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ID PMID Title PublicationDate abstract
11883318 [Sialic acid of glycoconjugates in amniotic fluid]. 2001 Dec OBJECTIVES: Sialic acid is a negatively charged monosaccharide attached to non-reducing end of N- and O-linked carbohydrate chains of glycoconjugates. The claimed biological functions of sialic acid include its participation in cell to cell recognition and interaction as well as affecting the function of receptors by providing binding sites for ligand. Increased sialic acid concentration have been observed in several diseases e.g. malignancies, diabetes, inflammatory disorders, rheumatoid arthritis and alcoholism. DESIGN: The aim of the present work was to determine if the amount of sialic acid attached to glycoconjugates of amniotic fluid changes during pregnancy. MATERIALS AND METHODS: The sialic acid content in 47 samples of amniotic fluid derived from pregnant women with gestational age between 13 and 42 was studied by sialic acid specific lectins immunosorbent assay. The patient samples were divided into seven groups. RESULTS: Time dependent changes in the degree of sialylation of glycoconjugates in amniotic fluid during pregnancy, particularly in advanced pregnancy were observed. Moreover, the highest sialic acid content on glycoconjugates in pregnancies complicated by premature rupture of membranes and is prolonged pregnancy were also detected. CONCLUSIONS: Sialic acid content determination in amniotic fluid could be a potentially useful marker of inflammation process of amniochorion during pregnancy.
11772244 ICE/Caspase-1 inhibitors as novel anti-inflammatory drugs. 2001 Jul In recent years, several strategies that selectively inhibit pro-inflammatory cytokines, have yielded effective protein-based therapies for inflammatory disorders, validating the therapeutic hypothesis that intervention in cytokine signalling can provide clinical benefit. However, these protein-based products must be administered by injection, a constraint associated with inconvenience, adverse effects and expense for patients, caregivers and insurers. Besides interfering with the effects of cytokines such as TNF-alpha or IL-1beta that have already been produced, inhibition of pro-inflammatory cytokine production or signalling with low-molecular weight orally-active drugs would combine the convenience of conventional pharmaceuticals with the focused efficacy of the protein therapies. Reducing IL-1beta and IL-18 production by inhibition of IL-1beta converting enzyme (ICE, caspase-1) is one promising strategy because of the key roles of these cytokines in many inflammatory diseases. Pralnacasan, the first orally available, potent and selective ICE inhibitor to enter clinical trials, is currently under investigation in rheumatoid arthritis.
11688831 Myelodysplastic syndrome accompanied by Addison's disease and multiple autoimmune phenomen 2001 Oct We report here a patient with myelodysplastic syndromes (MDS), which was complicated with several autoimmune disorders and asymptomatic immunologic abnormalities. An 82-year-old woman with refractory anemia (RA) rapidly developed thrombocytopenia with the appearance of symptoms such as purpura, fatigue, anorexia, and weight loss. Furthermore, clinical examinations revealed that she also had Addison's disease, rheumatoid arthritis, and autoimmune hematological diseases such as thrombocytopenia and hemolytic anemia. However, the cytopenia and all autoimmune disorders were remarkably improved after she received steroid therapy.
11587067 Linkage disequilibrium and haplotype analysis among four novel single-nucleotide polymorph 2001 Leukemia inhibitory factor (LIF) is a pleiotropic cytokine implicated in various pathological conditions, such as rheumatoid arthritis and osteoporosis. Despite the possible importance of LIF as a therapeutic target, little is known about the bioregulation of the human LIF gene. We here sequenced the entire structure of the LIF gene of 48 alleles in the Japanese population. These experiments identified four single-nucleotide polymorphisms (SNPs) and determined their allelic frequencies from a 48-allele sequence in the Japanese population. All four SNPs found in the LIFgene were located within exon 3, that is, a C/T at nucleotide (nt) position 3951, a C/G at nt position 4376, an A/C at nt position 4442, and a G/A at nt position 5961 (nucleotide numbering starts from the ATG start codon). Based on the genotypic data, we constructed four major haplotypes in the tested population. Two-way comparisons of SNPs revealed complete linkage disequilibrium between SNPs at positions 3951, 4376, and 4442. These results may prove to be useful as genetic markers for population-based disease-association studies in osteoporosis.
