Sclerotic hip medullary lesion evolving into a simple bone cyst--a case report.
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Adolescent↗
Biomedical subjects
M Segal
Publications and source records attributed to M Segal.
Peroxide modulation of slow onset potentiation in rat hippocampus.
Exposure of rat hippocampal slices to low concentrations of the muscarinic agonist carbachol (CCh) has been shown to produce a slow onset long-term potentiation (LTP) of reactivity to afferent stimulation in CA1 neurons. Although this potentiation shares a number of properties with tetanic LTP, muscarinic LTP (LTPm) is independent of activation of the NMDA receptor. We now demonstrate that low levels of hydrogen peroxide (H2O2) cause hippocampal slices to lose the ability to express LTPm. This powerful effect of H2O2 is selective in that it does not affect the reactivity of hippocampal neurons to higher concentrations of CCh. In fact, H2O2 also blocks induction of a slow onset, non-NMDA-dependent tetanic LTP (NN-LTP). The functional relevance of this action of H2O2 is exemplified by the fact that the hippocampus of aged rats, which produces higher levels of endogenous H2O2 than that of young rats, lacks LTPm and expresses a markedly reduced NN-LTP. In aged rats, the lack of LTPm contrasts with an apparently normal muscarinic suppression of the EPSP slope induced by higher concentrations of CCh. When hippocampal slices from aged animals are treated with catalase, an enzyme that breaks down H2O2, LTPm is restored, and NN-LTP is enhanced. Thus, our study proposes a unique and novel age-dependent peroxide regulation of LTPm in the brain and provides a link between the cholinergic system, aging, and memory functions.
Aging↗
Temporal trends and factors associated with survival after Pneumocystis carinii pneumonia in California, 1983-1992.
The authors investigated quarterly trends in survival after the diagnosis of Pneumocystis carinii pneumonia for 19,607 patients in California in the decade from January 1, 1983, through December 31, 1992. Subjects included all cases for whom P. carinii pneumonia was the initial (and only) acquired immunodeficiency syndrome (AIDS)-defining diagnosis as reported to the California human immunodeficiency virus/AIDS surveillance registry. There was a period of rapidly improving survival from approximately June 1986 until April 1988, coincident with the widespread introduction of antiretroviral therapy (zidovudine) and the institution of P. carinii pneumonia prophylaxis (with cotrimoxazole and pentamidine). There was no evidence, however, of meaningful improvements in survival for these patients after that period. The association of several covariates (risk transmission group, gender, race/ethnicity, certainty of P. carinii pneumonia diagnosis, age, region of residence, availability of CD4 count, and level of CD4 count) were also studied both by proportional hazards regression and by recursive partitioning (i.e., tree-based) survival analysis. The availability of a CD4 count (regardless of its level) was the single factor most strongly associated with survival (median survival 36 months among those with and 14 months among those without reported CD4 counts, p < 0.05). Data from this large, population-based surveillance registry of AIDS in California suggest that, despite earlier improvements in survival after the diagnosis of P. carinii pneumonia, the long-term survival of these patients remains poor (39% alive 2 years after diagnosis) and that no improvement in survival has occurred since 1988.
AIDS-Related Opportunistic Infections↗
Serotonin 5-HT1A receptors modulate hippocampal reactivity to afferent stimulation.
Hippocampal dentate gyrus reactivity to perforant path (PP) stimulation in the anesthetized rat was enhanced after systemic administration of the serotonin-releasing drug fenfluramine (FFA). This effect of FFA was mimicked by local application of the drug via the recording pipette, indicating that the effect of FFA is mediated by release of serotonin from intrahippocampal serotonergic terminals. The 5-HT1a antagonist NAN-190 and the 5-HT1b agonist CGS-12066-B, applied both systemically and locally, blocked the effect of FFA. This blocking action was not shared by the 5-HT2-4 receptor agonists or antagonists tested. The 5-HT1a receptor agonist 8-OH-DPAT, applied systemically, caused a marked reduction in population spike responses to PP stimulation, whereas an opposite effect was produced by local application of this drug. The effect of peripheral application of 8-OH-DPAT was blocked by depletion of serotonin. The local effect of FFA was blocked by a reducing neurotransmitter release with a pipette containing 10 mM Mg2+. Finally, local application of the GABA antagonist picrotoxin also enhanced population spike response to PP stimulation, and the effects of picrotoxin and FFA occluded. These results indicate that serotonin released from terminals in the hippocampus activates a 5-HT1a receptor on interneurons that suppresses their activity and thus enhances dentate granular cell population spike response to PP stimulation.
Afferent Pathways↗
Calcium-containing organelles display unique reactivity to chemical stimulation in cultured hippocampal neurons.
