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ID PMID Title PublicationDate abstract
12616672 Effect of rofecoxib on prednisolone and prednisone pharmacokinetics in healthy subjects. 2003 Feb Patients receiving nonsteroidal anti-inflammatory drug therapy may also require administration of corticosteroids, particularly patients with rheumatoid arthritis. To investigate the effect of rofecoxib on the single-dose pharmacokinetics of oral prednisone and intravenous prednisolone, the authors conducted a randomized, double-blind, placebo-controlled crossover study in 12 healthy subjects. Oral rofecoxib (250.0 mg/day for 14 days) failed to influence prednisone or prednisolone pharmacokinetics after intravenous prednisolone or oral prednisone administration. The geometric mean ratio (GMR) (90% confidence interval) of prednisolone AUC infinity (rofecoxib/placebo) following intravenous and oral corticosteroid was 0.97 (0.94, 1.01) and 0.99 (0.91, 1.08), respectively. Similarly, the prednisone AUC infinity GMRs (rofecoxib/placebo) after intravenous and oral corticosteroid were 1.03 (0.95, 1.11) and 1.08 (0.92, 1.28), respectively. The absence of an effect of rofecoxib on the pharmacokinetics of oral prednisone or intravenous prednisolone indicates that no adjustment in dose of this corticosteroid is necessary when administered concurrently with rofecoxib.
12607339 [Medical risk factors of tuberculosis and countermeasures]. 2002 Dec We describe the actual situation of and measures for medical risk factors of tuberculosis in compromised hosts and elderly people. Cases of diabetes mellitus, collagen disease and lung cancer administered corticosteroid preparations are taken up as compromised hosts. The frequency of TB patients having diabetes mellitus concurrently tends to increase, and the relative risk of diabetics developing tuberculosis is also high. Physicians giving diagnosis and treatment of diabetes mellitus should understand that diabetics belong to the high risk group of developing tuberculosis and perform chest X-ray examination periodically. In order to prevent the development of tuberculosis from diabetics, it is considered preferable to give chemoprophylaxis where there is no history of TB treatment and healing of TB has been found on the chest X-ray films. Where corticosteroid preparation, more than 10 mg in terms of prednisolone is administered over a long period of time for collagen diseases except rheumatoid arthritis and lung cancer, chemoprophylaxis is considered desirable. As for the present situation of the elderly TB patients among in-patients at our hospital, the elderly often had serious complications, their prognosis was poor and they often died of the diseases other than tuberculosis. To strengthen the measures to deal with tuberculosis in the elderly, early discovery and prophylaxis of pulmonary tuberculosis are considered. For the early discovery when the patient is symptomatic, the examination of sputum along with chest X-ray examination is important. As for the periodical health examination, the patients with the risk of infection to those around them being high need to undergo the health examination for sure. As the prophylactic measures, chemoprophylaxis is recommended where there is no history of TB treatment and healing of tuberculosis has been found on chest X-ray films.
12536174 [Anti-TNF alpha in dermatology]. 2002 Dec The discovery of the major role of TNF alpha in the physiopathology of certain inflammatory diseases and notably in rheumatoid arthritis and Crohn's disease has led to the development of anti-TNF alpha drugs. These new therapeutic arms issued from bio-technology have rapidly demonstrated their efficacy in the treatment of these two diseases. The anti-TNF alpha arsenal is currently dominated by etanercept, a fusion protein composed of a soluble TNF alpha receptor, and infliximab, a chimeric monoclonal antibody. However, new molecules will soon enrich this arsenal. TNF alpha is a major cytokine of inflammatory diseases of the skin. Many dermatological diseases will probably benefit from these new treatments. Two studies have already demonstrated their interest in cutaneous and articular psoriasis. Encouraging sporadic results suggest other potential indications (Behcet's disease, bullous dermatitis, neutrophilic dermatitis, toxic epidermal necrolysis, systemic vascularitis,.). These promising new treatments, although expensive, and with yet unknown long term side effects, justify rigorous assessment of their efficacy and tolerance in each indication. Here again the dermatologist has a major role to play in post-marketing pharmacovigilance.
