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ID PMID Title PublicationDate abstract
9077528 Studies on the contribution of c-fos/AP-1 to arthritic joint destruction. 1997 Mar 15 Features characteristic to rheumatoid joint destruction, including synovial overgrowth and bone resorption, are experimentally produced by augmenting c-fos gene expression. We tested here if arthritic joint destruction was inhibited upon inactivation of the c-fos/AP-1 signal by administering short double-stranded AP-1 DNA oligonucleotides into mice with collagen-induced arthritis to compete for the binding of AP-1 in vivo at the promoter binding site. Arthritic joint destruction was inhibited in a sequence-specific and dose-dependent manner by oligonucleotides containing the AP-1 sequence. The oligonucleotides inhibited gene expression at the transcriptional level. Nucleotide sequences besides AP-1 also appeared to be important structurally for binding of AP-1 onto DNA and for the stability of oligonucleotides against nucleases. Immunohistochemical chase experiment administering biotinylated oligonucleotides into arthritic mice showed that AP-1 oligonucleotides reached the inflamed joint. Thus, activation of c-fos/AP-1 appears essentially important in arthritic joint destruction.
11741347 Molecular cloning, expression and characterization of the Canis familiaris interleukin-4. 2001 Nov 7 Interleukin 4 (IL-4) is an important regulatory cytokine produced by activated T lymphocytes and mast cells, and regulates the growth and differentiation of cells such as B and T lymphocytes. The rapid amplification of cDNA ends (RACE) was used to clone the canine IL-4 gene. It was expressed in mammalian cells and Escherichia coli. Monoclonal antibodies were raised to rcIL-4 for use in an enzyme-linked immunosorbent assay (ELISA). This will facilitate studies on the role of cIL-4 in inflammatory diseases, particularly rheumatoid arthritis.
11506294 Angiogenesis factors. 2001 Jul Angiogenesis is a recent highlight in the medical field; the developmental process and pathological conditions for various diseases can be understood from the novel aspect of "angiogenesis". Many angiogenesis-related factors are involved in the development of vessels during embryogenesis (vasculogenesis), as well as the induction of new vessels in response to physiological or pathological stimuli. In particular, the appearance of hemangioblasts, precursor cells for vascular endothelial cells and blood cells, and blood islands are expected to play a "prelude" role in tubulogenesis. Gene knock out mice of vascular endothelial growth factor (VEGF)/VEGF receptor, ephrin-B2, and angiopoietin-1 results in a failure of normal vessels production. Dormant factors derived from proteolytic cleavage of various physiological substrates are expected to balance a homeostasis of "angiogenic states" in the host. Furthermore, angiogenesis under various pathological conditions of malignant tumors, ocular diseases, psoriasis, rheumatoid arthritis, atherosclerosis and other diseases is associated with complex angiogenesis networks, suggesting pleiotropic mechanisms for angiogenesis.
24383633 Quantification of bone volume on radiographs using NIH Image. 2000 Dec Abstract We attempted to quantify periarticular bone atrophy from radiographs of the proximal phalanx in patients with rheumatoid arthritis (RA) by means of the National Institutes of Health (NIH) Image computer program. The degree of brightness or darkness in four squares, each 20 × 20 pixels, in the right third proximal phalanx was measured using NIH Image, and the mean value of the 400 pixels was defined as the brightness/darkness index (BDI). The BDI was used to express bone volume. The BDI value was set at zero for an area of complete darkness and at 255 for an area of maximum brightness. The mean coefficient of variation in our hospital was 2.28%. The BDI was measured in 54 RA patients and 146 normal volunteers. The mean BDI at the midpoint of the diaphysis was 100 in RA patients and 176 in normal volunteers, while at the medial side of the proximal end it was 75 and 145, respectively. The difference between normal volunteers and RA patients was greatest in younger people. In some young RA patients, the BDI was significantly low at the medial side of the proximal end, clearly demonstrating periarticular bone atrophy. Periarticular bone atrophy can be quantified using the NIH Image computer program.
