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Biomedical subjects

C Pilgrim

Publications and source records attributed to C Pilgrim.

At least 37 records · Page 2Linked to original sources
PubMed1995

Ontogeny of aromatase messenger ribonucleic acid and aromatase activity in the rat midbrain.

Estrogen formation catalyzed by neural aromatase is crucial for the sexual differentiation of the brain. Ontogenic expression of aromatase mRNA and aromatase activity were studied in male and female rat midbrains. Aromatase mRNA was transiently expressed in both sexes showing maximum levels on postnatal day (P)2 and being absent on P20 and in adults. Developmental expression of aromatase mRNA preceded that of aromatase activity. These data demonstrate that the capacity for estrogen formation is present during a distinct phase of midbrain development. Our findings suggest an active role for estrogens in the differentiation of midbrain neurons.

Animals↗
PubMed1995

Neurotoxicity of dopamine and protective effects of the NMDA receptor antagonist AP-5 differ between male and female dopaminergic neurons.

Neurodevelopmental and neurodegenerative disorders related to dopaminergic transmission typically exhibit a sex-specific prevalence. In order to investigate the underlying cellular mechanisms, primary cultures of dissociated embryonic rat midbrain were subject to a 24 h treatment with dopamine in concentrations between 1 and 1000 microM. Dopamine caused a dose-dependent loss of neurons and reduction of neurites immunoreactive to tyrosine hydroxylase with a LD50 of about 100 microM. Application of D1-like or D2-like receptor agonists instead of dopamine did not induce cell loss. Neither D1-like or D2-like receptor antagonists nor the nitric oxide synthase inhibitor N-nitro-L-arginine were capable of blocking dopamine-induced cell death. When tissue from male and female donors was cultured separately, a twofold sex difference was consistently present: (1) Survival rates of female dopaminergic neurons in the presence of LD50 concentrations of dopamine were about twice those of male neurons. (2) The N-methyl-D-aspartate-receptor antagonist AP-5 was capable of rescuing female but not male dopaminergic neurons from dopamine-induced cell death. It is concluded that dopamine neurotoxicity is not mediated by dopamine receptors and is aggravated by glutamate excitotoxicity but not by nitric oxide. The male-specific vulnerability is the first direct evidence that the prevalence of certain neurodevelopmental or neurodegenerative disorders may have a basis in the biology of the single dopaminergic neuron.

2-Amino-5-phosphonovalerate↗
PubMed1995

Effects of sex and estrogen on tyrosine hydroxylase mRNA in cultured embryonic rat mesencephalon.

In order to elucidate cellular events responsible for sex differentiation of the nigro-striatal system, we studied the influence of estrogen on the expression of tyrosine hydroxylase (TH) in sex-specific dissociated cell cultures of embryonic day 14 rat mesencephalon. Cultures were raised in the absence or presence of 17 beta-estradiol (10(-12) M) and hybridized with a [35S]oligonucleotide specific to TH. Cultured cells and tissues were probed for estrogen receptor (ER) transcripts by hemi-nested PCR. More TH mRNA containing cells were present in control cultures from female than from male donors. Estrogen treatment resulted in an up-regulation of TH expression in male cells only and induced a reversal of the sex difference in TH mRNA levels present in early control cultures. ER message was detectable in hypothalamic and uterine tissues but not in mesencephalic tissue or cultured cells. Estrogen exposure failed to induce ER expression in cultured mesencephalic cells. It is concluded that there are sex differences in TH mRNA expression of developing midbrain dopaminergic neurons which are independent of the steroid environment. Estrogen can up-regulate TH mRNA in a sex-specific fashion by modulating signal transduction mechanisms other than the classical nuclear receptor pathway.

Animals↗
PubMed1995

Transcription of the Y chromosomal gene, Sry, in adult mouse brain.

The Y chromosomal gene Sry encodes a putative transcription factor which appears to serve as a master switch initiating testicular development. Here we show that this gene is transcribed in hypothalamus, midbrain, and testis of adult male but not adult female mice. In contrast to its circular transcripts in adult testis, those in brain are linear and may be translated. We propose that Sry exerts a role in the regulation of sex differentiation of the mammalian nervous system.

Animals↗
PubMed1995

Reversal of baseline relations and stimulus equivalence: I. Adults.

