bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autonomic nervous dysfunction in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA): possible pathogenic role of autoantibodies to autonomic nervous structures
Authors: MAULE S , QUADRI R , MIRANTE D , PELLERITO R A , MARUCCO E , MARINONE C , VERGANI D , CHIANDUSSI L , ZANONE M M 
Published: November 2003

SUMMARY
Autonomic nervous dysfunction has been previously reported in SLE, RA and systemic sclerosis, but the pathogenesis of such a complication is poorly understood. In the present study, four standard cardiovascular autonomic function tests were performed in 34 female patients with connective tissue diseases and in 25 healthy control subjects, and results expressed as cardiovascular (CV) test scores. Moreover, in each subject the presence of circulating complement-fixing autoantibodies directed against sympathetic and parasympathetic nervous structures, represented by superior cervical ganglia and vagus nerve, respectively, was simultaneously assessed by an indirect immunofluorescent complement-fixation technique, using rabbit tissue as substrate. None of the patients reported autonomic symptoms. However, an abnormal CV test score (≥ 5) was detected in 15% of the patients and in none of the healthy control subjects, approaching statistical significance (P = 0·07). No correlation was found between CV test results and disease duration, type of therapy or presence of conventional autoantibodies. One or two autoantibodies to autonomic nervous structures were detected in six patients (18%) and not in the control subjects (P &lt; 0·05). Values of deep breathing test were significantly lower in autoantibody-positive patients compared with those amongst the control subjects (P &lt; 0·05), and an abnormal CV test score was significantly associated with the presence of autoantibodies to autonomic nervous structures (P &lt; 0·05). In conclusion, we confirm that autonomic nervous function can be impaired in patients with connective tissue diseases, and suggest that autoantibodies directed against autonomic nervous system structures may play a role in the pathogenesis of the autonomic dysfunction.
Age- and sex-related resistance to chronic experimental autoimmune myasthenia gravis (EAMG) in Brown Norway rats
Authors: Hoedemaekers A , Graus Y , Van Breda Vriesman P , De Baets M 
Published: November 2003

Abstract
The influence of age and sex on the induction of chronic EAMG was analysed. Aged male rats, immunized with Torpedo acetylcholine receptor (tAChR), showed no clinical signs of disease or AChR loss. Immunization of young male Brown Norway (BN) rats resulted in both clinical signs of disease and 65% AChR loss. In contrast, both young and aged female BN rats showed comparable AChR loss (58% and 50%, respectively), although aged female rats did not develop clinical signs of disease. Differences in antibody titres, isotype distribution, fine specificity or complement activation could not account for the observed resistance. These results suggest that resistance against EAMG in aged rats is due to resistance of the AChR against antibody-mediated degradation, or to mechanisms able to compensate for AChR loss.
Hepatitis C virus (HCV)-induced IgG-IgM rheumatoid factor (RF) complex may be the main causal factor for cold-dependent activation of complement in patients with rheumatic disease
Authors: Wei G , Yano S , Kuroiwa T , Hiromura K , Maezawa A 
Published: November 2003

Abstract
A low serum complement level is commonly found in patients with rheumatic diseases. We evaluated 170 patients with such diseases to determine their serum levels of CH50, C3 and C4 protein. Persistent hypocomplementaemia was found in 19 of those patients, particularly in those with systemic lupus erythematosus (SLE). Cold-dependent activation of complement (CDAC) was demonstrated in nine of the 19 (47.4%), and six of the nine patients demonstrated infection with HCV (66.7%). The nine patients that exhibited CDAC had nearly normal haemolytic complement activity when the sera were separated either at 37°C or in EDTA-treated plasma. Conversely, it markedly decreased, even to the point of being immeasurable, when the sera were separated at 4–21°C. No significant deficiency in C3 and C4 protein levels was found in these patients. Clinical parameters other than levels of anti-HCV antibody, transaminase, and RF were not influenced by CDAC. In an attempt to isolate the causal factor for CDAC, we isolated IgG fractions from the CDAC patients by using a protein G column, in which case precipitates were collected from the eluates. The precipitates were mixed with normal serum and incubated at 4–21°C for 18 h. A decrease in the level of CH50 in normal serum was observed, which predominated (P&lt;0.001) when precipitates from HCV-infected patients were used. This indicated CDAC was possibly interrelated to the precipitates of such patients. This precipitate was proved to contain IgM besides IgG. It is therefore possible that an HCV-related IgG complex or an IgG-IgM RF complex may be formed at low temperature and be involved in activating the complement system in vitro.
IL-6 and soluble IL-6 receptors (sIL-6R and sgp130) in human pleural effusions: massive IL-6 production independently of underlying diseases
Authors: Doré P , Lelièvre E , Morel F , Brizard A , Fourcin M , Clément C , Ingrand P , Daneski L , Gascan H , Wijdenes J , Gombert J , Preud'Homme J L , Lecron J C 
Published: November 2003

