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Biomedical subjects

C A Pedersen

Publications and source records attributed to C A Pedersen.

At least 73 records · Page 4Linked to original sources

Detection of occult metastatic lobular carcinoma in axillary lymph nodes using anticytokeratin monoclonal antibodies.

To examine the importance of immunocytochemically detectable occult axillary lymph node metastases in patients with lobular carcinoma of breast, tumor registry data from 54 cases indexed as lobular carcinoma during the period 1973-82 were reviewed. Recurrences and/or deaths due to cancer were essentially confined to the group of patients with a component of invasive lobular carcinoma (ILC), therefore this subset was selected for further study. Seven of 20 cases had lymph node metastases diagnosed histologically at the time of mastectomy. Follow-up of these patients showed four dead of disease (DOD) at one, three, three, and seven years; one alive with disease (AWD) at one year; and two with no evidence of disease (NED) at four and five years. Eleven of 20 were node negative. Follow-up of this group showed nine NED and two DOD at two and four years. Two of 20 had unknown node status. Formalin-fixed, paraffin embedded lymph node blocks were available in 12 of 20 cases with a component of ILC. Of these, 4/12 cases had histologically positive nodes while 8/12 were originally diagnosed as negative. A cytokeratin monoclonal antibody cocktail (MAK-6, CAM 5.2 and AE1/AE3) was applied to all 12 cases. Cytokeratin immunoreactivity (CK-IR) was found in all four cases that were histologically positive. Five of eight histologically negative nodes lacked CK-IR, however the other three cases showed CK-IR in micrometastases. Review of newly prepared hematoxylin-eosin sections from the paraffin blocks failed to demonstrate metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Mating alters topography and content of oxytocin immunoreactivity in male mouse brain.

Sexual stimulation of males has been reported to affect hypothalamic oxytocinergic systems. In the present study we used radioimmunoassays of microdissected forebrain regions and immunocytochemical analysis of Vibratome sections to study the oxytocin systems of naive males, males killed after one mating, and males mated daily with different receptive females for 3 weeks. In males that had mated once, less oxytocin-immunoreactive neurons were observed in the paraventricular (PVN), supraoptic (SON) and periventricular (NPE) nuclei than in naive males. However, after repeated matings, the number of immunoreactive neurons and their staining intensity was increased in these regions. Furthermore, additional oxytocinergic neurons could be found in the lateral subcommissural nucleus, the zona incerta and the ansa lenticularis of repeatedly mated males. Oxytocin-immunoreactive neurons were only occasionally seen in these areas in unmated males or in animals that had been killed after initial mating. Radioimmunoassays of microdissected PVN, SON, NPE and the lateral hypothalamus confirmed the reduction in oxytocin-immunoreactive levels after a first mating by a male and the increase after repeated matings. It is likely that oxytocin secretion into peripheral and portal circulation is stimulated by the endocrine conditions associated with initial mating. These immediate effects may be followed by the activation of synthesis in oxytocin neurons in several sites of the basal forebrain.

Animals↗

Corticotropin-releasing hormone inhibits maternal behavior and induces pup-killing.

Behavioral responses to stressors and the effects of stressors on maternal behavior change with mothering experience. Corticotropin-releasing hormone (CRH) is released by stressors and produces stress-like behavioral effects. We tested the effects of ICV infusion of ovine CRH (0.5-4 ug) on pup-directed behaviors in ovariectomized, ovarian steroid-treated virgin rats that were either naive to pups or that had three days of mothering experience. CRH inhibited maternal behavior in naive and experienced rats in a dose-related manner. The magnitude and duration of inhibition, especially at the 1 ug dose, were less in rats with mothering experience. Higher doses of CRH (1 - 4 ug) significantly increased pup-killing in rats that were naive to pups. In contrast, CRH produced no pup-killing in rats with mothering experience.

Animals↗

Oxytocin selectively increases holding and licking of neonates in preweanling but not postweanling juvenile rats.

Preweanling rats exhibit components of maternal behavior (MB) after brief periods of contact with neonates; the latency of onset of MB rises considerably after weaning. Oxytocin (OXT) stimulates MB in adult rats. The effects of intracisternal (IC) administration of OXT (2 micrograms) on pup-directed and other behaviors in preweanling and postweanling juvenile rats were tested. Compared with saline and no treatment, OXT significantly increased active holding of pups in preweanling but not postweanling juvenile rats. No other components of adultlike MB were stimulated by OXT. OXT also decreased inactive touching of pups and robustly increased selfgrooming in juveniles at all ages tested. It is concluded that OXT facilitation of active pup-holding and licking in preweanling rats may be an extension of OXT-induced self-grooming to pups and may also be related to OXT activation of MB in adult rats.