Following the emergence of two four-member equivalence classes (A1B1C1D1 and A2B2C2D2), 5 students were exposed to a series of phases including a baseline conditional discrimination reversal (i.e., choosing D2 was reinforced and D1 punished given Sample A1; choosing D1 was reinforced and D2 punished given Sample A2), the delayed introduction of CD/DC transitivity/equivalence probes, DE conditional discrimination training, a second baseline conditional discrimination reversal (i.e., choosing C2 was reinforced given B1, etc.), and a return to original baseline reinforcement contingencies. Results showed that baseline and symmetry probe performances were extremely sensitive to baseline modifications. In contrast, patterns on transitivity/equivalence probes remained predominantly consistent with the originally established equivalence classes, although there were exceptions on some E probe relations for 2 subjects. The dissociation between baseline and symmetry versus transitivity/equivalence patterns may have important implications because it is not easily accounted for by current models of equivalence phenomena.

Journal Article↗
PubMed1995

Reversal of baseline relations and stimulus equivalence: II. Children.

In a systematic replication of a study using college-student subjects (Pilgrim & Galizio, 1990), 5- to 7-year-old children learned two conditional discriminations (i.e., A1B1, A2B2, A1C1, and A2C2) in a two-choice arbitrary match-to-sample task and showed the emergence of two three-member equivalence classes (A1B1C1 and A2B2C2). Baseline conditional discrimination performance were quickly controlled by reversals of the AC reinforcement contingencies (i.e., choosing Comparison Stimulus C2 was reinforced given Sample A1, and choosing C1 was reinforced given Sample A2) when the reversals were introduced in restricted baselines. On reflexivity, symmetry, and transitivity/equivalence probes following the reversal, there was some limited indication of equivalence-class reorganization (i.e., A1B1C2 and A2B2C1) in keeping with the concurrently performed baseline relations for 2 of 5 subjects, but the predominant pattern across probe trials was one of inconsistent conditional control. These findings suggest that, given similar challenges, equivalence-class performances may be more easily disrupted in young children than in adults.

Attention↗
PubMed1995

Stimulation of glucose utilization in the rat claustrum by pain.

The involvement of the claustrum in processing of somatosensory information was investigated using the formalin test as an established pain test. The metabolic activity of the claustrum and other brain structures belonging to the somatosensory system was assessed by autoradiographic method of the uptake of (3H)-labelled 2-deoxyglucose (2-DG). Glucose utilization in the claustrum was stimulated by subcutaneous injection of formalin into the front paw. The increase of radioactivity was observed not only in the claustrum, but also in the anterior pretectum, the ventral thalamic nucleus, the somatosensory, insular and piriform cortices on the contralateral side to formalin stimulation. After stereotactical injection of morphine into the contralateral pretectum to stimulation side, uptake of 2-DG in the claustrum was abolished. These results indicate that the claustrum is an important relay nucleus in the somatosensory system, which may convey somatosensory information from the pretectum to the cerebral cortex, thus by-passing the thalamus, throughout the pretecto-claustro-cortical pathways.

Animals↗
PubMed1994

Activation of cultured rat hypothalamic dopaminergic neurons by long-term but not short-term treatment with prolactin.

Pituitary prolactin (PRL) secretion is inhibited by hypothalamic GABAergic and dopaminergic (DAergic) systems. PRL, in turn, appears to be capable of activating these neurons, thus, providing for a negative feedback regulation. We have recently shown that cultured hypothalamic GABAergic- but not DAergic neurons respond to PRL with a rapid increase in intracellular free calcium. Here, we demonstrate that cultured hypothalamic DAergic neurons can be activated in terms of synthesis of dihydroxyphenylalanine (DOPA) by long-term PRL treatment. Short-term PRL treatment was ineffective. It is concluded that hypothalamic DAergic neurons are indeed capable of responding to PRL. However, their response differs from that of GABAergic neurons with respect to time scale and signal transduction. We suggest that the two types of hypothalamic cells are involved in separate feedback loops that provide for tonic and rapid regulation of pituitary PRL secretion, respectively.

Animals↗
PubMed1994

Differentiation of hypothalamic GABAergic neurons in vitro: absence of effects of sex and gonadal steroids.

