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

An overview of dermatological diseases which occur in conjunction with oral contraceptive (o.c.) use is presented. An increase in pigmentation during o.c. use is attributed to an increase in the binding of cortisol with transcortin caused by the estrogen component, which leads to an increase in melanin-stimulating hormone production. Sebum production is decreased during o.c. use, which has a beneficial effect in cases of acne and seborrhea oleosa. This effect is most pronounced with preparations containing chlormadinon acetate, which has an antiandrogenic effect. O.C. use can influence hair growth by disturbing the balance between anagenic and telogenic hairs. Androgenetic alopecia is most often caused by preparations containing nortestosterone. Peroral dermatitits, lupus erythmatodes visceralis and similar disorders, and allergic skin reactions have been observed among o.c. users. Porphyria cutanea tarda is generally found in young women in conjunction with o.c. use, which can be related to liver dysfunctions. Vaginal candidosis is also more frequently found among o.c. users, particularly in conjunction with combination preparations. Herpes gestationes can occur during o.c. use, mainly among women who developed it during pregnancy. Progesterone appears to be responsible for provoking the condition. 166 patients who developed dermatological disorders during o.c. use were studied according to the preparation each used. Acne vulgaris improved more frequently among Ovosiston users. A marked increase in vaginal fluor indicated an increase in trichomoniasis and candida mycosis. In all observed cases of porphyria cutanea tarda, liver damage (hepatitis, cyrrhosis, or fatty liver) could be ascertained.
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PMID:[Reactions and side effects of ovulation inhibitors on the skin]. 72 69

(2R,5R)-6-heptyne-2,5-diamine (MAP; MDL 72175), a potent irreversible inhibitor of L-ornithine decarboxylase (ODC), possesses immunosuppressive activities in vitro as the result of inhibition of lymphocyte polyamine biosynthesis. The effects of MAP were now studied in vivo in MRL-lpr/lpr female mice, an animal model for human systemic lupus erythematosus (SLE). Administration of MAP (0.2% in drinking water; drug intake: 0.25-0.35 g/kg body weight/day) to female mice for 15 weeks, starting 8 weeks after birth, reduced by 47% the number of spleen cells, retarded development of lymphadenopathy and, at that time, markedly prolonged the survival of the mice. At week 23, MAP reduced plasma IgG concentrations by 50% whereas, in contrast, those of IgM were elevated 1.5-fold. No statistically significant effects of MAP were observed on plasma levels of anti-DNA autoantibodies although serum anti-RNP and anti-Sm titres tended downwards during treatment. Neither glomerular lesions nor proteinuria were improved by MAP administration. Finally chronic administration of MAP for 45 weeks prolonged the median survival time from 29.75 to 35.5 weeks.
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PMID:Immunosuppressive effects of (2R,5R)-6-heptyne-2,5-diamine, an inhibitor of polyamine synthesis: II. Beneficial effects on the development of a lupus-like disease in MRL-lpr/lpr mice. 340 47

