Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bacterial protein toxins and their fragments have been isolated and purified for various reasons, including the development of efficient vaccines and for methods of identification of bacterial agents causing disease. This activity continues today but a new area of bacterial protein toxin research has recently emerged. Since it was shown that toxin molecules comprise several types of biological activity within their structural domains, it was suggested to use these domains (and their combinations) as biochemical tools for developing novel agents for disease imaging and and/or relieving. In this way eukaryotic cell-receptor specific fusion toxins have been developed to prevent malignancy in human. While human clinical trials of these preparations have only recently begun, the preliminary clinical findings are promising. Also fusion proteins which combine independent immunodominant epitopes from different antigens have also been developed thus opening a way for the generation of new vaccines for both human and veterinary use. Receptor binding fragments of microbial toxins when combined with other molecules may be useful in delivering these molecules into the cell. In this way novel agents may be developed with a potential for inducing specific changes at the molecular level for the correction of metabolic disorders causing human and animal diseases. Bacterial protein toxins such as anthrax, botulinum, cholera, pertussis and tetanus for which considerable progress has been achieved in structure-function analysis are promising candidates for such research. Particularly exciting appears the idea of extending this research to the cells of the nervous system, exploiting the unique specificity of the botulinum or tetanus toxin fragments which may bring long desired methods for treatment of various disorders of the nervous system. Data on functional domains of these toxins as well as methods of purification of the whole toxins and their fragments are considered in this review as they form a base for their further structure-function analysis and engineering applications.
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PMID:Purification of bacterial exotoxins. The case of botulinum, tetanus, anthrax, pertussis and cholera toxins. 136 26

Adenylate cyclase (AC) toxins produced by Bacillus anthracis and Bordetella pertussis were compared for their ability to interact with and intoxicate Chinese hamster ovary cells. At 30 degrees C, anthrax AC toxin exhibited a lag of 10 min for measurable cAMP accumulation that was not seen with pertussis AC toxin. This finding is consistent with previous data showing inhibition of anthrax AC toxin but not pertussis AC toxin entry by inhibitors of receptor-mediated endocytosis (Gordon, V. M., Leppla, S. H., and Hewlett, E. L. (1988) Infect. Immun. 56, 1066-1069). Treatment of target Chinese hamster ovary cells with trypsin or cycloheximide reduced anthrax AC toxin-induced cAMP accumulation by greater than 90%, but was without effect on pertussis AC toxin. In contrast, incubation of the AC toxins with gangliosides prior to addition to target cells inhibited cAMP accumulation by pertussis AC toxin, but not anthrax AC toxin. To evaluate the role of lipids in the interaction of pertussis AC toxin with membranes, multicompartmental liposomes were loaded with a fluorescent marker and exposed to toxin. Pertussis AC toxin elicited marker release in a time- and concentration-dependent manner and required a minimal calcium concentration of 0.2 mM. These data demonstrate that the requirements for intoxication by the AC toxins from B. anthracis and B. pertussis are fundamentally different and provide a perspective for new approaches to study the entry processes.
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PMID:Adenylate cyclase toxins from Bacillus anthracis and Bordetella pertussis. Different processes for interaction with and entry into target cells. 250 10

The adenylate cyclase gene of Bacillus anthracis, encoding the edema factor, a component of anthrax toxin, has been cloned and expressed in Escherichia coli. Clones were selected by their capacity to complement the cyclase deficiency (cya-) of an E. coli strain expressing the eukaryotic protein calmodulin, an essential activator of B. anthracis adenylate cyclase. The protein expressed in E. coli was shown to exhibit adenylate cyclase activity only in the presence of calmodulin. Experiments using a coupled in vitro transcription-translation system revealed that the protein synthesized from the cloned DNA fragment was enzymatically active, upon addition of calmodulin, and could be immunoprecipitated by antibodies directed against purified Bordetella pertussis adenylate cyclase toxin. This indicates that the two calmodulin-dependent adenylate cyclase toxins are immunologically related.
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PMID:Cloning and expression of the calmodulin-sensitive Bacillus anthracis adenylate cyclase in Escherichia coli. 284 Nov 99