12411136 [Treatment of infected total knee arthroplasty]. 2002 Sep OBJECTIVE: To investigate the treatment of infected total knee arthroplasty (TKA). METHODS: Between 1983 and 2000, 6 patients with infection after TKAs were treated, including 2 men and 4 women, aged on average 63 years (44 - 75 years). Initial knee arthroplasty was performed for osteoarthritis in 4 patients and for rheumatoid arthritis in 2 knees. The timing of diagnosis of infection after knee arthroplasty averaged 50 months (range, 1 month-11 years). Simple debridement and antibiotic treatment were prescribed for 3 patients, debridement and one-stage reimplantation for 1, debridement and two-stage reimplantation for 1, and athrodesis for 1. RESULTS: Of the 3 patients with simple debridement, one was cured, one failed but underwent athrodesis later, and one lost to follow up. Two patients with reimplantation were cured and had good function recovery. All of the 6 patients were followed up on average for 4 years. No infection recurred except one who lost to follow-up. CONCLUSIONS: Management of infection after total knee arthroplasty includes antibiotic suppression and debridement with prosthesis retention, insertion of another prosthesis as a one-stage or two-stage exchange technique, knee arthrodesis and amputation. These treatments have specific indications. To treat infection after total knee arthroplasty, suitable method should be taken according to patient's condition. Arthrodesis is the best salvage operation, though it may handicap patients' daily life. Reimplantation of another prosthesis could maintain a functional joint.
12181784 [Treatment of elbow joint ankylosis by repair of articular surface with periosteal autogra 2002 Jul OBJECTIVE: To evaluate the clinical effect of periosteal autograft in repair of ankylosis of elbow joint. METHODS: From May 1985 to November 1999, 18 cases of elbow joints ankylosis (6 cases of osteo-ankylosis, 12 cases of fibroankylosis) were treated by repairing articular surface with periosteal autografting. Out of 18 cases, 13 were caused by old dislocation and fracture of elbow joints, 3 by late rheumatoid arthritis, and 2 by old total joint tuberculosis. In this surgical approach, periosteum from upper end of tibia was transplanted into articular surface after correction of the elbow joint from ankylosis deformity, and continuous passive or active movement of the operated joint was adopted with skeletal traction through olecranon of ulna for 4 weeks after operation. All of the cases were followed up for 1-9 years, 5.2 years on average, before clinical evaluation. RESULTS: The elbow joints in 11 cases were restored to normal, the joints in 4 cases obtained active movement in the range of 100 degrees-0 degree, and the joints in the other 3 cases could only have limited movement because of severe muscular atrophy. CONCLUSION: The articular surface in arthroplasty of elbow joint ankylosis could be effectively repaired by periosteal autograft, and the function of the joints could be obviously improved by continuous movement of the joints after operation with skeletal traction.
12011696 Displaced intracapsular hip fractures: hemiarthroplasty or total arthroplasty? 2002 Jun The role of total hip arthroplasty for the treatment of displaced intracapsular fractures of the proximal femur in active patients is controversial. Some authors have shown that such patients, when treated with a bipolar or unipolar hemiarthroplasty, are at increased risk of having acetabular erosion develop that might require later revision to a total hip replacement. In fact, the results of some authors were not substantially different from those reported for elective total hip arthroplasty and were better than results reported for hemiarthroplasty. However, other authors have strongly recommended avoiding total hip replacement in active elderly patients without preexisting acetabular disease (osteoarthritis, rheumatoid arthritis, Paget's disease). Although the current belief is that there is a place for primary total hip arthroplasty after intracapsular hip fracture, and that this procedure should be reserved for patients with preexisting symptomatic acetabular disease, in a preliminary prospective comparative study of 46 active patients without preexisting acetabular disease, the current author found better results with cemented Charnley's total hip arthroplasty than with cemented Thompson's hemiarthroplasty. Long-term outcome and more detailed indications for total hip replacement as the primary treatment for intracapsular displaced fractures of the proximal femur are topics for additional study.
