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ID PMID Title PublicationDate abstract
11019967 Macrophages synthesize factor X and secrete factor X/Xa-containing prothrombinase activity 2000 Sep Activation of the coagulation cascade, mediated by various monocyte/macrophage procoagulants, is an important component in the pathology of inflammatory disease. The type of procoagulant expressed may vary between different monocyte/macrophage subtypes and may differ depending on how the cells are treated. In the present study we show that both murine peritoneal macrophages and human adherent synovial cells from rheumatoid arthritis lesions express prothrombinase activity that was inhibited by anti-Factor X antibodies. Northern blot analysis showed that Factor X was transcribed by the murine peritoneal cells and Western blot analysis showed the presence of Factor X antigen. Further experiments showed that the prothrombinase activity was secreted by the cells into the medium in a detergent-sensitive form, suggesting that the prothrombinase is released on small lipid-containing vesicles.
10841067 [Rheumatic disorders. Overview]. 2000 Of all rheumatic diseases, osteoarthritis (OA) and rheumatoid arthritis (RA) are the most frequently occurring. Although they differ in pathophysiology and the molecular mechanisms responsible for the destruction of cartilage (since RA is an inflammatory disease and OA is not), there are, however, a certain number of similarities and common pathways in the inflammatory processes of both diseases: mild inflammatory phenomena have been observed during OA, and both interleukin-1 and tumour necrosis factor-alpha seem to play key roles, as in RA. Although there is a dramatic difference between the 2 diseases in the intensity of inflammation, the inflammatory process is responsible for the synthesis of metalloproteinases and free oxygen radicals, and, subsequently, for progressive cartilage destruction. Both OA and RA engender important costs for the healthcare system. Direct costs result from practitioner visits, drug purchase and management, drug-related adverse effects, management or hospital care; indirect costs are linked to progressive functional disability. Although RA leads to significant individual costs, OA is more problematical for the healthcare system, since its prevalence is far higher than that of RA. Thus, rheumatic diseases have become a major public health problem. Optimal therapeutic strategies need to be determined in order to define the most effective procedure for controlling disease symptoms such as pain, stopping or slowing down disease progression and, finally, keeping patients active. But it is of paramount importance that the gain in efficacy be associated with a gain in drug safety.
10568426 Prevalence of joint complaints amongst individuals with Dupuytren's disease--from the Reyk 1999 It has been reported that Dupuytren's disease is very uncommon amongst patients with rheumatoid arthritis (RA). We investigated the prevalence of different joint complaints in a cohort of 1297 males, aged 46-74 years, participating in a prospective longitudinal health survey. Joint complaints were less frequently observed in men with Dupuytren's disease than in those who did not have any signs of this disease. When adjusted for age the Dupuytren's patients had less frequently history of morning stiffness (odds ratio (OR)=0.65; 95% confidence interval (CI)=0.44-0.98, P=0.04), joint swelling (OR=0.52; 95% CI=0.27-1.00, P=0.05), and attendance to doctors due to rheumatic disorders (OR=0.44; 95% CI=0.15-0.86, P=0.02) than those who did not have clinical signs of Dupuytren's disease. Furthermore, these associations were even stronger after adjustment for other potential confounding factors, such as smoking, lipids, diabetes, education, and occupation. The reason for a negative association between Dupuytren's disease and joint complaints is not clear but genetic and immunological factors may be important.
10517484 Measurement of leukocyte rheology in vascular disease: clinical rationale and methodology. 1999 The measurement of leukocyte rheology in vascular disease is a recent development with a wide range of new opportunities. The International Society of Clinical Hemorheology has asked an expert panel to propose guidelines for the investigation of leukocyte rheology in clinical situations. This article first discusses the mechanical, adhesive and related functional properties of leukocytes (especially neutrophils) which influence their circulation, and establishes the rationale for clinically-related measurements of parameters which describe them. It is concluded that quantitation of leukocyte adhesion molecules, and of their endothelial receptors may assist understanding of leukocyte behaviour in vascular disease, along with measurements of flow resistance of leukocytes, free radical production, degranulation and gene expression. For instance, vascular cell adhesion molecule (VCAM-1) is abnormally present on endothelial cells in atherosclerosis, diabetes mellitus and inflammatory conditions. Soluble forms of intercellular adhesion molecule (ICAM-1) or VCAM can be found elevated in the blood of patients with rheumatoid arthritis or infections disease. In the second part of the article, possible technical approaches are presented and possible avenues for leukocyte rheological investigations are discussed.