11563829 Corticosteroid-induced osteoporosis. 2001 Jul Since Harvey Cushing first noted the coexistence of excess cortisol and loss of skeletal mass over 50 years ago, it has been accepted that supraphysiologic doses of corticosteroids cause clinically significant bone loss. Currently, high-dose oral corticosteroids are used to treat people with a variety of medical conditions, including: rheumatic diseases, such as rheumatoid arthritis, polymyalgia rheumatica, systemic lupus erythematosus and vasculitis; inflammatory lung diseases, like asthma; gastrointestinal diseases, such as inflammatory bowel disease and chronic liver disease; skin diseases, in particular pemphigus, and more recently those who have undergone transplantation. Clinically significant bone loss occurs in the vast majority of patients exposed to corticosteroids, and fractures at the spine and hip have been reported with corticosteroid use. Between 30 and 50 percent of patients taking long-term corticosteroids will experience fractures. Today, fractures due to corticosteroid-induced osteoporosis may be prevented. A number of well-designed randomized controlled trials have been conducted that demonstrate preservation and, in some instances, actual increases in bone mass with the use of appropriate drug treatment. Some have even demonstrated reductions in fracture risk. As a result, it is extremely important for clinicians to appreciate the very high risk for vertebral fracture, particularly in postmenopausal women on corticosteroids.
11164236 Cryogelation in vitro. 2001 Jan 10 Cryogel is a physical gel formed by the heterophilic aggregation of extra domain A containing fibronectin (EDA(+)FN), plasma fibronectin (pFN), fibrinogen (Fbg) and heparin (Hep). Cryogelation is controlled by the interactions between each aggregate and the amount of aggregates. Therefore, the present study attempted to elucidate these properties by studying turbidity (tau). Although only Fbg formed a self-aggregate under low temperatures, from the temperature dependence of tau, the amount of aggregate in three-element (pFN/Fbg/Hep) solution surpassed that of the EDA(+)FN/Fbg/Hep system. The optimal condition for cryogelation was afforded by a solution with Fbg/EDA(+)FN/pFN/Hep expressed in the molar ratio of 12:0.04:0.79:1. This cryogel structure in solution was probably formed via structural changes induced by pFN in Fbg. The structural change in Fbg was examined by circular dichroism under optimal conditions. This concept was based on observations of the direct transmission scanning electron microscopy of a cryogel. The EDA(+)FN/pFN/Fbg/Hep aggregates displayed a network structure that manifested particulate crosslinkage. Cryogelation, a phenomenon related to induction of rheumatoid arthritis in humans, was facilitated by both the EDA(+)FN-Hep interaction and the structural changes of Fbg induced by pFN.
9746704 Recognizing and Managing the Oral Clues That Point to Sjögren's Syndrome. 1997 Sep Sjögren's syndrome (SS), a chronic autoimmune exocrinopathy, occurs mainly after age 40. Most SS patients--80% to 90%--are women. SS is characterized by dry eyes and mouth due to lacrimal and salivary gland lymphocytic infiltration. It may be primary or secondary in association with a connective tissue disease, usually rheumatoid arthritis. Lymphoproliferation may produce extraglandular manifestations in pulmonary, cardiac, genitourinary, vascular, and/or nervous systems. The risk of lymphoma is increased 40-fold among SS patients. Dry mouth, or xerostomia, hinders eating, speaking, and swallowing. A thorough patient history, serum analysis, and salivary function tests are essential to determine the genesis of the xerostomia. Insufficient salivary protection can cause rampant dental destruction and soft-tissue mycosis in the mouth. A biopsy of the minor salivary gland from the lower lip is used to detect hallmark inflammatory changes that confirm the diagnosis of SS. Therapy is symptomatic. Regardless of the cause of xerostomia, therapy has 3 fundamental aspects: preventive dental care, dietary counseling (reduction of sugar intake to avoid caries), and moisture replacement (including artificial salivas, frequent sips of water, and room humidifiers). Women taking xerostomic medications may need to lower the dose or substitute them with less xerogenic drugs if possible. Salivation can be stimulated by chewing gum, mints, or paraffin. Cracked lips are treated with petroleum. Dental flossing, supplemental fluoride, and dental appointments every 3 to 4 months are essential to control caries. Pilocarpine, a parasympathomimetic drug that increases salivation, has been found to reduce the severity of xerostomia from radiotherapy; multicenter trials in SS patients are ongoing.