15542440 Hematopoietic secretory granules as vehicles for the local delivery of cytokines and solub 2004 Jul Cytokines play an important role in the regulation of homeostasis and inflammation. A de-regulated cytokine function can subsequently promote chronic inflammation. This is supported by clinical evidence showing the beneficial effect of inhibiting TNF-alpha through injection of antibodies and soluble receptor in disorders such as rheumatoid arthritis and Crohn's disease. Systemic anti-TNF-alpha therapy however is associated with infectious complications. We therefore suggest a concept for the local deposition of therapeutically active agents into areas of inflammation or malignancy, based on the use of hematopoietic storage and secretory granules as delivery vehicles. Hematopoietic cells are induced to express the therapeutically active protein and to store it in the secretory lysosomes. The cells migrate into a tumour or site of inflammation, where the cells become activated and release the contents of their secretory lysosomes resulting in the local delivery of the therapeutically active protein. In support of this concept, gene transfer and granule loading can be achieved using the soluble TNF-alpha receptor (sTNFR1) after cDNA expression in hematopoietic cell lines. Endoplasmic reticulum (ER)-export can be facilitated by the addition of a transmembrane domain, and constitutive secretion can be prevented by incorporating a cytosol-sorting signal resulting in secretory lysosome targeting. The sTNFR1 is released from the transmembrane domain by proteolytic cleavage and finally, regulated sTNFR1-secretion can be triggered by a calcium signal. In vivo investigations are currently determining the feasibility of local protein delivery at sites of inflammation.
17491673 Mucosal tolerance to prevent type 1 diabetes: can the outcome be improved in humans? 2004 Fall The results of trials in which autoantigens have been fed to individuals affected by autoimmune diseases - multiple sclerosis, rheumatoid arthritis and type 1 diabetes - have been disappointing in terms of clinical improvement. This is in striking contrast to the results in experimental rodent models of these diseases. The outcome of the recent DPT-1 trial testing oral insulin in individuals at risk of type 1 diabetes was also disappointing, in contrast to the effects of oral insulin in the non-obese diabetic (NOD) mouse model of type 1 diabetes. However, it is premature to conclude that mucosal tolerance works only in in-bred rodents and not in humans with autoimmune disease. Except for oral insulin in DPT-1, the human trials were performed in individuals with end-stage disease when this form of immune regulation might not be expected to be effective. Importantly, in no trial was an immune response to the autoantigen documented, to demonstrate that the dose was at least bioavailable. Furthermore, mucosal autoantigen administration is a 'double-edged sword' and in rodents can lead not only to regulatory and protective immunity but also to pathogenic, tissue-destructive immunity and exacerbation of autoimmune disease. When suppression of autoimmune disease is observed it may be because autoantigen was administered under conditions which minimize induction of pathogenic immunity. Thus, clinical protocols for mucosal autoantigen administration may need to be modified to favor induction of regulatory immunity. In this short review, we discuss recent studies in autoimmune diabetes-prone NOD mice indicating that with novel modifications mucosal autoantigen administration could be harnessed to prevent type 1 diabetes in humans.