10415600 Prolactin and neuroimmunomodulation: in vitro and in vivo observations. 1999 Jun 22 Prolactin (PL) is a mammotropic neuropeptide produced by the pituitary and extrapituitary cells existing as several isoforms and belongs to the growth and lactogenic hormone family, which includes growth hormone and placental lactogens. The secretion of pituitary PL is under hypothalamic control. The cytokines IL-1, IL-2, and IL-6 also stimulate production, while IFN-gamma and endothelin-3 are inhibitory. PL exerts its effects via PL receptors (PLr) which exist as three isoforms. PL regulates reproduction, osmoregulation, and behavior and has potent immunomodulatory effects. PL is structurally related to members of the cytokine/hematopoietic family such as erythropoietin, GM-CSF, growth hormone, and IL-2 to IL-7. The PLr is a member of the cytokine/hematopoietic receptor family. Interaction of PL with PLr activates the Jak kinases which phosphorylate latent STAT proteins resulting in the activation of transcription. PL counteracts the effects of corticosteroids by enhancing Th1 cellular responses. Perturbations of PL physiology have significant immunologic effects. Hypoprolactinemia impairs immune function while hyperprolactinemia enhances active systemic lupus erythematosus, Reiter's disease, juvenile and adult rheumatoid arthritis (RA), autoimmune thyroiditis, multiple sclerosis, and cardiac allograft rejection. PL gene polymorphisms have now been shown to be linked to RA. Thus, manipulation of PL may have significant clinical utility. Further study of the relationship of the PL/PLr complex, other hormones, and the immune system will provide further insights into the potential therapeutic utility of this complex in immune diseases.
10030529 Unsafe and potentially safe herbal therapies. 1999 Jan 15 Unsafe and potentially safe herbal therapies are discussed. The use of herbal therapies is on the rise in the United States, but most pharmacists are not adequately prepared educationally to meet patients' requests for information on herbal products. Pharmacists must also cope with an environment in which there is relatively little regulation of herbal therapies by FDA. Many herbs have been identified as unsafe, including borage, calamus, coltsfoot, comfrey, life root, sassafras, chaparral, germander, licorice, and ma huang. Potentially safe herbs include feverfew, garlic, ginkgo, Asian ginseng, saw palmetto, St. John's wort, and valerian. Clinical trials have been used to evaluate feverfew for migraine prevention and rheumatoid arthritis; garlic for hypertension, hyperlipidemia, and infections; ginkgo for circulatory disturbances and dementia; ginseng for fatigue and cancer prevention; and saw palmetto for benign prostatic hyperplasia. Also studied in formal trials have been St. John's wort for depression and valerian for insomnia. The clinical trial results are suggestive of efficacy of some herbal therapies for some conditions. German Commission E, a regulatory body that evaluates the safety and efficacy of herbs on the basis of clinical trials, cases, and other scientific literature, has established indications and dosage recommendations for many herbal therapies. Pharmacists have a responsibility to educate themselves about herbal therapies in order to help patients discern the facts from the fiction, avoid harm, and gain what benefits may be available.
9575969 Chloroquine inhibits proinflammatory cytokine release into human whole blood. 1998 Apr Excessive synthesis and release of proinflammatory cytokines during endotoxemia causes severe pathophysiological derangements and organ failure. Because the lysosomotropic agent chloroquine has been effective in the treatment of diseases associated with increased secretion of proinflammatory cytokines such as malaria or rheumatoid arthritis, this study evaluates the potential effect of chloroquine on endotoxin-induced cytokinemia using human whole blood from healthy volunteers. Chloroquine revealed a dose-dependent inhibitory effect on endotoxin-induced secretion of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 that was associated with reduced cytokine mRNA expression. Moreover, ammonia and methylamine, which react as weak bases like chloroquine, reduced synthesis and secretion of proinflammatory cytokines. These data indicate a potent anti-inflammatory effect of chloroquine on endotoxin-induced synthesis of proinflammatory cytokines that may be due to its weak base effect. Thus chloroquine may be of therapeutic benefit not only, during chronic inflammation but also in diseases that are related to bacteria-induced inflammation.
