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)

We previously showed that anti-idiotypic mAb (mAb2) F16-16D7 (16D7) to the paratope (or paratope-related idiotope) of the anti-CD4 mAb HP2/6 induces anti-CD4 Abs in BALB/c mice. In view of the potential ability of 16D7 to induce anti-CD4 Ab in humans and the potential benefits of anti-CD4 Abs in the treatment of autoimmune diseases, we evaluated the immunologic response to and assessed the safety of four 2-mg 16D7 s.c. injections in one patient with systemic lupus erythematosus (SLE) and one with rheumatoid arthritis (RA). 16D7 induced anti-isotypic and anti-anti-idiotypic Abs (Ab3), which were almost exclusively of the IgG isotype. Ab3 specifically reacted with 16D7 as they inhibited its binding to mAb HP2/6. Although Ab3 did not react with cellular or recombinant CD4 (rCD4), single-cell enzyme-linked immunospot assays of anti-CD4 Ab production revealed many more spot-forming cells in rCD4- and 16D7-coated wells than in wells coated with BSA or 16D7 isotype-matched MK2-23. Spot-forming anti-CD4 Abs were specifically induced by 16D7, since rCD4-dependent spot formation 1) was not observed with PBL from one patient with SLE, one with mixed connective tissue disease, and one with melanoma immunized with MK2-23; and 2) was inhibited by 16D7 and not by MK2-23. Spot-forming anti-CD4 Abs recognize a CD4 epitope identical (or closely related) to that seen by HP2/6, since this specifically inhibited spot formation. A substantial, although transient, CD4+ T cell depletion was only observed in the RA patient. Local and/or general toxicity and laboratory and/or clinical signs indicative of immunodepression or diseases relapse were not observed during an 18-month follow-up.
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PMID:Human CD4-internal antigen anti-idiotypic monoclonal antibody: induction of a CD4-specific response in humans. 861 87

Dermatologic lesions are often associated with pulmonary disorders and vice versa. Diseases with pulmonary and cutaneous manifestations can be divided into four major categories: (a) congenital and developmental disorders with cutaneous-pulmonary manifestations (Ehlers-Danlos syndrome, generalized elastolysis, yellow nail syndrome, neurofibromatosis, hereditary hemorrhagic telangiectasia); (b) primary dermal diseases with associated pulmonary manifestations (septic vasculitis, malignant melanoma, Kaposi sarcoma); (c) primary pulmonary diseases with associated cutaneous manifestations (tuberculosis, Pseudomonas pneumonia, mycoplasmal pneumonia, adenocarcinoma, metastasis); and (d) cutaneous-pulmonary conditions (multisystem disorders) (progressive systemic sclerosis, systemic lupus erythematosus, Wegener granulomatosis, sarcoidosis). A series of selected cases is used to illustrate the radiologic and dermatologic features of conditions that affect both the lung and dermal tissue. Specific emphasis is placed on the dermatologic manifestations of disease. Diagnosis of a pulmonary-cutaneous disorder requires familiarity with the morphologic appearance of the cutaneous lesion.
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PMID:Imaging of pulmonary-cutaneous disorders: matching the radiologic and dermatologic findings. 883 76

In ancient times, the sun was venerated as a source of life in some cultures. Scientifically, the relationship between vitamin D and sunlight and the deficiency of vitamin D in patients with rickets were ultimately discovered. In 1903, Niels Finsen was awarded the Nobel Prize in medicine or physiology for his "Finsen light therapy" for infectious diseases, especially lupus vulgaris. In the 1930s and 1940s, the medical profession promoted sunbathing as beneficial for children. From these bases, the popularity of suntanning emerged, promoted by the availability of more leisure time and, eventually, the development of sunlamps and commercial tanning salons. Although the precise role of ultraviolet light in the pathogenesis of melanoma is uncertain, a melanoma epidemic began to be noticed in the 1970s. During the past 15 years, campaigns have attempted to educate the public about the potential dangers of suntanning and exposure to ultraviolet light. Whether the melanoma epidemic can be reversed remains to be seen.
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PMID:Suntanning: differences in perceptions throughout history. 914 90

Two regions of the genome contain members of the MAGE gene family; Xq27-qter and Xp21.3. We isolated a transcript, MAGE Xp-2, by screening a cDNA library from the human epithelial carcinoma cell line, HEp-2, using autoantibodies from patients with systemic lupus erythematosus (SLE). The open reading frame (ORF) of MAGE Xp-2 is entirely contained in exon 4, a signature feature of the MAGE gene family. While MAGE Xp-2 shares genomic homology with MAGE Xp-1, the predicted proteins are quite divergent. Specific primers were designed to reliably distinguish between MAGE Xp-1 and MAGE Xp-2 expression. MAGE Xp-2 is expressed in testis, but not in other normal tissues. It is also expressed strongly in two of seven melanoma cell lines and one of four breast carcinomas. MAGE gene expression may be important not only for tumor recognition and cancer therapy, but, because it is the apparent target of autoantibodies in SLE sera, it may also play a role in autoimmune diseases.
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PMID:MAGE Xp-2: a member of the MAGE gene family isolated from an expression library using systemic lupus erythematosus sera. 953 11

