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R Silver

Publications and source records attributed to R Silver.

At least 55 records · Page 3Linked to original sources
PubMed1997

Attachment site of grafted SCN influences precision of restored circadian rhythm.

Fetal hypothalamic grafts containing the suprachiasmatic nucleus (SCN) restore circadian locomotor rhythmicity when implanted into the third ventricle of SCN-lesioned hamsters. However, the quality of restored rhythms is variable, and the locomotor rhythms of grafted animals are generally less robust than those of intact animals. The present study explored whether anatomical features of the graft predict the quality of the recovered rhythm and whether such information might provide insight as to the target of the signal from the SCN that controls locomotor rhythmicity. The following graft parameters were assessed: distance between the attachment site of the graft and potential targets for the output signal from the SCN, number and overall size of SCN clusters, the size of the cluster closest to the SCN lesion site, and extent of vasoactive intestinal polypeptide (VIP) and vasopressin-associated neurophysin (NP) positive fiber outgrowth from the graft. The restored circadian activity rhythm was assessed by quantifying the precision of activity onset and the amount, period, and robustness of rhythmicity. The results indicate a significant positive correlation between the precision of activity onset and the proximity of the closest SCN cluster to the site of the lesioned host SCN. A more detailed analysis of the spatial location of the graft indicates that proximity of the graft in the dorsal and caudal directions, but not the rostral direction, is positively correlated with the precision of the recovered rhythm. This suggests two possibilities: the coupling signal may act on a site very near the SCN and travel preferentially in a rostro-caudal direction. Alternatively, the coupling signal may act on a site rostral to the SCN. That the site is not far rostral to the SCN was suggested by the lack of a correlation between the precision of the restored rhythm and the rostrally lying anterior medial preoptic nucleus. Finally, evaluation of NP- and VIP-ergic fibers in nuclei known to receive input from the SCN indicates that the extent of such innervation by graft efferents does not predict either the occurrence of recovery or the precision of the recovered rhythm. Overall, these results suggest that the target(s) of SCN pacemakers regulating locomotor rhythmicity lie in the hypothalamus, close to or rostral to the SCN.

Animals↗
PubMed1996

A diffusible coupling signal from the transplanted suprachiasmatic nucleus controlling circadian locomotor rhythms.

The mammalian suprachiasmatic nuclei (SCN) transmit signals to the rest of the brain, organizing circadian rhythms throughout the body. Transplants of the SCN restore circadian activity rhythms to animals whose own SCN have been ablated. The nature of the coupling signal from the grafted SCN to the host brain is not known, although it has been presumed that functional recovery requires re-establishment of appropriate synaptic connections. We have isolated SCN tissue from hamsters within a semipermeable polymeric capsule before transplantation, thereby preventing neural outgrowth but allowing diffusion of humoral signals. Here we show that the transplanted SCN, like neural pacemakers of Drosophila and silkmoths, can sustain circadian activity rhythms by means of a diffusible signal.

Animals↗
PubMed1996

Oxytocin and vasopressin immunoreactivity in rabbit hypothalamus during estrus, late pregnancy, and postpartum.

Mother rabbits construct an elaborate maternal nest before parturition and display a single, brief, daily nursing bout throughout lactation. These features present a unique model for investigating the relevance of changes in neuroendocrine secretion associated with pregnancy and parturition for the regulation of maternal behavior. In the present study we analyzed changes in the location, somal size, and number of oxytocin (OT)- and arginine vasopressin (AVP)-immunoreactive (IR) neurons in the hypothalamus of rabbits in estrus, late pregnancy (day 29), and postpartum day 1. From estrus to late pregnancy, the number of OT-IR neurons increased in the scattered cell groups located in the lateral hypothalamic area (LHA), but not in the magnocellular nuclei, i.e., paraventricular nucleus (PVN) and supraoptic nucleus (SON). On postpartum day 1 the increase in the number of OT-IR neurons was sustained in the LHA and became apparent also in the main body of the PVN, in which the number of OT-IR neurons doubled. Increases in the somal size of OT-IR cells were seen in all three nuclei only on postpartum day 1. No OT-IR cells were found in the suprachiasmatic nucleus (SCN). From late pregnancy and into postpartum day 1 increases in the somal size of AVP-IR neurons were detected in the PVN, SON, and LHA but not in the SCN. The number of AVP-IR neurons increased between late pregnancy and postpartum day 1 in the SON only. The changes observed in OT and AVP expression in specific hypothalamic nuclei may be related to specific somatic and behavioral events occurring around the time of parturition, e.g., nest-building, maintenance of homeothermy, elevation of blood volume, and nursing in mother rabbits.

