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Biomedical subjects

J F Nelson

Publications and source records attributed to J F Nelson.

At least 37 records · Page 2Linked to original sources

Differential contributions of ovarian and extraovarian factors to age-related reductions in plasma estradiol and progesterone during the estrous cycle of C57BL/6J mice.

The relative contributions of ovarian and extra-ovarian factors to the altered ovarian steroidal profiles of middle-aged mice were assessed by reciprocal, heterochronic ovarian grafting. Ovaries from cycling, young (2 months), and middle-aged (12 months) mice were exchanged by grafting under the renal capsules. Blood samples were obtained daily at midday throughout the estrous cycle for measurement of estradiol (E2) and 3-4 h after lights-out on proestrus to measure the preovulatory elevation of progesterone (P4). Middle-aged intact mice had lower mean concentrations of E2 during the cycle, no detectable midday preovulatory elevation of E2, and an attenuated preovulatory increase of P4 compared to young mice. Ovarian grafts from young donors failed to increase mean E2 levels of middle-aged mice, but did restore the preovulatory elevation of E2 and preovulatory P4 to levels of young controls. Reciprocal grafting confirmed these findings: ovaries from middle-aged donors in young hosts produced mean E2 levels equivalent to those of young mice but were unable to support a preovulatory increase of E2 or a preovulatory P4 level equivalent to that of young controls. These results reveal differential contributions of ovarian and extra-ovarian factors to age changes in E2 and P4. They indicate that ovarian aging plays an important role in attenuating the preovulatory increase of E2 and P4, but extra-ovarian, presumably neuroendocrine, age changes underlie the mean reduction of E2 levels across the estrous cycle.

Aging↗

Up-regulation of the uterine estrogen receptor and its messenger ribonucleic acid during the mouse estrous cycle: the role of estradiol.

Uterine estrogen receptor (ER) and ER mRNA were measured in cycling and ovariectomized (OVX) estrogen-treated mice to probe the physiological regulation of the intracellular distribution and biosynthesis of ER. On proestrus, when plasma estradiol (E2) levels are highest, the cell nuclear ER concentration was 2.4-fold greater than on metestrus. This increase was primarily attributable to an increase in total cellular ER (cytosolic plus nuclear ER) and only secondarily to an activation of ER, as measured by its redistribution from the cytosolic (i.e. nuclear-extractable) to the nuclear (nonextractable) fraction. Total cellular ER concentration was 1.8-fold higher on proestrus than on metestrus, whereas the fraction of total ER in the nuclear compartment (i.e. the percentage activated) was only 1.3-fold higher. The concentration of cellular ER mRNA was 3-fold greater on proestrus than on the other days of the estrous cycle, suggesting that the increased concentration of ER on proestrus was a consequence of increased ER gene expression. In OVX mice, physiological and, to a lesser extent, supraphysiological levels of E2 increased cell nuclear ER. As in proestrous mice, the increased ER content contributed more than ER activation to the increased cell nuclear ER concentration. Physiological, but not supraphysiological, concentrations of E2 increased ER mRNA in OVX mice. Together, these results suggest that up-regulation by E2 of ER mRNA and ER accounts for most of the increased nuclear binding of ER on proestrus. E2-dependent activation and consequent DNA binding of ER presumably initiate this process, but quantitatively account for only a small fraction of the increased nuclear binding of ER.

Animals↗

Ingesting an onlay. A case report.

When a patient attempted to speak during a dental procedure, she swallowed an onlay. After four weeks, it was mechanically removed from her colon.

Colon↗

Genetic influences on oestrous cyclicity in mice: evidence that cycle length and frequency are differentially regulated.

