Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calreticulin is a new human rheumatic disease-associated autoantigen that plays a multifaceted role in cell biology. In earlier studies, this protein was shown to share an intimate relationship with the Ro/SS-A autoantigen complex, although the nature of this association continues to be debated. Since modulation of the Ro/SS-A autoantigen in epidermal keratinocytes has been implicated in the pathogenesis of subacute cutaneous lupus erythematosus and neonatal lupus erythematosus, we have begun to examine the transcriptional regulation of calreticulin. A 504 bp calreticulin promoter fragment was subcloned into a reporter gene plasmid containing firefly luciferase. Calcium ionophore, heat shock, and heavy metals such as zinc and cadmium were consistently found to increase calreticulin transcriptional activities in A431 cells (a human epidermoid squamous carcinoma cell line) under transient transfection conditions. These studies suggest that (a) calreticulin is regulated at the transcriptional level, and (b) calreticulin, like some other LE-related autoantigens, appears to function as a heat shock/stress-response gene.
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PMID:Calreticulin is transcriptionally upregulated by heat shock, calcium and heavy metals. 867 89

Thyroid hormone preparations, especially thyroxine, are widely used either at replacement doses to correct hypothyroidism or at suppressive doses to abolish thyrotropin (thyroid-stimulating hormone) secretion in patients with differentiated thyroid carcinoma after total thyroidectomy or with diffuse/ nodular nontoxic goitre. In order to suppress thyrotropin secretion, it is necessary to administer slightly supraphysiological doses of thyroxine. Possible adverse effects of this therapy include cardiovascular changes (shortening of systolic time intervals, increased frequency of atrial premature beats and, possibly, left ventricular hypertrophy) and bone changes (reduced bone density and bone mass), but the risk of these adverse effects can be minimised by carefully monitoring serum free thyroxine and free liothyronine (triiodothyronine) measurements and adjusting the dosage accordingly. Thionamides [thiamazole (methimazole), carbimazole, propylthiouracil] are the most widely used antithyroid drugs. They are given for long periods of time and cause adverse effects in 3 to 5% of patients. In most cases, adverse effects are minor and transient (e.g. skin rash, itching, mild leucopenia). The most dangerous effect is agranulocytosis, which occurs in 0.1 to 0.5% of patients. This life-threatening condition can now be effectively treated by granulocyte colony-stimulating factor administration. Other major adverse effects (aplastic anaemia, thrombocytopenia, lupus erythematosus-like syndrome, vasculitis) are exceedingly rare.
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PMID:Adverse effects of thyroid hormone preparations and antithyroid drugs. 886 63

We report the response to risperidone in seven hospitalized, adult patients who presented psychotic symptoms etiologically related to a general medical condition. The conditions included brain surgery in two, and anticardiolipin syndrome, renal failure, epilepsy, lupus, and metastatic carcinoma in one each. Four patients had failed previous treatment with at least one typical antipsychotic agent. Response to risperidone was assessed by the Brief Psychiatric Rating Scale (BPRS). Serum was collected for measurement of steady-state trough risperidone and 9-hydroxyrisperidone concentrations at effective doses in three patients. Amelioration of psychotic symptoms was noted in all seven patients. Mean (+/- SD) BPRS scores were reduced significantly from baseline (63.0 +/- 15.1) to endpoint (27.0 +/- 3.5; p < 0.01). The mean effective daily dose of risperidone was 3.1 +/- .7 mg and time to response was 4.7 +/- 2.4 days. Risperidone was not present at detectable concentrations in the three patients studied. The mean steady-state trough serum concentration of 9-hydroxyrisperidone in the three patients assessed was 20.3 +/- 9.8 ng/ml. These preliminary findings, which suggest that risperidone is a safe and effective agent in patients with psychotic symptoms due to various medical conditions, need to be confirmed by randomized, antipsychotic comparison trials involving a larger number of patients.
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PMID:Psychosis in medical conditions: response to risperidone. 985 54