Age Factors↗

Immunocytochemical analysis of estrogen and progesterone receptors in benign stromal lesions of the breast. Evidence for hormonal etiology in pseudoangiomatous hyperplasia of mammary stroma.

Five cases of pseudoangiomatous hyperplasia of mammary stroma, together with seven examples of mammary hamartoma, were probed with monoclonal antibodies H222 and KD68 to investigate the possible role of estrogen and progesterone receptor expression in the pathogenesis of these benign stromal proliferations. All five cases of pseudoangiomatous hyperplasia showed patchy, intense labelling of the stromal cells with progesterone receptor antibodies, a pattern contrasting markedly with the absence of immunoreactivity in normal (nongestational) mammary stroma or the stromal component of common juvenile mammary hyperplasia. The stroma of the hamartoma group labeled inconsistently, with the notable exception of three myoid hamartomas. Stromal immunoreactivity was diffuse and intense in two of these, and patchy and distinct in the remaining case. These findings (a) support the contention that pseudoangiomatous hyperplasia represents a localized form of stromal overgrowth with a hormonal (primarily progestagenic) etiology and (b) further highlight the heterogeneity of so-called mammary hamartomas by demonstrating dramatically different progesterone receptor immunoreactivity patterns in myoid lesions as compared with other hamartoma variants.

Adult↗

Immunocytochemical identification of Helicobacter pylori in formalin-fixed gastric biopsies.

H&E and special histochemical stains are used by most laboratories to identify Helicobacter pylori (H. pylori) in gastric biopsy specimens. However, background staining can complicate recognition of H. pylori and small numbers of organisms may be overlooked. Additionally, histochemical stains do not distinguish H. pylori from other spiral organisms. We investigated two commercially available monoclonal antibodies, one directed against Campylobacter coli and C. jejuni (MAB002) and the other against a Campylobacter species flagellar antigen (MAB001), to evaluate potential use in immunocytochemical examinations of fixed tissues. MAB002 reacted with C. jejuni but not H. pylori organisms. MAB001 labeled C. jejuni as well as H. pylori and, therefore, was used to study 220 gastric biopsies from patients undergoing endoscopy. Acute and/or chronic gastritis was present in 60.5% (133/220) of the biopsies examined. MAB001 positivity was identified in 62.4% (83/133) of the tissues with gastritis. Only 2 of 87 (2.3%) specimens without gastritis demonstrated MAB001 labeling. The resulting immunoreactivity was easily identified, allowing specimens to be screened quickly and accurately. No labeling was seen with the non-Helicobacter/Campylobacter bacteria or normal tissues evaluated in this investigation. MAB001 can be used to identify H. pylori in histologically processed tissue and will assist pathologists, clinicians, and researchers studying the distribution and pathogenicity of this organism in humans and animals.

Antibodies, Bacterial↗

A uterotonic antagonist blocks the oxytocin-induced facilitation of female sexual receptivity.

The nonapeptide oxytocin (OXT) has been shown to facilitate female sexual receptivity when infused into the cerebral ventricles or the basal forebrain. Various selective antagonists have been used to block other behavioral effects of centrally administered OXT. In this study we compared the effects of equal doses of uterotonic, antidiuretic (V2) or vasopressor (V1) antagonists in blocking the facilitative effects of a simultaneous infusion of OXT into the basal forebrain. Ovariectomized (OVXed) animals were implanted with chronic cannulas in the basal forebrain. All animals were then given 0.5 micrograms estradiol benzoate daily for 3 days before testing. On the fourth day animals were tested to 8-10 mounts with a sexually vigorous male before and 20, 40 and 90 min after infusions of 500 ng OXT alone or in combination with a uterotonic, V2 or a V1 antagonist analogue. OXT significantly increased lordosis responding 20 and 40 min after its infusion into the medial preoptic area and anterior hypothalamus when compared to the receptivity of normal saline vehicle infused animals. The uterotonic antagonist significantly blocked the facilitation seen after OXT. The V1 and V2 antagonists at equal doses had no effect on the OXT-induced facilitation of lordosis postures. The V1 antagonist itself facilitated sexual receptivity 90 min after infusion. The facilitative effect of OXT on receptivity appears to be mediated by central uterotonic receptors, while central vasopressor receptors may serve an inhibitory role.

Animals↗

The presence of antithyroid antibodies in patients with affective and nonaffective psychiatric disorders.

