scholarly journals Interferon gamma increases survival in urine experimental cryptococcosis

1995 ◽  
Vol 37 (5) ◽  
pp. 391-396 ◽  
Author(s):  
Amadeo J. Bava ◽  
Javier Afeltra ◽  
Ricardo Negroni ◽  
Roberto A. Diez

Systemic disease by Cryptococcus neoformans (C. neoformans) is a common opportunistic infection in immunodeficient patients. Cellular immunity seems to be the most important determinant of resistance. The aim of this study was to assess the effect of recombinant rat interferon gamma (IFN-gamma) in murine cryptococcosis (Balb/c mice infected by IP route with the Rivas strain of C. neoformans), evaluating survival time, macroscopic and microscopic examination of the organs, and massive seeding of brain homogenate. IFN-gamma treatment, at a daily dose of 10,000 IU, did not modify significantly these variables when mice were challenged with a high inoculum (10(7) yeasts) and treatment was delayed to 5 days after infection (median survival 21 days in control mice vs. 23 days in IFN-treated). Another set of experiments suggested that IFN-gamma treatment, at a dose of 10,000 IU/day, begun at the moment of infection could be useful (it prolonged survival from 20 to 28 days, although the difference did not achieve statistical signification). When used simultaneously with infection by 3.5 x 10(5) yeasts, IFN-gamma at 10,000 IU/day for 15 days significantly prolonged survival of mice (p = 0.004). These results suggest that, depending on the experimental conditions, IFN-gamma can improve survival of mice infected with a lethal dose of C. neoformans.

2017 ◽  
Vol 235 (12) ◽  
pp. 3585-3592 ◽  
Author(s):  
S. Van der Stigchel ◽  
R. S. Hessels ◽  
J. C. van Elst ◽  
C. Kemner

Abstract Attentional disengagement is important for successful interaction with our environment. The efficiency of attentional disengagement is commonly assessed using the gap paradigm. There is, however, a sharp contrast between the number of studies applying the gap paradigm to clinical populations and the knowledge about the underlying developmental trajectory of the gap effect. The aim of the present study was, therefore, to investigate attentional disengagement in a group of children aged 9–15. Besides the typically deployed gap and the overlap conditions, we also added a baseline condition in which the fixation point was removed at the moment that the target appeared. This allowed us to reveal the appropriate experimental conditions to unravel possible developmental differences. Correlational analyses showed that the size of the gap effect became smaller with increasing age, but only for the difference between the gap and the overlap conditions. This shows that there is a gradual increase in the capacity to disengage visual attention with increasing age, but that this effect only becomes apparent when the gap and the overlap conditions are compared. The gradual decrease of the gap effect with increasing age provides additional evidence that the attentional system becomes more efficient with increasing age and that this is a gradual process.


1994 ◽  
Vol 179 (5) ◽  
pp. 1437-1444 ◽  
Author(s):  
B D Car ◽  
V M Eng ◽  
B Schnyder ◽  
L Ozmen ◽  
S Huang ◽  
...  

Antibody neutralization studies have established interferon gamma (IFN-gamma) as a critical mediator of endotoxic shock. The advent of IFN-gamma receptor negative (IFN gamma R-/-) mutant mice has enabled a more direct assessment of the role of IFN-gamma in endotoxin (lipopolysaccharide [LPS]-induced shock. We report that IFN gamma R-/- mice have an increased resistance to LPS-induced toxicity, this resistance manifesting well before the synthesis and release of LPS-induced IFN-gamma. LPS-induced lymphopenia, thrombocytopenia, and weight loss seen in wild-type mice were attenuated in IFN gamma R-/- mice. IFN gamma R-/- mice tolerated 100-1,000 times more LPS than the minimum lethal dose for wild-type mice in a D-galactosamine (D-GalN)/LPS model. Serum tumor necrosis factor (TNF) levels were 10-fold reduced in mutant mice given LPS or LPS/D-GalN. Bone marrow and splenic macrophages from IFN gamma R-/- mice had a four- to sixfold decreased LPS-binding capacity which correlated with similar reduction in CD14. Serum from mutant mice reduced macrophage LPS binding by a further 50%, although LPS binding protein was only 10% reduced. The expression of TNF receptor I (p55) and II (p75) was identical between wild-type and mutant mice. Thus, depressed TNF synthesis, diminished expression of CD14, and low plasma LPS-binding capacity, in addition to blocked IFN-gamma signaling in the mutant mice, likely to combine to manifest in the resistant phenotype of IFN gamma R-/- mice to endotoxin.