Animals↗
PubMed1996

Calbindin-D28K cells in the hamster SCN express light-induced Fos.

Although the suprachiasmatic nuclei (SCN) have been intensively analyzed, they contain a population of cells that has not yet been characterized. In this study, we examined the distribution of cells immunoreactive (ir) for calbindin-D28K (CaBP), calretinin (CR), parvalbumin, vasopressin-associated neurophysin (NP), substance P (SP), vasoactive intestinal peptide (VIP), and light-induced Fos-like protein. Previously unidentified cells in the core of the hamster SCN contained CaBP. Photic stimulation during the night induced Fos expression in about 75% of the CaBP-positive SCN cells, and about 50% of the Fos-positive cells in the core region expressed CaBP. These findings provide new information in the search for the cellular localization of pacemaker cells in the SCN, as photic input entrains the circadian system, and cells that receive photic input must be either part of the clock itself, or an upstream component of the clock.

Animals↗
PubMed1996

Brain mast cell degranulation regulates blood-brain barrier.

Mast cells synthesize vasoactive agents and a number of neurotransmitters. They are particularly numerous in the medial habenular region of the epithalamus, the attachment site of the choroid plexus. The present study examined whether degranulation of brain mast cells alters the permeability of the blood-brain barrier (BBB). To this end, doves were injected intramuscularly with the mast cell degranulator, compound 48/80 (C40/80), followed by i.v. injection of Evans blue. The distribution of the dye in the parenchyma was examined using digital imaging. Three brain areas were analyzed: the medial habenula (which also contains mast cells), the paraventricular nucleus (PVN, which abuts the third ventricle, but has no mast cells), and the lateral septal organ (LSO, a circumventricular organ with fenestrated capillaries). Significantly more Evans blue tracer and fewer toluidine blue-positive mast cells were detected in the medial habenula of subjects treated with C48/80 compared to saline controls. Evans blue did not enter the PVN in either the experimental or control group, while it entered the LSO equally in both. Degranulation of mast cells after C48/80 treatment was confirmed histochemically and ultrastructurally. The results support the hypothesis that brain mast cell degranulation locally alters BBB permeability. Activation of brain mast cells may provide a mechanism for regulated opening of the BBB.

Animals↗
PubMed1996

Mast cells in the brain: evidence and functional significance.

For the past two decades the brain has been considered to be an immune-privileged site that excludes circulating cells from the parenchyma. New evidence indicates that some hematocytes reside in the brain, while others traffic through it. Mast cells belong to both of these functional types. Moreover, the appearance of mast cells in the CNS can be triggered behaviorally. After a brief period of courtship, for example, there is a marked increase in mast cells in the medial habenula of sexually active doves compared with controls. Exposure to gonadal steroids that occur endogenously or that are administered exogenously increases both the number of mast cells and their state of activation in the brain. These results show that hematopoietic cells can provide targeted delivery of neuromodulators to specific regions of the brain, thereby influencing neural-endocrine interactions.

Brain↗
PubMed1996

Restoration of circadian rhythmicity by transplants of SCN "micropunches".

Although it is widely accepted that the suprachiasmatic nuclei (SCN) of the hypothalamus serve as biological pacemakers regulating circadian rhythmicity, a number of studies suggest that some circadian rhythms may be controlled by extra-SCN structures. Transplantation of fetal anterior hypothalamic tissue containing the SCN restores circadian locomotor rhythms in SCN-lesioned hosts. Such transplants, however, contain substantial extra-SCN hypothalamic tissue. In the present study, the authors examined the recovery of circadian locomotor rhythms in animals implanted with small grafts harvested by taking "micropunches" from vibratome-sectioned brain slices. Micropunches were taken from three areas of the hypothalamus known to receive retinal input: the SCN, the subparaventricular zone, and the supraoptic nucleus. The results indicate that transplants restricted to the SCN region are necessary and sufficient for restoration of circadian locomotor activity rhythms and that micropunches of tissues from other sources are ineffective.

Animals↗
PubMed1996

A contaminant of L-tryptophan enhances expression of dermal collagen in a murine model of eosinophilia myalgia syndrome.

