Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Secreted IgA plays a pivotal role in the mucosal immunity to maintain the front line of body defense. We found that the level of fecal IgA was dramatically decreased in aged (NZB x NZW)F(1) (BWF(1)) mice developing lupus nephritis, whereas levels in similarly aged New Zealand Black (NZB) and New Zealand White (NZW) mice remained unchanged compared with young mice. The number of cells obtained from Peyer's patches was markedly decreased in aged BWF(1) mice. Aged BWF(1) mice showed increased susceptibility to pathogenic bacterial infection. Furthermore, oral administration of OVA failed to inhibit secondary IgG response induced by systemic immunization, suggesting defective oral tolerance in aged BWF(1) mice. A significant amount of orally administered OVA was incorporated directly into the intestinal lamina propria in aged BWF(1) mice whereas it was mainly localized in subepithelial domes and interfollicular region in Peyer's patches in young mice. T cells obtained from renal and pulmonary lymph nodes of aged BWF(1) mice that had been orally administered with OVA showed an Ag-specific T cell proliferation, whereas those from young BWF(1), aged NZB, and aged NZW mice did not. Interestingly, aerosol exposure to OVA of aged BWF(1) mice, which had been orally administered with the same Ag, provoked an eosinophil infiltration in the lung. These results demonstrate that mucosal immunity in the gut is impaired and oral Ags induce systemic sensitization instead of oral tolerance in the development of murine lupus.
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PMID:Breakdown of mucosal immunity in the gut and resultant systemic sensitization by oral antigens in a murine model for systemic lupus erythematosus. 1584 48

Celiac disease (CD) is an inflammatory condition of the gut with a known autoimmune pathogenesis. Many similarities exist between the pathogenesis of CD and systemic lupus erythematosus (SLE); it is still unknown whether there is an association. There are 13 case reports in the literature of both diseases occurring simultaneously. We report another patient who was diagnosed with SLE and 8 years later, developed CD. A review of the literature is also presented.
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PMID:Celiac disease in a patient with systemic lupus erythematosus: a case report and review of literature. 1680 37

Cases of mesenteric vasculitis in systemic lupus erythematosus (SLE) are well described, however, individual patient with recurrent mesenteric vasculopathy producing repeated episodes with each exacerbation similar in character and quality has not been reported previously in the literature. We describe two SLE patients whose condition was complicated by repeated stereotypic, CT confirmed, episodes of lupus enteritis characterized by dramatic intestinal wall edema. Moreover, each flare was accompanied by significant hypocomplementemia and was rapidly reversible suggesting an acute gastrointestinal distress syndrome (AGDS) as a result of leukoaggregation and a gut capillary leak syndrome.
Lupus 2007
PMID:Acute gastrointestinal distress syndrome in patients with systemic lupus erythematosus. 1740 71

In patients with systemic connective tissue diseases were studied. The species structure intestinal microflora was characterized by decrease of dominating status of anaerobic bacteria and increase of role of opportunistic bacteria. The number of Lactobacillus decreased significantly. Bifidobacterium and Bacteroides was also decreased in number while their detection rate did not change. Opportunistic bacteria with hemolytic activity acquired greater significance in the forming of patients' intestinal microbiocenosis. Significant increase of Staphylococcus and opportunistic Enterobacteriaceae detection rate and density of intestine colonization was detected. Colonization of the intestine by S. aureus was revealed. Comparative analysis of the qualitative and quantitative structure of the intestinal microflora in patients with systemic lupus erythematosus and systemic scleriasis revealed similar patterns. However, colonization of the gut by opportunistic intestinal bacteria, Candida and microorganisms with hemolytic activity was more frequently observed in patients with systemic scleriasis.
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PMID:[Intestinal microecology in some systemic connective tissue diseases]. 1788 74

The prototypic autoimmune diseases involving skin (lupus, dermatomyositis) typically result in epithelial injury and autoantibodies to characteristic cellular antigens. Disease-specific autoantibodies are also found in scleroderma, but scleroderma is different from other cutaneous autoimmune diseases because epithelial injury does not occur. Multiple factors and combinations of factors (immune system, vascular and extracellular matrix abnormalities) are the most likely triggers in an individual with a genetic predisposition to scleroderma. These lead to increased synthesis of normal collagen in skin, lungs and gut in the systemic form of scleroderma, systemic sclerosis. The hypotheses for the pathophysiology of scleroderma are diverse and include abnormal immunologic processes such as cytokine and chemokine dysregulation, abnormal T cell signaling, B cell dysfunction, injury due to autoantibodies to endothelial cells, persistent wound healing condition due to dysregulation of matrix homeostasis, abnormalities in the fibrinolytic system, polymorphisms in critical molecules of the immune system and matrix homeostasis, and microchimerism due to fetal/maternal placental exchange of HLAcompatible cells. Systemic sclerosis/scleroderma is chronic and progressive. To date, no definitive therapy is effective for any of the scleroderma variants, although agents for the vascular dysfunction have some utility. Hematopoietic bone marrow or stem cell transplantation before significant tissue fibrosis has occurred may be the most effective treatment.
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PMID:Scleroderma. 1846 Aug 91