9646180 The chronobiology of human cytokine production. 1998 Cytokine production in human whole blood exhibits diurnal rhythmicity. Peak production of the pro-inflammatory cytokines IFN-gamma, TNF-alpha, IL-1 and IL-12 occurs during the night and early morning at a time when plasma cortisol is lowest. The existence of a causal relationship between plasma cortisol and production is suggested by the finding that elevation of plasma cortisol within the physiological range by the administration of cortisone acetate results in a corresponding fall in pro-inflammatory cytokine production. Cortisol may not be the only neuroendocrine hormone that entrains cytokine rhythms; other candidates include 17-hydroxy progesterone, melatonin and dihydroepiandrostene dione (DHEAS). The finding of diurnal cytokine rhythms may be relevant to understanding why immuno-inflammatory disorders such as rheumatoid arthritis or asthma exhibit night-time or early morning exacerbations and to the optimisation of treatment for these disorders. Diurnal rhythmicity of cytokine production also has implications for the timing of blood samples drawn for diagnostic T-cell assays. Finally, diurnal rhythmicity of immune function suggests that the nature of an immune response, for example in response to vaccination, may be modified by the time of day of antigen administration and raises the possibility that immune responses could be therapeutically manipulated by co-administration of immuno-regulatory hormones such as glucocorticoids.
9283840 Imaging of the hand: degeneration, impingement and overuse. 1997 Sep Degenerative and overuse diseases as well as impingement syndromes of the hand are illustrated and discussed in this review article. Osteoarthritis of the interphalangeal joints as described by Heberden and Bouchard is a ubiquitous articular disease often associated with synovitis and erosive joint destruction. Osteoarthritis of the trapeziometacarpal joint is classified into four stages for proper indication of operation. Overuse can result in stenosing tenosynovitis around the wrist and in synovitis with or without impingement of the flexor or extensor tendons of the digitis or ruptures of the annular and cruciform pulleys. Although diagnosis of these entities is usually made by history and clinical investigation, ultrasound and MRI can be helpful tools in imaging of these diseases. Scapholunate advanced collapse (SLAC) and scaphoid nonunion advanced collapse (SNAC) are the characteristic degeneration pattern of the wrist and represent the degeneration mechanisms in scapholunate insufficiency and nonunion of the scaphoid. SLAC wrist is a gradual degeneration classified in three stages and found in posttraumatic scapholunate rupture, calcium pyrophosphate dehydrate deposition disease (CPPD), rheumatoid arthritis, neuropathic diseases, trauma, and beta 2-microglobulin associated amyloid deposition. Ulna impaction syndrome is increasingly recognized as a cause of ulnar sided pain and exhibits a characteristic MRI appearance.
9225456 Clinical and mechanistic aspects of photopheresis. 1997 Jun Photopheresis is an extracorporeal form of photochemotherapy with 8-methoxypsoralen (8-MOP) and ultraviolet A (UVA) radiation. Photopheresis is used for the management of T-cell-mediated diseases, and such treatment leads to the induction of antigen-specific immune suppression directed to the pathogenic clone of T cells. Photopheresis is used to treat a wide variety of diseases--such as cutaneous T-cell lymphoma, systemic sclerosis; rheumatoid arthritis, lupus erythematosus--and is also successfully applied in the suppression of graft rejection. In addition to the clinical achievements, attention will be paid to results from animal studies. An important outcome of these studies is that photopheresis can be used to treat airway hyperreactivity. Furthermore, it was shown that the therapeutic strategy can be changed drastically: the presence of plasma during irradiation should be avoided and the amount of blood that must be treated to obtain the desired antigen-specific immunosuppression can be greatly decreased. Also, results from cellular experiments are discussed. An example of this is the increase in the major histocompatibility complex expression on the surface of cells found after treatment. The mechanism that underlies photopheresis has not yet been elucidated, but progress has been made. The following related points will be reviewed: models for investigation; and mechanistic aspects, with the emphasis on cellular biomacromolecules and on photosensitizers (drugs) other than 8-MOP.
