Research Interests: Biochemistry, Chemistry, Medicine, DNA, Humans, and 15 moreTemperature, Temperature Dependence, Room Temperature, Spermine, Energy Transfer, Protein Denaturation, Sodium Chloride, Nucleic Acid Conformation, DNA probes, Biochemistry and cell biology, Molecular beacon, Melting Temperature, Oligonucleotide, fluorescent dyes, and Medical biochemistry and metabolomics
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... In so doing, it destroys mutant cells (cells, in essence, becoming non-self) and invaders. In certain circumstances, the immune system breaks down and no longer leaves self alone; this is auto-immunity-the defense system attacks self.... more
... In so doing, it destroys mutant cells (cells, in essence, becoming non-self) and invaders. In certain circumstances, the immune system breaks down and no longer leaves self alone; this is auto-immunity-the defense system attacks self. ...
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To the Editor. —The article by Drs Feder and Hunt 1 will serve as a good reminder that the misdiagnosis of Lyme disease is not merely a problem in adults. However, although it is true that in later features of Lyme disease (eg, arthritis... more
To the Editor. —The article by Drs Feder and Hunt 1 will serve as a good reminder that the misdiagnosis of Lyme disease is not merely a problem in adults. However, although it is true that in later features of Lyme disease (eg, arthritis or tertiary neuroborreliosis) patients are usually seropositive, it is possible for a patient to have early disseminated Lyme disease (eg, carditis, meningitis, peripheral neuropathy, or facial palsy) and be seronegative. 2 If a patient has features suggestive of early Lyme disease and is seronegative on enzyme-linked immunosorbent assay (ELISA), one may detect serum antibodies by immunoblot or by cerebrospinal fluid evidence of immunoreactivity in the absence of measurable serum antibodies. 3 In patients with the earliest features of Lyme disease, the diagnosis may be made despite seronegativity. The authors point out that Lyme disease can be misdiagnosed in patients with neurologic, rheumatologic, and cardiac complaints in
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Lyme disease has become a major public health problem. One result of this anxiety is over-diagnosis and over-treatment in many endemic and near-to-endemic areas. The diagnosis of Lyme disease is often made solely on the basis of often... more
Lyme disease has become a major public health problem. One result of this anxiety is over-diagnosis and over-treatment in many endemic and near-to-endemic areas. The diagnosis of Lyme disease is often made solely on the basis of often misinterpreted serologic tests. Therefore, a major reason for inadequate response to antibiotic therapy is initial misdiagnosis. Persisting inflammation and tissue damage following treated Lyme disease does occur but is probably an uncommon cause of refractory symptoms and long-term debility post-Lyme disease.
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Research Interests: Immunology, Biology, Medicine, Lyme disease, Humans, and 15 moreBorrelia burgdorferi, Peptides, Comparative Analysis, Peptide, Antibody, Optometry and Ophthalmology, PBS, Amino Acid Sequence, Bovine Serum Albumin, Epitopes, Enzyme Linked Immunosorbent Assay, Antigen, Molecular Sequence Data, Hapten, and epitope
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In areas endemic for Lyme disease there is increasing concern and anxiety about possible chronic and untreatable manifestations of the disease. The authors have diagnosed fibromyalgia in many patients with chronic musculoskeletal... more
In areas endemic for Lyme disease there is increasing concern and anxiety about possible chronic and untreatable manifestations of the disease. The authors have diagnosed fibromyalgia in many patients with chronic musculoskeletal complaints in whom chronic Lyme arthritis had previously been diagnosed as the cause of their joint pains. Fibromyalgia is a common disorder, causing arthralgia (not true arthritis), fatigue, and debility. The repeated and/or long-term antibiotic therapy prescribed for "chronic Lyme disease" is not successful in curing the symptoms of fibromyalgia. Especially in areas where anxiety about Lyme disease is great, it is important to be careful in diagnosing chronic Lyme disease. Fibromyalgia is a potentially treatable and curable cause of chronic complaints and should be considered in the differential diagnosis of "refractory Lyme arthritis."
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A better understanding of the natural history of Lyme disease and of possible causes for persisting symptoms other than active infection is needed to optimize management of patients with persistent symptoms. Review of patients seen at a... more
A better understanding of the natural history of Lyme disease and of possible causes for persisting symptoms other than active infection is needed to optimize management of patients with persistent symptoms. Review of patients seen at a Lyme disease referral center and of the immunologic and clinical literature on Lyme disease suggests most symptoms that persist after therapy can be explained by one or more of seven proposed pathogenetic mechanisms, only one of which includes active ongoing infection. Individualization of care and reanalysis of patients problems are crucial if misdiagnosis and overtreatment of Lyme disease are to be avoided.
