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ID PMID Title PublicationDate abstract
10399316 Cyclooxygenase-1 and -2 isoenzymes. 1999 May The cyclooxygenase isoenzymes (COX-1 and -2) catalyze the rate-limiting steps in prostanoid biosynthesis. COX-1 and -2 genes encode two isoenzymes with overlapping yet distinct expression patterns and functions. Physiologically, various extracellular stimuli such as growth factors, cytokines and tumor promoters regulate the expression of COX-1 and -2 genes at both transcriptional and post-transcriptional levels. COX-2 is overexpressed in rheumatoid arthritis, colorectal and breast cancer. Prostanoids produced by the COX pathway signal via plasma membrane-localized, G-protein-coupled receptors as well as via nuclear receptors. Currently, several COX-2-selective inhibitors are developed to control the anti-inflammatory and anti-neoplastic activities of the COX-2 isoenzyme. Inhibition of the COX isoenzyme activity and/or expression may be the basis of future generation of anti-inflammatory and anti-neoplastic drugs.
10091383 Two sister cases of autoimmune hepatitis. 1998 Dec Two sister cases of autoimmune hepatitis are described. Case 1 involved a 49-year-old woman who suffered from bleeding gums and general fatigue. Her laboratory data showed a marked increase in transaminase levels, an elevated IgG level with titers 1:80 or more of both antinuclear and smooth muscle antibodies and thrombocytopenia. Histology of the biopsied liver revealed chronic active hepatitis with a moderate infiltration of mononuclear cells. A complication of idiopathic thrombocytopenic purpura was determined based on higher titers of PA-IgG and a normal bone marrow findings. Case 2 involved a 54-year-old woman, an elder sister of case 1, who suffered from general fatigue with jaundice. Her laboratory data showed a severe damage of liver function and an elevated IgG level with positive antibodies to nuclear and smooth muscle antigen. Histology of the biopsied liver revealed chronic active hepatitis. Both patients were negative to markers of hepatotrophic agents. Under diagnosis of autoimmune hepatitis, they have been treated with prednisone followed by a significant clinical improvement. HLA types of two patients were Bw54-DR4 and DR4. Among 4 other siblings, the eldest sister suffered from rheumatoid arthritis. The occurrence of two sister cases of type-1 autoimmune hepatitis has rarely reported and the fact would support a role of enviromental factors besides genetic factors for the onset of this disease.
10078018 [Synthetic glucocorticoid in the treatment of connective tissue diseases]. 1999 Feb Synthetic glucocorticoids are the most potent anti-inflammatory and immunosuppressive drugs, which have been used for almost 50 years as a core drug for the treatment of connective tissue diseases. The mechanism of action of glucocorticoids as anti-inflammatory or immunosuppressive drug is considered as the repression of inflammatory cytokines, receptors of cytokines, and adhesion molecules. When 60 mg of prednisolone is administered in 3 divided doses, the plasma concentrations are around 20-30 micrograms/dl during the day time, in which condition around 90% of GC receptors are occupied. However, the concentration will decrease almost to 0 microgram/dl in the next early morning. In case of methyl prednisolone pulse therapy, about 40 micrograms/dl of the steroid is present in the next morning. These kinetics are important when we consider the glucocorticoid therapy. In the treatment of connective tissue diseases, the combination of the steroid therapy with the immunosuppressive therapy should always be considered. In diffuse proliferative lupus nephritis, glucocorticoid dosage, started at high level to suppress the clinical activity of SLE, decrease rather rapidly while cytotoxic drugs are administered at least for 2 years. In the treatment of systemic sclerosis, normotensive scleroderma kidney is treated with moderate dose of glucocorticoid and cytotoxic drugs. It is our clinical impression that low dose glucocorticoid is quite effective in the treatment of rheumatoid arthritis. However, low dose glucocorticoid therapy is effective for the patient's sense of well-being, but is scarsely effective for the articular symptoms itself and shows intense rebound phenomenon when glucocorticoid is withdrawn.