Although the etiology of lupus is imperfectly understood, immune factors, heredity, viral infections, and hormonal status are known to play a role. Studies of the sex ratio of lupus patients indicate that before age 10, twice as many girls as boys are affected, but after 12 years, 9.6 females are affected for each male. The incidence of lupus is almost constant for males of all ages but is much higher for women of fertile age than for other women. The deleterious effect of synthetic estrogens was 1st reported in 1966, and various studies since then have confirmed the results. The etiologic role of pregnancy is debated, but pregnancies can be successfully carried to term in periods of remission. Certain lines of mice spontaneously develop an autoimmune disease resembling disseminated lupus erythematosus. Anti-DNA antibodies appear earlier in the female and death from renal insufficiency occurs earlier than in males. Prepubertal castration does not influence the survival of female mice but significantly reduces that of males. Treatment with estradiol diminishes survival of castrated males and females, while treatment with androgens increases survival time of castrated to control females and of castrated males to that of control males. The timing and dose of treatment modify the response. Progesterone administered alone does not influence survival time of females but somewhat increases that of castrated males. Cyproterone acetate, an antiandrogenous progestin, has no effect in 2-3 week old males. Danazol, a moderately active androgen, has no effect on female mice. Nafoxidine, an antiestrogen, increases survival times. These results support the opinion that estrogens aggravate lupus while androgens have a protective effect. Different hormonal treatments have been prescribed for human lupus. Some beneficial effect for female patients has been observed with danazol, but the drug entails significant hepatic, metabolic, and hypertensive risks and may produce androgenic side effects such as voice modifications and hirsutism. Cyproterone acetate, a derivative of 17-hydroxyprogesterone, is without vascular and metabolic side effects and can halt ovarian function at a dose of 50 mg/day. It behaves as a peripheral antiandrogen and may have androgen agonist activity in some tissues. The mechanism of interaction of sex hormones in lupus may be explained by their influence on cellular and humoral immunity. Estrogens appear to suppress cellular immunity and stimulate humoral immunity, while androgens appear to play a suppressive role at the 2 levels. Contraception for women with lupus must be effective. Combined oral contraceptives and low-dose norsteroid progestins are contraindicated because of their thromboembolic and vascular risks. Low-dose progestins may be used but cause hyperestrogenism in some women. Chlormadinone acetate at a daily dose of 10 mg has no significant vascular effect. IUDs may have reduced efficacy during corticotherapy and pose a risk of infection. Only mechanical vaginal methods ose no threats for lupus patients, but they must be understood and accepted by the patient.
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PMID:[Hormones and lupus]. 391 21

Alterations of membrane surface and membrane microviscosity were studied in peripheral blood lymphocytes from myasthenic patients and compared with those from healthy subjects and SLE patients. The membrane ultramicrostructure of myasthenic lymphocytes was changed less than those of healthy and SLE lymphocytes. It showed slightly clustered MAP with larger diameters and less density than the healthy lymphocytes and with less prominent wavy surfaces than SLE lymphocytes. The microviscosity of the myashtenic lymphocytes was significantly lower that of the healthy controls and correlated well with clinical severity and the titers of anti-AchR anti-body and T cell membrane binding antibody. Con A, AHLA, and myasthenic sera reduced the microviscosities of the healthy lymphocytes. These results showed that the morphological changes of the lymphocyte surface were reflected in the alteration of microviscosity of lymphocytes through the interaction between surface receptors of T lymphocytes and anti-membrane antibody, especially anti-AchR antibody and T cell membrane binding antibody in patients with myasthenia gravis.
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PMID:Freeze-fracture and microviscosity of lymphocyte membranes in myasthenia gravis. 696 7

Anti-Sm is a common and specific autoantibody found in systemic lupus erythematosus. The peptide PPPGMRPP from Sm B/B' is an early target of the autoimmune response in some anti-Sm-positive human patients. After immunization with this peptide on a MAP backbone, rabbits develop anti-Sm autoantibodies with B cell epitope spreading of the autoimmune response as well as other features of lupus autoimmunity. Various strains of inbred mice have been immunized with peptide PPPGMRPP or PSQQVMTP (nonantigenic region of Sm B/B') in Freund's adjuvant or with no peptide. All peptide-immunized mouse strains eventually develop high titers of specific anti-peptide of immunization Abs. Mice immunized with Freund's adjuvant alone have no measurable Ab binding to the PPPGMRPP peptide. With time, nearly half the mouse strains tested develop Abs that react with additional regions of Sm B/B' and Sm D. All the regions bound by mouse serum are major epitopes of the human systemic lupus erythematosus anti-Sm response. These same strains also develop significant anti-Sm and anti-nuclear ribonucleoprotein titers. In addition, some of these strains demonstrate positive anti-nuclear Abs and anti-dsDNA Abs. Experiments with congenic H-2 mice demonstrate that the H-2 region does not play a role in spreading the immune response from the peptide of immunization to other epitopes of the spliceosome. These results present a new murine model of B cell epitope spreading and lupus autoimmunity induced by peptide immunization that is strain specific and not apparently dependent upon the loci at H-2.
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PMID:A model of peptide-induced lupus autoimmune B cell epitope spreading is strain specific and is not H-2 restricted in mice. 955 9

