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)

Nitric oxide-releasing compounds were shown to activate an ADP-ribosyltransferase activity in the cytosol of Dictyostelium discoideum. The enzyme ADP-ribosylated a cytosolic protein of approximately 41 kDa, p41. Neither cGMP nor GTP and its analogues affected this ADP-ribosylation. p41 differs from other substrates ADP-ribosylated by cholera, pertussis, or diphtheria toxins. Treatment of ADP-ribosylated p41 with snake venom phosphodiesterase released adenosine 5'-monophosphate, indicating a mono-ADP-ribose-protein linkage. This linkage was stable to neutral hydroxylamine but was sensitive to mercury ions and iodomethane, suggesting an attachment to a cysteine residue. Treatment of intact cells with nitric oxide-releasing compounds appeared to stimulate the ADP-ribosylation of p41 and this modification was reversible.
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PMID:Nitric oxide stimulates the ADP-ribosylation of a 41-kDa cytosolic protein in Dictyostelium discoideum. 135 80

Intracellular calcium [Ca2+]i acts as an important intracellular messenger system for secretion and synthesis, cell growth and differentiation. In order to demonstrate definitively that a change in [Ca2+]i is responsible for a physiological event, one has to measure [Ca2+]i directly within intact cells and correlate the time course of any [Ca2+]i changes with the biological response. Measurement of [Ca2+]i was done in a single cell preloaded with fluorescent Ca indicator fura2 using a fluorescent unit (lonoquant) consisting of an inverted microscope (Zeiss IM 35) equipped with a mercury lamp and a rotating filter wheel containing filters at wavelengths of 340 and 380 nm. Cells were alternately excited and emission signals of fura 2-loaded cells were collected by a photomultiplier and recorded on-line on a computer screen. As a model system, the rat C-cell carcinoma cell line rMTC 6-23 secreting calcitonin was used. An acute elevation of extracellular calcium resulted in an increase in [Ca2+]i within 5 sec and rapid release of preformed calcitonin. This tight linkage between extracellular calcium and [Ca2+]i is mediated via Ca influx through voltage-dependent Ca channels. These channels are modulated by intracellular cAMP, yielding a rhythmic oscillation of [Ca2+]i, as well as by extracellular somatostatin blocking the Ca channel and the increase of [Ca2+]i via a pertussis toxin sensitive Gi protein. The change in [Ca2+]i is associated with changes in calcitonin secretion, confirming the stimulus secretion coupling via voltage-dependent Ca channels in C-cells.
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PMID:Measurement of free cytosolic calcium in single cells: method and application. 135 76

To elucidate mechanisms of mercury toxicity, the cell membrane potential has been determined continuously in cultured kidney (MDCK)-cells during reversible application of mercury ions to extracellular perfusate. Exposure of the cells to 1 microM mercury ions is followed by rapid, sustained, and slowly reversible hyperpolarization of the cell membrane, increase of cell membrane potassium selectivity, and decrease of cell membrane resistance. Thus, mercury ions enhance the potassium conductance of the cell membrane. Half maximal hyperpolarizing effect is elicited by approximately 0.2 microM. Higher concentrations of mercury ions (greater than 10 microM) eventually depolarize the cell membrane. At extracellular calcium activity reduced to less than 0.1 microM, 1 microM mercury ions still leads to a sustained hyperpolarization and increase of potassium selectivity of the cell membrane. As evident from fluorescence measurements, 10 microM, but not 1 microM mercury ions leads to a rapid increase of intracellular calcium activity. Pretreatment of the cells with either pertussis toxin or cholera toxin does not blunt the hyperpolarizing effect of mercury ions. In conclusion, mercury ions activate the potassium conductance by a mechanism independent of increase of intracellular calcium activity and of cholera toxin- or pertussis toxin-sensitive G-proteins. This activation of potassium conductance may account for early effects of mercury intoxication, such as kaliuresis.
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PMID:Activation of cell membrane potassium conductance by mercury in cultured renal epithelioid (MDCK) cells. 199 17

Two volumetric (electrocapacity plethysmography and mercury volumetry) and two linear methods (a new type of scale and a calliper rule) for rat-paw oedema measurement used in local reactivity of combined vaccines containing a B. pertussis component were compared. The reproducibility and sensitivity of the methods was tested on a diphtheria-tetanus-pertussis vaccine and a toxic pertussis suspension. The linear methods proved more adequate for measuring small and chiefly unidirectionally (vertically) progressing oedemas.
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PMID:Comparative study of rat-paw oedema tests for assessing reactivity of B. pertussis-containing combined vaccines. 288 22