9973470 Intranasally induced immunological tolerance is determined by characteristics of the drain 1999 Feb 15 Mucosal tolerance is a naturally occurring immunological phenomenon that prevents harmful inflammatory responses to ingested or inhaled environmental, predominantly nondangerous, Ags. The nasal mucosa is an extremely efficient compartment in the induction of immunological tolerance which can be exploited in Ag-specific treatment of autoimmune disease. With the use of a model Ag (OVA) and an Ag implicated in the autoimmune disease rheumatoid arthritis (human cartilage gp-39), we here show in a mouse model that the superficial cervical and internal jugular lymph nodes that drain the nasal mucosa are instrumental in the induction of tolerance. Removal of these lymph nodes abrogates tolerance induction, which can be restored by transplantation of superficial cervical lymph nodes, but not of peripheral lymph nodes. The results indicate that lymph nodes that directly drain the nasal mucosa constitute a unique microenvironment which favors the induction of immunological tolerance.
9858447 Multiple cerebellar infarction due to vertebral artery obstruction and bulbar symptoms ass 1998 Dec Ankylosing spondylitis (AS) results in disease-specific inflammation at the site of ligamentous insertion into the bone. Atlantoaxial joint subluxation and vertical subluxation of the axis may occur as a consequence of instability resulting from the inflammatory process. Spontaneous anterior atlantoaxial subluxation is a well recognized complication in about 2% of patients with AS, and presents with or without signs of spinal cord compression. Vertical subluxation may follow anterior or posterior subluxation. It was noted in 3-8% of patients with rheumatoid arthritis, but is an exceedingly rare complication of AS. Moreover, it has never been reported that multiple cerebellar infarction and bulbar symptoms developed spontaneously due to atlanto-occipital subluxation and vertical subluxation in a patient with a long [corrected] history of AS. We describe a man with AS who developed multiple cerebellar infarction due to vertebral artery obstruction and bulbar symptoms associated with atlanto-occipital subluxation and vertical subluxation.
9726322 An oblong revision cup for large acetabular defects: design rationale and two- to seven-ye 1998 Aug Loosening and migration of acetabular components often lead to extensive bony defects with an elongated, oval acetabular cavity. In these cases standard implants will not reestablish and maintain sufficient stability without leaving bone defects or using massive bone grafts or excess cement and additional metal rings or shells, disadvantages that are overcome by using an oblong revision cup without cement. The titanium shell is available in different sizes, is screwed to the autochthonous acetabular bone and houses an oblong polyethylene inlay, designed to reestablish the normal anatomic hip center. Of 109 consecutive revision cups, 102, implanted for American Academy of Orthopaedic Surgeons (AAOS) defects types I-IV, were followed up clinically and radiologically for 2 to 7 years (mean, 3.6 years). Primary stability was achieved in all cases. In 40% no bone grafting was necessary at all. The radiological follow-up revealed good remodeling of the surrounding bone and osseointegration of the implants. Zonal radiolucent lines, always smaller than 2 mm, were seen in 18 cases, only once completely and in only 5 cases partially progressing. Six cups migrated slightly (< or =2 mm), two moderately (3-5 mm), all without clinical symptoms, and two more than 5 mm. Migration and radiolucencies were mainly seen in patients with allografts and major defects, which indicates that bone ingrowth appears more unlikely in such cases. Few asymptomatic cases showed zonal sclerotic lines. There were two aseptic loosenings, one in a case with pelvic discontinuity, the other in a patient with severe rheumatoid arthritis following two previous revisions. Survivorship analysis based on implant removal because of aseptic loosening as the endpoint shows a cumulative success rate of 98.1% at 8 years.
9679211 Risedronate. 1998 Jul Risedronate is a pyridinyl bisphosphonate that can be administered orally in lower dosages than other antiresorptive bisphosphonates. Like others of its class risedronate inhibits osteoclast-mediated bone resorption. In experimental models of osteoporosis, risedronate inhibited bone loss and improved trabecular architecture. In patients with Paget's disease, pain diminished or disappeared and serum alkaline phosphatase levels decreased after treatment with oral risedronate 30 mg/day for < or = 3 months. Risedronate 30 mg/day orally for 2 months significantly reduced pain, whereas etidronate 400 mg/day orally for 6 months tended to reduce pain, in a randomised double-blind trial of patients with Paget's disease. Oral risedronate 5 mg/day for < or = 2 years increased bone mass in postmenopausal women with low or normal bone mass. Risedronate 2.5 mg/day prevented bone loss in postmenopausal women treated with glucocorticoids for rheumatoid arthritis. The incidence of gastrointestinal or other adverse events was similar in patients treated with risedronate or placebo in clinical trials.