Cultured rat hippocampal neurons grown on glass coverslips for 1-3 weeks were loaded with the calcium-sensitive fluorescent dye Fluo-3 and viewed with a confocal laser scanning microscope. Large pyramidal-shaped neurons were found to contain dye-accumulating organelles in their somata, primarily around nuclei and near the base of their primary dendrites. These organelles varied in size and increased in density over weeks in culture, and were not colocalized with the endoplasmic reticulum or with mitochondria. The Fluo-3 fluorescence in these calcium-containing organelles (CCOs) was transiently quenched by exposure to Mn2+, indicating that the dye is a genuine [Ca2+] reporter and is not just a site of accumulating Fluo-3 dye. Recovery of fluorescence in the CCOs after washout of Mn2+ involved activation of a thapsigargin-sensitive process. CCOs responded to stimuli that evoke a rise of cytosolic [Ca2+] ([Ca]i) in a unique manner; perfusion of caffeine caused a prolonged rise of [Ca] in the CCOs ([Ca]C), whereas it caused only a transient rise of [Ca]i. Pulse application of caffeine also caused a faster effect on [Ca]C than on [Ca]i. Glutamate caused a transient rise of both [Ca]i and [Ca]C, followed by a prolonged fall of only [Ca]C to below rest level. This fall was blocked by preincubation with thapsigargin. Ryanodine blocked the cytosolic effects of caffeine but not its effect on [C]C. A clear distinction between CCOs and the known calcium stores was seen in digitonin-permeabilized cells; in these, remaining Fluo-3 reported changes in store calcium, i.e., caffeine caused a reduction in Fluo-3 fluorescence in permeabilized cells, whereas it still caused an increase in [Ca]C. A possible role of CCOs in regulation of release of calcium from ryanodine-sensitive stores was indicated by the observation that CCO-containing cells exhibited a larger and faster response to caffeine than cells that did not have them. We propose that CCOs constitute a unique functional compartment involved in release of calcium from calcium-sensitive stores.
Aniline Compounds↗
Morphological plasticity of dendritic spines in central neurons is mediated by activation of cAMP response element binding protein.
While evidence has accumulated in favor of cAMP-associated genomic involvement in long-term synaptic plasticity, the mechanisms downstream of the activated nucleus that underlie these changes in neuronal function remain mostly unknown. Dendritic spines, the locus of excitatory interaction among central neurons, are prime candidates for long-term synaptic modifications. We now present evidence that links phosphorylation of the cAMP response element binding protein (CREB) to formation of new spines; exposure to estradiol doubles the density of dendritic spines in cultured hippocampal neurons, and concomitantly causes a large increase in phosphorylated CREB and in CREB binding protein. Blockade of cAMP-regulated protein kinase A eliminates estradiol-evoked spine formation, as well as the CREB and CREB binding protein responses. A specific antisense oligonucleotide eliminates the phosphorylated CREB response to estradiol as well as the formation of new dendritic spines. These results indicate that CREB phosphorylation is a necessary step in the process leading to generation of new dendritic spines.
Animals↗
Association between lifetime ambient ozone exposure and pulmonary function in college freshmen--results of a pilot study.
Human health effects due to chronic exposure to ozone (O3) have not been established due to problems with exposure assignment and the use of measures of lung function which may not reflect the site of O3 toxicity in the lung. We investigated the feasibility of retrospective assessment of O3 exposure-relevant covariates and derived lifetime "effective exposure" to ozone. Mid- and end-expiratory flows (FEF25-75%, FEF75%) were regressed against effective exposure and ecological lifetime exposure. A convenience sample of 130 UC Berkeley freshmen, ages 17-21, participated twice in the same tests (residential history, questionnaire, pulmonary function), 5-7 days apart. Students had to be lifelong residents of Northern (SF) or Southern (LA) California. Monthly ambient O3 concentrations (OZ) were assigned based on the lifetime residential history. An "effective time" (T) spent in OZ environments was derived for each residence and age stratum (0-2, 3-5, 6-11, 12+) with the use of questions about "total time spent outdoors" and time spent in "moderate" and/or "heavy" activity. Effective exposure was calculated over the lifetime (OZ x T) of each subject. Ozone metrics used were 8-hr averages (10 AM-6 PM) and "hours above 60 ppb." FEF25-75% and FEF75% decreased with both effective exposure and ecologic assignment of O3 exposure. For a 20 ppb increase (interquartile range) in 8-hr O3, FEF75% decreased 334 ml/sec (95%Cl:11-657 ml/sec), which corresponds to 14% (1.0-28.3%) of the population mean FEF75%. The corresponding effect on FEF25-75% was -420 ml/sec (95%Cl: +46 to -886, P = 0.08) or 7.2% of the mean. Use of time-activity data to define exposure had no impact on estimates. Negative confounding factors were region (SF vs LA), gender, and ethnicity. Lifetime 8-hr average O3 concentrations ranged from 16 to 74 ppb with little overlap between regions. There was no evidence for different O3 effects across regions. Effects were independent of lifetime mean PM10, NO2, temperature, or humidity. Effects on FEV1 tended to be negative whereas those for FVC, although negative in some models, where inconsistent and small. The strong relationship of lifetime ambient O3 on mid- and end-expiratory flows of college freshmen and the lack of association with FEV1 and FVC are consistent with biologic models of chronic effects of O3 in the small airways. Since the present study was designed as a pilot study, these findings have to be confirmed in a larger sample that is representative of the target population.