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This chapter addresses the psychological aspects of symptom persistence in patients who attribute such symptoms to 'chronic Lyme disease.' The 3 categories of patients with persistent complaints thought to be related to... more
This chapter addresses the psychological aspects of symptom persistence in patients who attribute such symptoms to 'chronic Lyme disease.' The 3 categories of patients with persistent complaints thought to be related to Lyme disease are described: (1) patients with current Lyme disease who may or may not have been treated previously with antibiotics; (2) patients who once had Lyme disease but no longer have active infection with Borrelia burgdorferi (post-Lyme disease syndrome, PLDS); and (3) patients who have never had Lyme disease but believes that Lyme disease is the cause of their ongoing complaints ('not Lyme'). The commitment to the diagnosis of 'chronic Lyme disease,' the role of psychiatric comorbidity and other psychological factors in PLDS and 'not Lyme,' and the role of physicians in the management of these patients are discussed.
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Cellular immune findings were studied in 48 patients with various stages of Lyme disease. At each stage, some patients, particularly those with neuritis or carditis, had elevated serum IgM levels and lymphopenia. During early disease,... more
Cellular immune findings were studied in 48 patients with various stages of Lyme disease. At each stage, some patients, particularly those with neuritis or carditis, had elevated serum IgM levels and lymphopenia. During early disease, mononuclear cells tended to respond normally to phytohemagglutinin, and spontaneous suppressor cell activity was greater than normal. Later, during active neuritis, carditls, or arthritis, the trend was toward heightened phytohemagglutinin responsiveness and less suppression than normal. By multiple regression analysis, serum IgM levels correlated directly wlth disease activity (p = 0.025) and inversely with the number of 1 cells (p = 0.02); during acute dlsease only, elevated IgM levels correlated with increased phytohemagglutlnin responsiveness (p = 0.004) and decreased suppressor cell activity (p = 0.03). Decreased suppression, observed later in the disease, may permit damage to host tissues because of either autoimmune phenomena or a heightened response to the Lyme spirochete.
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ABSTRACT
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Research Interests: Immune response, Biology, Medicine, Lyme disease, Cell line, and 15 moreHumans, Epitope mapping, Borrelia burgdorferi, Fluorescent Antibody Technique, Antibody, Lyme borreliosis, Glutathione Transferase, Amino Acid Sequence, Fusion Protein, Epitopes, Binding Site, Flagellin, Immunoblotting, epitope, and B cell
... Raphael B. Stricker, MD. California Pacific Medical Center. San Francisco, CA 94108. Next Section. The Editors welcome submissions for possible publication in the Letters section. Authors of letters should: ... 5.↵: Linder S,; Heimerl... more
... Raphael B. Stricker, MD. California Pacific Medical Center. San Francisco, CA 94108. Next Section. The Editors welcome submissions for possible publication in the Letters section. Authors of letters should: ... 5.↵: Linder S,; Heimerl C,; Fingerle V,; Aepfelbacher M,; Wilske B. Coiling ...
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Research Interests: Surgery, Medicine, Lyme disease, Placebo, Arthritis, and 3 moreAntibiotics, Erythromycin, and Penicillin
The cardiac features of Lyme disease usually occur within weeks to months of the infecting tick bite; the result may be disruption of the conduction system, leading to heart block and muscle dysfunction, causing a mild myopericarditis.... more
The cardiac features of Lyme disease usually occur within weeks to months of the infecting tick bite; the result may be disruption of the conduction system, leading to heart block and muscle dysfunction, causing a mild myopericarditis. Lyme carditis is usually mild, although permanent heart block and a few fatalities claimed to be due to Lyme carditis have been reported, the latter usually with poor documentation. In general, Lyme carditis is treatable and curable with antibiotic regimens in current use. Recent reports have suggested that Lyme disease may be a cause of chronic congestive cardiomyopathy. Lyme carditis should be considered in the proper clinical setting with appropriate use of diagnostic tests, recalling that patients with carditis early in Lyme disease may be seronegative and that all patients who are seropositive do not necessarily have Lyme disease.