We determined the frequency of antithyroglobulin and antimicrosomal antibodies in 173 consecutively admitted psychiatric inpatients. (We found antithyroid antibodies in 8% (5/65) of patients with DSM-III major depression, 13% (4/31) with biploar disorder, and in 0% (0/4) of those with schizoaffective disorder.) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole. The overall frequency of positive antithyroid antibody titers in patients with DSM-III affective disorder, 9% (9/99), did not differ from that in patients with nonaffective disorders, 10% (7/68). However, patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients. Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder, even in the absence of lithium exposure. However, as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders, the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation.

Adolescent↗

Topography of oxytocinergic estradiol target neurons in the mouse hypothalamus.

Combined (3H) estradiol autoradiography and oxytocin immunocytochemistry were used in order to study co-localization of cytoplasmic oxytocin immunoreactivity and nuclear uptake of (3H) estradiol in the forebrain of adult ovariectomized mice. Labelling with (3H) estradiol was found in subpopulations of neurons that constitute between 10 to 40% of the oxytocinergic cells in the paraventricular nucleus, the supraoptic nucleus and the intersupraoptico-paraventricular islands. Oxytocinergic neurons in the septohypothalamic nucleus, the anterior commissural nucleus, the periventricular nucleus and the zona incerta only occasionally showed nuclear uptake of (3H) estradiol. The results indicate that oxytocinergic cell groups within the classical magnocellular nuclei have much higher numbers of estrogen receptors than the so called accessory oxytocin neurons. Oxytocinergic neuronal systems seem to constitute functionally heterogenous populations of cells, differently influenced by estradiol.

Animals↗

Abnormal neuroendocrine responsivity to clomipramine in depression.

We used a pharmacologic probe that measures the neuroendocrine response to acute, intravenous "challenge" with the serotonin re-uptake inhibitor, clomipramine, in our studies of the biochemical bases of depressive illness. In two studies conducted at different sites, depressed patients consistently demonstrated blunted prolactin responses to clomipramine, compared with healthy control subjects. In order to clarify the mechanisms that might account for this abnormal neuroendocrine response to clomipramine in depression, we administered a thyrotropin-releasing hormone (TRH) stimulation test to 7 depressed patients who had also received a clomipramine challenge test. Although these patients demonstrated blunted prolactin responses to clomipramine, their prolactin responses to TRH were robust. These observations suggest that the blunted prolactin response to clomipramine in depression is not attributable to diminished hormonal secretory capacity in anterior pituitary lactotrophs and may be a reflection of dysregulation in central serotonergic systems.

Adult↗

Changes in immunostaining for oxytocin in the forebrain of the female rat during late pregnancy, parturition and early lactation.

Serial brain sections of female rats at late pregnancy, parturition or early lactation were immunostained for oxytocin. Immunoreactive perikarya were visible in the magnocellular nuclei in all experimental animals as well as in ovariectomized, nulliparous controls. During late pregnancy and at parturition additional immunostaining appeared in groups of perivascular neurons in the preoptic region, the lateral subcommissural nucleus, the perifornical region and scattered throughout the ventral portion of the hypothalamus. Immunostaining of almost all of these perivascular neurons disappeared by day two postpartum, while another population of oxytocin neurons, without association with blood vessels, appeared in these brain regions after parturition. Immunostaining of processes from oxytocinergic neurons in the periventricular nucleus increased markedly near parturition. Many of these processes projected toward the third ventricle. Oxytocinergic neuronal systems that are activated in late pregnancy and early postpartum may contribute to several physiological changes associated with parturition and lactation including the onset of maternal behavior.

Animals↗

Neonatal administration of oxytocin increases novelty-induced grooming in the adult rat.

Three-day-old Sprague-Dawley rat pups were intracisternally infused with a single dose of oxytocin (1 microgram/2 microliters) or saline, or were untreated. As adults, these animals were observed for novelty-induced grooming, analgesia measured by the hot-plate test, and behavior in the open field. Oxytocin treatment during infancy resulted in an elevation of novelty-induced grooming when compared to saline and untreated animals. There were no significant oxytocin treatment effects on analgesia response or open-field behaviors. Oxytocin given early in life may have permanent effects on certain behavioral responses to stress.

Aging↗

Dexamethasone effects on numbers of cells in lymphocyte subpopulations: changes associated with major depression and DST nonsuppression.

