Zucker gegen Gifte: Die Shiga‐Toxine 1 und 2 sind die wichtigsten Giftstoffe von E. coli O157:H7, wobei Shiga 2 wirksamer ist als Shiga 1. Biotinylierte Glycokonjugate können zwischen den ...strukturhomologen Toxinen unterscheiden (siehe Formel; R = OH: Shiga‐1‐selektiv; R = NHAc: Shiga‐2‐selektiv). Diese synthetischen Substanzen fangen die Toxine effizient und ohne Störung durch die Probenmatrix ein.
The nucleotide sequence downstream from the
Bordetella resistance to killing (
brk) locus in
Bordetella pertussis was determined. Analysis of the sequence revealed an operon consisting of two highly ...predicted open reading frames (ORFs). The deduced amino-acid sequence of each ORF has strong homologies to the heat-shock proteins/chaperonins Cpn60 and Cpn10. The promoter contains consensus sequences for both σ32 and σ70 binding, and it possesses the
CIRCE regulatory inverted repeat. A potential Rho-independent terminator was identified and appears to be shared with the
brkA gene.
Muscle sympathetic nerve activity (MSNA) is increased in patients with heart failure compared with healthy subjects. We applied spectral and correlation techniques to determine if qualitative as well ...as quantitative differences in MSNA differentiate heart failure patients from healthy subjects. We recorded MSNA, heart rate, and respiration in 11 heart failure patients and 10 healthy humans. Our results are as follows. 1) Statistically significant low-frequency modulation of MSNA at 0.029 +/- 0.002 Hz (mean +/- SE; range 0.026-0.038 Hz) was found in 10 of 11 heart failure patients but in only 2 of 10 healthy controls (differences between groups, P < 0.01; chi 2 test). 2) Heart rate and respiration also demonstrated significant low-frequency modulation in a similar range. 3) Spectral and correlation techniques revealed that low-frequency modulation of MSNA was highly correlated with low-frequency modulation of respiration in heart failure patients, but not in healthy subjects. In contrast, low-frequency modulation of MSNA did not correlate well with low-frequency modulation of heart rate. In summary, low-frequency modulation of respiration is coupled to low-frequency modulation of MSNA in heart failure patients, but not in normal subjects. We speculate that this low-frequency modulation of respiration may represent subclinical Cheyne-Stokes breathing, which has marked qualitative effects on MSNA in patients with heart failure.
A mouse model for encephalopathy induced by pertussis immunization has been described; it has features that closely resemble some of the severe reactions, including seizures and a shock-like state ...leading to death, occasionally seen after administration of Bordetella pertusssis (whooping cough) vaccine. Susceptibility to encephalopathy maps to genes of the major histocompatibility complex and correlates as well with the genetic regulation of the level of antibody response to bovine serum albumin. In this study we have investigated which bacterial determinant is responsible for the encephalopathy. Two lines of evidence implicate pertussis toxin as the active bacterial component. Single-site mutants of B. pertussis with single affected virulence factors were tested. A mutant that produces a defective pertussis toxin had greatly diminished capacity to induce encephalopathy, whereas a hemolysin- and adenylate-cyclase-deficient avirulent mutant had the same activity in the mouse model as a virulent strain. Purified pertussis toxin plus bovine serum albumin was tested and found to induce the lethal encephalopathy, demonstrating that the toxin was the critical constituent of B. pertussis responsible for encephalopathy.
To determine if there is a rationale for compartmentalized immunostimulation, we have carried out a series of experiments to evaluate whether intratracheal delivery of interferon-gamma ...(rRatIFN-gamma) can activate rat bronchoalveolar lavage cells (BAL) for in vitro expression of tumoricidal activity against xenogeneic P815 tumor cells and enhanced in vitro microbicidal activity against the intracellular protozoan Toxoplasma gondii. Treatment of rat alveolar macrophages in vitro activates them for both of these activities as well as enhanced production of superoxide anion. We found that a single intratracheal dose of 5,000-10,000 units of rRatIFN-gamma activated rat BAL for both microbicidal and tumoricidal activity. To determine the duration of activation, microbicidal activity was determined 1, 2, 3, 5, and 7 days after a single intratracheal dose of 5,000 units of IFN. Enhanced microbicidal activity was maintained through day 3 but returned to control levels by day 5. Alveolar macrophages always accounted for the majority of cells in the lavage populations. However, intratracheal IFN caused an increase in the number of polymorphonuclear leukocytes and lymphocytes in the lavageable cells and, although these cells were always in the minority, they may have contributed to both the tumoricidal and microbicidal activity of the lavage cells. These studies demonstrate that local administration of an immunostimulant can activate pulmonary defense cells and may be a feasible route of drug delivery for prophylaxis against pulmonary infections.
Systemic administration of biologic response modifiers (BRMs) is often limited by serious adverse effects. Local delivery of a BRM may provide a means to avoid systemic side effects while enhancing ...host defense. To test this hypothesis, the effects of intratracheal administration of the interferon inducer polyinosinic-polycytidilic acid (Poly-I:C) were examined. We demonstrated that intratracheal administration of Poly-I:C in rats results in alterations in pulmonary lavage cell number, population distribution, and function, suggestive of cellular activation. Following intratracheal instillation of 15, 75, or 150 mg of Poly-I:C, we observed a dose-dependent increase in Fc receptor-mediated phagocytosis, a dose-independent tumoricidal activity directed against xenogeneic P815 murine mastocytoma target cells, and a dose-independent decrease in superoxide anion (O2-) generation. With the exception of O2- generation, these functions returned to normal control levels by 7 days after a single dose of Poly-I:C. Thus, localized administration of Poly-I:C enhanced the host defense capability of pulmonary lavage cells, providing a rationale for compartmentalized immunoprophylaxis in the lung.
Individuals with limited literacy have low rates of cancer screening and more advanced cancer when cancer is detected. We implemented breast cancer screening at an adult literacy center to see if ...students would participate and determine the rate of abnormalities detected.
The Anchorage Literacy Project (ALP), in collaboration with Providence Cancer Center (PCC), offered breast cancer screening, including mammograms, on site at ALP to all 40 female ALP students aged > or =40. Prior to screening, PCC and ALP staff provided education to students about breast cancer screening and mammograms, and information about the Alaska Breast and Cervical Health Check program that would pay for treatment if cancer was detected.
Twenty-one women underwent screening. Three (14%) had significant abnormalities.
Cancer screening can be provided on site in adult literacy programs. The rate of abnormalities detected through such screening may be higher than the rate in the general population.
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