Studies in C57BL/6J, DBA/2J and C3H/HeJ mice and in two F1 hybrid strains (B6D2F1 and B6C3HF1) 2-5 months old revealed marked genotypic differences among inbred strains. C57 mice had three times as many regular (3-6 days) cycles as DBA and C3H mice, due largely to fewer pseudopregnant-like (7-14 day) cycles. C57 had longer regular cycles than DBA and C3H mice. Although the frequencies of regular cycles of DBA and C3H mice were similar, the cycles of C3H mice were shorter than those of DBA mice. The results indicated that the genetic determinants of the frequency of regular cycles differ from those specifying cycle length. Frequency of regular cycles of F1 hybrids was either intermediate between the parent strains (B6D2F1) or similar to the C57 strain (B6C3HF1), suggesting that regular cycle frequency shows additive genetic variation in the former crosses, but mostly dominant variance in the latter background. Regular cycles were either shorter than in both parent strains (B6D2F1) or similar to one of them (B6C3HF1), indicating heterosis and dominance for genes specifying short cycles. Although the lack of reciprocal crosses meant that maternal effects and possible genomic imprinting effects could not be assessed, these results reveal marked genetic influences on cycle length and frequency and suggest that some of the genes specifying these two traits differ.

Animals↗

Age-related alterations in estrogen receptor dynamics are independent of cycling status in middle-aged C57BL/6J mice.

The objective of this study was to determine whether changes in estrogen receptor (ER) levels and dynamics that were previously observed in old acyclic mice were present in middle-aged mice and whether the cycling status of the mice influenced those changes. Young (3-6 months) regularly cycling and middle-aged (12-14 months) C57BL/6J mice that were either acyclic or still cycling regularly were injected with a dose of E2 (0.05 microgram/10 g body wt) sufficient to achieve maximal levels of nuclear ER (ERn) in all tissues examined: hypothalamus (HYPO), pituitary (PIT), and uterus (UT). The rise and fall of ERn and the replenishment of cytosolic ER (ERc) were measured 0, 1, 2, 4, 8, 12, and 24 h later. Cycling status did not affect ER binding profiles in middle-aged tissues. Therefore, data from cycling and acyclic subgroups were pooled for comparison with young mice. The increase in ERn following E2 injection, measured as the integrated area under the ERn profile, was reduced 33, 23, and 17%, respectively, in HYPO, PIT, and UT of middle-aged mice. In addition, the duration of elevated ERn was selectively reduced in middle-aged HYPO. ERc levels were reduced in middle-aged HYPO and UT, but replenishment rates were not altered. Reductions in total ER (ERn + ERc) were sufficient to account for the decline in ERn in middle-aged HYPO and UT, but factors in addition to ER loss appear to contribute to reduced ERn in middle-aged PIT. These results indicate that alterations in ER levels and dynamics occur prior to the transition to acyclicity, that these alterations are not secondary to hormonal or other changes associated with acyclicity, and that receptor loss appears to account for most of the age-related reduction in nuclear ER binding.

Aging↗

Absence of estrogenic activity in a diet that promotes estrous cyclicity in C57BL/6J mice.

A breeder diet that shortens estrous cycles in mice has been reported to contain estrogenic substances, based on its ability to increase uterine weight of immature mice. However, the estrogenicity of the diet was inferred from uterine weight gain of immature mice that were intact. The increased uterine weight of mice on the breeder diet could thus have resulted from a precocious pubertal increase of endogenous estrogens induced by the diet rather than estrogenic substances in the diet. We therefore measured the estrogenicity of the breeder diet in ovariectomized animals. C57BL/6J mice were fed the breeder diet or a standard diet for 1 or 4 weeks. The breeder diet failed to increase uterine weights above control values for either treatment interval. Intact mice that were fed the breeder diet had twice the number of cycles of mice fed the standard diet, a confirmation of earlier studies. These results indicate that the breeder diet does not contain biologically significant estrogenic activity, and thus potentiates cyclicity by other means.

Animals↗

Dental care utilization among dental students.

The purpose of this study was to determine the proportion of needed dental care actually received by dental students during their dental education. This was accomplished by a review of dental records for recent Baylor College of Dentistry graduates. Collected data included restorative, periodontal, endodontic and extraction procedures planned and dental care actually accomplished prior to graduation. Comparisons of these findings were made based on gender, ethnicity and academic standing of the sample subjects. The sample size of 134 included 98 males and 36 females; 111 were Caucasian and 23 Minorities. Fifty-six individuals were in the upper academic third of their class, 37 in the middle third and 41 in the lower third. The treatments required were primarily operative dental restorations (7.28 +/- 7.19 surfaces per student), crowns (0.43 +/- 1.22 units per student) and extractions (0.90 +/- 1.58 per student). Periodontal and endodontic needs were minimal. Students received approximately 60% of the required care during their dental education. Minimal relationships were identified between gender, academic standing and ethnicity and the students' care needs and treatments. The results suggest a relatively low priority for receiving needed dental care among dental students.