An experimental model of systemic lupus erythematosus has recently been described in normal animals. We sought to confirm and extend this model, which involved immunization of normal rabbits and mice with a peptide of Sm B/B', PPPGMRPP. This peptide is an early target of the immune response in anti-Sm-positive patients with lupus. The peptide was used in a multiple Ag peptide format, with multiple copies of PPPGMRPP bound to an inert lysine backbone. New Zealand White rabbits and A/J and C57BL/10ScSn mouse strains were immunized with PPPGMRPP-MAP. Pepscan assays were used to determine the epitope spreading of the anti-PPPGMRPP-MAP response to other octamers of SmB/B' following immunization. We obtained high titer anti-PPPGMRPP-MAP IgG responses in the New Zealand White rabbits and A/J mice. The rabbits immunized with PPPGMRPP-MAP showed varying degrees of epitope spreading, while the A/J mice showed no spreading. We observed no autoantibodies to dsDNA or other anti-nuclear autoantibodies in our animals by ELISA or immunofluorescence, although anti-nuclear autoantibodies were found by Western blotting in some of the rabbits. No evidence of clinical disease was seen in our normal animals. These data underline the difficulties often associated with the reproduction of animal models in different laboratories.
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PMID:Immunization with a peptide of Sm B/B' results in limited epitope spreading but not autoimmune disease. 1022 79

We have previously reported that immunization with a peptide mimetope of dsDNA on a branched polylysine backbone (DWEYSVWLSN-MAP) induces a systemic lupus erythematosus-like syndrome in the nonautoimmune BALB/c mouse strain. To understand the mechanism underlying this breakdown in self tolerance, we examined the role of T cells in the response. Our results show that the anti-foreign and anti-self response induced by immunization is T cell dependent and is mediated by I-E(d)-restricted CD4(+) T cells of the Th1 subset. In addition, generation of the critical T cell epitope requires processing by APCs and depends on the presence of both DWEYSVWLSN and the MAP backbone. The breakdown in self tolerance does not occur through cross-reactivity between the T cell epitope of DWEYSVWLSN-MAP and epitopes derived from nuclear Ags. In this induced-model of SLE, therefore, autoreactivity results from the activation of T cells specific for foreign Ag and of cross-reactive anti-foreign, anti-self B cells. Despite the fact that tissue injury is mediated by Ab, the critical initiating T cell response is Th1.
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PMID:T cell studies in a peptide-induced model of systemic lupus erythematosus. 1116 Feb 9

Aberrant expression of the p21Ras proto-oncogene has been reported in lymphoid cells of SLE patients. We previously showed that the expression of the p21Ras stimulatory element, hSOS1, is reduced in PBMC from SLE patients with non-active disease. However, the significance of this finding regarding the regulation and function of the p21Ras pathway and its correlation to disease activity remained unclear. The expression, regulation and function of the p21Ras pathway were determined in 23 ambulatory SLE patients with active and non-active disease and eleven controls. Levels of p21Ras stimulatory element hSOS1 but not p21Ras and its inhibitory element p120GAP were significantly decreased in SLE patients. Early p21Ras signalling was down-regulated in SLE patients with active disease as indicated by the decreased membrane/cytoplasmic (M/C) ratios of the p21Ras regulatory elements hSOS1 and p120GAP and by the non-responsiveness of these ratios to cellular stimulation. Anchorage of p21Ras to the cellular membrane was also significantly decreased in these patients. In contrast, the late p21Ras signalling was up-regulated in SLE patients as indicated by the significantly higher constitutive activity of the p21Ras down stream key regulator enzyme MAP Kinase. Taken together, our data demonstrate for the first time a disease associated functional defect in p21Ras signalling in lymphocytes of SLE patients.
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PMID:Constitutive up-regulated activity of MAP kinase is associated with down-regulated early p21Ras pathway in lymphocytes of SLE patients. 1236 60

