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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The oxygen binding properties of hemoglobin and some hematological parameters in Eskimo dogs (belonging to Canis lupus familiaris) in Ilulissat/Jacobshavn, Greenland were analysed. The average [2,3-DPG] and [Hb] (n = 16) were 3.14 +/- 0.34 mmol l-1 blood and 9.53 +/- 0.65 g dl-1 (1.49 mmol l-1), respectively, giving a stoichiometric ratio of 2.11 mol 2,3-DPG/mol Hb. Oxygen binding analysis carried out on hemolysate in HEPES buffer at 20 and 37 degrees C revealed a high oxygen affinity (1.2 mmHg at pH 7.4, 20 degrees C) in the desalted condition, which decreased markedly in the presence of chloride and 2,3-DPG. A low apparent equilibrium constant for the binding of 2,3-DPG (1.0 x 10(-5) mol l-1) was found at pH 7.2 and 20 degrees C in the absence of chloride. Moreover, we show that chloride ions have an additive effect on oxygen affinity in the concentration range 10-300 mmol l-1 in the presence of 3 mmol l-1 2,3-DPG at low pH and temperature (pH < 7.4 and 20 degrees C). This feature may be of physiological importance to oxygen unloading under acidotic conditions when tissue temperature is low. Thermodynamic analysis reveal that in the presence of 3 mmol l-1 2,3-DPG and 100 mmol l-1 chloride, the Eskimo dog hemoglobin exhibits a low heat of oxygenation, which places this animal close to arctic ruminants with respect to the influence of temperature on oxygen binding in vivo.
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PMID:Functional characterisation of Eskimo dog hemoglobin: I. Interaction of Cl- and 2,3-DPG and its importance to oxygen unloading at low temperature. 917 89

Hemoglobin (Hb) from the Eskimo dog (belonging to Canis lupus familiaris) showed similar Bohr effect (delta log P50/delta pH) to human HbA in the presence of 100 mmol l-1 NaCl at 20 degrees C. The presence of 7% carbon dioxide in the desalted condition caused a positive (reversed) Bohr effect in the pH range 7.1-7.5 on Eskimo dog Hb, whereas in human HbA there was no Bohr effect within this pH range. A positive Bohr effect on Eskimo dog Hb in this condition was also observed at 37 degrees C. This could indicate differences in the pK values of the amino terminal residues of the two hemoglobins, with possible pH-dependent binding of both bicarbonate (HCO(3)-) and carbamate. Analysis of the effect of CO2 on oxygen affinity of Eskimo dog Hb in the pH range 6.7-7.6 in the presence of chloride and/or 2,3-diphosphoglycerate (2,3-DPG) support this theory. Our results indicate a competition between HCO(3)- and Cl- in affecting oxygen binding. Thermodynamic analysis reveals that bicarbonate binding lowers the apparent heat of oxygenation in Eskimo dog Hb nearly as much as chloride does in the presence of 2,3-DPG at physiological pH. This safeguards an effective oxygen unloading at lowered red blood cell concentrations of chloride. Moreover, we show that the oxygen affinity at high O2 saturation is less dependent on temperature in the presence than in the absence of CO2-.
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PMID:Functional characterisation of Eskimo dog hemoglobin: II. The interplay of HCO(3)- and Cl-. 917 90

Remains of carnivores from the Sima de los Huesos site representing at least 158 adult individuals of a primitive (i.e., not very speleoid) form of Ursus deningeri Von Reichenau 1906, have been recovered through the 1995 field season. These new finds extend our knowledge of this group in the Sierra de Atapuerca Middle Pleistocene. Material previously classified as Cuoninae indet, is now assigned to Canis lupus and a third metatarsal assigned in 1987 to Panthera of gombaszoegensis, is in our opinion only attributable to Panthera sp. The family Mustelidae is added to the faunal list and includes Martes sp. and a smaller species. The presence of Panthera leo cf. fossilis, Lynx pardina spelaea and Felis silvestris, is confirmed. The presence of a not very speloid Ursus deningeri, together with the rest of the carnivore assemblage, points to a not very late Middle Pleistocene age, i.e., oxygen isotope stage 7 or older. Relative frequencies of skeletal elements for the bear and fox samples are without major biases. The age structure of the bear sample, based on dental wear stages, does not follow the typical hibernation mortality profile and resembles a catastrophic profile. The site was not a natal or refuge den. The hypothesis that the site was a natural trap is the most plausible. If the Sima de los Huesos functioned as a natural trap (without an egress out), the human accumulation cannot be attributed to carnivore: activities and must be explained differently.
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PMID:The carnivore remains from the Sima de los Huesos Middle Pleistocene site (Sierra de Atapuerca, Spain). 930 Mar 40

