Thymus involution induced by 5-azacytidine

1986 ◽  
Vol 6 (7) ◽  
pp. 603-612 ◽  
Author(s):  
Adam Csordas ◽  
Konrad Schauenstein

Hypomethylation of DNA, which can be achieved by incorporation of 5-azacytidine, has been correlated with derepression of genes. In order to examine the in vivo effects of 5-azacytidine on organ development and differentiation, young rats were treated with the drug. There was an almost complete reduction of thymus and a marked reduction of spleen weight, while other organs, including testes were only marginally affected. Control experiments with cytosine-arabinoside suggest that treatment with an inhibitor of DNA replication per se is not responsible for the very rapid thymus involution triggered by 5-azacytidine in rats. In spite of the drastic reduction of thymus and spleen weight, lymphocytes of these organs were not impaired in their response to the T cell mitogen Concanavalin A.


1972 ◽  
Vol 14 (1) ◽  
pp. 91-95 ◽  
Author(s):  
GANESH NIRMUL ◽  
COLETTE SEVERIN ◽  
ROBERT N. TAUB


1980 ◽  
Vol 30 (2) ◽  
pp. 431-438
Author(s):  
R Dziarski

Staphylococcal peptidoglycan can modulate in vivo and in vitro antibody responses and is a B-cell mitogen. The effect of in vivo peptidoglycan treatment on the subsequent in vitro mitogenic responsiveness of mouse splenocytes to phytohemagglutinin, concanavalin A, pokeweed mitogen, and lipopolysaccharide was studied by measuring changes in deoxyribonucleic acid synthesis. Injection of peptidoglycan caused a 100% increase in responsiveness to phytohemagglutinin and pokeweed mitogen and a 45% increase in responsiveness to concanavalin A. Responsiveness to lipopolysaccharide was decreased by 40%. Increased phytohemagglutinin and decreased lipopolysaccharide responses were not due to changes in the kinetics of the response or optimal concentrations of these mitogens. Increased responsiveness to phytohemagglutinin lasted for 2 weeks after peptidoglycan injection. Neither increased background deoxyribonucleic acid synthesis nor changes in the proportion of T cells after peptidoglycan treatment fully accounted for the changes in responsiveness to the mitogens. In vitro costimulation with peptidoglycan and phytohemagglutinin, lipopolysaccharide, concanavalin A, or pokeweed mitogen resulted in interference of the response. Cell separation experiments indicated that peptidoglycan-induced modulation of mitogenic responsiveness was mediated by B lymphocytes.



1976 ◽  
Vol 66 (1) ◽  
pp. 17-21 ◽  
Author(s):  
Samuel J. Stegman ◽  
Kimie Fukuyama ◽  
William L. Epstein


2018 ◽  
Author(s):  
Haixin Li ◽  
Zhuqing Liang ◽  
Jian Yang ◽  
Dan Wang ◽  
Hanben Wang ◽  
...  

Expression of DAZ-like (DAZL) is a hallmark of vertebrate germ cells and essential for embryonic germ cell development and differentiation, yet gametogenic function of DAZL has not been fully characterized with most of its in vivo direct targets unknown. We showed that postnatal stage-specific deletion of Dazl in mouse germ cells did not affect female fertility, but caused complete male sterility with gradual loss of spermatogonial stem cells (SSCs), meiotic arrest and spermatid arrest respectively. Using the genome-wide HITS-CLIP and mass spectrometry approach, we found that DAZL bound to a large number of testicular mRNA transcripts (at least 3008) at 3′ UnTranslated Region (3′ UTR) and interacted with translation proteins including PABP. In the absence of DAZL, polysome-associated target transcripts, but not their total transcripts were significantly decreased, resulting in drastic reduction of an array of spermatogenic proteins and thus developmental arrest. Thus, DAZL is a master translational regulator essential for spermatogenesis.



2005 ◽  
Vol 289 (2) ◽  
pp. R332-R339 ◽  
Author(s):  
Vit Perlik ◽  
Zhongua Li ◽  
Sarita Goorha ◽  
Leslie R. Ballou ◽  
Clark M. Blatteis

The intravenous injection of LPS rapidly evokes fever. We have hypothesized that its onset is mediated by prostaglandin (PG)E2 quickly released by Kupffer cells (Kc). LPS, however, does not stimulate PGE2 production by Kc as rapidly as it induces fever; but complement (C) activated by LPS could be the exciting agent. To test this hypothesis, we injected LPS (2 or 8 μg/kg) or cobra venom factor (CVF, an immediate activator of the C cascade that depletes its substrate, ultimately causing hypocomplementemia; 25 U/animal) into the portal vein of anesthetized guinea pigs and measured the appearance of PGE2, TNF-α, IL-1β, and IL-6 in the inferior vena cava (IVC) over the following 60 min. LPS (at both doses) and CVF induced similar rises in PGE2 within the first 5 min after treatment; the rises in PGE2 due to CVF returned to control in 15 min, whereas PGE2 rises due to LPS increased further, then stabilized. LPS given 3 h after CVF to the same animals also elevated PGE2, but after a 30- to 45-min delay. CVF per se did not alter basal PGE2 and cytokine levels and their responses to LPS. These in vivo effects were substantiated by the in vitro responses of primary Kc from guinea pigs to C (0.116 U/ml) and LPS (200 ng/ml). These results indicate that LPS-activated C rather than LPS itself triggers the early release of PGE2 by Kc.



2018 ◽  
Vol 6 (3) ◽  
pp. 455-468 ◽  
Author(s):  
Haixin Li ◽  
Zhuqing Liang ◽  
Jian Yang ◽  
Dan Wang ◽  
Hanben Wang ◽  
...  

Abstract Expression of DAZ-like (DAZL) is a hallmark of vertebrate germ cells, and is essential for embryonic germ cell development and differentiation, yet the gametogenic function of DAZL has not been fully characterized and most of its in vivo direct targets remain unknown. We showed that postnatal stage-specific deletion of Dazl in mouse germ cells did not affect female fertility, but caused complete male sterility with gradual loss of spermatogonial stem cells, meiotic arrest and spermatid arrest. Using the genome-wide high-throughput sequencing of RNAs isolated by cross-linking immunoprecipitation and mass spectrometry approach, we found that DAZL bound to a large number of testicular mRNA transcripts (at least 3008) at the 3′-untranslated region and interacted with translation proteins including poly(A) binding protein. In the absence of DAZL, polysome-associated target transcripts, but not their total transcripts, were significantly decreased, resulting in a drastic reduction of an array of spermatogenic proteins and thus developmental arrest. Thus, DAZL is a master translational regulator essential for spermatogenesis.





Pneumologie ◽  
2014 ◽  
Vol 68 (06) ◽  
Author(s):  
E Lopez-Rodriguez ◽  
C Boden ◽  
S Knippenberg ◽  
A Pascual ◽  
J Perez-Gil ◽  
...  


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