bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective audit of adverse reactions occurring in 459 primary antibody-deficient patients receiving intravenous immunoglobulin
Authors: BRENNAN V M , SALOMÉ-BENTLEY N J , CHAPEL H M ,   Immunology Nurses Study, Abbey Jane , Askew Tracey , Cochrane Sheila , Fletcher Claire , Bennett Claire , Freud Cilla , Ryan Annie , Haines Mary , Powell Pauline , Saunderson Delene , Short Jan , Toolan John , Hendry Doreen , Wilkes Ann 
Published: July 2003

SUMMARY
Intravenous immunoglobulin (IVIG) is used as the standard replacement therapy for patients with primary antibody deficiencies. A previous study of adverse reactions in patients self-infusing at home over 1 year showed an overall reaction rate of 0·7%. A larger prospective study is reported here, involving a greater number of immunology centres and including children and adults who received infusions from medical or nursing staff as well as those self-infusing. Four hundred and fifty-nine patients were entered into this study and 13 508 infusions were given. The study showed that no severe reactions occurred and the reaction rate was low at 0·8%. This figure could have been lower, 0·5%, if predisposing factors responsible for some reactions had been considered before infusion. In conclusion, the study shows the importance of ongoing training for patients and staff to recognize the predisposing factors to prevent avoidable reactions. Because none of these reactions were graded as severe, the present guidance to prescribe self-injectable adrenaline for patients infusing outside hospital should be reviewed.
Immune complex–FcγR interaction modulates monocyte/macrophage molecules involved in inflammation and immune response
Authors: BARRIONUEVO P , BEIGIER-BOMPADRE M , FERNANDEZ G C , GOMEZ S , ALVES-ROSA M F , PALERMO M S , ISTURIZ M A 
Published: July 2003

SUMMARYThe interaction between receptors for the Fc portion of IgG (FcγRs) from monocytes/macrophages and immune complexes (IC) triggers regulatory and effector functions. Recently, we have demonstrated that IC exert a drastic inhibition of basal and IFN-γ-induced expression of MHC class II on human monocytes. Taking into account that the regulation of MHC class II molecules is a crucial event in the immune response, in this report we extend our previous studies analysing the effect of STAT-1 phosphorylation in the down-regulatory process, the fate of the intracellular pool of MHC class II molecules and the effect of complement on MHC class II down-regulation induced by IC. We also studied the effect of IC on the expression of MHC class II (I-Ad) in macrophages using a mouse model of chronic inflammation. We demonstrate that IC induce a depletion not only on surface expressed but also on intracellular MHC class II content and that IC-induced down-regulation of MHC class II is not mediated by the inhibition of STAT-1 phosphorylation. On the other hand, the effect of IC is not specific for the down-regulation of MHC class II, for it could be restricted to other molecules involved in inflammatory processes. Our experiments also show that the activation of the complement system could be a crucial step on the regulation of the effect of IC on MHC class II expression. In agreement with our in vitro experiments using human monocytes, IC treatment reduces the expression of MHC class II in a mouse model of chronic inflammation.
Monocytes and neutrophils from tuberculosis patients are insensitive to anti-inflammatory effects triggered by the prototypic formyl peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP)
Authors: BEIGIER-BOMPADRE M , ALEMÁN M , BARRIONUEVO P , FRANCO M C , RUBEL C J , SASIAIN M DEL C , PALERMO M S , ABBATE E , ISTURIZ M A 
Published: July 2003

SUMMARYTuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis where formyl peptides, which are cleavage products of bacterial and mitochondrial proteins, are present. In this study, we demonstrated that interferon gamma (IFN)-γ and interleukin (IL)-10 induced the overexpression of the receptor for the Fc portion of IgG I (FcγRI) in monocytes from tuberculosis (TB) patients, showing that these cells respond to IFN-γ and IL-10 signals. We also demonstrated that lower doses of IL-10 render monocytes from TB patients less responsive to higher doses of the cytokine. Although the prototypic formyl peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) is a well-known proinflammatory agonist, we have demonstrated previously that preincubation of monocytes with FMLP inhibited the up-regulation of FcγRI induced by IFN-γ or IL-10. This effect was not observed in monocytes from TB patientes. FMLP also induced the down-regulation of the expression of FcγRI in monocytes that had been activated already with IFN-γ. However, this effect of FMLP was not observed in monocytes from TB patients and supernatants from monocytes obtained from these patients were incapable of inducing the down-regulation of FcγRI. In contrast to normal donors, supernatants from FMLP-treated neutrophils from TB patients did not modify the basal level of expression of FcγRI in monocytes from normal donors. In conclusion, in this study we demonstrated the existence of two novel mechanisms that may contribute to the pathological effects generated by M. tuberculosis: the enhancement of FcγRI in response to IFN-γ and IL-10, and the unresponsiveness to the anti-inflammatory effects induced by formyl peptides.
Pre-neutralization of C5a-mediated effects by the monoclonal antibody 137-26 reacting with the C5a moiety of native C5 without preventing C5 cleavage
Authors: FUNG M , LU M , FURE H , SUN W , SUN C , SHI N Y , DOU Y , SU J , SWANSON X , MOLLNES T E 
Published: July 2003

