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Compensatory effect of TNFα on low natural killer activity in the elderly.

100%
Myśliwska J., Bryl E., Trzonkowski P., Myśliwski A.
Acta Biochimica Polonica
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2000
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vol. 47
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issue 2
301-311
EN
Regulatory effect of CD25, an activation antigen the α subunit of interleukin 2 receptor (IL2R) on the activity of natural killer (NK) cells was studied in fifty elderly (57-70 years old) and fifty young people (19-35 years old). Cytotoxic NK activity was assessed by 51Cr release assay, the levels of interleukin 2 (IL2) and tumour necrosis factors α (TNFα) were measured using bioassays and expression of CD16 and CD25 proteins by flow cytometry. Low NK activity in the elderly was associated with decline of full health, lowered serum concentration of IL2 and increased production of TNFα during NK reaction. Inhibition of TNFα activity by anti-TNF monoclonal antibody suppressed exclusively NK activity of low NK responders. Moreover, stimulation in vitro of blood mononuclear cells, with TNFα induced in the elderly low NK responders a significantly higher increase of the CD25 expression on the surface of NK cells as compared with that in the elderly high responders. Since the CD25 molecule constitutes a subunit of the high affinity receptor, binding IL2 to immunocompetent cells, its increased expression on NK cells of low NK responders would enable them to bind even low amounts of the endogenous IL2 available in this group of the elderly. Thus, an overproduction of TNFα seems to be a mechanism compensating, in the non-fully healthy elderly, for the decreased IL2 production, promoting efficient cytotoxic reaction.
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The effects of galactosamine on UTP levels in the livers of young, adult and old rats.

100%
Kmieć Z., Smoleński R. T., Zych M., Myśliwski A.
Acta Biochimica Polonica
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2000
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vol. 47
|
issue 2
349-353
EN
Galactosamine (GalN), a well-known hepatotoxin that depletes the cellular pool of uracil nucleotides, was previously shown to have greater impact on the inhibition of protein synthesis in hepatocytes of old rats as compared with young animals (Kmieć 1994, Ann. N.Y. Ac. Sci. 717, 216-225). In the present study we compared the effects of GalN on the nucleotide content (measured by ion-exchange HPLC) in the livers of young (4 months), adult (12 months), and old (24-26 months old) rats two hours after its intraperitoneal administration. UTP content of the livers of old control rats was significantly lower (by 28%) than that of young animals. GalN administration decreased the UTP content in the livers of young, adult and old rats by, respectively, 55%, 65% and 89%, and increased the content of UDP-sugars by 189%, 175% and 305%. The hepatic content of ATP, ADP, AMP, NAD, GTP except CTP did not differ significantly among the age groups of rats studied, and was not changed by GalN treatment. The content of CTP was significantly higher in old rats (P < 0.03) upon GalN treatment. The lower hepatic content of UTP may partially explain the increased sensitivity of hepatocytes and livers of old rats to the action of galactosamine, and possibly to other hepatotoxic compounds that decrease transcription in the liver.
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