Tumour necrosis factor (TNF) plays an important role in mediating the inflammation of inflammatory bowel disease, in particular, Crohn's disease. Strategies aimed at reducing tumour necrosis factor in patients with inflammatory bowel disease include the mouse/human chimeric monoclonal antibody infliximab, the humanized monoclonal antibody CDP571, the human soluble TNF p55 receptor onercept, the human monoclonal antibody D2E7 (adalimumab), the anti-TNF human antibody Fab' fragment-polyethelene glycol (PEG) conjugate CDP870, and the small molecules thalidomide and CNI-1493 (MAP-kinase inhibitor). Infliximab is effective for treating active Crohn's disease, maintaining remission, closing fistulas, maintaining fistula closure, and treating ankylosing spondylitis. Infliximab is also being investigated for the treatment of ulcerative colitis. Side-effects occurring in patients treated with infliximab include human anti-chimeric antibodies, infusion reactions, delayed hypersensitivity reactions, formation of autoantibodies, and, in rare circumstances, drug-induced lupus and serious infections, including tuberculosis. CDP571 is effective for treating active Crohn's disease, steroid sparing, and possibly for closing fistulas and maintaining remission. Side-effects occurring in patients treated with CDP571 include anti-idiotype antibodies, infusion reactions and the formation of autoantibodies. A controlled trial of etanercept in patients with Crohn's disease was negative. Pilot studies with onercept, thalidomide, and CNI-1493 have suggested benefit for Crohn's disease. There are no published data on the efficacy of adalimumab (D2E7) or CDP870 for either Crohn's disease or ulcerative colitis. Anti-tumour necrosis factor therapies are effective for the treatment of Crohn's disease and are being investigated for ulcerative colitis.
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PMID:Strategies for targeting tumour necrosis factor in IBD. 1261 86

One of the most interesting functions of the placenta is the regulation of the maternal immune response such that the fetal semi-allograft is tolerated during pregnancy. Trophoblasts are presumed to be essential to this phenomenon because they lie at the maternal-fetal interface, where they are in direct contact with cells of the maternal immune system. Trophoblasts do not express classic major histocompatibility complex (MHC) class II molecules. Surprisingly, cytotrophoblasts express more HLA-G, a MHC class Ib molecule, as they invade the uterus. Progesterone plays an important role in postovulatory regulation of the menstrual cycle. If fertilization occurs, progesterone supports implantation of the ovum and maintains the pregnancy. Progesterone has been named the 'hormone of pregnancy', because in preparing the endometrium for embryo implantation and facilitating endometrial development, it is critical to the very survival of a pregnancy. In addition, this key hormone inhibits the rejection of T cell-mediated tissue and also decreases myometrial activity and sensitivity throughout pregnancy. The cellular actions of progesterone are mediated through intracellular progesterone receptors (PRs), which are well studied gene regulators, not express classic major histocompatibility complex. The more used paradigm is relative to the alteration of relationship TH1/TH2, but the complexity of the respective distributions of cytokines at the materno-fetal interface, strongly suggest that, as useful as it certainly was for a while, the Th1/Th2 paradigm must now be considered as an oversimplification. Rather, the existing data point to sequential windows and are suggestive of a system where an extreme complexity is allied to very precise timing and tuning. They also suggest that the materno-fetal relationship is not simply maternal tolerance of a foreign tissue, but a series of intricate mutual cytokine interactions governing selective immune regulation and also control of the adhesion and vascularization processes during this dialogue. However, as shifting the immune response toward the Th2 pattern (IL-4, IL-5, IL-6) may benefit the fetus, whereas development of proinflammatory Th1 cells (secreting IL-2, IFN g, TNF a) may be harmful. Now we are working to open comprise the precise behaviour of NK populations, with the hope of obtaining a diagnostic test of the condition of abortion from 'immunological causes'.
Lupus 2004
PMID:Progesterone supplement in pregnancy: an immunologic therapy? 1548 93


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