10984137 Atypical methotrexate dermatitis and vasculitis in a patient with ankylosing spondylitis. 2000 Reports of histologically proven low-dose methotrexate (MTX)-induced vasculitis are uncommon and mostly found for patients with rheumatoid arthritis. Herein we present a patient with ankylosing spondylitis who developed large atypical erythematopurpuric cutaneous lesions after the second oral dose of 7.5 mg MTX therapy. The histological findings of a cutaneous lesion were consistent with vasculitis. The skin lesions regressed significantly after the discontinuation of MTX therapy. As the clinical picture of the patient's rheumatological condition became progressively severe, prednisolone therapy was initiated 8 days later and the skin rash resolved completely in a couple of weeks.
10818396 Maternal hypothalamic-pituitary-adrenal axis in pregnancy and the postpartum period. Postp 2000 During pregnancy, placenta-derived CRH increases exponentially in the plasma. Circulating levels of CRH-binding protein decrease considerably in the last trimester of pregnancy, resulting in further elevation of bioavailable plasma CRH. The adrenal glands during pregnancy gradually become hypertrophic because of the increase in ACTH, which parallels that of CRH. Thus, pregnancy is a transient period of relative hypercortisolism. The activation of the hypothalamic-pituitary-adrenal axis during pregnancy has been proposed to function as a biological clock. In this model, the placenta is perceived as a stress-sensitive organ and placental CRH as a timing starter, determining a preterm, term, or postterm labor. During pregnancy, as well as during the immediate postpartum period, the hypothalamic maternal CRH secretion is suppressed, because of the circulating levels of cortisol. Hypothalamic CRH secretion normalizes within 12 weeks. This transient postpartum maternal hypothalamic CRH suppression, together with the steroid withdrawal that follows parturition, might be causally related to the mood disorders and the vulnerability to autoimmune diseases such as thyroiditis or rheumatoid arthritis often observed during the postpartum period.
10658877 Pelvic stress fracture: assessment and risk factors. 2000 Jan OBJECTIVE: To discuss the case of a patient with a pelvic stress fracture and the differential considerations among patients presenting with hip and/or groin pain. FEATURES: A 42-year-old woman had hip pain after running. Initial radiograph of the pelvis was negative. Subsequent films showed a right inferior pubic ramus stress fracture. Stress fractures of the pelvis are relatively uncommon, accounting for only 1% to 2% of all stress fractures. INTERVENTION AND OUTCOME: Treatment included high-velocity, low-amplitude chiropractic manipulation, ultrasound, and stretching of the psoas and piriformis muscles. After 8 weeks, care was discontinued because the patient's hip pain had resolved. The pelvic fracture was left to heal with time. After 1 year, the patient still had delayed union of the fracture. CONCLUSION: When predisposing factors are present, such as osteoporosis and rheumatoid arthritis, pelvic stress fracture should be suspected in patients with groin or hip-area pain. However, because pelvic stress fractures are relatively rare, radiographic studies are often postponed, making diagnosis difficult.
10648941 Infrared photodetection for the in vivo localisation of phage-derived antibodies directed 1999 Dec 10 Angiogenesis, the formation of new blood vessels from pre-existing ones, is a characteristic process which underlies many diseases, including cancer, rheumatoid arthritis and blinding ocular disorders. Antibodies capable of selective targeting and occlusion of neovasculature would open diagnostic and therapeutic opportunities. We have recently demonstrated that phage-derived human antibody fragments with high affinity for the extra-domain B (ED-B) of fibronectin, a marker of angiogenesis, selectively localise in new-forming blood vessels upon intravenous injection. Here, we show that infrared fluorescence methodologies nicely complement radioactive techniques for the study of the antibody-mediated targeting of angiogenesis in a variety of animal models. Methods are presented for the construction and use of infrared fluorescence imagers, as well as for the production and characterisation of recombinant antibodies labeled with infrared fluorophores.