9258765 CD4+ CD7- T cells: a separate subpopulation of memory T cells? 1997 Jul The CD7 molecule is apparently involved in T cell activation but is absent in a substantial subpopulation of human T cells under physiological and certain pathological conditions. The majority of CD7- T cells expresses TCR alpha/beta and is of CD4+ helper and CD45R0+CD45RA- memory phenotype. After birth, percentages and absolute numbers of circulating CD7- T cells increase significantly during aging. A number of molecules thought to be involved in organ-specific T cell homing are preferentially expressed within the subset of CD4+CD7- T cells. Specific absence of CD7 antigen expression on T cells is observed in a variety of pathologic conditions such as cutaneous T cell lymphoma, HIV infection, rheumatoid arthritis, and kidney transplantation. Current in vitro results suggest that specific downregulation of CD7 antigen expression in T cells reflects a separate and stable differentiation state occurring late in the immune response. Expansion of CD7- T cells in vivo has been found in certain diseases associated with chronically repeated T cell stimulation. The potential pathophysiological significance of this T cell subset in certain human diseases is discussed.
9437493 Gene therapy: panacea or placebo? II. Main applications of gene therapy. 1997 For most disorders the ideal goal of gene therapy is the repair of the mutated gene in the target tissue. However, the techniques required for such an approach are still at an early stage of development. Most current research is directed towards delivery of normal gene sequences in order to generate active protein and compensate for the lack of endogenous production. This approach may be suitable for the treatment of recessive monogenic disorders, but is inappropriate for dominantly inherited disorders. Therefore, gene therapy was originally intended as a most promising approach for the treatment of inborn errors of metabolism. However, apart from the correction of heritable genetic disorders, gene delivery has many potential applications including treatment of malignancies, atherosclerosis and vascular proliferative disorders, rheumatoid arthritis and viral infections. The authors discuss significant examples marking progress in the development of gene therapy for specific diseases, present some hopes and hurdles that have arisen from some recent preclinical and early clinical trials.
9267739 A case of pyoderma gangrenosum stabilized with lymecycline, topical benzoyl peroxide and t 1997 Pyoderma gangrenosum is a chronic inflammatory ulcerative skin disease of unknown etiology, often associated with various systemic disorders such as inflammatory bowel disease, rheumatoid arthritis, chronic active hepatitis, diabetes mellitus and hematologic malignancies. The ulcers are characterized by their undermined violaceous borders. The disease remains a therapeutic challenge. Corticosteroids are the mainstay of therapy; however, side effects from this treatment and recalcitrant pyoderma gangrenosum require therapeutic alternatives. We report the case of a large subacute pyoderma gangrenosum stabilized with lymecycline, topical benzoyl peroxide and successfully treated by an autograft. This observation supports the opinion that the risk of pathergy of a graft can be avoided by the stabilization of the disease.
18475905 Dicyanogold effects on lymphokine production. 1999 Having identified dicyanogold(I) as a common metabolite of gold-based antiarthritis drugs, we are investigating the effects of the compound on the production of lymphokines. Handel, et al. 1 suggested that the transcription factor AP-1, critical to the production of a number of cytokines, might be the target for gold compounds because of a critical cysteine within its DNA binding region. Using Jurkat cells, an established cell line as a model for CD4(+) lymphocytes, we have shown that dicyanogold inhibits the binding of AP-1 to DNA and inhibits the synthesis of IL-2 mRNA and protein. In a macrophage line, THP-1, which synthesizes IL-1beta in response to mitogen, we have shown that dicyanogold inhibits the binding of a second transcription factor, CREB to DNA. Incubation of THP-1 cells with dicyanogold inhibits the production of IL-1beta mRNA. These results suggest that the mechanism of action of gold drugs may be through their interaction with transcription factors necessary for the immune activation seen in Rheumatoid Arthritis.