SUMMARYComplement C5a is aetiologically linked to inflammatory tissue damage in conditions like septicaemia, immune complex diseases and ischaemia-reperfusion injury. We here describe a monoclonal antibody (mAb), 137–26, that binds to the C5a moiety of human C5 and neutralizes the effects of C5a without interfering with C5 cleavage and the subsequent formation of lytic C5b-9 complex. Mouse anti-human C5 mAbs were generated and the reactivity with C5 and C5a was detected by ELISA and surface plasmon resonance. The inhibition of C5a binding to C5a receptor was studied using a radioligand binding assay. The effects of the antibody on C5a functions were examined using isolated neutrophils and a novel human whole blood model of inflammation. Haemolytic assays were used to study the effect on complement-mediated lysis. mAb 137–26 reacted with both solid- and solution-phase C5 and C5a in a dose-dependent manner with high affinity. The antibody competed C5a binding to C5a receptor and inhibited C5a-mediated chemotaxis of neutrophils. Furthermore, the antibody effectively abrogated complement-dependent E. coli-induced CD11b up-regulation and oxidative burst in neutrophils of human whole blood. mAb 137–26 was more potent than a C5a receptor antagonist and a previously described anti-C5a antibody. mAb 137–26 did not inhibit complement-mediated lysis, nor did it activate complement itself. Together, mAb 137–26 binds both the C5a moiety of native C5 and free C5a, thereby effectively neutralizing the biological effects of C5a. The antibody may have therapeutic potential in inflammatory diseases where C5a inhibition combined with an operative lytic pathway of C5b-9 is particularly desired.
Combined cyclosporin-A /prednisone therapy of patients with active uveitis suppresses IFN-γ production and the function of dendritic cells
Authors: FRASSANITO M A , DAMMACCO R , FUSARO T , CUSMAI A , GUERRIERO S , SBORGIA C 
Published: July 2003

SUMMARYIn this study, we assessed the Th1/Th2 polarization of the immune response and the involvement of dendritic cells (DC) and Th1 lymphocytes in the pathogenesis of uveitis. Thirty-seven patients with chronic idiopathic uveitis were enrolled: 21 of them had active uveitis and the remaining 16 were in complete remission. Patients with active uveitis were characterized as follows: 5 had intermediate uveitis, 5 panuveitis and the remaining 11 posterior uveitis. Thirteen healthy subjects were also studied as controls. Patients with active uveitis were treated with cyclosporin-A (CsA) associated to low doses of prednisone (PDS) and studied at baseline and after 6 months of therapy. Analysis of cytokine-producing CD3+ lymphocytes revealed a strong Th1 polarization of the immune response in patients with active uveitis. Th1 lymphocytes paralleled serum IL-12 levels and the response to therapy, which greatly reduced both IFN-γ +/CD3+ lymphocytes and serum IL-12 levels, associated with a general clinical improvement. In vitro studies demonstrated that DC from untreated patients with active uveitis were mature and functionally active. In fact, they showed a higher ability to stimulate cell proliferation of allogeneic T cells in primary mixed lymphocyte reaction (MLR) and produced larger amounts of IL-12 than DC from CsA/PDS-treated patients and those in remission. These results demonstrate that CsA/PDS therapy impairs the capacity of mature DC to secrete IL-12 and inhibits their MLR activity.
Hierarchical recognition of CpG motifs expressed by immunostimulatory oligodeoxynucleotides
Authors: KLINMAN D M , CURRIE D 
Published: July 2003

SUMMARYSynthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs trigger human PBMC to proliferate and secrete Ig, cytokines and chemokines. CpG ODN have entered clinical trials, and show promise as vaccine adjuvants, antiallergens, and for the treatment of infectious diseases and cancer. ODNs under consideration for human use vary in the sequence, number and location of the CpG motifs they contain. Yet little is known of the magnitude of the immune response elicited by these diverse ODNs, or the rules governing their interaction with immune cells. This work compares the proliferative, IgM, IL-6 and IP-10 response of PBMC from normal donors to a diverse panel of CpG ODNs. Results indicate that ODNs expressing 3–4 different CpG motifs are strongly stimulatory. The location of these motifs is important, with those at the 5′ end exerting the greatest influence on ODN activity. These findings provide a basis for the rational design of ODNs optimized for clinical use.
Rescue of the autoimmune scurfy mouse by partial bone marrow transplantation or by injection with T-enriched splenocytes
Authors: SMYK-PEARSON S K , BAKKE A C , HELD P K , WILDIN R S 
Published: July 2003

SUMMARYThe scurfy mutant mouse is the genetic and phenotypic equivalent of the single-gene human autoimmune disease immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX). The scurfy mutation disrupts the Foxp3 gene, a putative master switch for T regulatory cell development. Bone marrow transplant without conditioning was previously reported to be ineffective in scurfy mice, yet clinical remission occurs in transplanted human IPEX patients despite limited donor engraftment. In view of this contradiction, we sought to validate scurfy as a model for studying the pathogenesis and treatment of human IPEX, in particular the phenomenon of dominant immune regulation. One half of scurfy mice given bone marrow transplants after sublethal irradiation recovered and survived long-term with donor chimerism ranging from 1·7% to 50%. Early transfer of 2 × 107 normal T cell-enriched splenocytes also prevented or limited disease and permitted long-term survival. Donor T cells in rescued mice made up 3–5% of lymphocytes and became highly enriched for CD25+ T cells over time. Transfer of 106 CD4+ CD25+ sorted T cells showed some beneficial effect, while CD4+ CD25- cells did not. Thus, both partial bone marrow transplant and T-enriched splenocyte transfer are effective treatments for scurfy. These results indicate that scurfy results from a lack of cells with dominant immune regulatory capacity, possibly T regulatory cells. The potency of small numbers of normal cells indicates that IPEX may be a feasible target for gene therapy.
A novel inflammatory eye disease induced by lymphocytes from knockout mice sensitized against the deleted ocular antigen
Authors: GELDERMAN M P , CHARUKAMNOETKANOK P , BRADY J P , HUNG L , ZIGLER J S , WAWROUSEK E F , VISTICA B P , FORTIN E , CHAN C-C , GERY I 
Published: July 2003

SUMMARYLens-associated uveitis (LAU), a severe inflammatory eye disease, is thought to be mediated by autoimmunity against lens crystallins. Previously described animal models for this disease are antibody-mediated, since no cellular response to self crystallins could be induced in experimental animals. Here, we describe a new model for LAU, in which lymphocytes from knockout mice deficient in αB-crystallin are sensitized against the deleted protein and induce severe ocular inflammation when adoptively transferred into wild type recipients. Similar to LAU, the experimental disease developed only following rupture of the lens capsule, produced in this study by capsulotomy; no disease was detected in recipient eyes with no capsulotomy, or in those treated with cautery, or in eyes affected by systemic treatment with sodium iodate, lipopolysaccharide or X-irradiation. The ocular changes in affected eyes included heavy cellular infiltration and proteinaceous exudate in both the anterior and posterior segments of the eye, that reached their peak on day 4 following cell transfer and subsided quite rapidly thereafter.
Factors associated with long hospital stay in geriatric wards in Japan
Authors: Umegaki Hiroyuki , Ando Fujiko , Shimokata Hiroshi , Yamamoto Sayaka , Nakamura Akira , Endo Hidetoshi , Kuzuya Masafumi , Iguchi Akihisa 
Published: July 2003