Abstract
IL-6, soluble IL-6 receptor (sIL-6R) and soluble gp130 (sgp130) levels were measured in sera and pleural effusions from 42 patients with metastatic carcinoma, non-Hodgkin's lymphoma, tuberculosis, cardiac failure and miscellaneous diseases. Pleural IL-6 levels measured by ELISA were very high in all patient groups (mean 34.8 ± 15.3 ng/ml) without significant difference according to diseases. IL-6 was shown to be biologically active in a proliferative assay. Serum IL-6 levels were low (0.049 ± 0.014 ng/ml) and did not correlate with pleural fluid levels. Pleural IL-6 levels correlated with the number of polymorphonuclear cells in pleural fluid (P &lt; 0.03). Pleural sIL-6R levels (76 ± 8 ng/ml) were always lower than serum levels (196 ± 12 ng/ml; P &lt; 0.0001) but correlated with them (P &lt; 0.01). Pleural sIL-6R and albumin levels correlated (P &lt; 0.01), suggesting a transudation of sIL-6R from the serum. Pleural sgp130 levels (10.9 ± 1.0 ng/ml) were lower than serum levels (24.6 ± 2.8 ng/ml; P &lt; 0.002). After gel filtration of pleural fluid, the bulk of IL-6 (&gt;90%) was recovered in a 15 000–30 000 fraction, corresponding to the expected mol. wt of free IL-6. These results suggest a production and a sequestration of IL-6 in the pleural cavity in all studied conditions.
Dynamic expression of transforming growth factor-betas (TGF-β) and their type I and type II receptors in the synovial tissue of arthritic rats
Authors: Müssener Å , Funa K , Kleinau S , Klareskog L 
Published: November 2003

Abstract
A well characterized animal model that shares many characteristic features with rheumatoid arthritis (RA) is collagen-induced arthritis (CIA) in DA rats. Recent studies have demonstrated that TGF-β, a multifunctional cytokine, is an important modulator of the immune response in CIA, and possibly also in RA. In this study we have investigated the expression of the precursor forms of TGF-β1, TGF-β2, TGF-β3, as well as TGF-β type I receptor (TGF-βRI) and TGF-β type II receptor (TGF-βRII) in the synovial tissue of arthritic rats during the course of the disease. By using immunohistochemical techniques, an abundant expression of all three TGF-β isoforms and their receptors was observed in the arthritic synovia, an expression that increased with time after onset of disease. Antibodies to TGF-β1, TGF-β2, TGF-βRI and TGF-βRII stained blood vessels intensively, already at the early onset of inflammation, whereas the synovial lining layer and chondrocytes expressed strong immunoreactivity later on in the inflammatory process. The most intense staining with these antibodies was detected in fibroblasts within fibrotic tissue, in particular at the cartilage–pannus junction. Interestingly, TGF-β3 only stained macrophage-like cells and chondrocytes in the synovia. The data suggest that the abundant expression of TGF-β1, TGF-β2, TGF-β3 as well as TGF-βRI and TGF-βRII in the synovia, is of pathogenic importance in the development of CIA, although the question of how the different TGF-β isoforms may enhance or counteract different arthritogenic events remains open.
In contrast to their murine counterparts, normal human keratinocytes and human epidermoid cell lines A431 and HaCaT fail to express IL-10 mRNA and protein
Authors: Teunissen M B M , Koomen C W , Jansen J , De Waal Malefyt R , Schmitt E , Van Den Wijngaard R M J G J , Das P K , Bos J D 
Published: November 2003