Lupus nephritis results from an acute inflammatory and immunological response to renal immune complex deposition. The acute response is characterized by activation of circulating leukocytes and renal parenchymal cells, triggering the production of pro-inflammatory cytokines and growth factors. In all too many cases, this response is followed by a chronic response, which is characterized by excessive deposition of collagen and other extracellular matrix macromolecules and the development of end-stage renal disease. Mechanisms underlying this chronic response in progressive renal disease are not adequately defined. In this overview, potential roles of reactive oxygen species (ROS) generation and transforming growth factor-beta (TGF-beta) production in the pathogenesis of lupus nephritis are considered. ROS and TGF-beta may be key elements of a pathway leading to persistent and excessive matrix deposition in progressive lupus nephritis. Further studies to define the role of this pathway in lupus nephritis may lead to the development of additional, more specific therapeutic targets to prevent progression of renal disease.
Lupus 1998
PMID:Mechanisms of progression of renal damage in lupus nephritis: pathogenesis of renal scarring. 988 97

Minoeycline, a semisynthetic tetracycline, is often used to treat acne and rheumatoid arthritis. It has been considered an unlikely drug to be associated with systemic lupus erythematosus; however, many cases of drug-induced lupus related to minocycline have been reported. Some of those reports included pulmonary lupus, but none of the patients described developed respiratory distress. We describe a patient treated with minocycline for 2 years who presented with progressive dyspnea, severe hypoxia, and pulmonary infiltrates necessitating hospitalization and oxygen supplementation.
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PMID:Respiratory distress due to minocycline-induced pulmonary lupus. 1033 77

Drug-induced lupus is a side effect of deliberate ingestion of various medications, but its etiology, underlying mechanisms, and pathogenesis are puzzling. In vivo metabolic transformation of lupus-inducing drugs to reactive products explains how a heterogeneous set of drugs can mediate the same disease syndrome. Evidence has accumulated that drugs are transformed by extracellular oxidation from reactive oxygen species and myeloperoxidase produced when neutrophils are activated, maximizing the in situ accumulation of reactive drug metabolites within lymphoid compartments. The metabolite of procainamide, procainamide hydroxylamine, displays diverse biologic properties, but no apparent autoimmune effect has been observed. However, when procainamide hydroxylamine was introduced into the thymus of young adult normal mice, a delayed but robust autoimmune response developed. Disruption of central T-cell tolerance by intrathymic procainamide hydroxylamine resulted in the production of chromatin-reactive T cells that apparently drove the autoantibody response in the periphery. Drug-induced autoantibodies in this mouse model were remarkably similar to those in patients with procainamide-induced lupus. Therefore, this system has considerable promise to provide insight into the initiating events in drug-induced lupus and may provide a paradigm for how other xenobiotics might induce systemic autoimmunity.
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PMID:Initiation of autoimmunity by a reactive metabolite of a lupus-inducing drug in the thymus. 1050 46

Thoracic involvement occurs more frequently in systemic lupus erythematosus than in any other connective tissue diseases, and more than half of patients with the disease suffer from the involvement. Primary intrathoracic manifestations include pleural disease (effusions and/or thickening), acute lupus pneumonitis, subacute interstitial lung disease including bronchiolitis obliterans organizing pneumonia and non-specific interstitial pneumonia with fibrosis, chronic interstitial lung disease of usual interstitial pneumonia, pulmonary hemorrhage, pulmonary vascular disease, small airway disease of bronchiolitis obliterans, and pulmonary arterial hypertension. Secondary intrathoracic manifestations include atelectasis due to diaphragmatic dysfunction, opportunistic pneumonia, drug and oxygen toxicity, aspiration, and pleuropulmonary consequences of cardiac and renal failure.
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PMID:Thoracic involvement of systemic lupus erythematosus: clinical, pathologic, and radiologic findings. 1066 51

