Somatic hypermutation of immunoglobulin genes is independent of the Bloom''s syndrome DNA helicase

The aim of these studies was to examine the effects of imidazoles on testosterone secretion and testicular interstitial fluid (TIF) formation through measurement of serum LH, serum testosterone, TIF testosterone, and TIF volumes. Imidazole, 1-methylimidazole, 4-methylimidazole (4-MI), and ketoconazole, an oral imidazole antifungal agent, caused dose-dependent decreases in testosterone secretion and TIF formation. Imidazole, 2-methylimidazole, and 4-MI decreased LH secretion. 4-MI decreased testosterone secretion 1-6 h after injection, increased testosterone at 8-16 h, decreased LH secretion at 4 h, decreased TIF volumes at 1-8 h, and slightly increased TIF volumes at 24 h. 4-MI blocked the stimulatory effects of hCG on testosterone secretion and prevented an expected increase in LH secretion after the 4-MI-induced decrease in testosterone secretion. 4-MI also reversed the effects of three other stimulants of testosterone secretion that presumably act through three different testicular regulatory systems: N-methyl-D,L-aspartate, an excitatory amino acid; NG-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor; and naltrexone, an opioid antagonist. These results support the hypothesis that imidazoles inhibit testicular function and male reproductive function through inhibition of testosterone secretion, TIF formation, and LH secretion regulatory systems.     

The status and distance of cone biopsy margins as a predictor of excision adequacy for endocervical adenocarcinoma in situ

The purpose of this study was to begin to examine the influence of inhaled NO on O2 toxicity. The survival of Sprague-Dawley rats exposed to >95% O2, >95% O2 + 10 ppm NO, >95% O2 + 100 ppm NO, and >95% O2 + 3 ppm NO2 was determined. Survival at 120 h was 2/24 in >95% O2, 2/12 in >95% O2 + 10 ppm NO, and 1/12 in >95% O2 + 3 ppm NO2. Survival at 120 h was 21/30 in >95% O2 + 100 ppm NO (p < 0.01 compared with >95% O2). Three additional groups of rats were exposed for 60 h to: 21% O2, >95% O2, or >95% O2 + 100 ppm NO. The lungs were then assayed for total protein, reduced (GSH) and oxidized glutathione (GSSG), and 4-hydroxy-2(E)-nonenal. Both of the high O2 groups had significantly (p < 0.05) lower GSH/mg protein and GSH/GSSG ratios compared with the 21% O2 group. The >95% O2 group had a higher 4-hydroxy-2(E)-nonenal/mg of protein than either the 21% O2 group (p < 0.05), or the >95% O2 + 100 ppm NO group (p < 0.05 compared with >95% O2, not different from the 21% O2 group). Additional groups of rats were exposed to either 21% O2, >95% O2, or >95% O2 + 100 ppm NO for 0, 24, 48, and 60 h. The lungs were examined for neutrophil accumulation, which was increased at 60 h in the two groups exposed to >95% O2, but adding NO had no effect. Thus, the overall result was that 100 ppm inhaled NO improved the survival of rats in high O2.     

Rapid ganciclovir susceptibility assay using flow cytometry for human cytomegalovirus clinical isolates

Rapid, quantitative, and objective determination of the susceptibilities of human cytomegalovirus (HCMV) clinical isolates to ganciclovir has been assessed by an assay that uses a fluorochrome-labeled monoclonal antibody to an HCMV immediate-early antigen and flow cytometry. Analysis of the ganciclovir susceptibilities of 25 phenotypically characterized clinical isolates by flow cytometry demonstrated that the 50% inhibitory concentrations (IC50s) of ganciclovir for 19 of the isolates were between 1.14 and 6.66 microM, with a mean of 4.32 microM (+/-1.93) (sensitive; IC50 less than 7 microM), the IC50s for 2 isolates were 8.48 and 9.79 microM (partially resistant), and the IC50s for 4 isolates were greater than 96 microM (resistant). Comparative analysis of the drug susceptibilities of these clinical isolates by the plaque reduction assay gave IC50s of less than 6 microM, with a mean of 2.88 microM (+/-1.40) for the 19 drug-sensitive isolates, IC50s of 6 to 8 microM for the partially resistant isolates, and IC50s of greater than 12 microM for the four resistant clinical isolates. Comparison of the IC50s for the drug-susceptible and partially resistant clinical isolates obtained by the flow cytometry assay with the IC50s obtained by the plaque reduction assay showed an acceptable correlation (r2 = 0.473; P = 0.001), suggesting that the flow cytometry assay could substitute for the more labor-intensive, subjective, and time-consuming plaque reduction assay.     

Detection and several characteristics of leach genome palindromes

About 5% of the loach (Misgurnus fossillis L.) DNA reassociates at Cot values virtually equal to zero. 50% of the reassociate are resistant to nuclease S1 treatment and reveal the properties of double-stranded structure when chromatographed on hydroxyapatite. Some proofs of palindromic (hair-pin) nature of this fraction have been obtained. An introduction of nicked scissions into the palindromic DNA by pancreatic DNAse treatment under pessimal conditions made it possible to investigated reassociation kinetics of the nucleotide sequences forming palindromes. Two different types of nucleotide sequences appeared to exist in the palindromic fraction with repetition frequencies (ni) equal to 3 X 10(2) and about 1. Homologies were revealed between these sequences and the fraction of corresponding repetition frequency of the main part of the genome. Adjacent sequences contain repetitive regions with ni equal to 10(5) and 5 X 10(3). On the basis of the data obtained some conclusions were made about the distribution of usual and inverted repetitions in the loach genome.