Bordetella pertussis and Bacillus anthracis produce extracytoplasmic adenylate cyclase toxins (AC toxins) with shared features including activation by calmodulin and the ability to enter target cells and catalyze intracellular cyclic AMP (cAMP) production from host ATP. The two AC toxins were evaluated for sensitivities to a series of inhibitors of known uptake mechanisms. Cytochalasin D, an inhibitor of microfilament function, abrogated the cAMP response to B. anthracis AC toxin (93%) but not the cAMP response elicited by B. pertussis AC toxin. B. anthracis-mediated intoxication of CHO cells was completely inhibited by ammonium chloride (30 mM) and chloroquine (0.1 mM), whereas the cAMP accumulation produced by B. pertussis AC toxin remained unchanged. The block of target cell intoxication by cytochalasin D could be bypassed when cells were first treated with anthrax AC toxin and then exposed to an acidic medium. These data indicate that despite enzymatic similarities, these two AC toxins intoxicate target cells by different mechanisms, with anthrax AC toxin entering by means of receptor-mediated endocytosis into acidic compartments and B. pertussis AC toxin using a separate, and as yet undefined, mechanism.
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PMID:Inhibitors of receptor-mediated endocytosis block the entry of Bacillus anthracis adenylate cyclase toxin but not that of Bordetella pertussis adenylate cyclase toxin. 289 41

The microorganisms responsible for the production of an infection may be considered to be in two classes: classical microbes and host-defined microbes. Classical microbes are those pathogens which fulfill the Koch-Henle postulates, and their isolation from a host indicates infection. They are not normally part of the body's normal flora, although they may be acquired by the host and enter into a passive relationship known as the carrier state. Examples of this type of microbe are Bacillus anthracis (anthrax), Yersinia pestis (plague), and Bordetella pertussis (whooping cough). Pathogens that require specific hosts have largely replaced the classical pathogen as a cause of infection in hospitalized patients. Especially in recent years, with the advent of new modes of anticancer treatment and the general ability of the medical community to extent a patient's life span by chemotherapy and innovative surgery, the contribution to morbidity and mortality by microbes has substantially increased. These host-specific pathogens are largely part of the body's normal flora. It is incumbent upon the clinical microbiologist to be able to distinguish the patient's normal microbial load, an increased load due to physiological factors, but not representing infection, and a significant change from normal which should be considered infection. The ability to distinguish infection from noninfection is one of the prime responsibilities of the clinical microbiology laboratory and has contributed to the development of the infectious disease subspecialty of internal medicine. This article will examine a critical question: Is there a relationship between the numbers of microorganisms isolated from a specimen and the production of infection, and, if so, does this relationship vary for the different anatomical sites of the body?
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PMID:Methods of quantitative microbiological analyses that support the diagnosis, treatment, and prognosis of human infection. 727 38

The potency tests for bacterial vaccines are quite diverse. For some products (pertussis, cholera, anthrax, typhoid and BCG vaccines) these are specified as Additional Standards in the Code of Federal Regulations. For other products (tetanus and diphtheria toxoids, plague vaccine) the testing is done according to so-called Minimum Requirements, which have less regulatory authority than Additional Standards. Still other products (e.g., polysaccharide conjugate vaccines, acellular pertussis vaccine, live oral typhoid) are tested according to individualized criteria that are contained in their specific Product License Applications. For some products there is inadequate knowledge of the pathogenic mechanisms and/or protective factors to design valid in vitro potency tests. In these cases, animal testing with subsequent serologic evaluation or challenge testing is often necessary. Examples would include vaccines such as cholera and plague vaccines. The FDA supports the elimination of animal testing when suitable alternatives are available. Thus, many of the potency tests, especially for newer products, rely on in vitro characterization. For example, the immunogenicity of conventional polysaccharide vaccines is largely proportional to their molecular weight. Potency testing therefore relies heavily on physical characterization in terms of composition, molecular weight, and quantity.
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PMID:Potency testing of bacterial vaccines for human use. 811 90

Cytotoxic T lymphocytes (CTL) recognize antigens derived from endogenously expressed proteins presented on the cell surface in the context of major histocompatibility complex (MHC) class I molecules. Because CTL are effective in antiviral and antitumor responses, the delivery of antigens to the class I pathway has been the focus of numerous efforts. Generating CTL by immunization with exogenous proteins is often ineffective because these antigens typically enter the MHC class II pathway. This review focuses on the usefulness of bacterial toxins for delivering antigens to the MHC class I pathway. Several toxins naturally translocate into the cytosol, where they mediate their cytopathic effects, and the mechanisms by which this occurs has been elucidated. Molecular characterization of these toxins identified the functional domains and enabled the generation of modified proteins that were no longer toxic but retained the ability to translocate into the cytosol. Thus, these modified toxins could be examined for their ability to carry peptides or whole proteins into the cytosolic processing pathway. Of the toxins studied-diphtheria, pertussis, Pseudomonas, and anthrax-the anthrax toxin appears the most promising in its ability to deliver large protein antigens and its efficiency of translocation.
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PMID:Delivery of antigens to the MHC class I pathway using bacterial toxins. 929 31