17143695 Anticyclic citrullinated peptide antibodies in patients with mixed connective tissue disea 2004 The clinical significance of anticyclic citrullinated peptide (CCP) antibodies in patients with mixed connective tissue disease (MCTD) was assessed. Altogether, 86 sera from MCTD patients, 96 from rheumatoid arthritis (RA) patients, 42 from systemic lupus erythematosus (SLE) patients, 23 from systemic sclerosis (SSc) patients, 21 from polymyositis/dermatomyositis (PM/DM) patients, and 17 from those with Sjögren's syndrome (SjS) were tested for anti-CCP antibodies using an enzyme-lined immunosorbent assay. Among the 96 RA patients, anti-CCP antibodies were detected in 85%, with the frequency being significantly higher than in MCTD, SLE, SSc, PM/DM, and SjS patients (9%, 14%, 13%, 14%, and 18%, respectively; P < 0.001). Among eight MCTD patients who fulfilled the diagnostic criteria for RA, only 50% had anti-CCP antibodies, and the prevalence was significantly lower than for all RA patients (p < 0.01). All eight patients who fulfilled the criteria for RA had overlap of SLE and SSc, except one patient, whereas the four anti-CCP-positive patients who did not fulfill the criteria for RA had SjS without overlapping features of SLE and SSc; moreover, most of their antibody titers were low. These results suggested that anti-CCP antibodies are associated with RA in MCTD patients, but careful diagnosis of RA is required if patients with low titers of anti-CCP antibodies lack overlapping SLE and SSc.
15615187 [Clinical importance of determination of serum amyloid A]. 2004 Jul Serum amyloid A (SAA) is an acute phase first class protein discovered a quarter of the century ago. Its concentration depends on clinical findings of the patient, illness activity and the therapy applied. SAA increases moderately to markedly (100-1000 mg/l) in bacterial and fungal infections, invasive malignant diseases, tissue injuries in the acute myocardial infarction and autoimmune diseases such as rheumatoid arthritis and vasculitis. Mild elevation (10-100 mg/l) is often seen in viral infections, systemic lupus erythematosus and localized inflammation or tissue injuries in cystitis and cerebral infarction. SAA as sensitive, non-invasive parameter is used in organ transplantation where early and correct diagnosis is needed as well as where prompt therapy is required. Besides acute kidney allograft rejection, SAA is used in the diagnosis of rejection after liver transplantation, simultaneous pancreas and kidney transplantation and also in bone marrow transplantation (acute "graft vs. host disease"). Simultaneous determination of C-reactive protein (CRP) and SAA may point to acute kidney allograft rejection. Standard immunosuppressive therapy with cyclosporine A and prednisolone significantly suppresses the acute phase CRP reaction both in operation itself and acute rejection, but not in infection. On the other hand, SAA rejection in operation, acute allograft rejection and infection is present in spite of cyclosporine A and steroids therapy. Different reaction of SAA and CRP in transplant patients to cyclosporine A therapy helps in differentiation between the infection and rejection. Although CRP and SAA are sensitive and acute phase reactants, their serum concentrations cannot be valued as prognostic and diagnostic criteria without creatinine serum concentration and clinical findings. In addition, they offer important information for clinical diagnosis as well as the kind of therapy.
15547876 [Anti-cytokine therapy: present status and future perspectives in nephrology]. 2004 Sep The increasing understanding of the role of cytokines in chronic inflammatory disease, autoimmunity and neoplastic disease has led to a new generation of therapeutic agents, the anti-cytokine blocking agents. In this article, we review current knowledge of two different available approaches: the use of Thalidomide and the anti-cytokine antibody immune therapy. Thalidomide is an immunodulatory and antiangiogenic drug; the most pronounced effect of this drug is the inhibition of tumor necrosis factor-alpha (TNF-alpha ) production. A few years after its withdrawal from the European and Canadian markets due to severe teratogenic effects, the unexpected activity of Thalidomide in reactive lepromatous leprosy stimulated further study. After some confirmatory placebo-controlled trials, multiple researches are now in progress to evaluate the optimal dose of Thalidomide in several autoimmune and neoplastic diseases. Both passive and active immunization can safely, transiently and effectively be used, as documented by animal experimentation and confirmed by clinical trials. Novel anti-cytokine therapeutic compounds, based on passive antibody immunization, are now available to treat rheumatoid arthritis and have been shown to help in Crohn's disease and in several other autoimmune diseases, and to control neoangiogenesis in cancer patients. The durability of the benefit, safety and pharmacoeconomic issues will determine whether this early success will prove to be a major breakthrough in the treatment of these painful and incurable diseases and eventually of other chronic inflammatory conditions in uremic patients.
