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Biomedical subjects

Steven E Schutzer

Publications and source records attributed to Steven E Schutzer.

11 recordsLinked to original sources

Insect sting reactions to bees, wasps, and ants.

Abstract Arthropod bites and stings are capable of inflicting injury, inciting allergic reactions, and transmitting systemic disease. Members of the Hymenoptera order are of particular importance because they are nearly ubiquitous in nature, and their stings may cause life-threatening allergic reactions. Stings from bees, wasps, and ants produce a variety of clinical and histological manifestations. Anaphylaxis following an insect sting is the most serious complication. For individuals with a specific allergy to Hymenoptera venom, immunotherapy may be a relatively safe and effective treatment option.

Animals↗

Evidence of Borrelia autoimmunity-induced component of Lyme carditis and arthritis.

We investigated the possibility that manifestations of Lyme disease in certain hosts, such as arthritis and carditis, may be autoimmunity mediated due to molecular mimicry between the bacterium Borrelia burgdorferi and self-components. We first compared amino acid sequences of Streptococcus pyogenes M protein, a known inducer of antibodies that are cross-reactive with myosin, and B. burgdorferi and found significant homologies with OspA protein. We found that S. pyogenes M5-specific antibodies and sera from B. burgdorferi-infected mice reacted with both myosin and B. burgdorferi proteins by Western blots and enzyme-linked immunosorbent assay. To investigate the relationship between self-reactivity and the response to B. burgdorferi, NZB mice, models of autoimmunity, were infected. NZB mice infected with B. burgdorferi developed higher degrees of joint swelling and higher anti-B. burgdorferi immunoglobulin M cross-reactive responses than other strains with identical major histocompatibility complex (DBA/2 and BALB/c). These studies reveal immunological cross-reactivity and suggest that B. burgdorferi may share common epitopes which mimic self-proteins. These implications could be important for certain autoimmunity-susceptible individuals or animals who become infected with B. burgdorferi.

Animals↗

Genetic exchange and plasmid transfers in Borrelia burgdorferi sensu stricto revealed by three-way genome comparisons and multilocus sequence typing.

Comparative genomics of closely related bacterial isolates is a powerful method for uncovering virulence and other important genome elements. We determined draft sequences (8-fold coverage) of the genomes of strains JD1 and N40 of Borrelia burgdorferi sensu stricto, the causative agent of Lyme disease, and we compared the predicted genes from the two genomes with those from the previously sequenced B31 genome. The three genomes are closely related and are evolutionarily approximately equidistant ( approximately 0.5% pairwise nucleotide differences on the main chromosome). We used a Poisson model of nucleotide substitution to screen for genes with elevated levels of nucleotide polymorphisms. The three-way genome comparison allowed distinction between polymorphisms introduced by mutations and those introduced by recombination using the method of phylogenetic partitioning. Tests for recombination suggested that patches of high-density nucleotide polymorphisms on the chromosome and plasmids arise by DNA exchange. The role of recombination as the main mechanism driving B. burgdorferi diversification was confirmed by multilocus sequence typing of 18 clinical isolates at 18 polymorphic loci. A strong linkage between the multilocus sequence genotypes and the major alleles of outer-surface protein C (ospC) suggested that balancing selection at ospC is a dominant force maintaining B. burgdorferi diversity in local populations. We conclude that B. burgdorferi undergoes genome-wide genetic exchange, including plasmid transfers, and previous reports of its clonality are artifacts from the use of geographically and ecological isolated samples. Frequent recombination implies a potential for rapid adaptive evolution and a possible polygenic basis of B. burgdorferi pathogenicity.

Amino Acid Sequence↗

Identification of potential antibody markers in HIV-associated dementia.

Markers for HIV-associated dementia (HAD) are needed for diagnosis and management. Specific antibodies to brain and immune complexes (IC) in the cerebrospinal fluid (CSF) are potential markers. CSF IC were found in 4 of 4 HAD patients, 2 of 2 AIDS-central nervous system (CNS) lymphoma patients with dementia, 0 of 1 AIDS-CNS lymphoma patient without dementia, 0 of 1 AIDS-CNS toxoplasmosis patient without dementia, and 0 of 10 neurologic disease controls. By blinded immunoblots, antibrain antibodies in serum and CSF were found in 11 of 12 HAD cases and 7 of 19 HIV-1 patients without HAD. All 11 non-HIV-1 controls were negative. These and published data suggest antibrain antibodies and IC may serve as markers of HAD.

AIDS Dementia Complex↗

Preferential presence of decorin-binding protein B (BBA25) and BBA50 antibodies in cerebrospinal fluid of patients with neurologic Lyme disease.

Borrelia burgdorferi antibodies preferentially present in cerebrospinal fluid (CSF) were examined by differentially probing a B. burgdorferi expression library with CSF and sera from patients with neurologic Lyme disease. Several phage clones selectively reacted with CSF, and these genes were then expressed in recombinant form and used to detect specific antibody in an enzyme-linked immunosorbent assay. Decorin-binding protein B (BBA25) and BBA50 (hypothetical protein) elicited immunoglobulin G (IgG) or IgM detectable in CSF-but not sera-of patients, demonstrating preferential antibody production during neuroborreliosis.

Adhesins, Bacterial↗

Public health. Building microbial forensics as a response to bioterrorism.

Combating bioterrorism is a challenge to all of us. To be proactive, the U.S. Government has formalized the discipline of "microbial forensics" to deter and attribute perpetrators of such acts. This Policy Forum describes the foundations of the microbial forensics program: the creation of a national bioforensics laboratory, a partnership laboratory network, and a peer-consensus scientific working group and the promulgation of quality assurance guidelines.

Advisory Committees↗

Autoimmune markers in HIV-associated dementia.

The etiology of HIV-associated dementia (HAD) is still unknown although direct viral effects have not been supported. Although evidence supports a role for products of activated macrophages, other evidence suggested the possibility of associated autoimmune phenomena at least as a marker. In a blinded analysis, non-HIV-infected whole brain material was immunoblotted with samples of serum, and in certain cases cerebrospinal fluid (CSF), from HAD patients and controls. Distinct antibrain antibodies were detected in 11/12 of HIV+ HAD patients, 7/19 of HIV+ patients without HAD, and 0/11 HIV seronegative controls who were either healthy or had other neurologic diseases. Reactivity against control tissue was negative. Though the etiopathogenetic relation of these antibrain antibodies remains to be delineated, the data suggest that they may be a marker of HAD.

AIDS Dementia Complex↗

Early OspA immune complex formation in animal models of Lyme disease.

Infection with Borrelia burgdorferi, the cause of Lyme disease, has been accompanied by a puzzling delayed antibody (Ab) response to B. burgdorferi antigens (Ags) including the abundant organism-specific outer surface proteins, such as the 31-kD OspA. In humans the response to nonspecific B. burgdorferi Ags has required 3-6 weeks. The response to OspA has rarely been detected by conventional methodology until months after infection, despite demonstrable T cell reactivity. Tick inoculation and low-dose intradermal inoculation animal models have been characterized by a comparable response to OspA. Using more sensitive biotin-avidin immunoblots and immune complex (IC) dissociation techniques, we demonstrated in humans that Ab to OspA is formed early but may remain at low levels or bound in IC. To see if this was a universal biologic response, animal models were analyzed by these methods. The results with mice, monkeys and rabbits show that IC Ab to OspA may be detected at the onset of infection. The data suggest that these animal models may be used to understand the immune response to B. burgdorferi and the pathogenesis of Lyme disease. With attention to unique B. burgdorferi Ags, these results are likely to have both clinical and diagnostic importance.

Animals↗