Arylamine N-acetyltransferases (NATs) catalyse the N-acetylation of arylamines, arylhydroxylamines and arylhydrazines with the acetyl group being transferred from acetylCoenzyme A. As a result of many recent advances in NAT research there have been many recent reviews and the present paper gives a flavour of the excitement in the field. The NATs, which are cytosolic, were early examples of pharmacogenetic variation. Polymorphism in isoniazid inactivation resulting in slow acetylation was subsequently found to be due to SNPs in the gene encoding the human isoenzyme NAT2. There are two polymorphic genes (NAT1 and NAT2) encoded with a third pseudogene (NATP) at human 8p21.3. The gene structure of NAT1 and NAT2, with a single (NAT2) or multiple (NAT1) distant non-coding exons showing tissue specific splicing, opens possibilities for effects of polymorphisms outside the single coding exon. In humans, the substrate specificities of NAT1 and NAT2 are overlapping but distinct. The NAT2 isoenzyme, predominantly in liver and gut, acetylates sulphamethazine and arylhydrazine compounds. Slow acetylators are at increased risk of toxicity, e.g. isoniazid induced neurotoxicity and hydralazine-induced lupus. The human NAT1 isoenzyme is also polymorphic. It is expressed in many tissues, particularly in oestrogen receptor positive breast cancers. Human NAT1 has an endogenous role in acetylation of a folate catabolite with in vivo evidence from transgenic mice lacking the equivalent gene. For nomenclature see http://louisville.edu/medschool/pharmacology/NAT.html, the website maintained by David Hein. NAT homologues have been identified by bioinformatics analyses in zebrafish and these sequences are described, although the proteins have not yet been characterized. The first NAT crystallographic structure from Salmonella typhimurium identified the mechanism of acetyl transfer via a catalytic triad of Cys, His and Asp residues each essential for activity in all NATs. NATs from mycobacteria aided in identifying the substrate binding site and the acetylCoA binding pocket. Studies on the eukaryotic enzymes by NMR and crystallography have facilitated understanding substrate specificities of human NAT1 (5-aminosalicylate and p-aminobenzoic acid) and human NAT2 (sulphamethazine). The effect of "slow acetylator" SNPs in the coding region predominantly act through creating unstable protein that aggregates intracellularly prior to ubiquitination and degradation.
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PMID:Arylamine N-acetyltransferases: structural and functional implications of polymorphisms. 1885 12

Acute rehabilitation refers to the multidisciplinary rehabilitative treatment of patients in continuing need of integrated acute and rehabilitative longterm care. As a result of the advances in acute rheumatology and improved emergency services, an increasing number of patients survive episodes of severe disease and complications of immunosuppressive therapy. These patients require not only treatment of their acute medical problems but also specialized multidisciplinary acute rehabilitation starting as early as possible during their hospital stay. We describe 4 typical cases from the major fields of rheumatology. (1) Acute rehabilitation of a 63-year-old woman with rheumatoid arthritis after replacement of both preexisting knee endoprostheses in one session and removal of the left hip endoprosthesis due to infection and sepsis. (2) Rehabilitation of a 29-year-old man with a 7-year history of ankylosing spondylitis who lived in an adjustable easy chair for 2 years due to severe pain prior to admission. (3) A 61-year-old woman with active refractory Wegener's granulomatosis who developed respiratory insufficiency due to aspergillus and pseudomonas pneumonia. (4) The acute rehabilitation of a 21-year-old woman with systemic lupus erythematosus and a history of 14 laparotomies due to severe acute pancreatitis and multiple gut perforations. Acute rehabilitation was complicated by a large defect of the abdominal wall and significant critical illness polyneuropathy. Our report points out differences between acute, postacute, and longterm rehabilitation, describes the mobilization of patients in acute rheumatology units, and defines specific problems encountered in acute hospital-based rehabilitation of rheumatological patients.
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PMID:Severe disease activity and complications of immunosuppressive therapy: a challenge for acute hospital-based rehabilitation in rheumatology. 1953 61