15241146 Scandinavian Total Ankle Replacement (STAR). 2004 Jul Fifty-eight patients with either rheumatoid arthritis or osteoarthritis were treated with meniscal-bearing ankle prostheses. The concept was to mobilize, align, and stabilize the ankle before resurfacing it. Cement was used for prostheses fixation in 33 patients (1986-1989) and 25 patients had fixation without cement (1990-1995). All patients in one prospective series were followed up yearly with radiographs and with a clinical scoring system giving a maximum of 100 points. This allowed for a patient-controlled prospective study. No patients were lost to followup. The only detectable difference in the treatment was the fixation mode. For the purpose of comparing patients with cemented and uncemented prostheses, the patients who had surgery between 1986 and 1989 were not followed up after 1997, and patients who had surgery between 1990 and 1995 were not followed up after 2002. The mean followup was 9.4 years. Failure was defined as prosthesis revision or change to arthrodesis for any reason. In the cemented group, nine of 33 patients had revision surgery or fusion. In the uncemented group, one of 25 patients had revision surgery. Survivorship analysis for 12 years based on life tables showed a 70% survival rate (confidence limit, 60.3-78.5) for the cemented group and 95.4% survival rate (confidence limit, 91.0-99.9) for the uncemented group. The average clinical scores at the latest followup were 74.2 +/- 19.3 for the cemented group and 91.9 +/- 7.4 points for the uncemented group. Therefore, unconstrained meniscal-bearing ankle prostheses should be uncemented.
15160668 [Brachial plexus neuropathy following open-heart surgery]. 2004 Apr A 64-year-old woman underwent open-heart surgery for repair of atrial septal defect (ASD) and tricuspid valve regurgitation. Preoperative complications included rheumatoid arthritis with pain in both wrists treated with methotrexate. Following smooth endotrachial intubation, a pulmonary arterial (PA) catheter was inserted into the right jugular vein after several attempts. She was placed in a supine position with abduction of the shoulders to approximately 90 degrees and of the elbows to 60 degrees. Operation was performed through sternum splitting to second intercostal space, and the 4-h intraoperative course was uneventful. On the first postoperative day, she complained of inability to raise her right arm. Neurological examination revealed marked weakness of the deltoid and biceps brachialis muscles, and decreased sensitivity around the right shoulder. Iatrogenic brachial plexus injury was diagnosed. Administration of vitamin B12 and physical therapy were instituted. Symptoms improved gradually and had disappeared by 3 months postoperatively. Neuropathy might be attributed to stretch and compression of the brachial plexus caused by traction of the pectoralis minor muscle enhanced by sternotomy and/or malposition of the upper extremity, or direct injury due to cannulation of the PA catheter into the internal jugular vein.
15158740 Laboratory testing in autoimmune rheumatic diseases. 2004 Jun There are a number of pathological conditions in which tissue damage occurs in association with immune activation directed against components of normal tissue. The initial damaging events usually involve cells of the immune system, the T-cells, but the cell damage releases antigens that become targets for an antibody response. The detection and quantification of autoantibodies has become an important component in the diagnosis and management of autoimmune rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus, the systemic vasculitides and systemic sclerosis. Each of these diseases is associated with a particular autoantibody or group of autoantibodies. They are usually detected by their reaction against tissue components using subjective methods such as indirect immunofluorescence. Any positive samples are further analysed using more specific and quantitative methods for the 'quantification' of the specific autoantibody concentration. It is important that these autoantibodies are not considered to be 'gold standard' tests: they are no more than markers of the disease with significant limitations. They are best used as part of a diagnostic panel rather than as a marker indicating one particular disease. Techniques are gradually improving, giving numerical results rather than titres, but a lack of standardization makes these results extremely variable. Many of the markers show no correlation with disease activity. Their use should be restricted to the initial investigation and not repeated every time the patient is followed up. Other markers do, however, correlate with disease activity and can be used to monitor disease. When investigating patients who have symptoms associated with autoimmune rheumatic diseases, analytes such as immunoglobulins, complement components and C-reactive protein may all be measured.