1991 ◽  
Vol 11 (5) ◽  
pp. 2718-2722
Author(s):  
D Radzioch ◽  
L Varesio

Treatment of macrophages with interferon-gamma (IFN gamma) strongly decreased the induction of c-fos mRNA by 12-O-tetradecanoylphorbol-13-acetate (TPA), lipopolysaccharide, or calcium ionophore A23187 in macrophages. Under the same experimental conditions, IFN gamma induced oligo(A) synthetase mRNA and did not affect the constitutive expression of transforming growth factor beta mRNA, indicating that IFN gamma did not induce general degradation of mRNAs. Run-on experiments indicated that c-fos was constitutively transcribed at low levels and that TPA augmented c-fos transcription. IFN gamma did not inhibit constitutive or TPA-induced c-fos transcription. However, IFN gamma decreased c-fos mRNA stability, as assessed by measuring the half-life of c-fos mRNA in actinomycin D-treated cells. These results indicated that IFN gamma inhibited c-fos mRNA induction by TPA at the posttranscriptional level.


1991 ◽  
Vol 11 (5) ◽  
pp. 2718-2722 ◽  
Author(s):  
D Radzioch ◽  
L Varesio

Treatment of macrophages with interferon-gamma (IFN gamma) strongly decreased the induction of c-fos mRNA by 12-O-tetradecanoylphorbol-13-acetate (TPA), lipopolysaccharide, or calcium ionophore A23187 in macrophages. Under the same experimental conditions, IFN gamma induced oligo(A) synthetase mRNA and did not affect the constitutive expression of transforming growth factor beta mRNA, indicating that IFN gamma did not induce general degradation of mRNAs. Run-on experiments indicated that c-fos was constitutively transcribed at low levels and that TPA augmented c-fos transcription. IFN gamma did not inhibit constitutive or TPA-induced c-fos transcription. However, IFN gamma decreased c-fos mRNA stability, as assessed by measuring the half-life of c-fos mRNA in actinomycin D-treated cells. These results indicated that IFN gamma inhibited c-fos mRNA induction by TPA at the posttranscriptional level.


1999 ◽  
Vol 46 (3) ◽  
pp. 693-702 ◽  
Author(s):  
K N Al-Nedawi ◽  
Z Pawłowska ◽  
C S Cierniewski

The presence of protein kinase activity and its phosphorylated products has been demonstrated on the outer surface of the plasma membrane of endothelial cells. Extracellular phosphorylation was detected by incubation of primary endothelial cells (HUVEC's) and endothelial cell line EA.hy 926 with [gamma-32P]ATP. The reaction products were subjected to SDS/PAGE, autoradiography and scanning densitometry. Under the experimental conditions, five proteins with apparent molecular masses of 19, 23, 55, 88, and 110 kDa were prominently phosphorylated in both types of cells. Phosphorylation of the 19 kDa protein was the most rapid reaching maximum after 60 s and then the protein became dephosphorylated. Ecto-protein kinases responsible for the surface labeling of membrane proteins were characterized by using (a) protein kinase C inhibitors: K-252b, chelerythrine chloride, and [Ala113] myelin basic protein (104-118), (b) protein kinase A inhibitor Kemptide 8334, and (c) casein kinase II inhibitor 5,6-dichloro-1-beta-D-ribofuranosyl benzimidazole (DRB). Stimulation of endothelial cells with tumor necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma) is associated with 20-80% reduction of extracellular phosphorylation of all membrane proteins. IFN gamma bound to membrane receptors becomes rapidly phosphorylated. Only in the case of IFN gamma it was associated with the appearance of a strongly phosphorylated band of 17 kDa corresponding to IFN gamma itself. Phosphorylation of this 17 kDa exogenous substrate was prevented by an ecto-kinase inhibitor K-252b. The existence of ecto-phosphoprotein phosphatase activity in endothelial cells was evidenced by testing the effect of microcystin LR--a membrane impermeable reagent that inhibits both PP-1 and PP-2a phosphoprotein phosphatases. The extent of phosphorylation of 19 kDa and 110 kDa phosphoproteins significantly increased in the presence of microcystin. Our results suggest the presence of at least two ecto-kinase activities on endothelial cells that may play a significant role(s) in the regulation of cytokines function.