A prospective outcome analysis was conducted on 100 consecutive women who requested explantation of their silicone gel breast implants from January 6, 1992 (the moratorium), through 1995. Eighteen patients were referred by rheumatologists with a diagnosis of autoimmune or rheumatic disease. Six had autoimmune disease (systemic lupus, 2 patients; rheumatoid arthritis, 2 patients; multiple sclerosis, 1 patient; and Raynaud's disease, 1 patient). Twelve had rheumatic disease (fibromyalgia, 10 patients; inflammatory arthritis, 2 patients). All of these 18 patients had developed symptoms of their disease after they had received implants. All 100 patients were extensively evaluated pre- and postoperatively by interviews, clinical assessment, and by assay of the following laboratory tests: rheumatoid factor, ESR, ANA, and anti-Ro/SSA, -La/SSP, -Sm, -RNP, -double-stranded deoxyribonucleic acid, -Scl-70, -centromere, and -cardiolipin. Patients were also evaluated by a questionnaire that was sent at a mean time of 2.7 years postexplantation (range, 1-5 years), which had a 75% response rate. Reasons for implants were augmentation, 75%; lifting, 11%; reconstruction, 12%; and congenital aplasia, 2%. The mean age at first implant was 28.9 years (range, 13-55 years) and at explantation was 41.5 years (range, 25-65 years). The mean duration of implantation was 12.0 years (range, 1-27 years). Thirty-six percent of the patients had undergone at least one closed capsulotomy and 54% at least one open capsulotomy. The mean reasons for explantation were suspected silicone-related health problems, 76%; suspected rupture, 59%; breast firmness, 36%; breast pain, 36%; and musculoskeletal pain, 23%. Before explantation 75% of the questionnaire respondees had lost some sensitivity in their nipples following their breast augmentation. In 36% of those 75 patients, that loss was almost complete. Loss of sensitivity was related to capsular contracture and to pain (p < 0.05). Following explantation there was significant improvement in nipple sensitivity in 38% of breasts in the 75 respondees. A total of 186 implants were removed. Fifty-seven percent had failed by rupturing or leaking. Only 3.2% demonstrated extravasation extracapsularly. Twenty-five percent of the capsules were calcified, demonstrating visible plaques of calcification on their inner surface. Forty-two percent were colonized by bacteria. The prevalence of class III-IV capsular contracture was 61% and it was related to implant location, duration in situ, and capsular calcification (p < 0.05), but not to capsular colonization or implant integrity (p > 0.05). Only 43 of the 100 patients elected to have saline implants inserted. Of the others, 56% felt that the shell of the saline implant could be associated with medical problems. The others felt that breast size was of minor importance to them at this time. There were few complications from the explantation procedure. Two "masses" were discovered-one was an occult carcinoma, the other a galactocele. There was one wound infection, which responded to antibiotics. Three patients developed decreased sensitivity and 3 developed increased breast pain. From the patient questionnaires, in those women who did not have saline implants inserted, 15% felt that their breast appearance was improved after explantation, 36% were "pleased," 33% were disappointed, and 13% felt "mutilated". In women who did have saline implants inserted, 18% felt that their breast appearance was now improved, 60% were "pleased," and 14% were disappointed, mainly because of wrinkling. At a mean time of 2.7 years (range, 1-5 years) after explantation, 45% of the 75 questionnaire respondees felt that their implants had caused permanent health problems and 56% felt that they had not been given adequate informed consent by their original surgeon (particularly regarding implant rupture and a possible relationship to medical disease). (ABSTRACT TRUNCATED)
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PMID:An outcome analysis of 100 women after explantation of silicone gel breast implants. 967 80