15057267 Interleukin-10 polymorphisms in Spanish type 1 diabetes patients. 2004 Jun The MHC accounts for half of the genetic susceptibility to type 1 diabetes (T1D). Evidence suggests that an imbalance in Th1/Th2 responses may play a key role in the development of autoimmune diabetes. Since interleukin-10 (IL-10) modulates immune and inflammatory responses and has been implicated in many autoimmune diseases, it seemed interesting to examine whether IL-10 polymorphisms participate in diabetes predisposition. In fact, this is the first association study investigating the role of the IL- 10 polymorphisms in susceptibility to T1D in a Caucasian population. Three promoter polymorphisms (-1082G/A, -819C/T, -592C/A) and two CA-repeat microsatellites (IL-10R and IL-10G at -4 and -1.1 kb) were tested in a case-control study with 294 T1D patients and 574 healthy controls. Our results prove a minor role of IL-10 in the autoimmune diabetes risk, although we found the same association trend with IL-10G(*)12 allele as was previously observed for multiple sclerosis and rheumatoid arthritis.
15018020 Evaluating pain in osteoarthritis of the hands: the effect of patient information. 2003 The evaluation of osteoarthritis pain is principally based on a subjective rating scale. Accuracy in recording pain score is obviously important. In the present study we evaluated the effect of better standardization of information given to patients in determining the visual analog scale (VAS) score. Fifty-three consecutive male and female outpatients aged 18-65 years (40 women and 13 men) fulfilling the criteria for osteoarthritis of the hands were included in the study. Eligible patients attended the Rheumatology Center on three occasions: day 1, day 3 and day 6 of the study. Two information cards were prepared. On the first card, given to the patient at the end of the first visit, osteoarthritis of the hands was described as a less dangerous disease than rheumatoid arthritis. On the second card, given to patients at the end of the second visit, greater emphasis was placed on anatomo-pathological description of the destructive lesions. VAS score was recorded on days 1, 3 and 6 of observation. ANOVA for repeated measures demonstrated a significant reduction of VAS score between the first and the second assessment and a significant increase between the second and the third assessment. A further significant difference was found in the comparison between the first and third assessment. These results show that different standards of information given to patients may modify VAS score.
15004446 [Balneotherapy and spa therapy of rheumatic diseases in Turkey: a systematic review]. 2004 Feb AIM: Turkey has a lot of thermal and mineral springs and is looking back on a still vivid tradition of spa therapy and balneotherapy, applied especially for the treatment of rheumatic diseases. This tradition is predominantly empiric and intuitive, however, it has assumed some important aspects of modern balneotherapeutic methods as well. This article is aimed at presenting the characteristics of traditional and modern balneological and spa therapy forms in Turkey. METHOD: The studies which have been conducted between 1990 and 2000 in different spas in Turkey on the efficacy and effectiveness of spa therapy and balneotherapy for rheumatic diseases have been searched and analyzed independent of their design. A descriptive evaluation of the studies was carried out. RESULTS: A total of 15 published studies have been found and analyzed. The investigations have been carried out in 8 different spa resorts in Turkey. In these studies the effectiveness and efficacy of different balneological and spa therapies on a variety of rheumatic diseases (from osteoarthritis to fibromyalgia and from rheumatoid arthritis to low back pain) could be shown. Nearly all studied balneotherapeutic modalities were applied as bathing cures. Only in one study peloid therapy was applied. Balneotherapeutic therapy was applied in a modern and traditional way, and both open and stationary spa therapy forms were used at the same time. CONCLUSIONS: The review has shown the effectiveness of the investigated spa therapy and balneotherapy forms. It could be concluded that nearly all forms of spa therapy and balneotherapy used for the treatment of rheumatic diseases in Turkey are effective. A definitive conclusion, however, is not possible because of the heterogeneity of the study designs, methodological flaws, and the publication bias. In future good quality randomized controlled trials are needed.