Background:  To reduce the length of stay (LOS) in hospital, the factors associated with extended LOS have to be identified.Methods:   A comprehensive geriatric assessment (CGA) of patients in a geriatric ward was carried out to identify the factors associated with LOS of more than 28 days.Results:   Of 193 patients (> 65 years old) who had been admitted to the geriatric ward of Nagoya University Hospital from home, 118 patients had complete CGA data sets. The CGA items were studied within 1 week of admission and analysis was performed by Chi‐squared followed by multilogistic analysis. Chi‐squared analysis demonstrated that many of the basic activities of daily living (BADL) and instrumental ADL (IADL) had a significant association with longer LOS, but the contribution of psychological factors, assessed by mini‐mental state examination and Geriatric Depression Scale‐15, was relatively small. Multilogistic analysis showed that dependence on dressing assistance and medication assistance significantly increased the chance of having a LOS longer than 28 days.Conclusion:   Intervention to improve the ability to dress and take medication independently may reduce LOS.
Aged onset of amyloidosis caused by transthyretin gene mutations
Authors: Nakazato Masamitsu , Matsukura Shigeru 
Published: July 2003

Background:  The authors have established that missense mutations of the transthyretin gene cause middle age onset of familial systemic amyloidosis. The purpose of the present study was to investigate molecular abnormalities of the serum protein, transthyretin in patients with aged onset of cardiac amyloidosis or amyloidotic polyneuropathy in whom there was no positive family history of amyloidosis.Methods:  DNA and isolated amyloid fibril proteins were extracted from biopsy or postmortem tissue samples taken from five patients with cardiac amyloidosis and 15 patients with amyloidotic polyneuropathy, in whom histological diagnosis of amyloidosis had been established by immunostaining for transthyretin.Results:  DNA analysis of the transthyretin gene and protein sequencing of the amyloid fibrils revealed that three of the five patients with cardiac amyloidosis were associated with transthyretin Met 30, and the remaining two patients were associated with transthyretin Ile 50. Of the 15 patients with amyloidotic polyneuropathy, 12 were associated with transthyretin Met 30, two with transthyretin Ile 50, and one with transthyretin Ser 109.Conclusion:  The clinical findings, results of DNA sequencing and structural analysis of amyloid protein are presented here for six representative subjects. Molecular abnormalities of transthyretin are the cause of some patients with aged onset of amyloidosis without a positive family history. Even when transthyretin‐type amyloid was first diagnosed at autopsy, it was possible to identify transthyretin gene mutations by the use of small pieces of tissue samples.
Functional characterization of a neuropeptide F‐like receptor from Drosophila melanogaster
Authors: Feng Guoping , Reale Vincenzina , Chatwin Heather , Kennedy Karen , Venard Renée , Ericsson Christer , Yu Kweon , Evans Peter D. , Hall Linda M. 
Published: July 2003

AbstractA cDNA clone encoding a seven‐transmembrane domain, G‐protein‐coupled receptor (NPFR76F, also called GPCR60), has been isolated from Drosophila melanogaster. Deletion mapping showed that the gene encoding this receptor is located on the left arm of the third chromosome at position 76F. Northern blotting and whole mount in situ hybridization have shown that this receptor is expressed in a limited number of neurons in the central and peripheral nervous systems of embryos and adults. Analysis of the deduced amino acid sequence suggests that this receptor is related to vertebrate neuropeptide Y receptors. This Drosophila receptor shows 62–66% similarity and 32–34% identity to type 2 neuropeptide Y receptors cloned from a variety of vertebrate sources. Coexpression in Xenopus oocytes of NPFR76F with the promiscuous G‐protein Gα16 showed that this receptor is activated by the vertebrate neuropeptide Y family to produce inward currents due to the activation of an endogenous oocyte calcium‐dependent chloride current. Maximum receptor activation was achieved with short, putative Drosophila neuropeptide F peptides (Drm‐sNPF‐1, 2 and 2s). Neuropeptide F‐like peptides in Drosophila have been implicated in a signalling system that modulates food response and social behaviour. The identification of this neuropeptide F‐like receptor and its endogenous ligand by reverse pharmacology will facilitate genetic and behavioural studies of neuropeptide functions in Drosophila.
Anatomical organization of the telencephalic connections of the parafascicular nucleus in adult and developing rats
Authors: Vercelli Alessandro , Marini Gabriella , Tredici Giovanni 
Published: July 2003

