Search PubMed⌕ Search

Biomedical subjects

R R Delongchamp

Publications and source records attributed to R R Delongchamp.

29 records · Page 2Linked to original sources
PubMed1986

Effect of prenatal imipramine exposure on development of the postnatal rat heart and brain.

Imipramine (IMI) was administered s.c. at 0, 5, or 10 mg/kg/day to pregnant rats on gestation days 8-20 to assess possible alterations in postnatal heart and brain development. Maternal weight gain was significantly reduced in a dose-response manner, but litter size and pup weight on postnatal day (PND) 1 were unaffected. On PND 1, litters were culled to 10 pups for analysis on PNDs 4/5, 7/8, 14/15, and 21/22. Pup body weight was not affected at any age measured, but heart weight was significantly reduced at 10 mg/kg IMI on PNDs 4/5 and 7/8. Brain weight was increased in a dose-related pattern on PNDs 4/5 and 7/8 and was significantly higher at 5 mg/kg IMI on PND 14/15. No significant effect was observed in heart or brain protein and DNA content or in cardiac beta-adrenergic receptor concentration. Prenatal IMI exposure had no effect on basal cardiac ornithine decarboxylase (ODC), an enzyme associated with growth and development, but basal brain ODC was lower at 5 mg/kg IMI at all ages measured. Cardiac ODC stimulation by insulin was unaffected by prenatal exposure to IMI, but isoproterenol-stimulated ODC was increased on PND 21/22 at 5 mg/kg IMI. In conclusion, the IMI-related changes in several parameters suggest that when maternal IMI treatment is used, alterations in postnatal heart and brain development must be considered as possible outcomes.

Aging↗
PubMed1986

The effects of saccharin on the development of neoplastic lesions initiated with N-methyl-N-nitrosourea in the rat urothelium.

Saccharin has been reported to induce urinary bladder tumors in multigeneration rat feeding studies and to promote bladder carcinogenesis in rats initiated with known bladder carcinogens. To examine the dose-dependent effects of saccharin on tumor promotion, sodium saccharin was administered at six levels in the diet (5.0, 2.5, 1.0, 0.5, 0.1, and 0%) to female Sprague-Dawley rats which had received, by trans-urethral instillation into the bladder, either a single dose of saline or an initiating dose of N-methyl-N-nitrosourea (MNU), a potent direct-acting carcinogen. Additional groups with and without MNU treatment received sodium saccharin (2%) in the drinking water, acid-saccharin (5%) in the diet, or MNU, four weekly doses, as a positive control. Histopathologic examination of the urinary bladders from dead and moribund animals and from animals sacrificed after 102 weeks on dose was performed, and benign papillomas were commonly observed in those animals given MNU. A statistical analysis of the lesions indicated an increase in tumor incidence and a decrease in time to tumor with increasing saccharin dose in dead and moribund animals. This response was observed in the dose series of 0 to 2.5% saccharin in the diet. Dead and moribund animals which had received 5% sodium saccharin exhibited few tumors. An increasing incidence of tumors in MNU-treated control animals was observed during the final weeks of the study. Although this increase in background tumors in senescent animals complicated the interpretation of the total tumor incidences, the results in dead and moribund animals (about 60% of the total) indicated that saccharin served as a tumor promoter in this two-stage carcinogenesis model system by decreasing the latency period of the lesions.

Animals↗
PubMed1986

Interactive responses to diethylstilboestrol in C3H mice.

Female C3HeB/FeJ mice were fed diethylstilboestrol (DES) at a dietary concentration of 100 ppb beginning at 6 wk of age. Several oestrogen-sensitive target organs (uterus, vagina, bone and mammary gland) were removed and examined histologically when mice died, became moribund, were killed at scheduled intervals or were removed because of presumptive mammary tumours (palpable mass having a 1-cm diameter). Oestrogen-sensitive histological observations for which there was less than a 100% prevalence and/or severity included uterine fibrosis and glandular hyperplasia, vaginal mucoid stroma and keratinization, mammary adenocarcinomas and osseous trabecular proliferation or marrow fibrosis. Mice from this treated population were grouped according to the specific grade of uterine glandular hyperplasia. Each mouse having a given grade of hyperplasia was matched with a mouse that failed to develop glandular hyperplasia and was fed the 100 ppb DES diet for approximately the same time period. This procedure provided three sets of matched pairs (no hyperplasia v. grade 0; no hyperplasia v. grade 1 and no hyperplasia v. grade 2). Pairwise comparisons were then made in these groups for each of the other oestrogen endpoints. Within each set of matched pairs, mice with glandular hyperplasia had a greater prevalence and/or severity of uterine fibrosis and vaginal mucoid stroma and vaginal keratinization than those without hyperplasia and differences within matched sets were greater as the severity of hyperplasia increased. In contrast, the prevalence of osseous trabecular proliferation or marrow fibrosis were equivalent across all grades of glandular hyperplasia and the prevalence of mammary adenocarcinomas was inversely related to the severity of glandular hyperplasia. These data suggest the existence of a subpopulation of inbred mice that is especially sensitive to DES exposure for uterine and vaginal endpoints and highly insensitive to mammary tumour induction.