Adolescent↗
Muscarinic receptors involved in hippocampal plasticity.
The cholinergic septohippocampal system has been associated with learning and memory, as evidenced by the severe loss of these functions in lesioned animals as well as in senile demented patients. In an attempt to comprehend the physiological basis of the cholinergic innervation for hippocampal functions, numerous studies employed the in-vitro hippocampal slice preparation and analyzed the consequences of exposing the cells to cholinergic ligands. Many effects of activating a cholinergic receptor in the hippocampus were thus described, including blockade of several types of potassium conductances, yet few of these effects are intuitively related to the involvement of the cholinergic system in hippocampal plasticity. An alternative approach involves focusing on the possible effect of low concentration of cholinergic ligands on reactivity of the hippocampus to afferent stimulation. We found two new actions of acetylcholine (ACh); The first one is a fast onset, short lived increase in cellular responses to activation of the N-methyl-D-aspartate (NMDA) receptor, and the second one is a slow onset, long lasting increase in reactivity to afferent stimulation, resembling that produced by a tetanic stimulation, which we called muscarinic long term potentiation (LTPm). The latter effect is mediated by a postsynaptic M2 receptor, and it shares several properties with the more familiar tetanic LTP. In addition, LTPm involves a rise of intracellular calcium concentration and an activation of both a tyrosine kinase and a serine/threonine kinase. Intuitively, LTPm is better related to hippocampal plasticity than the other reported effects of ACh in the hippocampus. Indeed, aged rats, which are cognitively impaired, lack LTPm while they do express other muscarinic actions. It is proposed that LTPm is an important link between the cholinergic action and function in the hippocampus.
Acetylcholine↗
Hepatic mesenchymal hamartoma: a pediatric tumor that may be diagnosed prenatally.
Hepatic mesenchymal hamartoma is a benign tumor, defined as an excessive focal overgrowth of mature normal cells and stroma native to the liver. The increasing popularity of antenatal scanning has resulted in in utero diagnosis of congenital malformations and anomalies that previously became apparent only after delivery. Herein, we present a rare case of fetal mesenchymal hamartoma of the liver, which was initially sonographically detected at 29 weeks of gestation. A brief literature survey and obstetric recommendations for management and monitoring of such rare cases are included.
Adult↗
Dendritic spine density and LTP induction in cultured hippocampal slices.
Transverse hippocampal slices were cut from 8- to 9-day-old rats and maintained in an interface chamber for periods of 1-4 wk, in tissue culture conditions. Neurons in the slice preserved their spatial organization and connectivity. Dendritic spine density in CA1 neurons was very low at 1 wk in culture, and long, filopodia-like structures were abundant. Spine density increased in these neurons nearly threefold during the course of 3 wk in vitro, to approach values of those of the normal, in vivo hippocampus. The magnitude of long-term potentiation (LTP) of reactivity of Ca1 to stimulation of CA3 neurons also increased during weeks in culture in parallel with the change in spine density. Chronic exposure of slices to drugs that interact with synaptic activity caused changes in their dendritic spine density. Blockade of the N-methyl-D-aspartate (NMDA) receptors with the receptor antagonist 2-aminophosphonovalerate (D-APV) or blockade of action potential discharges with tetrodotoxin (TTX) prevented dendritic spine development in immature cultures. Enhancing synaptic activity by blockade of GABAergic inhibition with picrotoxin did not affect spine density to a significant degree. D-APV-treated slices expressed larger LTP than controls. TTX-treated slices expressed smaller LTP than controls. Picrotoxin treated slices did not express LTP. It is proposed that LTP and dendritic spine density are correlated strongly during development, whereas they are not correlated in the more mature slice/culture of the hippocampus where spine density can be modulated by chronic exposure to blockers of synaptic activity, which will not affect LTP in a similar manner.
Action Potentials↗
Re: Wyller TB, Sveen U, Bautz-Holter E. The Frenchay Activities Index in stroke patients: agreement between scores by patients and by relatives. Disability and Rehabilitation 1996; 18, 454-459.