AbstractThe parafascicular nucleus (PFN) of the rat, homologous to the human centre médian, is an intralaminar nucleus of the thalamus, classically considered as part of the ascending activating system. We have previously demonstrated that it is also connected to several subcortical nuclei. To obtain a more detailed picture of the connectivity of the PFN, the organization and the topography of the reciprocal parafascicular–telencephalic relationships were studied in both adult and developing rats, using anterograde and retrograde neuronal tracers. In the adult rat, the ascending parafascicular projections were densest to the striatum, dense to the frontal and least dense to cingulate cortex, and were strictly ipsilateral. They displayed a loose topography, with the more medial parafascicular neurons projecting to the medial frontal and cingulate cortex and medial striatum, and the more lateral neurons projecting to the lateral frontal cortex and lateral striatum. All these connections were already present at embryonic day 19. Parafascicular neurons projecting to the telencephalon in adult rats were mostly of the multipolar type, with a few bipolar neurons. In neonatal rats they showed a bipolar morphology at birth; they became mostly multipolar later on, with an increasing complexity of the dendritic arbor up to postnatal day 10. Neurons in the frontal cortex retrogradely labelled from the PFN were more numerous perinatally, and decreased as early as postnatal day 5. The telencephalic connections of the PFN were found to be more discrete and restricted than previously thought, thus suggesting a more specific functional role for the nucleus than cortical recruitment.
Substrates and routes of migration of early generated neurons in the developing rat thalamus
Authors: Ortino Barbara , Inverardi Francesca , Morante‐Oria Javier , Fairén Alfonso , Frassoni Carolina 
Published: July 2003

AbstractWe investigated the substrates supporting neuronal migration, and its routes, during early thalamic development in the rat. Neurons and axonal and glial fibres were identified in embryos with single and double immunohistochemistry; dynamic data were obtained with cell tracers in short‐term organotypic cultured slices. The earliest thalamic neurons, originating from the ventricular neuroepithelium between embryonic days 13 and 15, include those of the reticular thalamic nucleus. At this developmental stage, calretinin, calbindin or γ‐aminobutyric acid immunostaining revealed both radially and nonradially orientated neurons in the region of reticular thalamic migration, between the dorsal and ventral thalamic primordia. In cultured slices, injections of fluorescent dyes in the neuroepithelium labelled neurons in a migratory stream along radial glia in the same zone. Some labelled fusiform cells departed from this radial trajectory along orthogonal routes within the dorsal thalamus. Confocal microscopy revealed nonradially orientated neurons in close apposition with a fibre system parallel to the lateral thalamic surface. These fibres expressed axonal markers, including the intermediate filament protein α‐internexin and a polysialylated form of neuronal cell adhesion molecule. Active migration of nonradially orientated neurons along neuronal substrates was confirmed in living cultured slices. In addition, in vitro and ex vivo experiments revealed neurons migrating tangentially in association with glial fibres. These results provide novel evidence that: (i) early generated thalamic neurons follow nonradial routes in addition to glia‐linked radial migration; and (ii), nonradially migrating thalamic neurons move along both glial and axonal substrates, which could represent a distinctive feature of thalamic development.
Viral vector‐mediated gene transfer of the vole V1a vasopressin receptor in the rat septum: improved social discrimination and active social behaviour
Authors: Landgraf Rainer , Frank Elisabeth , Aldag John M. , Neumann Inga D. , Sharer Catherine A. , Ren Xianghui , Terwilliger Ernest F. , Niwa Masanobu , Wigger Alexandra , Young Larry J. 
Published: July 2003

AbstractThis study explores the effects of enhancing vasopressin V1a receptor expression in the septum using viral vector‐mediated gene transfer on social discrimination and social interactions. Bilateral infusion of an adeno‐associated viral vector containing the prairie vole V1a receptor gene (V1aR‐AAV) regulated by a neuron‐specific enolase promoter resulted in a stable increase in V1a receptor binding density in the rat septum without affecting oxytocin receptor density. Control animals were infused with a vector expressing the lacZ gene. In a social discrimination paradigm, only V1aR‐AAV‐treated animals succeeded in discriminating a previously encountered from a novel juvenile after an interexposure interval (IEI) of more than 2 h, demonstrating the functional incorporation of the vole V1a receptor in the rat septal circuits underlying short‐term memory processes. Microdialysis administration of synthetic vasopressin during the first juvenile exposure, used to mimic intraseptal release patterns of the neuropeptide, produced similar prolongations in recognition (up to an IEI of 24 h) in both V1aR‐AAV and control animals. Septal microdialysis administration of a selective V1a, but not oxytocin, receptor antagonist in both groups prevented discrimination even after an IEI of as short as 0.5 h, confirming the specificity of the vole V1a receptor involvement in social discrimination abilities. In addition, active social interactions were found to be increased among V1aR‐AAV rats compared to controls. Viral vector‐mediated gene transfer provides a valuable tool for studies on the role of localized gene expression on behavioural parameters.