Abstract
In mice, keratinocyte-derived IL-10 is up-regulated by ultraviolet-B (UVB) radiation and plays a major role in UVB-induced immunosuppression. The present study was designed to examine whether a comparable phenomenon can be detected in man. Freshly isolated or cultured normal human keratinocytes (NHK) and keratinocyte cell lines A431 and HaCaT were stimulated with graded doses of UVB (up to 200 J/m2) or with a variety of other stimuli. RNA was extracted at various time points post-stimulation and analysed by reverse transcriptase-polymerase chain reaction (RT-PCR) using four different IL-10-specific primer pairs and RNA from monocytes or T cells as positive controls. We failed to detect IL-10 mRNA in NHK from 40 different donors (breast, abdomen, leg, scalp, foreskin) and in A431 and HaCaT cells, irrespective of the stimulation used and despite successful stimulation. Supernatants of NHK, A431 and HaCaT cultures were negative for IL-10 protein, as tested by four different ELISAs and a bioassay. Murine keratinocytes, stimulated under comparable conditions and tested by the same techniques, displayed a strong expression of IL-10 mRNA and protein. Remarkably, an IL-10 mRNA signal could be detected in NHK after a second round of PCR amplification. Because NHK suspensions are contaminated with Langerhans cells, melanocytes and possibly fibroblasts, we tested pure populations of each individual cell type to determine the origin of this IL-10 mRNA. Our results clearly indicate that NHK, Langerhans cells and fibroblasts fail to express IL-10 and that melanocytes are the principal source of IL-10 mRNA in normal human epidermis.
Modulation of lymphocyte and monocyte activity after intravenous immunoglobulin administration in vivo
Authors: Aukrust P , Muüller F , Nordøy I , Haug C J , Frøland S S 
Published: November 2003

Abstract
In 12 patients with primary hypogammaglobulinaemia we investigated the in vivo effect of one bolus injection (400 mg/kg) of intravenous immunoglobulin (IVIG) on lymphocyte subsets and monocytes in peripheral blood, on plasma levels of soluble factors reflecting monocyte and lymphocyte activity and on lymphocyte proliferation and generation of reactive oxygen species (ROS) from monocytes analysed in vitro. Several immunological changes were induced by IVIG infusion. First, there was a significant decrease in CD4+/CD8+ lymphocyte ratio in peripheral blood, reflecting a significant increase in circulating numbers of CD8+ lymphocytes. Second, although there was no significant change in plasma levels of soluble CD8 antigen, there was a significant decrease in soluble CD8 antigen/CD8+ lymphocyte ratio, suggesting a down-regulation of CD8+ lymphocyte activity. Third, there was a significant increase in plasma levels of neopterin, suggesting in vivo activation of monocytes/macrophages. Fourth, the was a down-modulation of mitogen-stimulated lymphocyte proliferation in vitro, and this down-regulation was significantly correlated with the increase in plasma neopterin levels. Finally, there was a significant decrease in zymosan-stimulated, but not in phorbol myristate acetate-stimulated, ROS generation from monocytes as evaluated by nitroblue tetrazolium reduction. The ability of IVIG administration in vivo to down-modulate lymphocyte proliferation and ROS generation from monocytes in patients with persistent immune activation may be relevant for the clinical effects of IVIG in a variety of immune-mediated disorders.
Increased IL-6 and IL-8 in bronchoalveolar lavage fluids (BALF) from patients with sarcoidosis: correlation with the clinical parameters
Authors: Takizawa H , Satoh M , Okazaki H , Matsuzaki G , Suzuki N , Ishii A , Suko M , Okudaira H , Morita Y , Ito K 
Published: November 2003