Crowns↗

Reactions of rat odontogenic tissues to heat.

Twenty-four Wistar rats were anesthetized and 200 degrees C heat was applied for 4 minutes to each mandibular left first molar. Eight of these rats were then killed at 2, 8, and 14 weeks. The subject and control teeth were radiographed and compared. They were then prepared for histologic evaluation and scored for levels of inflammation in both the pulpal and periradicular tissues. Furcal, interproximal, and apical radiographic changes were found at all three time intervals. These changes involved progressively larger percentages of teeth at 8 and 14 weeks. Histologically, complete necrosis and/or abscess formation were found in the coronal portions of all experimental pulps. With time, inflammatory changes increased in intensity and progressed through the radicular pulps, resulting in necrosis or calcific changes and, finally, inflammatory changes in the periradicular areas. The pathosis created by the application of heat was devoid of microorganisms as evaluated by the Brown and Brenn stain.

Animals↗

Genetic influences on the timing of puberty in mice.

Genetic influences on the timing of three pubertal events--vaginal opening, first vaginal cornification, and onset of cyclicity--were studied in C57BL/6J, DBA/2J, and C3H/HeJ mice and in two F1 hybrid strains (B6D2F1 and B6C3HF1). Marked genotypic differences were found. Among inbred strains, differences in the onset of vaginal opening and first vaginal cornification (C3H less than DBA less than C57) did not parallel those for the onset of cyclicity (C3H much greater than DBA = C57). Compared to parental strains, F1 hybrid strains were intermediate for times of vaginal opening and first vaginal cornification, consistent with the model in which the genetic effects on the timing of these events are additive. By contrast, onset of cyclicity occurred significantly earlier in the F1 hybrids than in their parent strains, indicating heterosis for one or more genes specifying this event. Body weights also differed among the genotypes from weaning onward, but these differences were only partially correlated with the differences in the timing of the pubertal events. Thus, genetic influences other than those affecting body weight contribute to the differential timing of pubertal events in these mouse strains. These results reveal marked genetic variation in the timing of puberty, and indicate that the set of genes specifying the timing of vaginal opening and first vaginal cornification differs from those specifying the onset of cyclicity.

Age Factors↗

Effects of chronic exposure to estradiol on ovarian cyclicity in C57BL/6J mice: potentiation at low doses and only partial suppression at high doses.

Long-term exposure to ovarian hormones contributes to age-related changes in estrous cyclicity in rodents. Estrogens are implicated in this process, but the concentration of estrogen required to exert these effects is not well established. Also, although estrogens are presumed to alter vaginal cyclicity by affecting the hypothalamic-pituitary axis, they may also impair the ability of the vaginal epithelium to cornify. To address these issues, young and middle-aged ovariectomized (ovx) C57BL/6J mice were exposed for 7-10 wk to plasma levels of estradiol (E2) at one of three ranges (30-40, 50-80, or 120-160 pg/ml). Ovaries from young mice were then transplanted under the renal capsule, and vaginal cyclicity was monitored for 4 mo. Mice exposed to the lowest level of E2 not only failed to stop cycling, but had a higher monthly frequency of estrous cycles than did controls (nearly 1 extra cycle/mo). Mice exposed to the intermediate level of E2 showed no impairment in cyclicity. Although mice exposed to the highest concentrations of E2 showed no vaginal cyclicity, they continued to ovulate as evidenced by fresh, albeit reduced, numbers of corpora lutea. These results indicate that, in ovx mice, (1) chronic exposure to relatively low concentrations of E2 potentiates cyclicity, (2) very high levels of E2 are required to induce acyclicity, and (3) this acyclicity reflects vaginal as well as neuroendocrine alterations. The results also indicate that vaginal acylicity may be a poor indicator of ovulatory acyclicity in mice that have been chronically exposed to E2.

Aging↗

Follicular depletion during the menopausal transition.