9442367 Non-steroidal anti-inflammatory drug-induced renal failure: a brief review of the role of 1998 Jan Non-steroidal anti-inflammatory drugs are efficacious treatments for rheumatoid arthritis and osteoarthritis. However, an adverse effect of treatment with non-steroidal anti-inflammatory drugs is acute renal failure, particularly in a subset of patients that are in a state of effective volume depletion. The frequency of this side-effect in the general treated population is not known, but is probably less than 1% per year. Non-steroidal anti-inflammatory drugs act by inhibiting the synthesis of prostaglandins, which are important mediators of renal function. In the volume-depleted state prostaglandins may counter the vasoconstriction associated with the activation of the renin-angiotensin system. Cyclooxygenase is the rate-limiting enzyme involved in the synthesis of prostaglandins. Cyclooxygenase exists in two forms: a constitutive form (cyclooxygenase-1) and an inducible form (cyclooxygenase-2), which is associated with inflammation. Non-steroidal anti-inflammatory drugs are non-specific inhibitors of both forms of cyclooxygenase. New data are emerging regarding the role of cyclooxygenase-2 in the control of renal function. In normal rat and dog kidney, cyclooxygenase-2 is sparsely expressed in the macula densa, but expression is upregulated when animals are volume depleted. This review explores the possible role of cyclooxygenase-2 in the maintenance of normal renal function in volume depleted states.
9372757 How outcome studies have changed total hip arthroplasty practices in Sweden. 1997 Nov The Swedish Hip Registry has defined the epidemiology of total hip replacement in Sweden. Most hip implants are fully cemented. Serious complications and rates of revision associated with total hip replacement have declined significantly despite an increasing number of patients at risk. During the past 5 years only 9% to 10% of hip replacement procedures are revision procedures. Aseptic loosening with or without osteolysis is the major problem and constitutes 73% of the revisions, but the incidence has decreased four times during the past 15 years to less than 3% at 10 years. Even septic complications can be prevented effectively. Demographics are important because male gender and young age increase the risk for revision because of aseptic loosening. Young female patients with rheumatoid arthritis and male patients with a previous hip fracture have five times higher revision rates than elderly patients. The quality of the surgical technique is the most important factor for reducing the risk for revision because of aseptic loosening, but choice of implant is also important. The variations among hospitals in type of surgical technique used is big enough to cause a 100% difference in revision rate for aseptic loosening. Total hip replacement practice in Sweden has improved based on information from this Registry about individualized patient risks, implant safety, and the efficacy of improving surgical and cementing techniques.
9348670 Cell biology of autoimmune diseases. 1998 Autoimmune diseases such as insulin-dependent diabetes mellitus, rheumatoid arthritis, and multiple sclerosis are common in the western world and are often devastating diseases which pose serious health problems. The key feature of such diseases is the development and persistence of inflammatory processes in the apparent absence of pathogens, leading to chronic breakdown of selected tissues. To date, no comprehensive explanation can be given for the onset or persistence of autoimmunity. As a rule, the chronic activation of helper T lymphocytes reactive against self proteins appears to be crucial for fueling the destructive autoimmune process, but why this occurs remains to be established. In this review, we present an overview on the rules that govern activation of T lymphocytes and on the factors that control it. The contribution of both genetic and environmental factors are discussed, clarifying that most autoimmune disease are of multifactorial origin. Special emphasis is given to the contribution of infectious events and the role of stress proteins in the process. In attempts to dissect the mechanisms involved in autoimmunity and to develop ways of blocking disease, experimental animal models are widely employed. We describe the various experimental models that exist for the study of multiple sclerosis, diabetes, and other autoimmune diseases and on the experience that has been gained in such models with experimental therapies to block the activation of self-reactive T lymphocytes. The lessons that can be drawn from these studies provide hope that continued efforts will lead to the successful development of antigen-specific strategies which block the development of autoimmunity also in humans.
