruger A , Gerken G , Schneider P M , Meyer Zum Büschenfelde K-H , Rittner C 
Published: March 2003

SUMMARY
Cytokines such as TNF-α and interferon gamma (IFN-γ) are important for the elimination of infected hepatocytes during acute hepatitis B virus (HBV) infection. Two G versus A transitions in the TNF-α promoter region at positions −308 and −238 possibly influence TNF-α expression. We investigated these TNF-α polymorphisms in 71 patients with chronic HBV infection, in 32 subjects that had spontaneously recovered from acute HBV infection, and in 99 healthy controls. The −238 A promoter variant was present in 18 (25%) of 71 patients with chronic HBV infection compared with two (6%) of 32 subjects with acute infection (P &lt; 0.04), and seven (7%) of 99 controls (P &lt; 0.003). By contrast, the prevalence of the variant at position −308 was similar in all investigated groups. The observed differences could not be explained by linkage disequilibrium to HLA-B or -DRB1* alleles. These findings suggest an association between the TNF-α promoter polymorphism at position −238 and the development of chronic HBV infection. This promoter variant appears to be linked to defective viral clearance.
Effects of granulocyte colony-stimulating factor (G-CSF) treatment on granulocyte function and receptor expression in patients with ventilator-dependent pneumonia
Authors: Hustinx W N M , Van Kessel C P M , Heezius E , Burgers S , Lammers J-W , Hoepelman I M 
Published: March 2003

SUMMARYConsiderable experimental evidence in animals suggests that treatment with G-CSF may have a beneficial effect in the management of severe infections in non-neutropenic hosts. This beneficial effect is attributed to an enhancement of granulopoiesis and neutrophil function, the latter possibly involving up-regulation of receptors on neutrophils that are involved in antibody-mediated cytotoxicity and killing of microorganisms. We compared neutrophil function and phenotype in blood and bronchoalveolar lavage fluid (BALF) of 10 patients with severe ventilator-dependent pneumonia, at baseline and following initiation of G-CSF treatment as adjunct to standard therapy. G-CSF treatment was associated with three-fold increased blood neutrophil counts at day 3 of treatment compared with baseline counts. Mean serum G-CSF concentration increased from 313 to 2007 pg/ml. After correction for lavage dilution effects, BALF G-CSF levels did not differ significantly from baseline, nor did neutrophil receptor expression (FcγRI, FcγRII, FcγRIII, CR3, and l-selectin) or indicators of neutrophil function such as respiratory burst activity, phagocytosis and killing of Candida albicans in BALF or blood. The mortality in this group of patients was 30% and compared favourably to the APACHE II-derived predicted mortality of 60%. We conclude that the possible therapeutic benefit of G-CSF administration in the early phase of severe bacterial pneumonia is not readily explained by its effect on baseline indicators of neutrophil function or receptor expression.
Induction of unresponsiveness against IgA in IgA-deficient patients on subcutaneous immunoglobulin infusion therapy
Authors: Sundin U , Nava s , Hammarström L 
Published: March 2003

SUMMARYPatients with IgA deficiency often demonstrate circulating antibodies against IgA, which have been suggested to be associated with transfusion reactions. Sera from three patients with common variable immunodeficiency (CVID) and one with a selective IgA deficiency with anti-IgA antibodies receiving subcutaneous gammaglobulin replacement therapy were analysed for serum levels of IgG, IgA and anti-IgA before and during a treatment period of 4–7 years. Treatment with gammaglobulin preparations containing significant amounts of IgA (&lt; 5 mg/ml) resulted in a decrease or disappearance of the anti-IgA antibodies. Analysis of serum fractions, however, revealed anti-IgA activity in the complex-containing fractions. In vitro experiments gave similar results with a shift of anti-IgA activity from the monomeric to the complex-containing fractions (that could not be detected in whole serum). When the patients were subsequently switched to treatment with a preparation containing less IgA (&lt; 80 μg/ml) or made an interruption in the treatment schedule, the anti-IgA antibodies reappeared. Importantly, however, one of the patients lost his anti-IgA activity during a 3-month period on the preparation containing the higher IgA levels, and these antibodies did not reappear after switching to the low IgA-containing preparation. After 5 years on this preparation, anti-IgA can still not be detected, suggesting induction of unresponsiveness.
Immunity to type IX collagen in rodents: a study of type IX collagen for autoimmune and arthritogenic activities
Authors: Cremer M A , YE X J , Terato K , Griffiths M M , Watson W C , Kang A H 
Published: March 2003