Adenocarcinoma↗
PubMed1986

The effects of various lighting schedules upon the circadian rhythms of 23 liver or brain enzymes of C57BL/6J mice.

The activities of 23 brain or liver enzymes were studied in 5-6 week old C57BL/6JNctr male and female mice that had been fed ad libitum and standardized for 2 weeks to either (1) 12 hr of light (0600-1800) alternating with 12 hr of darkness (1800-0600) (LD 12:12), (2) staggered sequences of 12 hr of light and 12 hr of dark (SLD 12:12) or (3) continuous illumination (LL 12:12) for 2 weeks. Mice in the LD 12:12 and LL 12:12 experiments were killed at 4 hr intervals along a 24-hr span in order to sample at six different circadian stages. Lighting schedules for mice in the SLD 12:12 experiment were organized such that six different circadian stages were sampled when all mice were killed at one time of day. All 23 enzymes demonstrated a prominent circadian rhythm in at least one of the experiments. Moreover, about two-thirds of the enzymes in LD and SLD 12:12 had a statistically significant fit to a 24-hr cosine curve, while only one-third of the enzymes in LL 12:12 had significant fits to cosine curves. Peak activities of enzymes from mice in LD 12:12 were clustered at the time of transition from light to dark. This was also the trend for the activities of enzymes from mice in SLD 12:12, but resynchronization did not appear completed within the 2-week span. This, along with the observation that mesors (mean 24-hr activity) were reduced and amplitudes altered, indicated that the 2-week standardization period was not sufficient for some enzymes. Times of peak activities, mesors and amplitudes were affected for most enzymes from mice in the LL 12:12 environment. This suggests that individual mice became desynchronized from one another with respect to the original light-dark schedule and that rhythms were altered or lost because individual mice were free running with frequencies different from 24 hr.

Animals↗
PubMed1986

Insulin stimulation of ornithine decarboxylase activity in developing rat heart.

Ornithine decarboxylase (ODC; EC 4.1.1.17) is an important enzyme in the synthesis of polyamines and is associated with growth and differentiation. Insulin stimulation of cardiac ODC has been proposed as a marker of the functional completion of the sympathetic pathway to the rat heart. However, earlier studies, using subsaturating substrate concentrations and a single time point measurement after insulin treatment, have been inconsistent concerning the postnatal age at which significant insulin stimulation of ODC occurs. The present study, using a validated near-saturating substrate assay, examines more thoroughly early neonatal insulin induction of cardiac ODC with respect to both the magnitude and the time course of response. Insulin (20 IU/kg s.c.) significantly increased ODC activity at several time points at each postnatal age measured (days 2, 5, 8, 15 and 22), with maximum ODC activity occurring by 2.5 to 3 hr after insulin injection at all ages. Insulin-stimulated ODC activity was increased over control levels by 86, 84, 87, 150 and 127% on days 2, 5, 8, 15 and 22, respectively. These results demonstrate that age is not a variable in the time of peak insulin stimulation of ODC activity and, in contrast to earlier reports, show that significant insulin induction of cardiac ODC activity occurs reliably across ages in the early postnatal period. The inconsistency of earlier studies may be due to a number of factors, including the use of subsaturating enzyme assays only, known to be subject to several types of error.

Age Factors↗
PubMed1985

The effect of age on the circadian rhythms of 23 liver or brain enzymes from C57BL/6J mice.