The eosinophilia-myalgia syndrome was associated with the ingestion of L-tryptophan products containing a number of contaminants, one of which has been identified as 1,1'-ethylidene-bis-(L-tryptophan) (EBT), also known as peak E or peak 97. In earlier studies, we demonstrated that EBT induces inflammation and fibrosis in dermal and subcutaneous tissue of C57BL/6 mice. Others have shown EBT to be a potent stimulus for fibroblast activation and collagen synthesis in vitro, and dermal tissue from EMS patients reveals evidence of enhanced collagen gene expression. In the present study using Northern blot analysis and in situ hybridization, we demonstrate enhanced expression of genes for types I, III, and VI collagen in the dermis and subcutis of C57BL/6 mice treated with EBT for 3-21 days. Increased type I procollagen mRNA was noted on day 6 of EBT treatment and was followed by enhanced expression of type III and VI procollagen mRNA at day 21. L-Tryptophan, free of contaminants associated with the eosinophilia-myalgia syndrome epidemic, increased dermal collagen mRNA to a lesser extent than did EBT. Increased procollagen gene expression was accompanied by evidence of enhanced TGF-beta 1 expression in the dermis and subcutis. This animal model provides additional evidence for EBT as a causal agent of the eosinophilia-myalgia syndrome and should prove useful in the study of the pathogenesis of that syndrome.

Animals↗
PubMed1996

Sex differences in the solitary and assaultive fantasies of delinquent and nondelinquent adolescents.

Self-images expressed in response to the Draw-A-Story task were examined for differences in gender, age, and delinquency. Subjects included 64 adolescents in detention in California and 74 normal controls attending schools in Ohio, New York, and Florida; 82 were males (53 delinquents, 29 controls); 56 were females (11 delinquents, 45 controls). Their ages ranged between 13 and 17. The first analysis evaluated whether gender or delinquency was related to self-image scores. No significant differences were found. The second analysis evaluated whether the proportions of drawings about solitary subjects or assaultive relationships differed depending on gender or delinquency. Significant gender differences were found in both solitary and assaultive content. The findings of assaultive content were reversed for solitary content. For assaultive content, the differences in proportion between male and female control subjects reached significance. The difference between male and female delinquents did not reach significance. Control males differed significantly from control females, but delinquent males did not differ significantly from delinquent females. Solitary content also distinguished between delinquent and control groups, as well as gender. The gender difference was large in the control group but small in the delinquent group. Delinquent female drawings were more like the male drawings of both groups. Thus greater gender differences were found among normal adolescents than among delinquent adolescents. Implications of the findings for access to fantasies and to screen for emotional needs are discussed.

Adolescent↗
PubMed1995

Location of neurons projecting to the hypophysial stalk--median eminence in ring doves (Streptopelia roseogrisea).

The median eminence/pituitary stalk represents the final common pathway for fibers from neurons that project to the pituitary gland. We have used the lipophilic fluorescent tracer 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) to determine the location of neurons projecting to the median eminence/pituitary stalk in ring doves. The tracer can be precisely applied to fixed tissue, in areas to which it is otherwise difficult to gain access. Following application of DiI to the median eminence/pituitary stalk, labeled neurons were detected in six distinct regions: the ventro-medial hypothalamic nucleus, paraventricular nucleus, supraoptic nucleus, in and ventral to the lateral forebrain bundle, preoptic area, and lateral septum. Labeled fibers branched extensively in the diencephalon, particularly along the third ventricle and in the septal-preoptic area. Sparse fiber labeling occurred caudal to the tuberal hypothalamus, even though these regions were close to the application site of the tracer. Labeled cerebrospinal-fluid-contracting cells were seen in the paraventricular region of the third ventricle. The results indicate that the avian neuronal system that projects to the median eminence and neural lobe occurs in diffuse clusters largely along the midline region of the hypothalamic septal-preoptic area. The paucity of fiber staining caudal to the tuberal hypothalamic region indicates that cells of these regions do not project to the median eminence/pituitary.

Afferent Pathways↗
PubMed1995

Intraventricular prolactin inhibits hypothalamic vasoactive-intestinal polypeptide-expression in doves.

While the role of prolactin in promoting the development of the crop-sac in members of the pigeon family (Columbiformes) is well established, its action in the central nervous system is less well understood. In the present study, prolactin was administered intracerebroventricularily (i.c.v.) in ring doves, and central expression of vasoactive-intestinal polypeptide (VIP) and gonadotropin-releasing hormone (GnRH), and the display of sexual behavior was investigated. Ovine-prolactin (1 microgram in 2 microliters o-prl) was injected daily for six days through chronically implanted cannula either prior to a 2-h period of courtship, or late in incubation. Control subjects were given vehicle injections and were otherwise identical to experimental animals. Prolactin administered prior to courtship resulted in a reduction of sexual behavior, and in a decrease in testicular weight but had no detectable effect on the number of neurons expressing VIP or GnRH. In contrast, i.c.v. prolactin during incubation resulted in a reduced number of infundibular VIP-positive neurons and decreased crop weight. We conclude that during incubation prolactin regulates its own synthesis and/or release by modulating VIP expression in infundibular neurons.