As dermatologists, we have all been active in educating patients about sun awareness and sun protection. This is even more important for children, as childhood exposure to ultraviolet light is a significant risk for both melanoma and nonmelanoma skin cancers. The importance of an educational approach in appropriate sun awareness in childhood is further underscored by the recent findings by Rivers et al., in the Vancouver Moles Cohort study, presented at the 1999 American Academy of Dermatology meeting. In a placebo-controlled trial, the findings of Rivers et al. clearly demonstrated that the use of sunscreens can significantly decrease the formation of nevae in children, providing further evidence to support sun awareness education initiatives. The lead article by Gooderham and Guenther in the Basic and Clinical Sciences section evaluates the effectiveness of a particular sun awareness program, and gives valuable insights into how more effective approaches may be used in the future. In addition to ultraviolet light playing a causal role in cutaneous malignancies, it is known to induce a number of other skin problems. One particularly difficult group of disorders is the photosensitive dermatoses, including solar urticaria. Bissonnette et al. describe an innovative approach to the management of refractory solar urticaria with plasma exchange. In the Grand Rounds section, Strauss et al. review the case of an acute SLE and give an insightful discussion related to bullous eruptions in acutely ill children. The mechanism of ultraviolet-light-induced carcinogenesis involves UV-induced DNA damage. Over the past decade, it has become clear that tumour suppressor genes can regulate these processes. In the Review section, Tron et al. discuss the role of the suppressor gene p53, which is mutated or lost in nonmelanoma skin cancer. P53 is crucial in protecting keratinocytes from the harmful effects of ultraviolet radiation, and in their instructive article, these authors use gene-targeted mutant mice lacking p53 to further evaluate the role in UV-induced DNA damage. With the warm weather upon us, we are spending more time in the outdoors and, as a result, are exposed to a vast number of environmental onslaughts. These include such things as Rickettsial disease, summarized in our CME section Summary Notes. Furthermore, in a comprehensive review, Dr. Sasseville examines another outdoor threat as he delineates the wide spectrum of plant contact dermatitis. This represents an important and in-depth reference on phytodermatitis. Our specialty, and indeed all of medicine, is being dramatically altered by recent advances in our understanding of disease at a molecular level. This new understanding of disease has led to the potential of modifying gene expression through the use of gene therapy. This is particularly attractive in skin disease, where gene therapy can be delivered quite readily through the skin. This advancement is insightfully discussed in the article by Somani et al., "Gene Therapy and Dermatology," which is both valuable for the cognoscenti and noncognoscenti alike, and serves as an important reference work in this area.
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PMID:Editorial 1038 44

Clinical data of 34 patients with DM, who have been treated during the years 1971 and 1998 were evaluated. 79% of the patients (27 patients) were female, 21% of them (7 patients) were male. 59% of the patients (20 pts) were between the ages of 41 and 50 years. The characteristic heliotrop rash were observed in 26 patients, Gottron's papules in 20 patients, poikiloderma in 2 patients, calcification, ulcers, Raynaud syndrome in 1 patient. 3 of the 34 patients presented with strongly itching erythematopapulosus symptoms, most prominently on the scalp. Cardiac involvement were present in 10 patients (29%), lung involvement in 8 patients (23%), gastrointestinal complaints in 11 patients, dysphagia, dysphonia in 4 patients, joint pain in 5 patients. Overlap syndrome--scleroderma-dermatomyositis, SLE-dermatomyositis--was present in 2 patients. 9 of the 34 patients (26%) suffered from malignant tumours: gastric, breast, lung, epipharynx carcinoma, malignant melanoma. 13 of the 34 patients have been treated with corticosteroids together with immunosuppressor agents, in most cases azathioprin was administered. Cyclosporin was given in 7 cases, chloroquine in 2 cases.
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PMID:[Dermatomyositis: clinical study of 34 patients]. 1069 80

The aim of our review is to summarize common genetic variations of some receptors associated with clinical consequences, which were not outlined in the previous special issue of this journal. Because of the multiple pathomechanisms of diseases, a set of genetic variation can play a role in the development of pathological conditions. From the data available three articles would merit a greater interest. In systemic lupus erythematosus the associations related to some polymorphisms of Fc-, tumor necrosis factor (TNF) alpha- and interferon receptor may explore new autoimmunological and inflammatorical pathomechanisms. In the endocrinology, the androgen receptor repeat polymorphism will exert significant aspects in the development of prostate cancer. The pleoitropic responsibility of vitamin D3 receptor polymorphism in the pathogenesis of immunological disorders (primary biliary cirrhosis, inflammatory bowel disease, type 1 diabetes mellitus) and of malignancies (malignant melanoma, breast cancer) shed light on the importance of common nuclear receptors. Nevertheless, in the future studies a more consistent approach minimizing requirement bias in the selection of patients will approve our understanding the role of genetic influence on the pathogenesis of diseases.
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PMID:Receptor polymorphisms and diseases. 1123 Sep 90