9244961 [Restless legs syndrome--current aspects]. 1997 Apr 30 Although the Restless-Legs-Syndrome (RLS) is harmless, it can be considerably bothersome on occasions. It seems to affect 1-5% of the population. The minimal criteria for diagnosis are: Symmetric or asymmetric dysesthesias of the lower, sometimes also of the upper extremities, present at rest, especially at night. This induces a need to move. Moving gives always relief, but only for a few seconds. Occasionally, dysesthesia can be painful. Additional features are: Involuntary, rhythmic retraction movements occurring especially at night, during sleep stages I und II. Sleep is disrupted and superficial, followed by daytime fatigue. Aetiologically, it is a mostly primary or hereditary disease, but may go along with uremia, diabetes and rheumatoid arthritis. Pathophysiologically there seems to be a malfunction of dopamine and opiate receptors in the central nervous system. Recently, morphological modifications have been found in peripheral nerves. Coffeine has been claimed as causative factor, but its role remains questionable. Therapy shows a high success rate. Some patients may complain about some remaining symptoms even with high doses of medication. Although carbamazepine, clonazepam and clonidine showed satisfactory results in controlled studies, dopaminergic agents and opiates have many advantages. In contrast to the former compounds, the latter are also effective against periodic movements in sleep. Side effects will be discussed according to the literature. In the second part of this paper, practical aspects concerning the care of RLS patients are considered.
9472670 Glucocorticoid inhibition of adjuvant arthritis synovial macrophage nitric oxide productio 1998 Jan Nitric oxide (NO) is a mediator of inflammatory injury which is inhibited by glucocorticoids and is implicated in rheumatoid (RA) and adjuvant arthritis (AA). The glucocorticoid-induced anti-inflammatory molecule lipocortin 1 is expressed in RA synovium, but the effects of lipocortin 1 on synovial inflammation have been little studied. We investigated the effects of glucocorticoids and lipocortin 1 on inducible NO synthase (iNOS) and glucocorticoids on the induction of lipocortin 1 in AA synovial macrophages. NO production was measured by Griess assay in supernatants of day 14 AA rat synovial explants and of synovial macrophages purified from enzyme-digested synovium and treated with lipopolysaccharide (LPS) 1 microg/ml, dexamethasone (DEX) 10(-7) M, and anti-lipocortin 1 MoAb. iNOS and lipocortin 1 expression were detected by flow cytometry using specific MoAb. Cell surface lipocortin was determined by Western blot. NO was produced by all AA synovial explants and NO was released by cultured synovial macrophages (14.5 +/- 2.1 micromol/24 h). iNOS was detected in synovial macrophages (ED-1+) by permeabilization flow cytometry. LPS increased synovial macrophage NO release (P < 0.0001) and iNOS expression (P = 0.04). DEX inhibited constitutive (P = 0.002) and LPS-induced (P < 0.001) NO release and iNOS expression (P = 0.03). DEX inhibition of synovial macrophage NO was associated with induction of cell surface and intracellular lipocortin 1. Anti-lipocortin 1 MoAb treatment reduced the inhibition of NO release by DEX (P = 0.002), but had no effect on iNOS expression. These findings demonstrate a role for lipocortin I in the inhibition by glucocorticoids of AA synovial macrophage iNOS activity.
15616658 Phospholipase A2 activating protein induces tumor regression. 1998 Mar There has been increasing interest in attempts to harness the body's normal inflammatory response mediated through the eicosanoid pathway to treat tumors. Accumulating data indicate that the growth of several different cancers is modulated by a group of pro-inflammatory bioactive lipids, the best known of which are the eicosanoids. Eicosanoid pathway constituents modulate cell function in several important ways, and an agent that activates PLA(2) and up-regulates LTB(4) levels could be expected to be an effective cytotoxic tumor agent, especially if it stimulated NK cells. PLAP is a 28-kDa polypeptide that is a member of the WD-repeat protein, G-protein-transducin superfamily. The pro-inflammatory properties of PLAP have been elucidated using a number of different approaches. PLAP has been found in inflamed tissues and synovial fluid from patients with rheumatoid arthritis. Based on knowledge of PLAP as a pro-inflammatory agent, its capacity to modulate the immune response and the role of the inflammatory and immune responses in immune surveillance, the role of PLAP in cancer therapy was explored. Significant tumor regression was observed 72 hours following a single treatment with PLAP in an animal air pouch model of glioma. PEG-PLAP treatment increased the life expectancy of animals with Lewis lung cancer, and in preliminary studies in MTVL breast tumors in mice, PLAP treatment resulted in a similar increase in life expectancy. These findings suggest that PLAP holds promise as a potential therapy for cancer, and warrants further study.