Analysis of Variance↗
PubMed1995

The factor V Leiden mutation which predisposes to thrombosis is not common in patients with antiphospholipid syndrome.

Antiphospholipid syndrome is associated with venous, arterial, and placental thrombosis, possibly through autoantibody impairment of phospholipid-dependent protein C activation. Recently, a missense mutation in the factor V gene (1691 G-->A) has been identified that results in an abnormal factor V product (1). This mutation, known as the Leiden mutation, causes an amino acid substitution of glutamine for arginine at position 506 in the factor V molecule and renders the protein resistant to proteolytic inactivation by activated protein C and thus predisposes to thrombosis (2, 3). We hypothesized that some individuals with antiphospholipid syndrome may also carry the Leiden mutation, and thus have a "second hit" predisposition to thrombosis. To test this hypothesis, allele-specific hybridization and allele-specific restriction analysis were used to test for the Leiden mutation in thirty women with the antiphospholipid syndrome, 10 of whom had a history of thrombosis. None of the women were heterozygous or homozygous for the factor V mutation. We conclude that the presence of the factor V Leiden mutation is not a prerequisite for the thrombotic events in patients with antiphospholipid syndrome, due to the occurrence of thrombosis seen in patients lacking the factor V mutation.

Alleles↗
PubMed1994

Host resets phase of grafted suprachiasmatic nucleus: a 2-DG study of time course of entrainment.

The object of the present experiment was to examine whether in an intact animal implanted with a hypothalamic graft, the phase of the host and grafted suprachiasmatic nucleus (SCN) would become synchronized. To this end, we first established the time at which daily fluctuations in local cerebral glucose utilization were maximal in the SCN in our population of adult hamsters. Next, we verified that rhythms of (14C)2-deoxyglucose uptake could be measured on the day after birth in pups that were to provide donor tissue. Host and donor animals were housed in opposite light:dark cycles. We then transplanted fetal SCN tissue into the third ventricle of intact hamsters, placed the grafted animals in constant darkness with access to running wheels and examined the phase of metabolic activity in host and donor SCN. For several days after grafting, there was no circadian fluctuation in the metabolic activity of either the host SCN or of the grafted SCN. During this time, the circadian locomotor rhythms were not disrupted, suggesting that pacemaker activity was not interrupted. By day 14 after transplantation, metabolic activity in the host SCN was elevated during subjective day and host and donor SCN were in synchrony, invariably with the phase of the host animal. We conclude that a signal from the host SCN resets the grafted SCN and not vice versa and that pacemaker cells communicate with each other rather than exerting independent effects on target sites.

Animals↗
PubMed1994

Host resets phase of grafted SCN: influence of implant site, tissue specificity and pineal secretion.

The suprachiasmatic nuclei (SCN) have daily fluctuations in energy consumption with glucose utilization high in the day, and low at night. In a previous study, we used [14C]2-deoxyglucose (2-DG) uptake to index the phase of the SCN, and found that in intact hamsters bearing SCN grafts in the third ventricle (3V), the native and grafted SCN, which were initially 12 h out of phase, became synchronized to the phase of the host clock [32]. In the present study, adult males (host animals) and pregnant females (source of donor tissue) were housed in opposite light-dark cycles. Host animals were sacrificed 14 days after implantation with either (1) SCN grafts into the lateral ventricle (LV), or (2) cortical grafts into 3V, or (3) SCN grafts in 3V of pinealectomized hamster. The results indicate that rhythms of 2-DG uptake are not induced in cortical tissue grafts, that the host SCN does not entrain SCN grafts located in the LV, and that entrainment of the grafted SCN (located in 3V) by the host circadian system occurs in the absence of pineal secretions.

Animals↗
PubMed1994

Mast cells with gonadotropin-releasing hormone-like immunoreactivity in the brain of doves.