This study was undertaken to assess our experience with the first 50 patients who underwent CABG without cardiopulmonary bypass. In seven patients left internal mammary artery to left anterior descending artery (LIMA-LAD) grafting was performed through a short left anterior thoracotomy. In 43 other patients median sternotomy was used. Primary CABG was performed in 48 patients; there were two reoperations. Eleven patients had unstable angina. Three patients had left ventricular ejection fraction (LVEF) equal to or lower than 25%. One patient had carcinoma of the right lung coexisting with unstable angina and underwent also right lower lobectomy. In each patient the clinical course, 12-lead ECG, transthoracic echocardiography and the serum levels of creatine kinase (CPK), alanine aminotransferase (ALAT), aspartate aminotransferase (AspAT) were assessed. The need for inotropic or intraaortic balloon counterpulsation (IABP) support and blood transfusion was also recorded. There were three deaths, all in the sternotomy group (6%). A patient with systemic lupus erythemetodes (SLE) died of postoperative MI due to graft thrombosis. Another patient who was found to have porcelain aorta and had LIMA-LAD grafting as a rescue procedure died of MI with low cardiac output. The third patient with unstable angina and ejection fraction of 30% developed postoperative MI with ventricular arrhythmia. One patient with LIMA-LAD graft in whom percutaneous translaminal coronary angioplasty (PTCA) had been abandoned because of coronary spasm developed acute myocardial ischaemia 5 h postoperatively. He had a vein graft placed to LAD in cardiopulmonary bypass, his further course was uneventful. Six patients had IABP support. Nine patients needed inotropic support. Ten patients received blood transfusion. Twelve-lead ECG did not show acute ischaemia or MI, apart from the above described cases. Echocardiographic check showed improved IVS contractility in three patients and better apex motion in one case. In the other survivors the echocardiographic findings were the same as before the procedure. ALAT and AspAT serum levels were normal in all the survivors, and the CPK levels did not exceed 200 IU/ml. One patient from the mini-thoracotomy group had recurrent angina 2 months after the procedure. His left internal mammary artery (LIMA) graft was occluded; we replaced it with a vein graft. All 47 survivors remain asymptomatic, with the mean follow-up time of 6 months. Coronary surgery without cardiopulmonary bypass seems a valuable alternative for high-risk patients.
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PMID:Coronary artery bypass grafting without cardiopulmonary bypass--initial experience of 50 cases. 981 90

Fifteen patients with cerebral venous thrombosis were ascertained retrospectively. Their case notes were reviewed, and stored or new blood was assayed for factor V Leiden (FVL) mutation, prothrombin gene mutation 20201A, and 5,10 methylene tetrahydrofolate reductase (MTHFR) C677T mutation. A clinical risk factor was identified in 13 patients--the oral contraceptive pill (5), puerperium (1), HRT (1), mastoiditis (1), dehydration (1), lumbar puncture and myelography (1), carcinoma (1), lupus anticoagulant (2). In addition, two patients had the FVL mutation and five (one of whom also had the FVL mutation) were homozygous for the MTHFR mutation. The latter showed a higher than expected frequency compared to 300 healthy controls from South Wales (OR 3.15.95% Cl 1.01-9.83). No patient had the prothrombin 20201A mutation. Two patients died and three had a monocular visual deficit following anticoagulation (13) or thrombolytic (2) treatment, but there was no association between the presence of a primary prothrombotic risk factor and outcome. These results confirm the importance of investigating patients for both clinical predisposing factors and primary prothrombotic states.
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PMID:Inherited prothrombotic risk factors and cerebral venous thrombosis. 1002 25

Immunoglobulin (Ig) A-associated vasculitis is commonly equated with the multiorgan systemic vasculitic syndrome Henoch-Schonlein purpura (HSP), which occurs predominantly in the pediatric age group. By natural language search of the databases of two outpatient dermatopathology practices, the authors selected for review 37 cases of IgA-associated vasculitis, 23 of which were associated with antecedent infection, most commonly of the upper respiratory tract. Criteria for a diagnosis of HSP were met in 15 cases, 13 of which were in the setting of prior infection. Lower extremity skin involvement was ubiquitous. A more widespread form of vasculitis was also seen, particularly in the setting of previous infection. Several of the patients with previous infection had underlying medical illnesses including rheumatoid arthritis, atopy, renal failure, lupus erythematosus, insulin dependent diabetes mellitus, autoimmune thyroid disease, and Wegener's granulomatosis. In those patients lacking an apparent microbial trigger, Sjogren's disease with anti-Ro antibodies and hypergammaglobulinemia, lupus erythematosus, inflammatory bowel disease, IgA paraproteinemia, bronchogenic and prostatic carcinoma, cryoglobulinemia, and lymphoma were uncovered. Regardless of whether an infectious stimulus was implicated, certain cofactors with the potential to enhance vascular injury were uncovered; these included anti-Ro antibodies, antineutrophil cytoplasmic antibody, diabetic microangiopathy, and a hyperviscosity state. In the infective group, a pustular vasculitis, defined as a neutrophilic vascular reaction in concert with epithelial pustulation, was seen in 81% of cases versus 33% in the noninfectious group (p = 0.02). The prototypic histomorphology in the noninfective group was one of a mild cell poor leukocytoclastic vasculitis; Vasculitis was of greater severity in patients with antecedent infection (p = 0.026). An infectious trigger, typically of mucosal origin, can frequently be identified in patients with cutaneous IgA-associated vasculitis, especially those with the symptom complex of HSP. The light microscopy appears to distinguish patients who have an infectious trigger from those who do not. IgA-associated vasculitis may be a clue to the presence of certain underlying disorders where there is immune dysregulation or enhanced susceptibility to immune complex entrapment.
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PMID:A clinical and histologic study of 37 cases of immunoglobulin A-associated vasculitis. 1038 44