From mid-fetal life, the human ovary steadily loses follicles. While age-related alterations at the level of the hypothalamus-pituitary appear to determine the timing of menarche, the number of follicles remaining in the mature ovary is the major determinant of the timing of both the perimenopause and the menopause. As the residual follicle reserve nears exhaustion, some of the remaining follicles appear to be defective, as evidenced by the higher incidence of chromosomal abnormalities in the ova of older women. It is presently not possible, however, to distinguish the specific contribution of the ovum to the age-related decrease in fecundity and higher abortion rate because of such confounding variables as aging sperm or changes in the endometrium. When follicle counts from peri- and postmenopausal ovaries are placed with those from previous studies of younger women and children there appears to be an acceleration in the rate of follicle loss in the decade preceding menopause. We hypothesize that the elevated FSH levels observed in normal women in the decade preceding the menopause may be responsible for this apparent acceleration in the rate of follicle loss.

Aging↗

Differential effects of aging on estrogen receptor dynamics in hypothalamus, pituitary and uterus of the C57BL/6J mouse.

Estrogen receptor (ER) dynamics and content were measured in the hypothalamus (HYPO), pituitary (PIT) and uterus (UT) of aging mice because of their potential importance to age-related changes in sensitivity to estrogen. Young (3-6 months), and old (22-24 months) C57BL/6J mice were injected with a dose of E2 (0.05 micrograms/10 g body wt) sufficient to achieve maximal levels of nuclear ER (ERn) in all tissues, and the rise and fall of ERn and the depletion and replenishment of cytosolic ER (ERc) were measured 0, 1, 2, 4, 8, 12 and 24 h later. Integrated areas under the ERn profiles in old HYPO, PIT and UT were reduced 34, 28 and 19%, respectively. These reductions were due to (1) lower levels of ERn throughout the profiles, (2) delays in attainment of peak ERn in UT and PIT, and (3) accelerated loss of peak ERn in HYPO. ERc levels were also reduced in old mice, and replenishment of ERc was delayed in old HYPO and PIT, but not in UT. Reductions in total ER (ERn + ERc) were sufficient to account for all reductions and altered dynamics of ERn, except for the delayed attainment of peak ERn in UT. These results indicate that levels and dynamics of nuclear ER are altered during aging, and that most of these changes are secondary to alterations in ER content and turnover rather than a reduced ability of ER to bind to nuclear sites.

Aging↗

Acquired immune deficiency syndrome presenting as a palatal perforation.

Head and neck manifestations are particularly frequent in the acquired immune deficiency syndrome. An unusual case of acquired immune deficiency syndrome in a female prostitute whose initial presentation included a palatal perforation is reported. This case is also noteworthy because the patient died of disseminated miliary tuberculosis, a disease only recently included in the Centers for Disease Control case definition of AIDS.

Acquired Immunodeficiency Syndrome↗

Longitudinal studies of estrous cyclicity in C57BL/6J mice: III. Dietary modulation declines during aging.

Dietary modulation of estrous cyclicity was studied throughout the reproductive lifespan to assess the stability of age-related changes in cyclicity and to probe underlying mechanisms. Animals were fed a standard diet or an isocaloric breeder diet that differed in nutrient composition to promote fecundity. In young mice, the breeder diet more than doubled the frequency of short (4-day) cycles, and, as a result, increased the total number of cycles during the cycling lifespan by 10%. Dietary potentiation of short cycles disappeared between 7 and 9 months of age, and most subsequent age-related changes in cyclicity were resistant to dietary influence. The breeder diet had no effect on the transition from 4- to 5-day cycles, the onset of acyclicity, or on the incidence or duration of persistent vaginal cornification. It only delayed the increase of very long (greater than 5-day) cycles by 1 month. These results show that most age-related changes in cyclicity are not influenced by dietary differences that affect cyclicity in young mice, and that diminished responsiveness to dietary variation is among the earliest age-related changes in the reproductive system. In addition, the results suggest that differences in cycle frequency and, presumably, in cumulative exposure to pre-ovulatory elevations of ovarian steroids do not influence the cycling lifespan in this strain of mouse.