9374252 Graft survival and risk factors of penetrating keratoplasty for microbial keratitis. 1997 Aug PURPOSE: To evaluate graft survival rates and prognostic factors in relation to penetrating keratoplasty for microbial keratitis. METHODS: The records of 95 patients treated with penetrating keratoplasty for microbial keratitis during a twenty-year period were reviewed. Data were analysed by construction of survival curves using the Kaplan-Meier non parametric method. RESULTS: The overall survival of a clear cornea was 72% after one year, 71% after two years and 52% after five years. A significantly lower survival rate (p<0.05) was found in the presence of preoperative local risk factors such as wear of contact lenses and trauma and in inflamed eyes. In contrast, systemic diseases like diabetes, cancer or rheumatoid arthritis did not affect survival and neither did recipient age nor the degree of vascularization of the eye. Male donor buttons showed superior survival compared to female ones (p < 0.05), while females seemed to constitute the best recipients. Recurrence rates of microbial keratitis postoperatively were 11%, 16% and 24% after one, two and five years, respectively. Corresponding graft rejection rates were 9%, 15% and 27%. CONCLUSIONS: Patients suffering from microbial keratitis have a relatively high risk of graft failure. To improve the prognosis care should be taken to minimize local risk factors. Surgery should whenever possible be performed on quiet eyes. The unexpected finding of a better prognosis for male donor buttons might suggest the preferred use of male donors in patients suffering from microbial keratitis, but the observation needs further documentation.
19078169 Molecular biology and immunology for clinicians DNA polymerase and the polymerase chain re 1997 Jun By using enzymes that underlie the molecular mechanisms of normal cell function, scientists have advanced the molecular biology of research and diagnostic testing. Normal cells divide and in so doing must accurately replicate their DNA; one of the enzymes crucial in making exact copies of DNA is DNA polymerase, which is at the heart of the polymerase chain reaction. This technique allows one to make billions or trillions of copies from a single molecule of DNA in a few hours, levels of DNA easily detectable by techniques described earlier in this series. The polymerase chain reaction can be used for clinical testing, e.g., identification of DNA derived from a micro-organism. Also, one can clone DNA in large quantities and then determine the specific nucleotide sequences. This then allows one to study the DNA of certain proteins in individuals with a specific disease process and how these DNA sequences differ from those in unaffected people. With this new technology, we can identify the following: variant collagens that underlie familial osteoarthritis; the presence of the DNA of micro-organisms, such as Ureaplasma and Chlamydia, at the site of inflammatory joint diseases, establishing the infectious nature of the synovitis; different human leukocyte antigen (HLA)-B27 alleles that predispose patients to the development of the seronegative spondylarthropathies; and characteristics of different HLA class II molecules that may yield insights into antigen presentation and its role in the pathogenesis of rheumatoid arthritis.
15992047 The therapeutic utility of Interleukin-11 in the treatment of inflammatory disease. 1998 Sep Interleukin-11 (IL-11) is a pleiotropic cytokine that exhibits anti-inflammatory and mucosal protective effects in a variety of animal models of acute and chronic inflammation, such as mucositis, inflammatory bowel disease and autoimmune joint disease. This reduction in inflammation and epithelial damage is mediated in part through effects of recombinant human (rh) IL-11 on macrophage effector function and epithelial cell growth. In vitro studies indicate that rhIL-11 inhibits tumour necrosis factor (TNF)-alpha, IL-1beta, IL-12, IL-6, and nitric oxide production from activated macrophages. Analysis of the effects of rhIL-11 on transcription factors that activate pro-inflammatory cytokines demonstrate that the level of induced nuclear factor kappa B (NF-kappaB) binding activity in the nucleus of rhIL-11-treated peritoneal macrophages is significantly reduced. Studies of normal intestinal epithelial cells indicate that rhIL-11 reduces the rate of cellular proliferation. Analysis of cell-cycle progression demonstrates that growth inhibition of epithelial cells by rhIL-11 correlates with delayed entry into S phase and suppression of pRB phosphorylation. IL-11 also protects intestinal crypt stem cells from radiation- or chemotherapy-induced insults. Such immunomodulatory and epithelial activities may contribute to the protective effects of this cytokine and support the clinical utility of rhIL-11 in the treatment of mucositis, as well as a variety of chronic inflammatory diseases, such as Crohn's disease and rheumatoid arthritis.
