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Alpha Adrenergic Modulation of Impulse Initiation in Normal and Ischemic Cardiac Fibers
Published in Samuel Sideman, Rafael Beyar, Analysis and Simulation of the Cardiac System — Ischemia, 2020
To test whether this same control mechanism occurred in cardiac tissue in situ, we performed a series of experiments on adult canine Purkinje fibers.31 Some of these were incubated in pertussis toxin for 24 h to ADP ribosylate the 41-kDa regulatory protein; others were incubated in Tyrode’s solution, alone, as controls. We found that of the control fibers incubated in Tyrode’s solution, about two thirds showed a decrease in automaticity and a relatively high pertussis toxin substrate (approximately 25 fmol/mg of crude protein); the other one third showed an increase in automaticity and a lower substrate level (about 15 fmol/mg). Exposure to graded concentrations of pertussis toxin reduced the concentrations of substrate that were detectable, until at 0.5 μg/ml of toxin, no substrate at all was detectable. As the substrate concentration decreased, the proportion of fibers showing a decrease in automaticity also diminished until, at 0.5 μg/ml of toxin, all fibers showed increased automaticity.
Bordetella pertussis
Published in Firza Alexander Gronthoud, Practical Clinical Microbiology and Infectious Diseases, 2020
The acellular vaccine (DTaP) was introduced after 1997 and contains up to five purified antigens: pertussis toxin (PT), filamentous haemagglutinin (FHA), pertactin (PRN) and fimbria proteins 2 and 3. The upside of DTaP is a similar efficacy as DTwP, but lower rate of sideeffects. The downside is a shorter-term protection compared to DTwP.
Melanoma Growth Stimulatory Activity: Physiology, Biology, Structure/Function, and Role in Disease
Published in Richard Horuk, Chemoattractant Ligands and Their Receptors, 2020
Ann Richmond, Rebecca L. Shattuck
Once G-proteins uncouple from the receptor after the ligand binds, in some cells there is an activation of phospholipase C (PLC). Usually the β1 and β2 isoforms are activated.122–125 Interestingly, for the chemokine receptors, there is as yet very little information regarding the activation of PLC after receptor binding. IL-8 has been shown to activate phospholipase D (PLD) in neutrophils,126 while MGSA/GROα and NAP-2 do not.127 Pretreatment with pertussis toxin inhibited this activity.126 These data suggest that the effects of IL-8 on PLD activity are mediated through the IL-8 RA and not the IL-8 RB. The IL-8 stimulation of PLD activity was reduced or eliminated when cells were pretreated with the tyrosine kinase inhibitors erbstatin and herbimycin A, respectively. L’Heureux et al. concluded that while tyrosine kinase activation in response to IL-8 is necessary for stimulation of PLD activity, it is not sufficient.127 IL-8 stimulated both significant superoxide production and CD1 lb expression, whereas MGSA/GROα and NAP-2 did not, thus indicating that the signal transduction through the A and B receptors in neutrophils is apparently different, though one cannot rule out the possibility that some of the differences are derived from expression of differing numbers of these two receptors on neutrophils.
Exposure to a mixture of 23 chemicals associated with unconventional oil and gas operations alters immune response to challenge in adult mice
Published in Journal of Immunotoxicology, 2021
Colleen T. O’Dell, Lisbeth A. Boule, Jacques Robert, Steve N. Georas, Sophia Eliseeva, B. Paige Lawrence
After 8 weeks on water containing the mixture or control, mice were immunized by subcutaneous injection of an emulsion of myelin oligodendrocyte glycoprotein (MOG35–55; 200 μg/mouse; AnaSpec, Freemont, CA, USA) and complete Freund's adjuvant (4 mg/ml; M. Tuberculosis; Becton Dickinson, Franklin Lakes, NJ, USA) (Stromnes and Goverman 2006). This is considered Day 0 for triggering EAE. Two IP doses of pertussis toxin (400 ng/mouse; List Biologicals, Campbell, CA, USA), were also administered; one contemporaneously with MOG peptide and the other 2 days later. Mice were maintained on drinking water containing the chemical mixture or vehicle control following immunization and for the duration of the disease. After administration of MOG peptide, disease progression was monitored and scored every other day for 42 days, using the following scoring system: 0 = normal mouse, 1 = limp tail, 2 = limp tail and hind limb weakness, 3 = partial hind limb paralysis, 4 = complete hind limb paralysis, 5 = moribund (Robinson et al. 2014). The percentage and number of T-cell subsets in the cervical lymph nodes were determined on Day 42 after immunization.