We report the occurrence of aggressive vulvar carcinoma associated with condyloma acuminata in three patients under 33 years old. Discussion of the role of the human papilloma virus (HPV) in the development of vulvar cancer is also presented. Three patients with condyloma associated with aggressive vulvar squamous cell carcinoma, in situ (1 case) and invasive (2 cases), documented by biopsy and/or vulvectomy are presented. In situ hybridization (ISH) was used to characterize the subtypes of HPV. One patient with erythematous systemic lupus developed in situ carcinoma after 5 years. The other two cases also developed aggressive multicentric, invasive squamous cell carcinoma after 10 years of diagnosis of condyloma. In all cases HPV cytological abnormalities were seen throughout the pathological examination. HPV 16 and 18 were present in cells of invasive squamous cell carcinoma in cases 2 and 3. HPV 6 and 11 were detected only in the condyloma area in case 2. HPV 30 was seen only in the condyloma area in case 3. This report emphasizes the need for biopsies of all unusually persistent or treatment-resistant condylomas, particularly in young and/or immunosuppressed patients.
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PMID:Vulvar carcinoma in young patients and its relationship with genital warts. 1041 Aug 83

White lesions usually contain an increased amount of keratin. Some are rare congenital conditions, such as white sponge naevus and dyskeratosis congenita, unlikely to be seen in general dental practice. Inflammatory causes include candidosis and hairy leukoplakia, both now common in HIV disease. Non-infective causes include the common lesion of lichen planus, and the less common condition lupus erythematosus. Neoplastic and possibly preneoplastic causes include carcinoma, keratoses and leukoplakia. This article discusses the more common causes of oral white lesions. The first article in this series presented several general observations on diagnosis and treatment which should be borne in mind in relation to this article.
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PMID:Orofacial disease: update for the dental clinical team: 3. White lesions. 1052 53

Two case reports and a review of the literature on paraneoplastic figurate erythemas with lupus erythematosus (LE)-specific histolopathology illustrate cutaneous paraneoplasia as an immunological phenomenon. Subacute cutaneous lupus erythematosus (SCLE) is characterized by photosensitive, annular or papulosquamous skin lesions with LE-specific histopathology in association with circulating anti-SS-A (Ro) auto-antibodies. The SS-A (Ro) antigen is a complex of cytoplasmic ribonucleoproteins that translocate to the surface of keratinocytes under UV irradiation. Sequestered cytosolic antigen that is expressed on the cell surface is presented to T lymphocytes by professional antigen presenting cells in the context of specific MHC class II molecules. The initiation of the specific immune response, the expansion of antigen-specific T helper cells, and the differentiation of B cells to antibody producing plasma cells depend on the further interaction with antigen. The risk of a self-perpetuating autoimmune response relies on further release of auto-antigen. It is conceivable that in paraneoplastic SCLE tumor antigen with homology to SS-A (Ro) leads to photosensitive autoreactivity. The review of the literature reveals 9 other cases of SCLE associated with internal malignancy. The most common associated tumors were bronchial and mammary carcinoma. The latency between the appearance of skin lesions and the diagnosis of an underlying tumor was between one month and three years (mean: 10 months). In all cases, skin lesions improved with cancer therapy, in three cases they (re)appeared in association with relapse of tumor.
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PMID:[Cutaneous paraneoplastic syndrome as an immunologic phenomenon exemplified by paraneoplastic subacute cutaneous lupus erythematosus]. 1058 50


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