PubMed · 9867482
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M Omura. 1998. [Decrease in sperm count of human semen].. https://pubmed.ncbi.nlm.nih.gov/9867482/
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We have investigated the age-dependent modifications in the expression of eight different subunits of the gamma-aminobutyric acid, type A (GABA(A)) receptor (alpha1, alpha2, alpha3, alpha5, beta2, beta3, gamma2S, and gamma2L) and all four subunits of the alpha-amino-3-hydroxy-5-methylsoxazole-4-propionate (AMPA) receptor (GluR1-4) in the hippocampus of 24-month-old rats. All aged hippocampi displayed a remarkable increase (aged/adult ratio, 3.53 +/- 0.54) in the mRNA levels of the short version of the gamma2 subunit in parallel with a similar increase in the gamma2 subunit protein (aged/adult ratio, 2.90 +/- 0.62). However, this increase was not observed in the mature receptor. On the other hand, the expression of the different alpha subunit mRNAs increased moderately with aging, displaying a heterogeneous pattern. The most frequent modification consisted in an increase in the expression of the alpha1 subunit mRNA (aged/adult ratio, 1.26 +/- 0.18), in parallel with a similar increase on the alpha1 protein (aged/adult ratio, 1. 27 +/- 0.12) and in the alpha1 incorporated to the assembled GABA(A) receptor (tested by immunoprecipitation; aged/adult ratio, = 1.20 +/- 0.10). However, in the same hippocampal samples, no major modifications were observed on the expression of the AMPA receptor subunits. As a whole, these results indicated the existence of an increased expression of the GABA(A) receptor subunits and a preservation of the AMPA receptor at the hippocampal formation. These modifications could reflect the existence of specific deficiencies (neuronal loss and/or deafferentiation) on the GABAergic system in the aged rats.
HYPOTHESIS: Maternal measles immunity in the United States today is primarily vaccine induced, with corresponding lower antibody titers in infants, as compared to infants born in an earlier era to mothers with naturally acquired measles immunity. We hypothesized that, due to lower titer of passively transferred maternal measles antibody, administration of measles vaccine at 12 months of age would result in seroconversion and antibody persistence comparable to vaccination at 15 months of age. POPULATION: Children at both an urban hospital and a suburban clinic. METHODS: Informed consent was obtained from mothers for the infants to receive M-M-R(R)II vaccine at either 12 or 15 months and to have serum samples obtained before vaccination and 4 weeks post-vaccination (PV). Between 9 and 39 months PV, a third serum sample was obtained from 28% of seroconverters. A diary of adverse experiences was kept for 3 weeks PV. Sera were assayed by a microneutralization assay (NT) and an enzyme immunoassay (EIA) for measles antibody. RESULTS: Both age groups tolerated vaccination well with minor and transient side effects. Forty-four of 47 (94%) 12-month-old infants seroconverted by NT, compared to 45 of 46 (98%) 15-month-olds (p=NS). There was no statistically significant decline in median NT titers or EIA titers in nineteen 12-month-olds and thirteen 15-month olds followed for 9-39 months PV. CONCLUSION: This study showed comparable serologic responses in 12- vs 15-month-old infants born to measles vaccine-immune mothers; however, the sample size was too small to have adequate power and further study is indicated. Titers of antibody were constant in both the 12-month-old and the 15-month-old infants, over a 9-39 month period, suggesting that waning immunity over this period of time is not a problem in either age group.
The in vitro effect of cyclosporine A (CsA) was studied in reference to the production of reactive oxygen species (peroxides and superoxide anion) and to cell enzyme-mediated antioxidant defence in hepatocytes isolated from rats aged 2 and 12 months. Primary cultures of hepatocytes were incubated in the presence of concentrations of cyclosporine in the range of 0 to 50 microM for 24 hr, and the release of lactate dehydrogenase into the culture medium was evaluated as a parameter of cytotoxicity and membrane lysis. Peroxides were quantified by using 2',7'-dichlorodihydrofluorescein diacetate, and superoxide anion levels were evaluated by the fluorescence of dihydroethidium. Enzyme activity and gene expression of catalase and Mn- and Cu,Zn-superoxide dismutase were also assayed. CsA cytotoxicity was significantly higher in hepatocytes from rats aged 12 months when compared to those aged 2 months. Intracellular peroxide content resulted in a dose-dependent increase, while the anion superoxide intracellular level slightly decreased as CsA increased from 0-50 microM. The progressive increase in intracellular peroxides in cell cultures in the range from 0-50 microM CsA was associated with the loss of cell viability and accompanied by significantly higher levels of Mn- and Cu, Zn-superoxide dismutase enzyme activities and mRNAs, and slight increases in catalase activity and mRNA. We conclude that, in primary hepatocyte cultures, the cytotoxicity of CsA was dose-dependent in both age groups and significantly higher in cultures from 12-month-old rats when compared to those from 2-month-old animals. The non-coordinated regulation of the gene expression of antioxidant enzyme systems, i.e. catalase and Mn- and Cu,Zn-superoxide dismutases, evidenced to a greater extent in hepatocytes from the older group of rats, could be one of the mechanisms involved in CsA toxicity.