Ribosomal RNA gene dosage as a function of tissue and age for mouse and human.

The average number of rRNA genes per haploid genome (rRNA gene dosage) of the cells present in liver and brain was determined throughout the lifespan of the inbred C57BL/6J mouse strain and of human. Ribosomal RNA gene dosage was determined using the RNA-excess DNA - RNA hybridization technique. DNA was extracted and purified using a CsCl/chloroform method with a high percent yield (over 90%) to minimize any possible effects of tissue and age-dependent selective loss or gain of rRNA genes. Radioactive rRNA was from the liver of the youngest age group for either mouse or human in all hybridization experiments, with DNA from the different tissues and age groups being the only variable. In the young mouse (35-49 days), the rRNA gene dosage was 36% higher in brain (114 genes), as compared to liver (84 genes). The rRNA gene dosage remained essentially constant as a function of age for mouse brain; but between the age of about 220 to 440 days, it increased in liver, attaining approximately an equal value to that of brain. No significant difference was found in the rRNA gene dosage of brain or liver between different mice of the same age. In contrast to this result, a significant difference was found between human tissues of similar age. The rRNA gene dosage ranged about 2-fold (148-289) between 2 months to 75 years of age. An age-dependent trend, similar to that for mouse liver, was found when the averages of four different age groups totaling 20 individuals were compared. However, this was not statistically significant. No difference in the rRNA gene dosage as a function of sex or tissue was apparent. Several models are discussed to account for these results.     

Response of patients to upper gastrointestinal endoscopy: effect of inherent personality traits and premedication with diazepam.

The influence of personality traits on the reaction of patients to upper gastrointestinal endoscopy was studied prospectively in 86 patients. High N (neuroticism) scores on the Eysenck personality inventory were associated with poor tolerance to and future compliance with the procedure. Although premedication with diazepam did not affect the degree of discomfort and distress during the procedure, it guaranteed acceptance of repeat endoscopy by virtue of its strong amnesic effect. By contrast, not giving premedication to patients who were anxious and had high N scores jeopardized future compliance. These findings suggest that a version of the Eysenck personality inventory should be used to assess patients'' neurotic phenotype and their need for premedication before endoscopy. Alternatively, all patients might be given premedication.     

Influence of mouse age and erythrocyte age on glutathione metabolism.

In order to determine whether the biological age of a mouse influences erythrocyte metabolism and erythrocyte aging in vivo, blood samples were collected from male C57/BL6J mice of different biological ages ranging from mature (10 months) to "very old" (37 months). In the very old mouse, compared with the mature mouse, the erythrocyte survival time was decreased, erythrocyte densities were increased, the concentrations of total free thiol and reduced glutathione, and glutathione reductase activity were decreased. Erythrocytes were separated into different density (age) groups by phthalate ester two-phase centrifugation or by albumin density-gradient centrifugation. The density-age relationship of erythrocytes was established by pulse-labelling with 59Fe in vivo and by subsequent determinations of specific radioactivity of erythrocyte fractions of different densities prepared during a chase period of 60 days. The age of erythrocytes in mice of all ages was directly related to density. Also, in older erythrocytes compared with younger erythrocytes, decreased concentrations of total free thiol and reduced glutathione, and decreased glutathione reductase activity were observed. These were the lowest in the old erythrocytes of very old mice. These results in aging erythrocytes from aging mice suggest that the glutathione status the erythrocyte may be an index of aging, not only of the cell but also of the organism.     

Influence of dosage and dietary sodium on the first-dose effects of prazosin.

The effects of the first dose of prazosin were assessed in hypertensive patients on different sodium intakes. Patients received 250, 100, or 30 mmol sodium per 24 hours for a week before taking 2 mg or 0-5 mg prazosin. The acute effects of prazosin on blood pressure and pulse rate were milder with a high sodium intake. On the 100-mmol intake symptomatic postural hypotension occurred in five out of seven patients given 2 mg prazosin and in two out of four given a 0-5-mg dose, whereas those taking 2 mg or 0-5 mg and a 250-mmol sodium intake experienced no postural symptoms. These findings indicate that particular care should be taken in starting prazosin treatment in sodium-depleted patients.     

Influence of previous gold toxicity on subsequent development of penicillamine toxicity.

The incidence of penicillamine toxicity was determined in 250 patients who had never previously received gold, 76 patients who had received gold without toxic reaction, and 79 patients with a previous history of gold toxicity. The results suggest that there may be a higher incidence of penicillamine toxicity in patients who have previously shown toxic reactions. The interval between stopping the gold and starting the penicillamine did not influence incidence of toxicity. The development of a rash during gold treatment does not seem to influence the development of a rash during penicillamine treatment, but patients who have had proteinuria or bone-marrow depression during gold treatment may have an increased likelihood of developing a similar side effect with penicillamine.     