The effects of halide salts of mercury, platinum and palladium on the synthesis of total and specific serum IgE and of total IgG were studied in groups of Hooded Lister rats immunised with antigen (ovalbumin) in the presence and absence of an adjuvant (Bordetella pertussis vaccine or aluminium hydroxide). Repeated intraperitoneal injections of mercuric chloride alone rapidly enhanced total IgE levels in control rats, independent of adjuvant. Injections of the platinum salt, however, elevated total IgE levels more slowly and then only in the B. pertussis-treated group. The halide salt of palladium was ineffective. In rats immunised with antigen and adjuvant, mercury treatment rapidly produced enhancement of the titre-specific IgE antibodies, whereas treatment with platinum again raised these levels more slowly. The palladium salt had no such effect.
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PMID:Enhancement of antibody production by mercury and platinum group metal halide salts. Kinetics of total and ovalbumin-specific IgE synthesis. 373 32

The role of G proteins in the functional modulation and potentiation by mercury chloride of the GABA(A) receptor-channel complex in rat dorsal root ganglion neurons was studied by using the whole-cell patch clamp technique. Stimulation of Gs proteins by application of GTP-gamma-S in the patch pipette or by incubation of neurons with cholera toxin reduced GABA-induced currents, suggesting modulation of GABA-induced currents via a Gs-protein-coupled pathway. GDP-beta-S in the pipette solution or pretreatment of dorsal root ganglion neurons with pertussis toxin suppressed GABA-induced currents, suggesting that basal Gi/Go-protein activity positively modulates the GABA(A) receptor-channel complex. Mercury chloride potentiation of GABA-activated currents was blocked by application of GTP-gamma-S in the patch pipette or by incubation of neurons with cholera toxin. Mercury chloride potentiation of GABA-activated currents was blocked by application of GDP-beta-S in the patch pipette or by incubation of neurons with pertussis toxin. G proteins, probably Gi/Go proteins, underlie the mercury chloride potentiation of GABA-induced currents.
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PMID:The role of G proteins in the activity and mercury modulation of GABA-induced currents in rat neurons. 951 33

The archetypal two-component signal transduction systems include a sensor histidine kinase and a response regulator, which consists of a receiver CheY-like domain and a DNA-binding domain. Sequence analysis of the sensor kinases and response regulators encoded in complete bacterial and archaeal genomes revealed complex domain architectures for many of them and allowed the identification of several novel conserved domains, such as PAS, GAF, HAMP, GGDEF, EAL, and HD-GYP. All of these domains are widely represented in bacteria, including 19 copies of the GGDEF domain and 17 copies of the EAL domain encoded in the Escherichia coli genome. In contrast, these novel signaling domains are much less abundant in bacterial parasites and in archaea, with none at all found in some archaeal species. This skewed phyletic distribution suggests that the newly discovered complexity of signal transduction systems emerged early in the evolution of bacteria, with subsequent massive loss in parasites and some horizontal dissemination among archaea. Only a few proteins containing these domains have been studied experimentally, and their exact biochemical functions remain obscure; they may include transformations of novel signal molecules, such as the recently identified cyclic diguanylate. Recent experimental data provide the first direct evidence of the participation of these domains in signal transduction pathways, including regulation of virulence genes and extracellular enzyme production in the human pathogens Bordetella pertussis and Borrelia burgdorferi and the plant pathogen Xanthomonas campestris. Gene-neighborhood analysis of these new domains suggests their participation in a variety of processes, from mercury and phage resistance to maintenance of virulence plasmids. It appears that the real picture of the complexity of phosphorelay signal transduction in prokaryotes is only beginning to unfold.
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PMID:Novel domains of the prokaryotic two-component signal transduction systems. 1155 34