Chloroquine is a drug with over 60 years of safe clinical use in the treatment of malaria. The multiple mechanisms of chloroquine action have appeared to be useful in the therapy of many miscellaneous disorders well beyond its original antimalarial purposes. This paper is focused on the application of chloroquine for the treatment of malaria, porphyria cutanea tarda, rheumatoid arthritis, palindromic rheumatism and lupus. The possibility of the use of chloroquine in the therapy of other disorders such as diabetes mellitus, AIDS, hyperlipidemia, sarcoidosis, hypercalcemia, and melanoma is reviewed. Mechanisms of action of the drug as well as side effects on metabolism are discussed in view of recent discoveries.
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PMID:[Chloroquine--miscellaneous properties of the antimalarial drug]. 1210 61

Interferon alpha (IFNalpha) is used for the treatment of several disorders, such as chronic hepatitis or malignant melanoma. During the therapy, IFNalpha may cause severe neuropsychiatric syndromes including depression with suicidal ideation, paranoid psychoses, or confusional states. The reasons and management of these side effects are widely unknown. Our aim is to review research evidence for the contribution of IFNalpha for the etiopathology of psychiatric syndromes. Therefore, research findings of neuropsychiatric syndromes induced by IFNalpha treatment, the putative mechanisms underlying those syndromes, and their treatment are-reviewed. Furthermore, neuropsychiatric syndromes in diseases with high IFNalpha levels such as systemic lupus erythematosus (SLE) are discussed. Finally, the question is addressed whether IFNalpha may contribute to the etiopathology of endogenous psychiatric disorders. IFNalpha may cause psychiatric syndromes in a subset of treated patients. The underlying pathogenetic mechanisms include various effects on neuroendocrine, cytokine, and neurotransmitter systems. Research data on the role of IFNalpha in the pathogenesis of endogenous psychiatric disorders are conflicting. Future research should improve our understanding of the role of IFNalpha for the etiopathology of psychiatric syndromes and has an impact on treatment of IFNalpha-induced psychiatric syndromes.
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PMID:Interferon alpha (IFNalpha) and psychiatric syndromes: a review. 1218 6

Oral contraceptives (OCs) can affect the skin through their hormonal effects or through iatrogenic effects associated with their toxicity in certain individuals. They may also be beneficial in certain androgen-dependent dermatoses. Toxic effects of OCs are rare but potentially serious; they should be diagnosed early and require permanent termination of OC use. The clinical manifestations are variable and not specific to the medication. The most frequently reported manifestations are allergic vascularities which may lead to serious renal complications, fixed pigmented erythema, urticaria, which may have other etiologic factors, and lichenoid eruptions. Combined OCs, because of their estrogen content, may cause sensitivity to light in susceptible women. Other dermatoses can be initiated or aggravated by OCs without direct relation to their hormonal effects. OCs are therefore contraindicated if there is a personal or family history of porphyries or a personal history of systemic lupus erythematosus, erythema nouex, herpes gestationis, or malignant melanoma. Hormonal-related dermatological effects caused by either progestins or estrogens have become less frequent as dose levels have declined. Chloasma, either melasma or a poorly defined spotty pigmentation, accounts for 2/3 of cases of OC-related dermatoses. It is more common in women of Mediterranean background. 80% of affected OC users have a history of "mask of pregnancy", but the condition is also found in nulliparas. Exposure to sunlight is a factor. Women with a history of chloasma of pregnancy and dark coloring should not use OCs. Seborrhea is directly related to the androgen effect of OCs and is less likely to occur with 17 OH progesterone derivatives than with 19 norsteroid derivatives. The role of androgens in acne is well known, but 2 other factors are necessary: an anomaly in keratinization and proliferation of corynebacterium acnes, a saprophyte of the follicles. OCs do not necessarily need to be suspended during well-conducted acne treatment. Alopecia is rare but difficult to diagnose because of its psychological aspects. Androgenic alopecia is aggravated by progestins derived from 19 norsteroids. True hirsutism caused by an androgen-producing ovarian pathology is not related to OC use. Estrogens are incriminated in the etiology of telangiectasies, permanent dilatations of the arterioles. Once developed the condition does not regress and requires treatment with sclerosing agents, electrocoagulation, or laser. The various dermatological risk factors should be ruled out before prescription of an OC. Classic contraceptive pills are not commonly used in treatment of common acne because the strongly estrogenic climate required for therapeutic utility carries the risk of hypertriglyceridemia, thrombophlebitis, and possibly carcinogenesis. The recent development of pills containing the antiandrogen cyproterone acetate instead of a progestin in combination with ethinyl estradiol reduces androgenic effects in women. This pill may be useful in cases of severe acne, severe seborrhea, androgenic alopecia, or excessive facial hair.
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PMID:[Cutaneous effects in hormonal contraception]. 1228 Dec 76


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