Abstract
A variety of cytokines have been implicated in the pathogenesis of pulmonary sarcoidosis, but the exact roles of IL-6 and IL-8 are not yet clear. We studied these cytokine levels in BALF from patients with pulmonary sarcoidosis, idiopathic pulmonary fibrosis (IPF), systemic screlosis (SSc) with interstitial lung disease and control subjects. IL-6 and IL-8 levels were significantly elevated in sarcoidosis, IPF and SSc with interstitial lung disease compared with control subjects. Subjects with sarcoidosis had significantly increased levels of both cytokines compared with controls when the cytokine values were corrected by the total albumin content and the two cytokine levels correlated with each other (r=0.876). BALF IL-6 levels correlated with percent lymphocytes and percent CD3+ cells. Moreover, when sarcoidosis patients were divided into three groups, those who needed steroid therapy or had progressive disease showed increased cytokine levels in BALF over stable or improved patients. These observations suggest that locally derived IL-6 and IL-8 were increased in sarcoidosis and correlated with activity of this granulomatous lung disease.
Progression of HIV disease is associated with increased expression of FcγRI and CR1 on alveolar macrophages
Authors: Gilbody J , Lipman M C I , Johnson M A , Atkins M , Poulter L W 
Published: November 2003

Abstract
The expression of receptors for complement and the Fc region of immunoglobulin by alveolar macrophages (AM) constitutes a valuable aid to effector function of these cells. However, during HIV infection such expression may also act to increase binding of immune complexes, thus facilitating viral infection of these cells. This study was designed to determine whether changes in the expression of these receptors occurs in situ during HIV infection. Lung macrophages were isolated by bronchoalveolar lavage in groups of HIV+ subjects segregated on the basis of peripheral CD4 count. A group of normal subjects was also investigated. Expression of CR1 and FcγRI was quantified by measuring the optical density of reaction product following controlled immunoperoxidase staining with MoAbs CD35 and CD64. Both CR1 and FcγRI were increased over normal in all HIV+ subjects. This increase was progressive with advancing disease as determined by correlation with declining peripheral CD4 count. Comparison of asymptomatic and symptomatic subjects with HIV infection showed no difference in CR1 expression but a rise in FcγRI expression in the latter group. An overall inverse correlation was also found between peripheral CD4 count and FcγRI expression, but not CR1 expression. These data demonstrate a significant increase in the expression of these receptors on AM from HIV+ subjects, and show that this increase may occur before any symptoms in these patients.
The effect of repeated administration of hexarelin, a growth hormone releasing peptide, and growth hormone releasing hormone on growth hormone responsivity
Authors: Massoud Ahmed F. , Hindmarsh Peter C. , Matthews David R. , Brook Charles G. D. 
Published: November 2003

OBJECTIVE Hexarelin is a synthetic six‐amino‐acid compound capable of releasing GH in animals and in man. Its mechanism of action is not understood and little is known about the GH response after repeated administration. The aim of this study was to determine the GH response to the administration of two intravenous boluses of hexarelin, growth hormone releasing hormone (GHRH) or hexarelin with GHRH.DESIGN Single boluses of hexarelin (1 μg/kg), GHRH‐(1–29)‐NH2 (1 μg/kg) or hexarelin with GHRH‐(1–29)‐NH2 were administered intravenously. Each study was performed on two further occasions, with a second bolus being administered 60 or 120 minutes after the first. A control study was performed giving saline intravenously. Studies were performed in a random order.SUBJECTS Six healthy adult males (25.4–34.1 years) were studied.MEASUREMENTS Serum GH was measured by radioimmunoassay. GH secretion rates were derived from the measured serum GH concentrations using the technique of deconvolution analysis.RESULTS The peak GH secretion rate following the first intravenous bolus of hexarelin was greater than that following the first bolus of GHRH‐(1–29)‐NH2 (P < 0.001), and was greatest following the administration of hexarelin with GHRH‐(1–29)‐NH2 (P < 0.001). The coadministration of the two secretagogues resulted in peak GH secretion rates significantly greater than the arithmetic sum of those following their isolated administration (P = 0.001), demonstrating synergism. Compared to saline, the administration of a second bolus of hexarelin, GHRH‐(1–29)‐NH2 or both resulted in significant further GH secretion (P = 0.02, P = 0.002, P = 0.03, respectively).The administration of a second bolus of hexarelin or hexarelin with GHRH‐(1–29)‐NH2 120 minutes after the first bolus resulted in lower peak GH secretion rates (P = 0.03). The reductions in peak GH secretion rates following the 60‐minute boluses were not statistically significant. The peak GH secretion rates following the first GHRH‐(1–29)‐NH2 boluses were similar to those following the 60 and 120‐minute GHRH‐(1–29)‐NH2 boluses (P = NS). Irrespective of the interval between the boluses of hexarelin with GHRH‐(1–29)‐NH2, the peak GH secretion rates following the second boluses were not significantly different from the arithmetic sum of those following the administration of the second boluses of hexarelin or GHRH‐(1–29)‐NH2, indicating loss of synergism on repeated administration.CONCLUSIONS This study shows that hexarelin is a potent GH secretagogue active after two successive doses; the magnitude of the GH response to the second dose was influenced by the dosing interval. Hexarelin and GHRH‐(1–29)‐NH2 are synergistic, a property which is lost after repeated administration. These findings may help our understanding of GHRPs and may have implications for the potential use of hexarelin and other GHRPs as therapeutic agents.
Specific stimulation of brain serotonin mediated neurotransmission by dexfenfluramine does not restore growth hormone responsiveness in obese women
Authors: Kars Michael E. , Pijl Hanno , Cohen Adam F. , Frölich Marijke , Schoemaker Hendrik C. , Brandenburg Henry C. R. , Edo Meinders A. 
Published: November 2003