It has been shown in animal toxicity models that administration of Cyclosporine, CsA, to a pregnant mouse greatly increases the risk that the offspring will develop autoimmunity. Immunization starting at birth has been shown to prevent autoimmunity in other animal models of autoimmunity and early immunization is associated with the prevention of diabetes in humans. Experiments were performed to see if early immunization could also prevent CsA induced autoimmunity. Mice were injected with CsA during the first week of life and then immunized with killed human vaccines, including common pediatric vaccines, starting in the second week of life for a total of 3-4 doses. Administration of CsA during the first week of life resulted in the development of antigastric autoantibodies which were measured at week 8 of life. Only 12% of mice treated with CsA alone lacked anti-agastric antibodies compared to 61% in the group receiving the CsA and the diphtheria, tetanus, pertussis, and anthrax vaccines (p = 0.0005). The results indicate early immunization can prevent CsA induced autoimmunity and provide further evidence that the effect of starting immunization in the first month should be compared to starting immunization after 2 months in humans.
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PMID:Cyclosporine induced autoimmunity in newborns prevented by early immunization. 960 30

Antimicrobial prophylaxis is used by clinicians for the prevention of numerous infections, including sexually transmitted diseases, human immunodeficiency virus infection, tuberculosis, rheumatic fever, recurrent cellulitis, meningococcal disease, recurrent uncomplicated urinary tract infections in women, spontaneous bacterial peritonitis in patients with cirrhosis, influenza, malaria, infective endocarditis, pertussis, plague, anthrax, early-onset group B streptococcal disease in neonates, and animal bite wounds. Certain opportunistic infections such as Pneumocystis carinii pneumonia in immunocompromised patients also can be effectively prevented with primary antimicrobial prophylaxis. Perioperative antimicrobial prophylaxis is recommended for various surgical procedures to prevent surgical site infection. Optimal antimicrobial agents for prophylaxis are bactericidal, nontoxic, inexpensive, and active against the typical pathogens that cause surgical site infection postoperatively. To maximize its effectiveness, intravenous perioperative prophylaxis should be given within 30 to 60 minutes before the time of surgical incision. Antibiotic prophylaxis should be of short duration to decrease toxicity, antimicrobial resistance, and excess cost.
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PMID:Antimicrobial prophylaxis in adults. 1063 Jul 64

An investigation of the possible interactions between combinations of vaccines and pyridostigmine bromide (PB) has been undertaken in the guinea pig. This study is part of a research programme funded by the UK Government to determine any effects of the pretreatment regimes given to UK Forces during the Persian Gulf conflict of 1990-1991. The study was designed to simulate PB administration and to model multiple vaccination protocols that were experienced by UK Forces, modelling a "worst case" situation in which all ten vaccines and PB were administered within a short period of time. Seven of the vaccines were health and hygiene (H+H) vaccines given to protect against endemic diseases and two vaccines to protect against the biological warfare agents anthrax and plague. In addition, pertussis vaccine was administered as an adjuvant to reduce the time to achieve immunity against anthrax. Four groups of eight animals were treated with 1/20th, 1/10th or 1/5th human doses of vaccines or vehicles, respectively. The PB or saline was delivered by implanted 28 day mini-osmotic pumps to achieve a mean red blood cell acetylcholinesterase (AChE) inhibition of around 30%. Body weight, temperature, immunological response, biochemical indices and spontaneous activity were monitored for 72 days. Although immunological responses to bacterial vaccines were observed, there were no remarkable findings in the parameters measured other than minor changes in body weight (4.9% decrease at the 1/5th human dose of vaccines) and temperature increases in response to vaccination. Animals in all groups remained generally healthy and active without visible adverse signs throughout the study. Reproduced with the permission of Her Majesty's Stationery Office. Published by John Wiley & Sons, Ltd.
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PMID:Biological consequences of multiple vaccine and pyridostigmine pretreatment in the guinea pig. 1118 Feb 81


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