Characterization of parameters required for effective use of tamoxifen-regulated recombination

Conditional gene targeting using the Cre-loxp system is a well established technique in numerous in vitro and in vivo systems. Ligand regulated forms of Cre have been increasingly used in these applications in order to gain temporal and spatial control over conditional targeting. The tamoxifen-regulated Cre variant mer-Cre-mer (mCrem) is widely utilized because of its reputation for tight regulation in the absence of its tamoxifen ligand. In the DT40 chicken B cell line, we generated an mCrem-based reversible switch for conditional regulation of a transgene, and in contrast with previous work, observed significant constitutive activity of mCrem. This prompted us to use our system for analysis of the parameters governing tamoxifen-regulated mCrem recombination of a genomic target. We find that robust mCrem expression correlates with a high level of tamoxifen-independent Cre activity, while clones expressing mCrem at the limit of western blot detection exhibit extremely tight regulation. We also observe time and dose-dependent effects on mCrem activity which suggest limitations on the use of conditional targeting approaches for applications which require tight temporal coordination of Cre action within a cell population.     

Microbiological degradation of diazepam.

In studying the transformation of diazepam (7-chloro-1-methyl-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one) by fungi isolated from soil. N1-demethylation and cleavage of the diazepine ring were observed. Three metabolites: 7-chloro-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 2-acetamido-2"-benzoyl-4"-chloroacetanilide and 2-acetamido-2"-benzoyl-4"-chloro-N-methylacetanilide were isolated and identified.     

Cytologic diagnosis of human papillomavirus. Influence of age and pregnancy stage.

In a review of cytologic findings in 446,038 premenopausal women whose smears were examined during a five-year period ending in 1990, it was established that cytomorphologic evidence of human papillomavirus infection was significantly more common in the younger groups: those under 30 years of age had about twice the rate of the older groups. Similarly, in a group of 29,153 pregnant women it was found that cytologic signs of human papillomavirus were reported twice as often during the second half of pregnancy as in the first.     

Influence of diazepam on regenerating adrenal cortex in Wistar rats

The influence of diazepam on the mitotic activity of regenerating adrenal cortex in male Wistar rats was investigated. Diazepam administration (5 mg/kg/day) was shown to inhibit the mitotic index of adrenocortical cells on the 4th and 8th day after adrenal enucleation combined with contralateral adrenalectomy. The possible mechanism of diazepam action is discussed.     

Association of paternal alcohol use with gestational age and birth weight.

Paternal alcohol use has been associated with a number of adverse reproductive outcomes in laboratory animals and there is one epidemiologic report of a detrimental effect on infant birth weight. To expand the epidemiologic evidence, data from the Child Health and Development Studies were analyzed. Data collected from the onset of prenatal care in 10,232 women enrolled in the Kaiser Foundation Health Plan and residing in the San Francisco East Bay area between June 1959 and September 1966 were available, including information on the mother's report of paternal alcohol consumption and a number of potential confounders. Pregnancy outcomes included preterm delivery (< 37 weeks completed gestation), moderately low birth weight (1,501-2,500 g), very low birth weight (< or = 1,500 g), small-for-gestational-age (< 10th percentile of weight for gestational age), and mean birth weight. Paternal alcohol use, analyzed in intervals from 0 to 2.0 or more drinks per day, showed no association with any of the outcomes of interest. Adjusted prevalence odds ratios ranged from 0.7 to 1.5, with no indication of a monotonic dose-response gradient. Mean birth weight was also virtually unrelated to paternal alcohol use. Compared with the earlier report, this population had a very modest level of alcohol consumption. Nonetheless, within the range that was studied there appears to be no association between paternal alcohol use and birth outcome.     

Influence of taurine dosage on cobalt epilepsy in mice

The present work addresses itself to answering several questions in relation to the antiepileptic action of taurine (see Introduction). For this purpose, cobalt epileptic mice, treated with isoosmolar saline or not treated, were compared with groups of mice that had received doses of taurine varying between 1.0 and 10.0 mg/kg. Whereas all the taurine doses employed effectively reduced seizure incidence, with 10.0 mg/kg giving the best results, none of these doses had ameliorated the amino acid abnormalities in the cortex after two days of treatment in comparison with the group that had received isoosmolar saline. On the contrary, the largest amino acid abnormalities occurred in the group of mice (10.0 mg/kg) that had improved the most clinically. We conclude that the acute antiseizure action of taurine, and its effect on restoring normal amino acid patterns in the cortex, represent two separate properties of taurine.