The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is involved in the control of sexually dimorphic brain functions, such as pituitary secretion and reproductive behavior. Hypothalamic GABAergic systems in vivo exhibit sexually dimorphic functional properties. Sexual dimorphisms in the rat brain are currently thought to be brought about by the organizational influence of gonadal steroids during the perinatal developmental period. The present study is concerned with the question of whether developing hypothalamic GABAergic neurons are primary targets of sex hormones. Since it is impossible to distinguish direct from indirect effects of experimental manipulations of the hormonal environment of the in vivo brain, sex-specific primary cultures raised from embryonic day 14 rat diencephalon and cultured for up to 8 days in vitro (DIV) were used as a model system. Effects of sex steroids were investigated on high affinity uptake of [3H]GABA. GABA transport was already mature at 3 DIV. [3H]GABA uptake was sensitive to inhibition by nipecotic acid and the transmitter was taken up by high affinity transport (Km = 15.2 microM). Immunocytochemical preparations demonstrated extensive networks of GABA-immunoreactive fibers at 8 DIV. Concomitantly with the outgrowth of neurites, there was a marked increase in maximum uptake velocity (Vmax). No differences could be detected regarding cell numbers or uptake kinetics between cultures from male and female donors. Neither cell numbers nor GABA uptake were affected by short- and long-term treatment with estradiol-17 beta or testosterone. It appears that hypothalamic GABAergic neurons in vitro do not develop sex differences in cell numbers or GABA transport.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Increasing mammography utilization: a controlled study.

BACKGROUND: Despite the effectiveness of breast cancer screening for women older than 50 years of age, only about one third of these women in the United States receive annual mammography. PURPOSE: This study was designed to determine if a community-wide intervention could increase use of mammography screening for breast cancer. Secondary end points were determination of changes in women's knowledge and attitudes toward mammography and physicians' self-reported screening practices. METHODS: We conducted a controlled study from January 1987 through January 1990 in two eastern North Carolina communities--New Hanover County (the experimental community) and Pitt County (the control community). Before development and implementation of the intervention program in New Hanover County and after the program had been in operation for 1 year, 500 women of ages 50-74 years and all primary-care physicians in each community were interviewed by telephone. In these interviews, we determined the use of mammography for breast cancer screening and the knowledge and attitudes about it. We also established the number of screening mammograms performed in 1987 and 1989 in each county and reviewed medical records to determine the percentage of women the physicians had referred for mammograms. RESULTS: The percentage of women who reported receiving a mammogram in the previous year increased from 35% to 55% in the experimental community and from 30% to 40% in the control community (difference of differences, 10%; P = .03 after adjustment for race, education, age, and having a regular doctor; 95% confidence interval, 1%-18%). Increases were greater in New Hanover County regardless of age, race, income, and education. However, the increase was less for Black women than for White women, both overall and in most demographic subgroups. The total number of mammograms performed increased 89% in the experimental community and 45% in the control community. Women's knowledge about mammography changed little, but the intention to get a mammogram increased 30% in New Hanover County, compared with a 17% increase in Pitt County--a statistically significant difference (P < .01). Physician reports and medical record reviews in the two communities showed similar increases in the number of mammograms ordered. CONCLUSIONS: A community-wide effort to increase use of breast cancer screening was successful, but more work must be done to reach the National Cancer Institute's goal of annual mammograms for 80% of women of ages 50-74.

Age Factors↗
PubMed1993

Improving clinical breast examination training in a medical school: a randomized controlled trial.

To evaluate a new program for teaching clinical breast examination, a class of 156 second-year medical students were randomized into an experimental group (practice and feedback on silicone breast models and women volunteers) and a control group (lecture only). During a simulated practical clinical examination routinely conducted at the end of the second year, the experimental group students used more suggested palpation techniques during a patient examination (4.6 vs 2.0; p < 0.0001) and found more simulated lumps in a silicone model (4.7 vs 4.4; p < 0.05). Practice with immediate feedback is more effective than lecture alone in teaching clinical breast examination.

Breast Neoplasms↗
PubMed1992

Sex differences of hypothalamic prolactin cells develop independently of the presence of sex steroids.