OBJECTIVE Growth hormone release in response to all known stimuli of GH secretion is blunted in obese subjects. Several studies, using dl‐fenfluramine (dl‐FF) as a serotoninergic tool, suggest that brain serotonin plays a role in the pathogenesis of this phenomenon. However, the effect of dl‐FF appears to be dependent on the stimulus used to induce GH release. Furthermore, dl‐FF has catecholamingergic properties apart from its capacity to stimulate serotonin release and to block its re‐uptake. In this study, we investigated whether subchronic treatment with the highly selective serotoninergic drug dexfenfluramine (d‐FF) affects the GH response to galanin or GHRH in obese subjects.DESIGN The study had a randomized, cross‐over, placebo controlled design. d‐FF was administered in a dose of 15 mg twice daily during 6 days. On days 5 and 6 of treatment (with either d‐FF or placebo) an i.v. bolus injection of 100 μg hGHRH(1‐44) or a continuous infusion of p‐galanin (40 pmol/kg/min over 40 minutes) were administered in randomized order. All tests were performed in the follicular phase of two consecutive menstrual cycles.PATIENTS Eight obese women (body mass index (BMI) 34.5 ± 3.6 kg/m2); 7 normal weight (BMI 21.9 ± 1.9 kg/m2) age‐matched control women. All women had a regular menstrual cycle. None used oral contraceptive drugs.MEASUREMENTS GH response to either stimulus was measured both during treatment with d‐FF and during treatment with placebo.RESULTS The GH response to galanin and the response to GHRH were significantly smaller in obese subjects. d‐FF significantly reduced the galanin induced GH secretion in obese subjects, but not in normal weight controls. It did not significantly affect GH release in response to GHRH in either group.CONCLUSION This study confirms that GH secretion in response to stimuli with varying mechanisms of action is blunted in obese subjects. A decrease of central serotonin mediated neurotransmission does not appear to play a role in the pathogenesis of this phenomenon.
The consequences of clutch size for incubation conditions and hatching success in starlings
Authors: Reid J. M. , Monaghan P. , Ruxton G. D. 
Published: November 2003

Abstract1. Starling (Sturnus vulgaris) clutches were manipulated so that sibling eggs were incubated within either natural‐sized clutches, or clutches that had been experimentally enlarged but were still within the natural range of variation. Thus the consequences of incubated clutch size for hatching success were investigated.2. Eggs incubated within enlarged clutches hatched less successfully than eggs incubated within natural‐sized clutches, suggesting that clutch size affects the conditions experienced by embryos during incubation.3. Eggs incubated in enlarged clutches may have hatched poorly because clutch enlargement altered nest microclimate, causing increased water loss during the incubation period.4. There was no evidence that enlargement altered nest microclimate by energetically constraining parents from incubating effectively. Instead, intrinsic physical properties of enlarged clutches affected clutch temperature directly.5. Parents that had incubated experimentally enlarged clutches subsequently fledged fewer chicks than control parents, suggesting that constraints imposed during incubation may influence the optimal number of eggs that parents should lay.6. Future studies should investigate whether parents laying naturally large clutches can minimize the problems of incubating many eggs by adaptively tailoring the shape and composition of their eggs to their expected clutch size.