10611674 The genetics of complex diseases. 1999 Dec Genetic factors influence virtually every human disorder, determining disease susceptibility or resistance and interactions with environmental factors. Our recent successes in the genetic mapping and identification of the molecular basis of mendelian traits have been remarkable. Now, attention is rapidly shifting to more-complex, and more-prevalent, genetic disorders and traits that involve multiple genes and environmental effects, such as cardiovascular disease, diabetes, rheumatoid arthritis and schizophrenia. Rather than being due to specific and relatively rare mutations, complex diseases and traits result principally from genetic variation that is relatively common in the general population. Unfortunately, despite extensive efforts by many groups, only a few genetic regions and genes involved in complex diseases have been identified. Completion of the human genome sequence will be a seminal accomplishment, but it will not provide an immediate solution to the genetics of complex traits.
10509074 Non-surgical treatment of purulent pericarditis, due to non-encapsulated Haemophilus influ 1999 Sep A 59-year-old woman suffering from rheumatoid arthritis was admitted with pleural empyema and pericarditis due to non-encapsulated H. influenzae, and developed signs of cardiac tamponade. Purulent pericarditis resolved after ultrasound-guided percutaneous aspiration and systemic antimicrobial therapy. Serial echocardiographic examinations showed a slowly vanishing effusion. Long term follow-up revealed no evidence of pericardial constriction. This case illustrates that life-threatening purulent pericarditis in an immunocompromised patient may respond well to non-surgical treatment.
10234081 Subcutaneous phaeohyphomycosis caused by Phaeoacremonium rubrigenum in an immunosuppressed 1999 BACKGROUND: Phaeohyphomycosis refers to infection by dematiaceous fungi with pigmented hyphae or yeast-like cells in the tissue. In humans, this disease is usually considered to be an opportunistic infection. The causal agents of phaeohyphomycosis include numerous species belonging to different genera and they are increasing as a result of the development of intensive medical therapy. OBSERVATION: We report the case of a 61-year-old Japanese female under corticosteroid treatment for malignant rheumatoid arthritis. An asymptomatic subcutaneous tumor developed on the back of her left foot. Histological examination of the excised material revealed mixed cell granuloma (H&E) and the presence of branched hyphal elements (periodic acid-Schiff). A fungus grown in pure culture was identified as Phaeoacremonium rubrigenum. CONCLUSION: The hyphomycete genus, Phaeoacremonium, was proposed in 1996 by Crous et al. Three species belonging to this genus have been isolated from clinical specimens: P. inflatipes, from a human toenail, human synovial fluid and human mycetoma of the foot, P. parasiticum, from a subcutaneous lesion on a kidney transplant patient and several other sources, and P. rubrigenum, from a human patient with pneumonia. To our knowledge, however, this is the first report of phaeohyphomycosis caused by Phaeoacremonium rubrigenum.
9689839 Familial Mediterranean fever in two Italian brothers. 1998 Jun Familial Mediterranean fever (FMF) is an autosomal recessive disease of unknown etiology, characterized by recurrent self limited episodes of fever and polyserositis. Some patients develop generalized amyloidosis, which can be fatal. Colchicine therapy modifies the natural history of the disease by decreasing the attack frequency and preventing amyloid deposition. The disease is common among Sephardic Jews, Arabs, Armenians and has also been sporadically found in other ethnic groups of Mediterranean origin. We report two cases of FMF in brothers living in Abruzzo, Italy. They were born from consanguineous parents and complained typical symptoms since childhood. The boy suffered from one febrile attack every week; he presented three episodes of acute scrotum at age 8 and 9. The elder sister showed a spontaneous partial relief during adolescence. Juvenile rheumatoid arthritis was suspected and Aspirin was used for many years without any clinical improvement. Treatment with colchicine 1 mg/day was established at age 13 and 17 respectively, and a sudden reduction of frequency of attacks was obtained. A gingival biopsy did not show amyloid. The three elder brothers are, at present, in good health. Our experience point out the diagnostic difficulties of FMF especially in a country where the disease is uncommon.