Age Factors↗

The decidual cell response in aging C57BL/6J mice is potentiated by long-term ovariectomy and chronic food restriction.

The effects of long-term ovariectomy (LOVX) and chronic food restriction on the decidual cell response were examined in aging mice. At 2 mos of age, mice were either ovariectomized, started on a regimen of food restriction (70% of ad lib intake), or left untreated. At 10 mos, the decidual cell response (DCR) was induced in all groups and measured by uterine weight gain, alkaline phosphatase activity, and DNA content. The DCR was also examined in young (4.5 mos) mice. LOVX and, to a lesser extent, food restriction (FR) potentiated the DCR, as indicated by 20-75% greater alkaline phosphatase activity and uterine weight relative to age-matched controls. In contrast to previous reports, however, there was no age-related reduction of the DCR. These results show that both LOVX and FR can enhance uterine function in middle-aged mice and indicate that, under some experimental conditions, there is no age-related impairment in the DCR.

Aging↗

On the relation of calcium to ovine parotid secretion.

The effects of Ca2+-active agents on ovine salivary flow rate and composition were measured in parotid glands under several conditions: no stimulation, submaximal stimulation of the secretomotor nerve, or stimulation by the cholinergic agents carbachol or bethanechol. Agents were infused into the arterial blood supply of parotid glands and those investigated were: calcium chloride, the calcium ionophores Bay K8644 and A23187, the calcium chelators EGTA and EDTA, the voltage-dependent calcium channel blocker verapamil and congeners, the calmodulin inhibitor trifluoperazine (TFP) and congeners. None of the agents affected the flow rate of saliva from unstimulated or pharmacologically stimulated glands. Increased plasma [Ca2+] and the ionophores did not affect salivary flow in nerve-stimulated glands. In nerve-stimulated glands, EGTA and TFP reduced salivary flow rate and verapamil increased it. The effect of EGTA was reversed by restoring plasma [Ca2+] to normal (1.0-1.2 mmol/l) or above, but the responses to TFP and verapamil were not reversed by increasing plasma [Ca2+]. In all three conditions of stimulation, infusions of EGTA, verapamil or TFP increased salivary [HPO4(2-)] and reduced [HCO3-] and pH. The ionophores had the opposite effects but increased plasma [Ca2+] had no effect. At the same time, EGTA, verapamil or TFP increased salivary [Na+ + K+], Bay K8644 had the opposite effect but increased plasma [Ca2+] had no effect. The osmolality of the saliva was not altered in any of these circumstances. Salivary [Ca2+] was increased by Ca2+ infusion and reduced by EGTA. Glandular blood flow increased with infusion of agents which increased salivary [HPO4(2-)], fell with infusion of ionophores, and was unchanged by increased plasma [Ca2+]. Thus, there appear to be three calcium-related activities in ovine parotid salivary gland in vivo: (1) salivary flow rate by action at the neuroeffector site, (2) salivary composition by alteration of the ratio of HPO4(2-): HCO3-, and (3) rate of blood flow through the gland by altering vascular resistance.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Recent studies of bone appetite in cattle.

Cows depleted of phosphorus by loss of saliva from a parotid fistula and low dietary phosphate developed an avid appetite for bones. The behaviour is innate and predominantly cued by olfactory stimuli. Meat, blood or fat were not attractive and bones became more attractive after aging for 1.5-2.0 years. The appetite was also shown for guano-derived rock phosphate and bird excreta. There was no interest in inorganic calcium and phosphate salts or ashed bone. The attractant is therefore an organic constituent of aging bone and was found to be at highest concentration in the marrow fraction. Water, ether and vacuum distillation extracts of old bone or marrow, added to unattractive materials e.g., ashed bone, rendered them attractive. The residues of such extraction were of diminished interest. The attractiveness of the fractionated extracts was highest in the neutral fraction. The bone appetite was abolished by increasing the phosphate concentration in plasma but not in cerebrospinal fluid. The phosphate concentration in the blood appears, therefore, to regulate the bone appetite. The sensors could be in brain regions without a blood-brain barrier. Chronic severe phosphorus deficiency was associated with bone resorption, reduced osteoblastic and hemopoietic activities, and abnormal blood progesterone cycles.

Animals↗