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Research Interests: Computer Science, Enzyme Inhibitors, Cancer Research, Medicine, Humans, and 13 moreMagic Bullet, World Wide Web, Monoclonal Antibodies, Clinical Sciences, Kinase, Internet privacy, Rheumatic diseases, Login, Proteome, Philadelphia Chromosome, Tyrosine Kinase, Receptor Tyrosine Kinase, and Protein tyrosine kinases
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The adaptive immune response specializes in reacting efficiently and rapidly with protein antigens. Many pathogens and host cells are coated with carbohydrates (more about lipid antigens and the response thereto in a future installment of... more
The adaptive immune response specializes in reacting efficiently and rapidly with protein antigens. Many pathogens and host cells are coated with carbohydrates (more about lipid antigens and the response thereto in a future installment of this series). The carbohydrate arrays on pathogens are remarkable for their relative lack of diversity, remarkable conservation, and how different they are from the carbohydrates found on mammalian cells. Thus, they represent excellent targets for the innate immune response, which is characterized by limited effector molecule heterogeneity. Defense collagens are a class of innate immune response recognition proteins targeting these common carbohydrate motifs, a class you may not have encountered previously. These invariant germ-line encoded proteins are not produced as a specific response to a particular antigen. Nonetheless, they too have an antigen-binding site, called the carbohydrate recognition domain with the other end of the molecule (made up of collagen-like domains) devoted to the transmission of biologically relevant information, analogous with the antibody molecule's Fc component, but this is where the similarities end. Defense collagens have been broadly viewed as an "anti-antibody," broadly similar in structure and function. Despite the fact that they are germline-encoded and do not have individual antigen specificity, their phylogenetic longevity and durability prove the value of defense collagens in maintaining the host. On the basis of emerging studies, they may play important roles in the defense against many pathogens and in the pathogenesis of rheumatologic and other diseases. Thus, they are good targets for studies to better understand our diseases and to craft therapeutic manipulations in the future.
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The development of an antigen-specific immune response depends on the peptide-loaded MHC molecule on the surface of the antigen-presenting cell being found by the antigen-specific receptor on the cell about to be activated (the T-cell... more
The development of an antigen-specific immune response depends on the peptide-loaded MHC molecule on the surface of the antigen-presenting cell being found by the antigen-specific receptor on the cell about to be activated (the T-cell antigen receptor for T-cells or the membrane-bound immunoglobulin molecule on B-cells). The details of this process are becoming clear now with the appreciation of the supramolecular organization of the structures that make this cell-cell interaction. In the last 6 years has come an appreciation of the heterogeneity of the lipid bilayer membrane (a concept first put forth over 20 years ago), with certain lipids and membrane-bound proteins segregating into discrete ships called "lipid rafts" sailing in the surrounding more liquid lipid bilayer membrane. Knowledge of these microscopic structures leads to a better understanding of how antigen-specific responses are triggered and how aberrant responses are avoided; as one leader in the field put it, "keeping T-cells rested but ready."Membrane heterogeneity directly contributes to the rapid development of a more formalized cell-cell interaction that has been termed the "immunologic synapse." It is at this synapse that the acquired immune response, antigen specificity, is learned. In addition to antigen presentation, lipid rafts have also been implicated in signaling through a large number of receptors, endocytosis, cell interactions with pathogens and toxins, budding of viruses from host cell membrane, and the pathogenesis of prion disorders. Yet again, an insight in one discrete field of cell biology is proving to be of great relevance in a host of other areas of study.
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The object of this study was to determine the incidence of seropositivity to B. burgdorferi by the commonly available enzyme-linked immunosorbent assay (ELISA) in patients with SLE and other rheumatic diseases and to evaluate immunoblot... more
The object of this study was to determine the incidence of seropositivity to B. burgdorferi by the commonly available enzyme-linked immunosorbent assay (ELISA) in patients with SLE and other rheumatic diseases and to evaluate immunoblot analysis as a tool to differentiate true from false positive ELISA. Sera were obtained from patients with SLE ( n = 35), rheumatoid arthritis ( n = 26), seronegative arthritis (n = 28) and Lyme disease ( n = 18). Reactivity to B. burgdorferi antigens was analysed by two available diagnostic techniques: ELISA and immunoblot. Correlations were made between seroreactivity to B. burgdorferi and standard serological tests of autoimmunity: antibodies to nuclear antigens, dsDNA, cardiolipin, SSA and SSB. Seroreactivity to B. burgdorferi antigens by the ELISA system was detected in 40% of patients with SLE, 8% of patients with rheumatoid arthritis and 4% with seronegative arthritis. Among patients seropositive by ELISA, immunoblots were negative in all cases. However, eight of 14 patients with rheumatoid arthritis (57%) showed cross-reactivity to multiple borrelial antigens. No significant correlations were found between Lyme seropositivity by ELISA and other autoantibodies except IgM rheumatoid factor (r = 0.61, P < 0.01 ) in patients with rheumatoid arthritis. In conclusion: a positive ELISA for Lyme disease was found in up to 40% of patients with established SLE and also in other rheumatic diseases. However, specific serum antibodies to Borrelia were not confirmed by the more specific immunoblot technique. We conclude that immunoblot analysis can help differentiate a false from true positive ELISA for Lyme disease. These findings should caution the clinician with regard to the limitations of current diagnostic testing for Lyme disease, particularly in patients with connective tissue disease.