9631755 Tuberculous spondylitis as a cause of inflammatory spinal pain: a report of 4 cases. 1998 May Patients are said to have inflammatory spinal pain if they fulfill at presentation 4 of the following 5 criteria: duration of spinal discomfort for at least 3 months, spinal morning stiffness, age less than 40, insidious onset of symptoms, and no relief from pain with rest, but improvement with exercise. Inflammatory spinal pain is typical of the spondylarthropathies. Only in a minority of the cases it is found in other rheumatic disorders such as rheumatoid arthritis, fibromyalgia or infectious spondyilitis. Tuberculous spondylitis is rarely mentioned as a possible cause of inflammatory spinal pain. We describe 4 patients with tuberculous spondylitis seen over a 3-year period who met the clinical criteria for inflammatory spinal pain at presentation. We conclude that inflammatory spinal pain may be a presenting feature, albeit rare, of tuberculous spondylitis. Awareness of this finding should help facilitate the proper diagnosis and the institution of appropriate therapy.
9402857 Cryptic T-cell epitopes and their role in the pathogenesis of autoimmune diseases. 1997 Nov Immune recognition of self-proteins features prominently in the early pathogenesis of autoimmune rheumatic diseases such as rheumatoid arthritis (RA), Sjögren's syndrome (SS), systemic lupus erythematosus (SLE) and systemic sclerosis. The mechanisms which provide lymphocytes with access to such autoantigens are therefore fundamental in creating the opportunity for autoimmune responses to develop. It has long been thought that the tissue or cellular location of some self-proteins may determine that they are normally 'hidden' from immune recognition, thereby reducing their potential for autoantigenicity. Recently, this concept has been extended to apply even to different epitopes within the same protein. Many studies, encompassing a wide variety of antigens, have shown that some epitopes are not presented for recognition by T lymphocytes unless they are produced in unusually large concentrations or unless they are freed from the configuration of their native antigen. Epitopes for which this phenomenon occurs are described as cryptic. There is increasing interest in the possibility that crypticity may be an important characteristic of epitopes which are recognized by T lymphocytes in autoimmune pathogenesis. The evidence which has led to this theory and its significance are reviewed.
9331541 Incidence and recognition of interstitial pulmonary fibrosis in developing countries. 1997 Sep Interstitial pulmonary fibrosis in developing countries is now diagnosed with an increased frequency. Increased awareness and more frequent availability of computed tomography and fiberoptic bronchoendoscopy have helped in making the diagnosis more often. The spectrum of diseases causing pulmonary fibrosis is broadly similar to that seen in the West. Connective tissue disorders such as systemic sclerosis and rheumatoid arthritis and sarcoidosis are more common causes. Idiopathic fibrosis is seen in approximately half the patients. Pneumoconiosis such as silicosis are also important. Diagnosis is often established on the basis of clinical features and radiologic findings alone. Transbronchial lung biopsy is used as a frequent method to make histologic diagnosis. Some of the causes described from India are rather rare. One of the interesting examples included a patient in whom pulmonary fibrosis was related to his ascent to very high altitude. Extreme cold, solar radiation, and other factors complicating low atmospheric oxygen pressure were implicated as causative factors. Lung fibrosis, secondary to exposure to toxic gas (methyl isocyanate), is reported in survivors of the Bhopal gas leakage tragedy of 1984. Serial bronchoalveolar studies have show elevated fibronectin levels and the presence of macrophage-neutrophilic exudate in the lavage fluid.
9273990 Coombs-negative severe hemolysis associated with hepatitis A. 1997 Jul Mild anemia can occasionally be observed during viral hepatitis, but severe hemolysis has previously only been reported in a few patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. We report a case of massive acute hemolysis associated with an acute hepatitis A in a 39-year-old woman in the absence of G6PD-deficiency. The patient was also suffering from mild rheumatoid arthritis. All known factors responsible for hemolysis were ruled out. Although tests for autoimmune hemolytic anemia were negative the patient made a dramatic recovery after treatment with corticosteroids, suggesting an immune mediated mechanism nonetheless.