AbstractType IX collagen (CIX), a cartilage-specific glycoprotein, constitutes ≤ 10% of cartilage collagen. To ascertain whether CIX can induce arthritis as shown for type II and XI collagen (CII and CXI), outbred rats were sensitized with bovine, chick and human CIX; inbred rats, mice, and guinea pigs were sensitized with bovine CIX. Mice and guinea pigs proved resistant to arthritis, as did rats sensitized with CIX/Freund's incomplete adjuvant (FIA). Arthritis was seen in rats when 100 μg of Mycobacterium tuberculosis (Mtb) were added to FIA, but seldom with smaller doses of Mtb, suggesting the arthritis was adjuvant-induced. High levels of antibodies to rat CIX, containing complement-fixing subclasses, were detected in rat sera in addition to DTH and lymphocyte proliferation responses to rat CIX. Given the potential for CIX-induced disease, CIX-sensitized rats were injected intraperitoneally with lipopolysaccharide (LPS) to stimulate proinflammatory cytokine release, and intra-articularly with rat CIX to stimulate arthritis. LPS stimulation was ineffective; however, intra-articularly injected CIX produced transient synovitis. When rats with stable adjuvant arthritis were sensitized with CIX/FIA, significant increases in paw volume were measured compared with controls given CI/FIA. Immunohistochemical studies of actively and passively sensitized rats revealed deposits of CIX antibody, but not C3, at the joint margins where proteoglycan staining was weak. Together, these findings suggest that autoimmunity to CIX, in contrast to CII and CXI, is not directly pathogenic but may contribute to joint injury provided arthritis is initiated by an independent disease process.
Down-regulation of MHC class II molecules and inability to up-regulate class I molecules in murine macrophages after infection withToxoplasma gondii
Authors: Lüder C G K , Lang T , Beuerle B , Gross U 
Published: March 2003

SUMMARYToxoplasma gondii is able to invade phagocytic cells of the monocyte-macrophage lineage and replicates within a parasitophorous vacuole. Since macrophages may activate specific T lymphocytes by presenting pathogen-derived antigens in association with molecules of the MHC, we investigated the in vitro expression of host cell molecules involved in antigen processing and presentation before and during infection of murine bone marrow-derived macrophages (BMM) with T. gondii. Fifty-one hours after addition of T. gondii tachyzoites at different parasite-to-host ratios, up-regulation of total MHC class II molecules by interferon-gamma (IFN-γ) was dose-dependently abrogated in up to 50% of macrophages compared with uninfected control cultures. Quantitative analyses by flow cytometry revealed that the IFN-γ-induced surface expression of class II antigens as well as the IFN-γ-induced up-regulation of class I molecules was significantly decreased in T. gondii-infected macrophage cultures compared with uninfected controls. However, the constitutive expression of MHC class I antigens was not altered after parasitic infection, and infected BMM remained clearly positive for these molecules. After infection of macrophages preactivated with IFN-γ for 48 h, T. gondii also actively down-regulated an already established expression of MHC class II molecules. Furthermore, kinetic analysis revealed that the reduction in intracellular and plasma membrane-bound class II molecules started ≈ 20 h after infection. While MHC class II antigens were most prominently reduced in parasite-positive host cells, culture supernatant from T. gondii-infected BMM cultures also significantly inhibited expression of these molecules in uninfected macrophages. However, down-regulation of MHC class II molecules was not mediated by an increased production of prostaglandin E2, IL-10, transforming growth factor-beta or nitric oxide by infected BMM compared with uninfected controls. Our data indicate that intracellular T. gondii interferes with the MHC class I and class II antigen presentation pathway of murine macrophages and this may be an important strategy for evasion from the host's immune response and for intracellular survival of the parasite.
Selective depletion of CD14+ CD16+ monocytes by glucocorticoid therapy
Authors: Fingerle-Rowson G , Angstwurm M , Andreesen R , Ziegler-Heitbrock H W L 
Published: March 2003

SUMMARYGlucocorticoids (GC) are potent anti-inflammatory and immunosuppressive agents that act on many cells of the body, including monocytes. Here we show that a 5-day course of high dose GC therapy differentially affected the CD14++ and the CD14+ CD16+ monocyte subpopulations in 10 patients treated for multiple sclerosis. While the classical (CD14++) monocytes exhibited a substantial increase from 495 ± 132 to 755 ± 337 cells/μl, the CD14+ CD16+ monocytes responded with a pronounced decrease from 36 ± 15 to 2 ± 3 cells/μl (P &lt; 0.001). In 4/10 patients the CD14+ CD16+ monocytes fell below detection limits (&lt; 0.2 cells/μl). This observation was confirmed when the CD14+ CD16+ monocytes were identified by virtue of their low CD33 expression as these cells decreased as well. After discontinuation of GC therapy the CD14+ CD16+ monocytes reappeared and reached normal levels after 1 week. The profound depletion of CD14+ CD16+ monocytes by GC as described here is a novel effect of GC action in vivo and may contribute to GC-mediated immunosuppression. Determination of the number of this monocyte subset may also serve to monitor the effectiveness of GC therapy in patients requiring immunosuppressive treatment.