There is evidence for a hypothalamic prolactin (PRL) system that expresses sexually dimorphic traits. The aim of this in vitro study is to gain an insight into the process of sexual differentiation of hypothalamic PRL cells. In particular, we wanted to determine whether sexual differentiation of these cells can occur independently of the surge of gonadal testosterone which, in the male rat embryo, takes place at embryonic day (E) 18 and is commonly believed to start the critical period of sexual differentiation of the brain. Gender-specific cell cultures were prepared from E 14 or E 17 rat diencephalon and raised in the absence of gonadal steroids. After 10 days in vitro, numbers of PRL-immunoreactive (IR) cells and PRL levels were quantified by immunocytochemistry and Western blotting, respectively. Numbers of PRL-IR cells and PRL levels were 2-3 times higher in cultures prepared from female than from male embryos of either age. It is concluded that sexual differentiation of hypothalamic PRL cells starts well before the generally acknowledged onset of the critical period and may proceed independently of the action of gonadal testosterone. Besides gonadal steroids, other mechanisms, such as cell-intrinsic realization of a sex-specific genetic program, may be responsible for initiating the development of sexually dimorphic neuronal phenotypes.

Analysis of Variance↗
PubMed1992

Sex differences in densities of dopaminergic fibers and GABAergic neurons in the prenatal rat striatum.

On the basis of observations on dopaminergic neurons developing in gender-specific cultures of embryonic rat mesencephalon, we have hypothesized that as yet unknown sexual dimorphisms might be found in projection areas of dopaminergic neurons. Therefore we searched for possible sex differences in the striatum during the period when massive ingrowth of mesencephalic afferents occurs and the striatal gamma-aminobutyric acid (GABA)ergic neurons differentiate. Male and female rats of embryonic days (E) 16, 18, 20, and 21 were fixed by perfusion through the heart. Vibratome sections were cut from the striatal anlage and sequentially immunostained for GABA by the immunogold-silver technique and tyrosine hydroxylase (TH) by the avidin-biotin-peroxidase method. Ultrathin sections were scanned for numbers of GABA- and TH-immunoreactive (IR) elements. Densities of TH-IR axons as well as of GABA-IR cell body profiles progressed with time. Contacts between TH-IR axons and GABA-IR and immunonegative cells were observed as early as E-16, increasing in numbers toward later stages. Throughout prenatal development, female striata displayed higher densities of both TH-IR axon and GABA-IR cell body profiles than male ones. This is the first report of a distinct anatomical sex difference regarding two major components of a key center of motor control. Prenatal sexual differentiation of the striatum may lead to a sexually dimorphic extrapyramidal circuitry, the existence of which, in the adult, is suggested by experimental and clinical data.

Animals↗
PubMed1992

Nuclear receptor sites for vitamin D-soltriol in midbrain and hindbrain of Siberian hamster (Phodopus sungorus) assessed by autoradiography.

Autoradiograms were prepared from midbrains and hindbrains of male and female Siberian hamsters (Phodopus sungorus), kept under short-day or long-day illumination, after injection of tritium-labeled 1,25-dihydroxycholecalciferol (vitamin D, soltriol). Concentration and retention of radioactivity was noted in nuclei of certain neurons, glial cells, and ependymal cells, and in choroid epithelium. Labeled neurons of varying intensity were found throughout the brainstem in distinct populations at characteristic topographical sites, which include cranial nerve motor nuclei, the nucleus (n.) reticularis tegmenti pontis, the caudoventral region of the n. raphe dorsalis, the n. trapezoides, the n. vestibularis lateralis and n. vestibularis superior, neurons in the various nuclei of the sensory trigeminus, accessory optic nuclei, scattered neurons in nuclei of the reticular formation, the n. ambiguus, certain cells in the area postrema, and many others. Glial cells with nuclear labeling, probably microglia, were scattered predominantly in or near myelinated nerve fascicles. The choroid epithelium showed strong nuclear labeling throughout the ventricle. Nuclear labeling of ependyma was variable and weak, mainly at ventral and lateral extensions (recesses) of the ventricle. The extensive presence of nuclear binding in select neural structures indicates that vitamin D exerts specific genomic effects on cell populations that are known to be involved in the regulation of motor, sensory, autonomic, neuroendocrine, metabolic, and immune functions. The results of these studies, in conjunction with those from other brain and peripheral tissues, recognize vitamin D-soltriol as a steroid hormone with a wide scope of hormone-specific target cells, similar to estrogen, androgen, and adrenal steroids, and which are topographically distinct and characteristic for its functions as the steroid hormone of sunlight.

Animals↗