12146060 [Towards non-viral gene therapy]. 2001 In vivo gene transfer might be useful for gene therapy application such as cancer or therapeutic neoangiogenesis. Non-viral gene therapy, which uses plasmid DNA as expression vector, presents several advantages. In particular, plasmids are more simple to develop than viral vectors, and they are not immunogenic. We have improved the safety and efficiency of non viral gene therapy by optimizing plasmid backbone and developing new gene delivery technologies. Backbone optimized minicircles are gene expression vectors of minimal size, which are devoid of bacterial origin of replication and of antibiotic resistance gene. Triple helix affinity chromatography allows rapid obtention of highly purified plasmid preparation, with minimal contamination by endotoxins and bacterial chromosomal linear DNA. Electrotransfer is a physical gene delivery technique with leads to high transgene expression in muscle and tumors after direct intratissular injection. In skeletal muscle, plasmid DNA electrotransfer leads to sustained protein production, for more than 18 months, and the transgene products can be released in the circulation. Preclinical evidence suggests that this technology might be useful for the treatment of hemophilia, beta-thalassemia, rheumatoid arthritis, or metabolic disorders. Finally, chemical DNA delivery vectors might prove useful for the targeting of disseminated metastasis.
11763520 [DNA-abzymes and their clinical significance in systemic lupus erythematosis]. 2001 AIM: To evaluate occurrence of DNA-abzymes with catalytic (DNA-hydrolysing) and cytotoxic properties in patients with systemic lupus erythematosus (SLE) for examination of clinical value of DNA-abzymes in diagnosis of autoimmune syndrome and apoptosis level in different variants of immunopathology. MATERIAL AND METHODS: The study group consisted of patients with verified SLE diagnosis (n = 120). They were compared to 72 patients with rheumatoid arthritis (RA), 82 patients with scleroderma systematica (SS), 60 patients with discoid lupus erythematosus (DLE), 88 patients with focal scleroderma (FS) and 198 autoimmune uveitis (AU) patients. 128 donors served control. Catalytic and cytotoxic activity of DNA-abzymes were determined by methods of molecular biology and enzymology. All the patients were examined for blood levels of IgG, IgM and IgA, anti-DNA, anti-Sm and other IgG-autoantibodies, CIC titers, phagocyting activity, content of main D-cell subpopulations. Key immunoregulatory indices were also estimated. RESULTS: DNA-abzymes were detected more often in SLE and RA patients. In SLE, catalytic and cytotoxic activities of DNA-abzymes reached their maximum. There was a correlation with leading clinicoimmunological signs of SLE. The disease was most severe with apparent immunopathology in patients with maximal catalytic and cytotoxic activity of DNA-abzymes. With lowering cytotoxic activity of DNA-abzymes more patients demonstrate low SLE activity without severe organic lesions and alleviated symptoms of immunopathology. CONCLUSION: An important role of DNA-abzymes in pathogenesis of SLE is shown. They are also valuable tools in diagnosis of various clinicoimmunological variants of the disease.
11734496 A cyclooxygenase-2 inhibitor impairs ligament healing in the rat. 2001 Nov Celecoxib was the first of a new class of nonsteroidal antiinflammatory drugs, the cyclooxygenase-2 (COX-2) specific inhibitors, marketed as having the same antiinflammatory efficacy as other nonsteroidal antiinflammatory drugs without their increased risk of gastrointestinal ulceration. Among the widest uses of nonsteroidal antiinflammatory drugs is in the treatment of acute soft tissue injuries. Although the benefits of celecoxib have been shown when used for rheumatoid arthritis and osteoarthritis, we are unaware of any studies concerning its effect on soft tissues. We used the surgically incised medial collateral ligament of male Sprague-Dawley rats as an experimental model for acute ligament injuries to investigate the effects of celecoxib on ligament healing. Fifty rats underwent surgical transection of the right medial collateral ligament. Postoperatively, half were given celecoxib for the first 6 days of recovery, the other half were not. The animals were sacrificed 14 days after the operation, and both the injured and uninjured medial collateral ligaments were mechanically tested to failure in tension. Celecoxib-treated/injured ligaments were found to have a 32% lower load to failure than untreated/injured ligaments. The results of this study do not support use of cyclooxygenase-2 specific inhibitors in the treatment of ligament injuries.