17039161 Symptoms and functional health status of individuals with Ehlers-Danlos syndrome (EDS). 2001 Oct Ehlers-Danlos syndrome (EDS) is an inherited connective tissue disorder that can have a substantial impact on daily life. The aims of this study were to describe the symptoms reported in a group of individuals with EDS and to investigate the impact on functional health status by means of the Sickness Impact Profile (SIP). Seventy-seven individuals, members of the Swedish EDS Association, completed 2 mailed questionnaires. The most frequent symptoms were related to activity, e.g., joint problems (75%), to pain (71%), and to skin/tissue (52%). Pain was reported by 37 individuals (48%) as their most severe symptom. The SIP results showed an overall mean score of 13.0 (females 13.9, males 5.6), compared with a Swedish reference group with a SIP score 1.3. Women with EDS reported a better functional health status than females with rheumatoid arthritis (overall SIP score 13.9 versus 21.4). In comparison with women with fibromyalgia, the EDS females rated their functional health status as worse on the physical dimension (p <0.05) and the subscale home management (p <0.05), and as better on the subscale work (p <0.05). Impact of EDS on the individual's daily life needs to be acknowledged, assessed, and evaluated in healthcare.
11777106 Beyond unfavorable thinking: the illness cognition questionnaire for chronic diseases. 2001 Dec The literature on chronic diseases recognizes the role of illness cognition as a mediator between stress and illness. Few conceptualizations and instruments, however, give an indication of both unfavorable and favorable ways of adjusting to an uncontrollable long-term stressor, such as a chronic disease. The authors propose 3 generic illness cognitions that reflect different ways of reevaluating the inherently aversive character of a chronic condition: helplessness as a way of emphasizing the aversive meaning of the disease, acceptance as a way to diminish the aversive meaning, and perceived benefits as a way of adding a positive meaning to the disease. A self-report instrument, the Illness Cognition Questionnaire, was developed to assess these cognitions across different chronic diseases. The results support the reliable and valid assessment of these illness cognitions in patients with rheumatoid arthritis and multiple sclerosis and indicate the maladaptive function of helplessness and the adaptive function of acceptance and perceived benefits for the long-term physical and psychological health of patients with a chronic disease.
11677089 Gene therapy in autoimmune disease. 2001 Dec Recent work on gene therapies for autoimmune disease has continued to provide insight into the pathogenesis of autoimmunity. Reliable, effective and targeted gene therapy applications have been achieved by using transduced dendritic cells and antigen-specific T cells as delivery vehicles. Bioluminescence imaging has been implemented to visualize cell trafficking and homing in vivo. As a first step into human gene therapy, a phase I clinical trial for assessing the feasibility and safety of gene transfer has been completed in a group of rheumatoid arthritis patients.
11468410 Expression, purification, crystallization and preliminary X-ray diffraction analysis of th 2001 Aug MRP14 is a protein that is specifically expressed in myeloid and epithelial cells during the stages of acute or chronic inflammatory states such as rheumatoid arthritis or sarcoidosis. MRP14 has EF-hand motifs as Ca(2+)-binding sites and belongs to the S100 family of proteins. This paper deals with the sample preparation (cloning, overexpression and purification), crystallization and preliminary crystallographic analysis of recombinant human MRP14. Crystals of MRP14 were obtained by the hanging-drop vapour-diffusion method. MRP14 crystals belong to space group P2(1), with unit-cell parameters a = 57.59, b = 178.44, c = 61.23 A, beta = 113.17 degrees, and diffract to 2.1 A resolution.
11422223 The pathological consequences of anaemia. 2001 Feb Many patients with chronic diseases such as chronic renal failure, chronic inflammatory bowel disease and rheumatoid arthritis are anaemic. Recently congestive heart failure (CHF) has also been found to be associated with anaemia. In all these diseases this anaemia or chronic disease is at least partially due to excessive production of cytokines and leukotrines that interfere both with the effect of erythropoietin (EPO) at the bone marrow and the release of stored iron in the reticuloendothelial system. Treating this anaemia with subcutaneous EPO and IV iron improves the weakness, fatigue, cachexia, nutritional state, mood, cognitive function and quality of life. In the case of CHF it also improves cardiac function and patient functional class, prevents deterioration of renal function and markedly reduces hospitalization. Very few agents in medicine improve so many aspects of the patient so well and so quickly. Unfortunately (for the suffering patient) this anaemia is often ignored and goes untreated.