1. The authors studied the effects of administration of 1 mg of dexamethasone on the number of cells in discrete subpopulations of lymphocytes in major depressed and psychiatric control patients with depressive symptoms. 2. Dexamethasone significantly decreased the total lymphocyte count and numbers of T and helper T lymphocytes in control patients. 3. In contrast, dexamethasone failed to significantly decrease the numbers of cells in any of the subpopulations of lymphocytes studied in major depressed patients. 4. Among major depressed patients both DST suppressors and nonsuppressors were insensitive to the suppressive effects of dexamethasone on lymphocyte numbers. 5. However, in DST nonsuppressors, but not in DST suppressors, dexamethasone administration significantly increased the number of cytotoxic/suppressor T lymphocytes and natural killer cells. 6. The authors conclude that insensitivity to the suppressive effects of dexamethasone on lymphocyte numbers is specific to major depression and is not associated with DST status. However, DST nonsuppression is associated with a facilitating effect of dexamethasone on the number of cells in some subpopulations of lymphocytes.

Adolescent↗

Medial preoptic area oxytocin and female sexual receptivity.

Intracerebroventricular (icv) administration of the nonapeptide oxytocin (OXT) increases sexual receptivity in female rats. The medial preoptic area (MPOA) appeared to be the most sensitive brain area to the facilitative effects of OXT. Bilateral infusions of 100 ng of OXT into the MPOA significantly elevated lordosis quotients in ovariectomized (OVX), estrogen-treated rats. This dose of OXT was ineffective when infused icv or into the ventromedial hypothalamus, mesencephalic central gray, or ventral tegmental area. A 500-ng dose of OXT significantly elevated lordosis responding when infused icv, corresponding with our previous findings. Mounting by males significantly increased immunoreactive levels of OXT and decreased the number of OXT immunostaining cells in the MPOA of sexually receptive rats pretreated with estrogen and progesterone. The MPOA is a primary site of the OXT facilitation of sexual receptivity where OXT may be released during mating.

Animals↗

Immune correlates of stress and depression.

This paper reviews the evidence for alterations in immunity associated with depression and stressful events. The reviewed studies examine a variety of immune parameters (e.g., mitogen response, natural killer cell activity and number, T-cell, and T-cell subpopulations) in relation to depression and in relation to a number of stressful events (e.g., death of spouse, examinations). There is considerable variability in the findings of the available studies. However, the review finds considerable evidence for an association between a variety of stressful events and lowered immunity and between severe depression and lowered immunity. The clinical relevance of these psychoimmune relationships remains in question.

Depressive Disorder↗

Ovarian steroids and sexual interaction alter oxytocinergic content and distribution in the basal forebrain.

The immunoreactive levels of oxytocin (OXY) were assessed by radioimmunoassay (RIA) and immunohistology after treatments with estradiol or estradiol and progesterone in ovariectomized rats that were mounted or not mounted by males. In micropunches from the medial preoptic area (MPOA) OXY immunoreactive levels increased significantly in estrogen-progesterone-treated receptive animals (mean lordosis quotient (LQ) = 82.9 +/- 4.4) that were mounted by males over levels in estrogen-treated unreceptive animals (mean LQ = 2.3 +/- 1.3). No other areas demonstrated significant changes in OXY levels across these treatments, although the paraventricular nucleus also had elevated OXY levels in receptive mounted females. In other animals, immunocytochemistry revealed that the number of oxytocinergic perikarya in the MPOA decreased in receptive animals (LQ = 86.7 +/- 4.9) that were mounted. The number of oxytocinergic perikarya per 50 microns vibratome section in the lateral subcommissural nucleus was lower in all estrogen-treated groups than in oil vehicle-treated controls. We suggest that the combination of increasing immunoreactive levels of OXY in the MPOA with decreasing numbers of oxytocinergic perikarya indicates that preoptic OXY is moved out of cell bodies, in receptive rats that are mounted by males, to a state that is more accessible to the RIA.

Animals↗

Major depression and immunity: preliminary evidence of decreased natural killer cell populations.

1. Alterations in cellular immunity have been suggested to occur in major depressed patients. 2. To investigate the populations of B-cells, T-cells and T-cell subsets in major depression, the authors utilized monoclonal antibody techniques to enumerate the number of total lymphocytes, B-cells and T-cell subpopulations in recently admitted patients with major depression or non-affective disorders. 3. The authors also studied the relationship between the immune state and hypercortisolism as measured by post-dexamethasone serum cortisol. 4. The preliminary findings from this pilot study suggest that major depressed patients may have altered cellular immunity as demonstrated by lower numbers of natural killer cells. 5. Further study will be necessary to confirm the trend for lower numbers of T-cell lymphocytes and T-cell subpopulations including helper cells, suppressor cells and natural killer cells in patients with non-suppression of serum cortisol following dexamethasone.

B-Lymphocytes↗