1998 ◽  
Vol 36 (5) ◽  
pp. 269-273
Author(s):  
SZKARADKIEWICZ ◽  
SZPONAR ◽  
KRZEMINSKA-JASKOWIAK ◽  
TUECKA

Membranes ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 460
Author(s):  
Bastiaan Blankert ◽  
Bart Van der Bruggen ◽  
Amy E. Childress ◽  
Noreddine Ghaffour ◽  
Johannes S. Vrouwenvelder

The manner in which membrane-fouling experiments are conducted and how fouling performance data are represented have a strong impact on both how the data are interpreted and on the conclusions that may be drawn. We provide a couple of examples to prove that it is possible to obtain misleading conclusions from commonly used representations of fouling data. Although the illustrative example revolves around dead-end ultrafiltration, the underlying principles are applicable to a wider range of membrane processes. When choosing the experimental conditions and how to represent fouling data, there are three main factors that should be considered: (I) the foulant mass is principally related to the filtered volume; (II) the filtration flux can exacerbate fouling effects (e.g., concentration polarization and cake compression); and (III) the practice of normalization, as in dividing by an initial value, disregards the difference in driving force and divides the fouling effect by different numbers. Thus, a bias may occur that favors the experimental condition with the lower filtration flux and the less-permeable membrane. It is recommended to: (I) avoid relative fouling performance indicators, such as relative flux decline (J/J0); (II) use resistance vs. specific volume; and (III) use flux-controlled experiments for fouling performance evaluation.


2021 ◽  
Vol 11 (15) ◽  
pp. 6900
Author(s):  
Su-Kyung Sung ◽  
Sang-Won Han ◽  
Byeong-Seok Shin

Skinning, which is used in skeletal simulations to express the human body, has been weighted between bones to enable muscle-like motions. Weighting is not a form of calculating the pressure and density of muscle fibers in the human body. Therefore, it is not possible to express physical changes when external forces are applied. To express a similar behavior, an animator arbitrarily customizes the weight values. In this study, we apply the kernel and pressure-dependent density variations used in particle-based fluid simulations to skinning simulations. As a result, surface tension and elasticity between particles are applied to muscles, indicating realistic human motion. We also propose a tension yield condition that reflects Tresca’s yield condition, which can be easily approximated using the difference between the maximum and minimum values of the principal stress to simulate the tension limit of the muscle fiber. The density received by particles in the kernel is assumed to be the principal stress. The difference is calculated by approximating the moment of greatest force to the maximum principal stress and the moment of least force to the minimum principal stress. When the density of a particle increases beyond the yield condition, the object is no longer subjected to force. As a result, one can express realistic muscles.


2021 ◽  
Vol 186 (Supplement_1) ◽  
pp. 681-687
Author(s):  
Mark Pitkin ◽  
Laurent Frossard

ABSTRACT Introduction Osseointegrated implants for direct skeletal attachment of transtibial prosthesis carry risks that are yet to be fully resolved, such as early loosening, mechanical failure of percutaneous and medullar parts of implant, periprosthetic issues, and infections. Underloading could lead to early loosening and infection. Overloading might compromise the bone–implant interface. Therefore, Goldilocks loading regimen applied by transtibial bone-anchored prostheses is critical for safe and efficient development of osseointegration around the implant during rehabilitation and beyond. We hypothesized that Goldilocks loading could be achieved when ambulating with a so-called anthropomorphic prosthetic ankle showing moment–angle relationship similar to a sound ankle. Materials and Methods Quantitative characteristics of the moment–angle curve of the sound ankle during dorsiflexion phase of a free-pace walking were extracted for 4 able-bodied participants (experiment 1). A slope of the moment–angle curve (stiffness) was calculated twice: for the first half and for the second half of the moment–angle curve. The difference of stiffnesses (those at the second half minus at the first half) was called the index of anthropomorphicity (IA). By definition, positive IA is associated with concave shape of the moment–angle curve, and the negative IA is associated with convex shape. In experiment 2, the same recordings and calculations were performed for 3 participants fitted with transtibial osseointegrated fixation during walking with their usual feet and the Free-Flow Foot (Ohio Willow Wood). The Free-Flow Foot was selected for its anthropomorphicity demonstrated in the previous studies with amputees using traditional socket attachment. Results The IA was 5.88 ± 0.93 for the able-bodied participants, indicating that the stiffness during the first part of the dorsiflexion phase was substantially fewer than during the second parts, as the calf muscles resisted to angulation in ankle substantially less than during the second part of dorsiflexion phase. For amputees fitted with Free-Flow Foot, IA was 2.68 ± 1.09 and −2.97 ± 2.37 for the same amputees fitted with their usual feet. Conclusions Indexes of anthropomorphicity, while of different magnitude, were positive in control able-bodied group and in the amputee group wearing Free-Flow Foot, which was qualitatively associated with concave shape of their moment–angle curves. The 3 usual feet worn by the participants were classified as nonanthropomorphic as their individual moment–angle curves were convex and the corresponding IAs were negative. Furthermore, this study showed that a foot with anthropomorphic characteristics tends to decrease maximal loads at the bone–implant interface as compared to the nonanthropomorphic feet and possibly may minimize the risks to compromise the integrity of this interface.


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