12818097 [The prevalence of autoimmunological diseases in families of children with type I diabetes 1999 BACKGROUND: type I diabetes mellitus is considered as an autoimmune disease and is often associated with other diseases of that etiology. The genetic susceptibility to autoimmune disorders causes type I diabetes to occur more frequently in relatives of the diabetic patients. OBJECTIVE: To evaluate the prevalence of type I diabetes and other autoimmune diseases in families of the children with type I diabetes. MATERIAL AND METHODS: The prevalence of type I diabetes mellitus and other autoimmune endocrinopathies was evaluated in I, II and III degree relatives of 155 children with type I diabetes mellitus and 90 control children. RESULTS: It was observed that: 1) diabetes mellitus occurred more often in relatives of diabetic children (in 22 families - 14.2%) in comparison with the control group (in 2 families - 2.2%); 2) other autoimmune diseases occurred frequently in families of diabetic children and they affected 2 or more members of one family more often than in the control group (18 families vs 4); 3) rheumatoid arthritis occurred more frequently in families of diabetic children. CONCLUSIONS: The familial prevalence of type I diabetes mellitus and the tendency to more frequent prevalence of other autoimmune diseases in families of diabetic children was confirmed.
9641505 HLA-DR gene frequencies in a Zaïrean population with particular reference to rheumatic di 1998 Epidemiological studies have shown that rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus are uncommon in black Africans, and in this population the prevalence and the clinical features of these rheumatic diseases are variable. Environmental and genetic factors have been pointed out to explain this variability. In the present study, HLA-DR genes have been determined in a Zaïrean population in order to compare our results with those found elsewhere in other black populations of the same Bantu origin. Our results show that the frequency of HLA-DR1 is higher than in Nigerians, Zimbabweans and Xhosas, the decrease in Xhosas being statistically significant (p < 0.006). The HLA-DR3 frequency is higher in Zaïreans than in Nigerians but not significantly, while it is lower than in Xhosas (p < 0.003) and in Zimbabweans (not significant). The HLA-DR4 frequency is higher in Zaïreans than in Nigerians but it is lower than in Xhosas and Zimbabweans; the differences are not statistically significant. The HLA-DR8 frequency is lower in Zaïreans than in Nigerians while it is higher than in Xhosas (p < 0.002) and in Zimbabweans (not significant). These data suggest that genetic factors partly explain the clinical and epidemiological variability of rheumatic diseases in black Africans.
9532339 Prevention and treatment of postpartum Graves' disease. 1997 Oct Postpartum Graves' disease requires differentiation from postpartum thyroiditis and subacute thyroiditis in addition to other causes of hyperthyroidism. This may be done by assessing thyrotropin receptor antibody and radioiodine uptake together with clinical examination and thyroid scanning. The effect of pregnancy on thyroid function causes changes in iodine metabolism, thyroid hormone transport proteins and thyroid gland size. Amelioration of autoimmune disease such as Graves' disease, systemic lupus erythematosus and rheumatoid arthritis is often observed during pregnancy followed by postpartum exacerbation. The immunological effects of pregnancy involve placental factors as well as a transient diversion from T helper (Th) 1 to Th2 T-cell cytokine profile in addition to a change in B-cell lymphopoiesis. Prevention of postpartum Graves' disease by immune strategies which have been experimentally performed to reduce expression of diabetes in the non-obese diabetic mouse are attractive but not currently feasible in humans. Treatment of Graves' disease prior to pregnancy or postpartum with 131I is effective. Therapy with anti-thyroid drugs with or without thyroxine is variably effective.