11309703 Multiple Myeloma. Diagnostic challenges and standard therapy. 2001 Apr In the diagnosis of multiple myeloma (MM), the clinician must exclude other disorders in which a plasma cell reaction may occur such as rheumatoid arthritis and connective tissue disorders, or metastatic carcinoma where the patient may have osteolytic lesions associated with bone metastases. Patients with smoldering multiple myeloma (SMM) or monoclonal gammopathy of undetermined significance (MGUS) have none of the complicating features of MM and do not require treatment with potentially toxic agents. The plasma cell labeling index can help make a differential diagnosis of MM from SMM. Patients with a high labeling index have a high risk of complications and should be monitored carefully. However, the labeling index can be low in active MM. In addition, SMM or MGUS patients have few or no circulating plasma cells. High-dose chemotherapy and stem cell support prolong overall survival in contrast to conventional therapy. If stem cell transplantation is considered, it is important to harvest the cells before using alkylating agents to obtain a sufficient number of cells. Supportive treatment consists of the occasional use of erythropoietin to maintain adequate hemoglobin levels and adequate hydration to protect renal function. Vaccination against pneumococcal infections and the prophylactic use of antibiotic therapy during the first 2 months of treatment can be beneficial. Recognizing the symptoms of spinal cord compression and initiating dexamethasone therapy promptly to prevent paraplegia are critical.
11200499 Naturally occurring and synthetic inhibitors of NF-kappaB functions. 2000 Aug Nuclear factor (NF)-kappaB is a transcription factor that induces the immunoglobulin kappa chain, cytokines such as interleukin (IL)-1, IL-2, IL-6, IL-8, tumor necrosis factor (TNF)-alpha and interferon gamma, and cell adhesion proteins. It also induces anti-apoptotic proteins, and inhibits TNF-alpha and anticancer drug-induced apoptosis. Therefore, NF-kappaB function inhibitors may be useful as anti-inflammatory and anticancer agents. Microbial products such as panepoxydone, cycloepoxydon and gliotoxin are known to inhibit activation of NF-kappaB. We have designed and synthesized new NF-kappaB inhibitors from the structure of an antibiotic, epoxyquinomicin C. The designed compound, DHM2EQ, inhibited TNF-alpha-induced activation of NF-kappaB and showed a therapeutic effect in mouse rheumatoid arthritis model.
11172703 Nerve growth factor in neurological and non-neurological diseases: basic findings and emer 2001 Jan Nerve growth factor (NGF) is known to be essential for the survival of peripheral and brain neurons, and according to more recent studies also for a variety of cells localized in the immune system. Basic and preclinical findings published in the last 15-20 years have prospected the hypothesis that NGF can be pharmaceutically useful for promoting healing in certain peripheral and central neurological insults. We have recently provided evidence that NGF applied topically, has a therapeutic potentiality for human corneal and pressure ulcers, and more recently in vasculitis induced by rheumatoid arthritis. This review will summarize previous and ongoing evidence supporting the role of NGF in the nervous and immune system and discuss NGF potentiality as a pharmacological tool for basic and clinical studies.
11036380 [Newly discovered human retroviruses. Association with disease is still undetermined]. 2000 Aug 23 Retroviruses are enveloped RNA viruses which can transcribe RNA to DNA and integrate into the chromosomal DNA of their host cell. Heritable integrations give rise to endogenous retroviral sequences (ERVs). The rest is exogenous, infecting from individual to individual. This survey highlights an emerging scenario in human retrovirology. Humans have thousands of distinct ERVs. Although most are damaged by mutations, many are expressed as RNA, a few also as proteins and viral particles. The latter are not known to be infectious. Obviously, human ancestors encountered many different exogenous retroviruses, some of which may still be extant. In fact, an exogenous retrovirus related to ERVs was recently discovered. It is the fifth human exogenous retrovirus, human retrovirus 5 (HRV-5). It succeeds the two human T-lymphotropic viruses (HTLVs) and the two human immunodeficiency viruses (HIVs). The newly discovered endogenous and exogenous human retroviruses are now being investigated for association with disease. There are indications of selective ERV activation in multiple sclerosis, schizophrenia and seminoma. HRV-5 has been associated with rheumatoid arthritis, systemic lupus erythematosus and non-Hodgkin lymphoma. It is not yet known whether these first observations signal a pathogenic role for the newly discovered retroviruses.