11717807 Lck inhibitors as a therapeutic approach to autoimmune disease and transplant rejection. 2001 Sep T-cells play an important role in the pathogenesis of many diseases. These include diseases with large commercial markets and also with significant unmet medical needs, such as rheumatoid arthritis and asthma in addition to those with smaller markets such as organ transplantation, multiple sclerosis, inflammatory bowel diseases, type 1 diabetes, systemic lupus erythematosus and psoriasis. The use of currently available immunomodulatory agents is often limited by the appearance of dose-limiting side effects that result from the actions of these agents on non-lymphoid tissues. LSTRA cell kinase (lck), one of eight known members of the human src family of non-transmembrane protein tyrosine kinases, has a pivotal role in T-cell signaling. Lck expression is restricted to lymphoid cells, so an lck-selective inhibitor would be expected to have a significantly improved safety profile for the treatment of T-cell-driven diseases.
11677661 Proximal interphalangeal joint surface replacement arthroplasty. 2001 Jul A consecutive series of 20 joints in 13 patients underwent arthroplasty with the RMS PIP joint surface replacement implant. Twelve joints were treated for painful osteoarthritis (all females). Two joints were implanted for rheumatoid arthritis, two for post-traumatic pain and stiffness, two for post-traumatic stiffness and one each for post-traumatic pain and pain-free post-traumatic instability. Excellent, often total long-term pain relief was obtained in 18 joints. The other two patients with (compensible work-related) post-traumatic pain and stiffness reported "50-70% pain reduction". No patients lost movement and 14 out of 20 joints were pain-free with a 73.1 degrees average arc of motion. Six joints from the first half of the series had poor motion (average arc of 19.6 degrees ), even after open extensor tenolysis or manipulation under anaesthesia. As experience was gained, reliably better results were achieved with a more intensive regimen of hand therapy, particularly within the first post-operative week.
11571098 Cumulative duration of breast-feeding influences cortisol levels in postmenopausal women. 2001 Sep Cortisol levels dramatically increase during pregnancy, peak at birth, and subsequently decline. However, all previous studies examined women during pregnancy and early postpartum. None examined the long-term association of parity and lactation with cortisol levels. We examined the relation of reproductive history to cortisol levels in postmenopausal women. Subjects were 749 women, aged 50-89, who were not using estrogen in 1984-1987 when morning cortisol was measured. Parity was not significantly associated with cortisol. However, women who breast-fed for >12 months had significantly higher cortisol levels than women who breast-fed for shorter durations or not at all (p = 0.003). This association was stronger among women with three or more births. Duration of breast-feeding is a determinant of cortisol levels in postmenopausal women. Because both increased cortisol and increased duration of breast-feeding may play protective roles in certain autoimmune diseases, such as rheumatoid arthritis, we suggest that the beneficial effect of lactation on the course of these diseases may be mediated by cortisol.
11536154 Inhibition of tumor necrosis factor reduces the severity of virus-specific lung immunopath 2001 Sep TNF antagonists are effective treatments for rheumatoid arthritis and Crohn's disease, and have been tried with variable success in other diseases caused by immune damage. To test the hypothesis that viral lung diseases caused by respiratory syncytial virus or influenza virus are partly due to overproduction of TNF, we used anti-TNF antibody to treat mice with lung disease caused by these viruses. TNF depletion reduced pulmonary recruitment of inflammatory cells, cytokine production by T cells and the severity of illness without preventing virus clearance. These broad beneficial effects suggest that TNF antagonists might be tested as treatments of human viral lung diseases.