11777000 [Forgotten episodes of the birth of cortisone]. 2001 During World War II, a rumor reached the United States and the United Kingdom that the Germans were successfully using an adrenal hormone product to protect Luftwaffe pilots from the adverse effects of high altitudes. The product was said to be obtained from adrenal glands collected in a huge amount in Argentina and transported by U-boats to Germany. The U. S. and the U. K. exerted their war efforts by setting up urgent research projects to produce similar products. The war ended in 1945, however, before the goal was achieved. The German rumor turned out to be groundless. Cortisone acquired fame in 1949 as "a miracle drug" for the relief of rheumatic pain. Its therapeutic discovery was an outcome of the untenable assumption that rheumatoid arthritis patients must have suffered from adrenal insufficiency and hormone deficiency. The war efforts have led to successful syntheses of cortisone after the war, and its industrial production has reduced its cost drastically from $200.00 per gram in 1949 to $10.00 in 1951. To overcome the cumbersome synthetic routes for cortisone, natural product sources were sought as possible starting materials, but without much success. A microbiological transformation of steroidal compounds was developed in 1952 to introduce an oxygen function into the molecular position 11 by a microorganism found at a window of a laboratory. The fermentation process required progesterone which found its timely supply in Mexico. The cost of progesterone went down from $2.00 per gram to $0.15 and that of cortisone further from $10.00 to $3.50 in 1955. An ample supply of cortisone at an affordable price was admirably achieved by the combination of progesterone derived from diosgenin of the Mexican yam and a microbiological oxidation process developed by a chance discovery of suitable organisms. The former is attributed to R. E. Marker and the latter to D. H. Peterson.
11707861 DAB(389)IL-2 (denileukin diftitox, ONTAK): review of clinical trials to date. 2000 Nov Clinical trials of DAB(389)IL-2 (denileukin diftitox, ONTAK) have been conducted in a variety of disease states as well as in normal volunteers. The individuals treated include 45 volunteers in pharmacokinetic testing, 195 patients with noncancer indications, and 216 patients with lymphoma, including ongoing trials. The noncancer trials involved patients with rheumatoid arthritis, psoriasis, HIV infection, and insulin-dependent diabetes mellitus. Two large trials involving 143 lymphoma patients provide the definitive data and formed the basis for seeking and receiving Food and Drug Administration approval for DAB(389)IL-2. The focus of this paper will be a review of the efficacy and toxicity trials with DAB(389)IL-2 completed to date in cancer, in particular those that involved patients with cutaneous T-cell lymphoma, as well as the rationale for these trials.
11208454 Newer uses of glucose-insulin-potassium regimen. 2000 Nov Diabetic ketoacidosis and moderate degree of hyperglycemia can be managed by glucose-insulin-potassium (GIK) regimen. The GIK regimen is also useful in the treatment of acute myocardial infarction (AMI). But, the exact mechanism(s) of the beneficial action of GIK regimen is not known. I suggest that glucose-insulin can suppress the secretion and antagonize the harmful effects of tumor necrosis factor alpha (TNF alpha) and macrophage migration inhibitory factor (MIF). If this is true, it suggests that GIK regimen may be useful in septicemia and septic shock, and other inflammatory conditions such as ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus and cancer, conditions in which TNF alpha and MIF appear to play a major role.
11035201 Linear and cyclic LFA-1 and ICAM-1 peptides inhibit T cell adhesion and function. 2000 Aug Short peptides derived from functional proteins have been used in several instances to inhibit activity of the parent proteins. In some cases, stability and efficacy were found to be increased by cyclization of these peptides. Inhibition of interaction of the two cell adhesion counter receptors leukocyte function-associated antigen (LFA)-1 and intercellular adhesion molecule (ICAM)-1 is being studied as a method for modulating autoimmune diseases such as rheumatoid arthritis and for facilitating organ transplantation. Here, several 10-amino acid peptides derived from the contact domains of LFA-1 and ICAM-1 were evaluated for their ability to interfere with intercellular adhesion by T cells and to inhibit a more biologic, mixed lymphocyte reaction. Both linear and cyclic forms of the peptides were effective at inhibiting intercellular adhesion. Cyclic forms were effective at inhibiting T cell activation and proliferation in the mixed lymphocyte reaction.