The aim of this study was to describe the microbial communities in the distal gut of wild wolves (Canis lupus). Fecal samples were collected from three healthy unrelated adult wolves captured at the nearby of Dalai Lake Nature Reserve in Inner Mongolia of China. The diversity of fecal bacteria was investigated by constructing PCR-amplified 16S rRNA gene clone libraries using the universal bacterial primers 27 F and 1493 R. A total of 307 non-chimeric near-full-length 16S rRNA gene sequences were analyzed and 65 non-redundant bacteria phylotypes (operational taxonomical units, OTUs) were identified. Seventeen OTUs (26%) showed less than 98% sequence similarity to 16S rRNA gene sequences were reported previously. Five different bacterial phyla were identified, with the majority of OTUs being classified within the phylum Firmicutes (60%), followed by Bacteroidetes (16.9%), Proteobacteria (9.2%), Fusobacteria (9.2%) and Actinobacteria (4.6%). The majority of clones fell within the order Clostridiales (53.8% of OTUs). It was predominantly affiliated with five families: Lachnospiraceae was the most diverse bacterial family in this order, followed by Ruminococcaceae, Clostridiaceae, Peptococcaceae and Peptostreptococcaceae.
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PMID:Phylogenetic analysis of 16S rRNA gene sequences reveals distal gut bacterial diversity in wild wolves (Canis lupus). 2030 30

In the preantibiotic era, TB of the skin was treated successfully with UV light. By the 1920s, pulmonary TB was being treated with regular sun exposure. During the last decade, basic laboratory research into the antimicrobial actions of vitamin D has provided new insights into these historical observations. Vitamin D has a critical role in the innate immune system through the production of antimicrobial peptides - particularly cathelicidin. Vitamin D would appear to have an important role in respiratory tract, skin and potentially gut health. A number of autoimmune diseases, including multiple sclerosis, Type I diabetes, systemic lupus erythematosus and rheumatoid arthritis, are associated with vitamin D deficiency. Vitamin D could have an important role in the prevention and possible treatment of these conditions; however, much of the current evidence relates to basic science and epidemiological research. In many situations, appropriate double-blind, randomized controlled trial data to guide clinicians treating infectious and autoimmune disease is still lacking.
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PMID:Vitamin D: emerging roles in infection and immunity. 2113 62

With the increasing use of mycophenolic acid (MPA) as an immunosuppressant in solid organ transplantation and in treating autoimmune diseases such as systemic lupus erythematosus, the need for strategies to optimize therapy with this agent has become increasingly apparent. This need is largely based on MPA's significant between-subject and between-occasion (within-subject) pharmacokinetic variability. While there is a strong relationship between MPA exposure and effect, the relationship between drug dose, plasma concentration and exposure (area under the concentration-time curve [AUC]) is very complex and remains to be completely defined. Population pharmacokinetic models using various approaches have been proposed over the past 10 years to further evaluate the pharmacokinetic and pharmacodynamic behaviour of MPA. These models have evolved from simple one-compartment linear iterations to complex multi-compartment versions that try to include various factors, which may influence MPA's pharmacokinetic variability, such as enterohepatic recycling and pharmacogenetic polymorphisms. There have been major advances in the understanding of the roles transport mechanisms, metabolizing and other enzymes, drug-drug interactions and pharmacogenetic polymorphisms play in MPA's pharmacokinetic variability. Given these advances, the usefulness of empirical-based models and the limitations of nonlinear mixed-effects modelling in developing mechanism-based models need to be considered and discussed. If the goal is to individualize MPA dosing, it needs to be determined whether factors which may contribute significantly to variability can be utilized in the population pharmacokinetic models. Some pharmacokinetic models developed to date show promise in being able to describe the impact of physiological processes such as enterohepatic recycling. Most studies have historically been based on retrospective data or poorly designed studies which do not take these factors into consideration. Modelling typically has been undertaken using non-controlled therapeutic drug monitoring data, which do not have the information content to support the development of complex mechanistic models. Only a few recent modelling approaches have moved away from empiricism and have included mechanisms considered important, such as enterohepatic recycling. It is recognized that well thought-out sampling schedules allow for better evaluation of the pharmacokinetic data. It is not possible to undertake complex absorption modelling with very few samples being obtained during the absorption phase (which has often been the case). It is important to utilize robust AUC monitoring which is now being propagated in the latest consensus guideline on MPA therapeutic drug monitoring. This review aims to explore the biological factors that contribute to the clinical pharmacokinetics of MPA and how these have been introduced in the development of population pharmacokinetic models. An overview of the processes involved in the enterohepatic recycling of MPA will be provided. This will summarize the components that complicate absorption and recycling to influence MPA exposure such as biotransformation, transport, bile physiology and gut flora. Already published population pharmacokinetic models will be examined, and the evolution of these models away from empirical approaches to more mechanism-based models will be discussed.
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PMID:The evolution of population pharmacokinetic models to describe the enterohepatic recycling of mycophenolic acid in solid organ transplantation and autoimmune disease. 2114 65


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