Using an antiserum (LR-1) raised against mammalian gonadotropin-releasing hormone (GnRH), we previously identified a nonneuronal cell that was more numerous in the medial habenula (MH) of courting ring doves than in individuals housed in visual isolation. The current studies suggest that they are mast cells. Both acidic toluidine blue and toluidine blue dissolved in water/butanediol revealed metachromatic cells with a distribution and morphology similar to that obtained by immunostaining with the GnRH antiserum in the MH. Some cells had granules reactive to safranin in the presence of alcian blue, indicative of a highly sulfated proteoglycan of the heparin family. Immunocytochemical studies demonstrated that all MH cells containing GnRH-like immunoreactivity contained histamine, another mast cell marker. The GnRH-immunoreactive cells had a unilobular, ovoid nucleus. Secretory granules within the cells were electron dense and displayed a variety of internal structures. Fine filamentous processes appeared evenly distributed on the cell surface whether cells were located on the pial surface or within the brain parenchyma. All of these features are characteristic of mast cells. To test whether the epitope recognized by the GnRH antiserum was produced by the mast cells or endocytosed from the cerebrospinal fluid, an iodinated GnRH analog was injected intracerebroventricularly at the initiation of courtship. Radioautography revealed no radioactive cells in the brain, indicating that the GnRH antibody recognized a molecule synthesized by the nonneuronal cells rather than internalized by a receptor-mediated mechanism. These observations suggest an interaction between a component of the immune network and specific regions of the central nervous system.

Animals↗
PubMed1994

Results of endoscopic sinus surgery in pediatric patients with chronic sinusitis and asthma.

OBJECTIVE: To determine the efficacy of endoscopic sinus surgery in pediatric patients with chronic sinusitis and asthma. SETTING: Patients were selected from the tertiary care practice of a pediatric pulmonologist (R.S.) and immunologist (R.L.W.); all underwent sinus surgery at Children's Medical Center at Dallas (Tex). PATIENTS: Fourteen pediatric patients aged 3.5 to 13 years with severe asthma requiring at least intermittent systemic steroid therapy. All patients had a history of sinusitis aggravating asthma and all had computed tomographic evidence of chronic sinus disease. INTERVENTION: All patients underwent endoscopic sinus surgery consisting of bilateral total ethmoidectomies and middle meatus antrostomies at a minimum. MAIN OUTCOME MEASURES: The period 12 months prior to surgery was compared with 12 months postoperatively with regard to total hospitalization days for asthma treatment, number of school days missed, pulmonary function test results, and systemic glucocorticoid medication requirements. Symptom scores for asthma and sinusitis were assessed via parental questionnaire both preoperatively and postoperatively. RESULTS: No significant difference was found for pulmonary function test results. Eleven of 14 patients demonstrated a significant reduction in hospitalization and school days missed. Twelve of 14 patients experienced a reduction in glucocorticoid requirements. Eleven of 14 and 13 of 14 patients experienced a significant improvement in asthma and sinusitis symptom scores. CONCLUSION: Endoscopic sinus surgery was effective in reducing sinusitis and improving the overall management of asthma in a majority of study patients.

Absenteeism↗
PubMed1994

Increased VIP and decreased GnRH expression in photorefractory dark-eyed juncos (Junco hyemalis).

Most temperate zone birds show dramatic seasonal cycles in responsiveness to light. In the spring the hypothalamo-pituitary-gonadal axis of photosensitive birds is stimulated by long days. In the late summer birds no longer respond to long days, their gonads regress, and they are said to be photorefractory. After several weeks of refractoriness birds regain photosensitivity. During refractoriness circulating concentrations of luteinizing hormone are low and prolactin levels are high. These fluctuations in peripheral hormones result from changes in the brain rather than in the pituitary and/or the gonads. In the present study we examined seasonal changes in expression of vasoactive-intestinal polypeptide (VIP) and gonadotropin-releasing hormone (GnRH) in the brain of dark-eyed juncos (Junco hyemalis). Birds were photosensitive and exposed to long photoperiod (20:4 LD) for 1 day, 45-60 days, or not at all, or they were photorefractory (housed in 20:4 LD). The results indicate that VIP expression was similar in all photosensitive birds. However, photorefractory birds had significantly higher numbers of VIP-positive neurons in the infundibulum compared to photosensitive birds. The number of GnRH-positive neurons in the preoptic area was significantly lower in photorefractory birds and significantly higher in long-term photostimulated birds. These results indicate that the inverse relationship between circulating prolactin (released by VIP) and luteinizing hormone (released by GnRH) during refractoriness may result from neural changes in VIP and GnRH expression, respectively.

Animals↗