9232494 Regnauld procedure in the surgical treatment of metatarsalgia: interpretation of follow-up 1997 May In lesser ray metatarsalgia (rays 2 through 5) due to an altered Lelievre's metatarsal formula (depending on the respective lengths of the metatarsals), the resection of metatarsal heads aims at restoring a correct metatarsal support. This being a destructive procedure, metatarsal head resection is best indicated in the treatment of severe forefoot deformities such as those resulting from rheumatoid arthritis. In all metatarsalgias that recognize biomechanical origin, the enclavement procedure, according to Regnauld's original report, should be preferred. The aim of this study is analysis of the radiographic evolution of the metatarsal epiphysis following the Regnauld procedure on the basis of anatomic and pathological events occurring during the attachment process. The procedure was performed on 31 feet and the patients were followed-up for 24 months postoperatively. The enclavement process evolved favorably in all cases. It consists of four anatomic/pathologic phases corresponding to typical radiographic features. While graft consolidation is achieved in 3 to 4 months postoperatively, complete recovery of the metatarsal bony architecture and functional adaptation requires 18 to 24 months.
9029512 Development of a novel TNF alpha ligand-receptor binding assay for screening NATCHEM Libra 1997 Jan The TNF alpha receptor is a major therapeutic target since over production of TNF alpha plays a key role in the development of septic shock following bacterial infection and has been implicated in the pathogenesis of many inflammatory disorders such as rheumatoid arthritis. To screen our NATCHEM Libraries for novel natural product inhibitors of this target we have developed a sensitive immobilised TNF alpha receptor binding assay based on a commercially available recombinant soluble TNF alpha receptor (p55) and [125I]-TNF alpha.
9093800 Interleukin-1, -6, and -8 levels in juvenile chronic arthritis. 1997 Mar The immunoinflammatory pathogenesis of juvenile chronic arthritis (JCA) involves the activation of many pathways including various cytokines. We have evaluated the levels of interleukin(IL)-1, IL-6 and IL-8 in 29 JCA patients. The age range was 1-16 with a mean of 10.1. A disease activity score was developed on the basis of: 1. constitutional symptoms and/or morning stiffness, 2. presence of joint swelling, 3.warmth, 4.limited range of motion, and 5.joint pain. This score correlated very significantly with laboratory disease activity markers such as erythrocyte sedimentation rate (ESR) and CRP (both p = 0.006) and also correlated with IL-1 and IL-6 levels. The levels of IL-1 decreased in four of the five patients with improved disease activity. IL-6 but not IL-1 correlated significantly with the number of inflamed joints (p = 0.013); IL-6 also strongly correlated with rheumatoid factor supporting this cytokine's role in B cell induction (p = 0). Haemoglobin values correlated negatively with the activity index, ESR, CRP, IL-1 and IL-6. IL-8 did not correlate with disease activity markers. In the systemic patients all cytokines tended to be higher. Our data suggest that interleukins 1 and 6 are effective in the pathogenesis of JCA. Whether cytokines may be used for monitoring therapy may be clarified with further studies.
14987553 Vascular endothelial growth factor-C: a growth factor for lymphatic and blood vascular end 1998 Oct The endothelial cells lining all vessels of the circulatory system have been recognized as key players in a variety of physiological and pathological settings. They act as regulators of vascular tone via the inducible nitric oxide system and in angiogenesis, the formation of blood vessels de novo. Aberrant regulation of endothelial cells contributes to tumor formation, atherosclerosis, and diseases such as psoriasis and rheumatoid arthritis. Among the most recently discovered growth factors for endothelial cells are newly isolated members of the platelet-derived growth factor/vascular endothelial growth factor (VEGF) family, VEGF-B, VEGF-C, and VEGF-D. VEGF-C is the ligand for the receptor tyrosine kinase VEGFR-3 (also known as Flt4), which is expressed predominantly in lymphatic endothelium of adult tissues, but a proteolytically processed form of VEGF-C can also activate VEGFR-2 of blood vessels. The lymphatic vessels have been known since the 17th century, but their specific roles in health and disease are still poorly understood. With the discovery of VEGF-C and its cognate receptor VEGFR-3, the regulation and functions of this important component of the circulatory system can be investigated.