Mice were standardized to 12 h of light exposure alternating with 12 h of darkness and were fed ad libitum. The mice in the first group were 8 weeks old and in the other 104-116 weeks old. Subgroups of 7 animals from each age group were killed at 6 circadian stages. Enzyme activities of 23 enzymes from liver or brain were measured by an analysis of variance for each age group. All but 1 enzyme from young mice, and all but 9 from older mice showed significant changes over time (p less than 0.01). The data from the 22 enzymes from young mice and the 14 enzymes from old mice were fit to the cosinor regression model to further characterize the rhythm. 15 enzymes from the young and 8 from the aged mice showed a significant regression to a 24-hour cosine curve (p less than 0.01); of the 8, 7 were the same enzymes in both groups. Amplitude changes, where they could be compared from the cosinor data (7 enzymes), were not statistically different. When total variance was compared, 12 enzymes showed unequal variance. Of these, old mice had the larger variance in 9 enzymes. Another difference between the young and the old was changes in mean enzyme activities. 12 enzymes from aged mice had decreased mesors, 2 had increased mesors, and 9 were unchanged. In general, our data suggest that some enzyme activity rhythms were lost, others were altered and a few were not affected by aging. In the case of many enzymes, older mice have a diminished ability to synchronize to the light signals.

Animals↗
PubMed1984

Circadian dependent effect of epidermal growth factor, insulin and glucagon on hepatic pyruvate kinase and malic enzyme of mice.

The influence of epidermal growth factor (EGF), 0.75 micrograms g1; insulin, 1.5 micrograms g-1; glucagon, 1.25 micrograms g-1 and their combinations on the activities of hepatic pyruvate kinase (PK) and malic enzymes (ME) was monitored. Male CD2F1 mice were treated toward the end of the light or dark periods, 9 or 23 hours after lights on (9 or 23 HALO), and subgroups of six mice were killed at 4, 8 or 12 hr post-treatment. PK and ME activities from control mice were well characterized by cosine curves. The PK activity was maximal when ME activity was minimal at the transition from light to dark (9 HALO plus 4 hr) and PK was at a minimum when ME was highest (23 HALO plus 4 hr). Both enzymes were influenced by at least one peptide hormone, and the effects were strongly circadian-stage dependent. The only effect attributed to EGF was an increase of PK activity (23%) 12 hr after injection at 23 HALO. PK activity was increased by insulin (23%) at 23 HALO (4 hr after injection), but not at 9 HALO, and decreased (17%) by glucagon 12 hr after injection at 9 HALO. Several reductions in PK activity in response to various combinations of peptides were observed, and appeared to be caused by glucagon but influenced by insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Pleiotropic and other genetic effects influencing the activities of brain and liver enzymes in congenic lines of C57BL/6J mice with defined electrophoretic variant markers.

A single genetic factor may affect the realization of several enzymes. To investigate the extent of pattern pleiotropy in the mouse, the activities of 28 enzymes in livers and brains from an inbred stock of C57BL/6JNctr and five F1 stocks heterozygous for known electrophoretic variants were measured. Five congenic backcross stocks of C57BL/6J, each homozygous for one or more electrophoretic markers, were mated with C57BL/6JNctr to construct the heterozygous variant F1 stocks. One of the five F1 stocks had no enzyme activities significantly different from those of C57BL/6JNctr, while two had one enzyme, one had four enzymes, and another had six enzymes with activities that were significantly different from those of C57BL/6JNctr. The latter two F1 stocks with multiple activity differences were those having the largest proportion of their genome of donor origin. Two of the F1 stocks were different from each other for one enzyme, and two were different for another enzyme. These differences and the relationship of these enzyme activities to the variant genes suggest that several genetic factors may affect an enzyme's realization.

Animals↗
PubMed1982

Development of a new biochemical mutation test in mice based upon measurements of enzyme activities. I. Theoretical concepts and basic procedure.

A test procedure is described for detecting germ cell mutations which alter activity of enzymes in in vivo mammalian tissues. The objective is to identify those individuals, among a population of F1 animals from treated parents, that are heterozygous for a mutation at an unspecified locus which results in an altered activity of one or more of the enzymes monitored. Animals are evaluated through three analysis screens with emphasis on identification of mutant individuals. In the first screen, activity values of a battery of enzymes are compared to their respective normal ranges to identify those which are aberrant. The mean activities and coefficients of variation useful in defining the normal ranges for 19 enzymes in C57BL/6J Nctr mice are presented along with a set of theoretical normal animal misclassification probabilities for each of these enzymes. The second screen is a Michaelis-Menten kinetic analysis of aberrant enzymes, the goal of which is to correct misclassifications of normal animals made in the first screen. A third screen of aberrant enzyme activities in a subsequent generation is used to demonstrate inheritance and confirm the mutation. The advantages and the limitations, as well as possible variations of the basic procedure are discussed.

Animals↗