14973643 Use of infliximab, an anti-tumor necrosis alpha antibody, for inflammatory dermatoses. 2003 Sep BACKGROUND: Infliximab is a monoclonal antibody against tumor necrosis factor alpha currently approved by the U.S. FDA for the treatment of Crohn's disease and rheumatoid arthritis. Recently, a controlled trial reported its effectiveness for psoriasis. OBJECTIVE: The object of our study was to evaluate the efficacy and safety of infliximab for inflammatory or autoimmune cutaneous disorders. METHODS: A retrospective chart review was performed for patients who received infliximab at the University of Miami, Cedars Medical Center. RESULTS: Patients with various disease, including panniculitis, pityriasis rubra pilaris, eosinophilic fasciitis, discoid lupus erythematosus, and necrobiosis lipoidica diabeticorum, received infliximab infusion at a dose of 5 mg/kg. All patients had refractory disease or adverse effects to previous therapy, which included cyclosporine, systemic steroids, azathioprin, clofazimine, mycophenolate mofetil, acitretin, UVB, and thalidomide. Six out of the seven patients improved after treatment. CONCLUSIONS: Infliximab was well tolerated in most patients and the majority benefited from the use of infliximab.
14639004 [VEGF-receptor inhibitors for anti-angiogenesis]. 2003 Dec Angiogenesis is deeply involved in the progression of major diseases such as cancer, diabetes, and rheumatoid arthritis. Molecular mechanism on angiogenesis was extensively studied, and several signaling systems including VEGF (VEGF-A), angiopoietin, PDGF, and ephrin were shown to be crucial for physiological angiogenesis. Interestingly, among these factors, VEGF appears to play key roles in most of the pathological angiogenesis, and other factors are considered to have additional effects on its development depending on the situation. VEGF binds and activates two tyrosine kinase receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1), and stimulates endothelial cell growth, survival, and vascular permeability. VEGF induces not only tumor angiogenesis but also blood-vessel-dependent metastasis. Based on the importance of VEGF in diseases, many companies and institutes are now trying to generate appropriate small molecules as well as proteins that strongly antagonize the VEGF-VEGFR system. Several molecules quite effective for suppression of tumorigenesis and pathological angiogenesis in animal models are under clinical trials.
12884735 [Detection of anti-early endosome antigen 1 antibody in sera showing cytoplasmic vesicular 2003 Jun An early endosome antigen previously reported by F.T. Mu could be stained on cytoplasmic vesicles of HEp-2 cells. Here, we have investigated autoantibodies against cytoplasmic vesicular antigens, especially against early endosome antigen 1. Twelve sera were selected on the basis of cytoplasmic vesicular staining patterns of HEp-2 cells. Protein-immunoprecipitation using 35S-methionine labeled HeLa lysates, and RNA immunoprecipitation using 32P-labeled HeLa lysates were conducted to characterize the cognate antigens. Nine of 12 sera reacted with proteins in the range of 162-180 kDa, three of which were found to react specifically with the 162 kDa 35S methionine labeled recombinant early endosome antigen 1. These proteins were not associated with common RNA. Although complete clinical information was not available, some of the patients had rheumatoid arthritis(RA). In addition, the RNA-IPP results suggest that other patients included one each with SLE, SSc, polymyositis, and Sjögren's syndrome. Anti-early endosome antigen 1 antibody was found in 25%(3 of 12) of sera known to stain cytoplasmic vesicles. The reactive sera came mostly from patients with RA. The sera was from one case each of clinical-confirmed RA, SLE and Sjögren's syndrome.