Inflammation produces reactive oxygen intermediates (ROI) that cause vascular damage and activate T lymphocytes. Conversely, antioxidants not only protect tissue from oxidative damage but also suppress immune reactivity. The objective of this study was to examine immunomodulatory effects of the non-enzymatic antioxidants, N-acetylcysteine (NAC) and cysteamine (CYST), on autoimmune disease, glomerulonephritis, and mortality in the female B/W mouse model of human systemic lupus erythematosus (SLE). The development of murine lupus was assessed during the lifespan of female B/W mice given NAC or CYST. Morbidity and mortality were assessed daily. At 6 week intervals mice were examined for weight change, albuminuria, serum BUN, antibodies to DNA, and IgG immunoglobulin levels. Serum prolactin, estrogen and progesterone were measured at 18 weeks of age. In a parallel study, NAC- and CYST-treated and control B/W mice were examined at 24 weeks of age for interval renal histopathology, lymphocyte adhesion molecule expression, and antibody titers and in vitro cytokine production in response to immunization with DNP-KLH. CYST significantly suppressed development of albuminuria and azotemia at 36 and 42 weeks of age compared to control and NAC-treated mice. NAC significantly suppressed anti-DNA antibody levels at 24 weeks. In contrast CYST significantly increased anti-DNA antibody levels at 18 weeks of age (P < 0.001 CYST vs control and NAC-treated mice). Kidneys of CYST-treated mice also had accelerated inflammatory histologic changes despite their lower incidence of albuminuria and azotemia. Mean (+/- s.e.m.) survival of control mice was 33 +/- 2 weeks compared to 38 +/- 2 weeks in NAC-treated mice (P < 0.05 vs control), and 48 +/- 2 weeks in the CYST-treated group (P < 0.01 vs control mice). The antioxidants, NAC and CYST, significantly improved mortality in the female B/W mouse model of SLE. NAC suppressed autoantibody formation and modestly prolonged survival. CYST, despite its augmentation of anti-DNA levels and renal inflammatory changes, inhibited the development of renal insufficiency and markedly improved survival. These findings suggest that ROIs play a role in the pathogenesis of lupus nephritis and that antioxidants reduce the damage causing renal insufficiency. Antioxidants may be a beneficial adjunctive therapy in the treatment of human SLE.
Lupus 2001
PMID:Antioxidants suppress mortality in the female NZB x NZW F1 mouse model of systemic lupus erythematosus (SLE). 1134 Nov 2

Pulmonary hypertension (PH) sometimes occurs in patients with systemic lupus erythematosus (SLE). We report a case of 51-year-old-woman with PH associated with SLE. She had been diagnosed as SLE on the basis of pericardial effusion, hematological disorder, positive antinuclear antibody, and hypocomplementemia. Despite minimal lupus activity, she had marked elevation of pulmonary arterial pressure (101/53 mmHg) and decreased cardiac index (1.5 l/min/m2). Symptoms related to PH were progressive under treatment with oral corticosteroids, oxygen, calcium antagonists, and warfarin. After 17 months of epoprostenol treatment, she died of pulmonary infarction. SLE-associated PH is often severe and progressive even in association with minimal activity.
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PMID:Severe pulmonary hypertension in a patient with systemic lupus erythematosus and minimal lupus activity. 1186 96

Abnormal death signaling in lymphocytes of systemic lupus erythematosus (SLE) patients has been associated with elevation of the mitochondrial transmembrane potential (Delta psi(m)) and increased production of reactive oxygen intermediates (ROI). The resultant ATP depletion sensitizes T cells for necrosis that may significantly contribute to inflammation in patients with SLE. In the present study, the role of mitochondrial signal processing in T cell activation was investigated. CD3/CD28 costimulation of PBL elicited transient mitochondrial hyperpolarization and intracellular pH (pH(i)) elevation, followed by increased ROI production. Baseline Delta psi(m), ROI production, and pH(i) were elevated, while T cell activation-induced changes were blunted in 15 patients with SLE in comparison with 10 healthy donors and 10 rheumatoid arthritis patients. Similar to CD3/CD28 costimulation, treatment of control PBL with IL-3, IL-10, TGF-beta(1), and IFN-gamma led to transient Delta psi(m) elevation. IL-10 had diametrically opposing effects on mitochondrial signaling in lupus and control donors. Unlike healthy or rheumatoid arthritis PBL, cells of lupus patients were resistant to IL-10-induced mitochondrial hyperpolarization. By contrast, IL-10 enhanced ROI production and cell death in lupus PBL without affecting ROI levels and survival of control PBL. Ab-mediated IL-10 blockade or stimulation with antagonistic lymphokine IL-12 normalized baseline and CD3/CD28-induced changes in ROI production and pH(i) with no impact on Delta psi(m) of lupus PBL. The results suggest that mitochondrial hyperpolarization, increased ROI production, and cytoplasmic alkalinization play crucial roles in altered IL-10 responsiveness in SLE.
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PMID:Persistent mitochondrial hyperpolarization, increased reactive oxygen intermediate production, and cytoplasmic alkalinization characterize altered IL-10 signaling in patients with systemic lupus erythematosus. 1209 18


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