Thimerosal is an ethylmercury (49.55% mercury by weight) preservative historically added to some vaccines. Toxicokinetic studies showed children in the United States received doses of mercury from Thimerosal-containing vaccines (TCVs) in excess of safety guidelines. In the United States during the 1990s, diphtheria-tetanus-pertussis (DTP) and Haemophilus influenzae type b (Hib) vaccines (maximally, 50 mug mercury per joint administration) and diphtheria-tetanus-pertussis-Haemophilus influenzae type b (DTPH) vaccines (25 mug mercury per administration) were given to children in the same childhood vaccination schedule at 2, 4, 6, and 15-18 mo, so that children receiving DTP and Hib vaccines may have maximally received an additional 100 mug more mercury exposure from TCVs than children administered DTPH vaccines. A case-control epidemiological study of neurodevelopmental disorders (NDs) reported to the Vaccine Adverse Event Reporting System (VAERS) (online public access version; updated 31 August 2004) following administration of DTP vaccines in comparison DTPH vaccines manufactured by Lederle Laboratories (Pearl River, NY) from 1994 through 1998 was undertaken. Significantly increased odds ratios for autism, speech disorders, mental retardation, infantile spasms, and thinking abnormalities reported to VAERS were found following DTP vaccines in comparison to DTPH vaccines with minimal bias or systematic error. Additional ND research should be undertaken in the context of evaluating mercury-associated exposures, especially since in 2005 the Institute of Medicine issued a report calling into question handling of vaccine safety data by the National Immunization Program of the Centers for Disease Control and Prevention.
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PMID:An evaluation of the effects of thimerosal on neurodevelopmental disorders reported following DTP and Hib vaccines in comparison to DTPH vaccine in the United States. 1676 80

The complete 41,268 bp nucleotide sequence of the IncP-1beta plasmid pBP136 from the human pathogen Bordetella pertussis, the primary aetiological agent of whooping cough, was determined and analysed. This plasmid carried a total of 46 ORFs: 44 ORFs corresponding to the genes in the conserved IncP-1beta backbone, and 2 ORFs similar to the XF1596 and XF1597 genes with unknown function of the plant pathogen Xylella fastidiosa. Interestingly, pBP136 had no accessory genes carrying genetic traits such as antibiotic or mercury resistance and/or xenobiotic degradation. Moreover, pBP136 had only two of the kle genes (kleAE) that have been reported to be important for the stability of IncP-1 plasmid in Pseudomonas aeruginosa. Phylogenetic analysis of the Kle proteins revealed that the KleA and KleE of pBP136 were phylogenetically distant from those of the present IncP-1 plasmids. In contrast, IncC1 and KorC, encoded upstream and downstream of the kle genes respectively, and the replication-initiation protein, TrfA, were closely related to those of the IncP-1beta 'R751 group'. These results suggest that (i) pBP136 without any apparent accessory genes diverged early from an ancestor of the present IncP-1beta plasmids, especially those of the R751 group, and (ii) the kle genes might be incorporated independently into the backbone region of the IncP-1 plasmids for their stable maintenance in various host cells.
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PMID:Plasmid pBP136 from Bordetella pertussis represents an ancestral form of IncP-1beta plasmids without accessory mobile elements. 1715 99

Possible connections between immunization and developmental disorders, most notably autistic disorders, have been the subject of a great deal of debate and have caused much concern for parents who want to make the safest choices for their children. Anxiety has risen steadily since the mid-1990s, when a medical investigative team led by A Wakefield postulated that the measles-mumps-rubella (MMR) vaccine may be a causative factor in the development of autism spectrum disorder. Since this initial publication, immunization remains controversial for some parents and the uptake of the MMR vaccine has fallen in some countries, despite much discussion regarding the safety of MMR, a lack of evidence for an association between MMR and autism, and the risks of insufficient protection against wild measles virus infection. The Canadian uptake of MMR in 1998 was 95%, but data do not exist to document any change in Canada since that time. Many clinicians are concerned that the uptake in younger siblings of children with autism is considerably lower.Further anxiety for parents has been caused by the suggested association between developmental disorders and mercury toxicity due to thimerosal, which is used as a preservative in some vaccines. Many Canadian parents, while continuing to seek chelation therapy in response to this suggestion, are not aware that, in Canada, thimerosal has never been added to MMR, and has not been present in diphtheria-pertussis-tetanus-poliomyelitis or pentavalent vaccines since 1992. It is found in only Hepatitis B vaccine in some provinces.The present article is intended to be a guide for physicians as they counsel parents.
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PMID:Immunization and children at risk for autism. 2004 42


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