Pertussis-like syndrome often not associated with Bordetella pertussis: 5-year study in a large children’s hospital
Published in Infectious Diseases, 2020
Qin Xiong, Shiying Hao, Lei Shen, Jian Liu, Tingting Chen, Guoqin Zhang, Yu-juan Huang
The diagnosis of PLS was made for patients who met the clinical diagnostic criteria of pertussis but with indeterminate aetiology. In this study we found that the majority (96.0%) of PLS patients were infants less than 12 months. Infants are at increased risk of airway obstruction, due to unique anatomical features they have such as narrow trachea and bronchus, soft cartilage, lack of elastic tissue, poor airway support ability, poor cilia movement, and weak sputum elimination ability. Infants’ respiratory muscles are underdeveloped, and their lungs cannot expand sufficiently, leading to hypoxia and carbon dioxide storage. In addition, their poor innate immune response limits the ability of removing foreign bodies and pathogens that are invading the respiratory tract. When the pathogen is immersed in the respiratory tract, the pathogen adheres to the surface of ciliated epithelial cells of throat and bronchiole mucosa, where a variety of toxins are produced. The toxins can cause epithelial cell cilia paralysis and cell degeneration, leading to the accumulation of mucus and necrotic epithelial cells in the small bronchi. Such accumulation blocks the secretion and irritates the peripheral nerves of the respiratory tract, which induces whooping cough, rash, vomiting, and other typical symptoms of pertussis [25]. Pertussis toxin is associated with the onset of pertussis-like symptoms. It is not a necessary condition to cause pertussis-like symptoms though.
Transgenic rice seeds expressing altered peptide ligands against the M3 muscarinic acetylcholine receptor suppress experimental sialadenitis-like Sjögren’s syndrome
Published in Modern Rheumatology, 2020
Hanae Kudo, Hiroto Tsuboi, Hiromitsu Asashima, Hiroyuki Takahashi, Yuko Ono, Saori Abe, Fumika Honda, Yuya Kondo, Yuhya Wakasa, Fumio Takaiwa, Makoto Takano, Minoru Matsui, Isao Matsumoto, Takayuki Sumida
The M3R−/− mice were immunized intradermally at the base of the tail with an M3R peptide mixture (N-terminal regions: N1 [MTLHSNSTTSPLFPNISSSWVHSPSEAGLP], N2 [VHSPSEAGLPLGTVSQLDSYNISQTSGNFS], N3 [NISQTSGNFSSNDTSSDPLGGHTIWQV]; and 3 extracellular loops: first [FTTYIIMNRWALGNLACDLW], second [QYFVGKRTVPPGECFIQFLSEP], third [VLVNTFCDSCIPKTYWNLGY]; each 20 µg) emulsified with Freund’s incomplete adjuvant (IFA; Difco) containing 250 mg of inactivated Mycobacterium tuberculosis (H37Ra; Difco). Pertussis toxin (500 mg; Sigma-Aldrich) was injected intraperitoneally on the day of immunization. Ten days after the immunization, each mouse received another intradermal injection of the same peptides emulsified with IFA containing H37Ra. On day 20 after the first immunization, splenocytes from the M3R−/− mice were isolated and resuspended in PBS, and 1 × 107 cells were injected intravenously into the Rag1−/− mice (Figure 2).