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Activities of Daily Living↗
Lasting effects of glutamate on nuclear calcium concentration in cultured rat hippocampal neurons: regulation by calcium stores.
1. Changes in free intracellular calcium concentrations ([Ca2+]i) were measured in the nucleus and perinuclear regions of cultured rat hippocampal neurons using either fura-2 or fluo-3 calcium indicators. 2. Brief application of glutamate caused a transient rise of [Ca2+]i in all cell compartments, which recovered to pre-drug levels in all but the nuclear region. The new, higher level of nuclear calcium ([Ca2+]n) was sustained for as long as the cell was monitored. 3. The new level of [Ca2+]n was dependent on the magnitude of the calcium transient, and was higher in older cells in culture, but it did not affect responses to subsequent applications of glutamate. 4. The sustained elevation of [Ca2+]n was prevented by drugs which affect calcium stores (caffeine, ryanodine and Ruthenium Red), indicating that an extranuclear calcium store interacts with [Ca2+]n.
Aniline Compounds↗
Constitutive overexpression of Cu/Zn superoxide dismutase exacerbates kainic acid-induced apoptosis of transgenic-Cu/Zn superoxide dismutase neurons.
Cu/Zn superoxide dismutase (Cu/Zn SOD) is a key enzyme in the metabolism of oxygen free radicals. The gene resides on chromosome 21 and is overexpressed in patients with Down syndrome. Cultured neurons of transgenic Cu/Zn SOD (Tg-Cu/Zn SOD) mice with elevated activity of Cu/Zn SOD were used to determine whether constitutive overexpression of Cu/Zn SOD creates an indigenous oxidative stress that predisposes the Tg-Cu/Zn SOD neurons to added insults. Neurons from three independently derived Tg-Cu/Zn SOD strains showed higher susceptibility than nontransgenic neurons to kainic acid (KA)-mediated excitotoxicity, reflected by an earlier onset and enhanced apoptotic cell death. This higher susceptibility of transgenic neurons to KA-mediated apoptosis was associated with a chronic prooxidant state that was manifested by reduced levels of cellular glutathione and altered [Ca2+]i homeostasis. The data are compatible with the thesis that overexpression of Cu/Zn SOD creates chronic oxidative stress in the transgenic neurons, which exacerbates their susceptibility to additional insults such as KA-mediated excitotoxicity.
Animals↗
Regulation of dendritic spine density in cultured rat hippocampal neurons by steroid hormones.
The effects of gonadal steroid hormones on dendritic spines were studied in hippocampal neurons that were dissociated and grown in culture for 2-3 weeks. Exposure to estradiol caused up to a twofold increase in dendritic spine density in these neurons. The effect of estradiol was stereospecific and blocked by the steroid antagonist tamoxifen. The estradiol-induced rise in spine density was blocked by the NMDA antagonist APV, but not by the AMPA/KA antagonist DNQX. The estradiol-induced rise in spine density was blocked by the serine/threonine kinase inhibitor H7, but not by the tyrosine kinase inhibitor genestein, and was partially mimicked by PMA, an activator of protein kinase C. Estradiol also caused an increase in the fluorescence intensity of synaptophysin-immunoreactive terminals, corresponding to presynaptic boutons. Finally, estradiol caused a rise in [Ca]i reactivity of the cultured neurons to topical application of glutamate. These studies are the first to examine receptor and second messenger regulation of dendritic spines, and they illustrate the viability of cultured neurons as a powerful test system to address issues related to the regulation of dendritic spine maturation.
Animals↗
The effects of raphe grafts on hippocampal electrophysiology in aged rats.
In previous studies we have demonstrated that raphe grafts, implanted into serotonin-depleted rat hippocampus can restore behavioral and physiological functions impaired by serotonin depletion. Since aging is associated with a reduction in serotonergic functions, we explored the possibility that grafting embryonic raphe tissue will ameliorate age-associated reduction of serotonergic functions in the hippocampus. Aged rats were implanted with E14 embryonic neural tissue, containing the raphe, or part of the parietal cerebral cortex. Three months later, the rats were anesthetized, and the responses of the dentate gyrus to perforant-path stimulation were measured. Serotonin-containing neurons were found in the raphe-grafted hippocampi. No differences were found between the two groups in the volume of the graft in the host brain. Raphe-grafted rats were not different from the cortex-grafted rats in reactivity to perforant path stimulation or in the response to a second of a pair of stimuli to the perforant path. They did, however, express a pronounced commissural inhibition, unlike the cortex-grafted rats. These results are similar to those found previously with a pharmacological enhancement of serotonergic neurotransmission. It is suggested that a graft of serotonergic neurons can ameliorate age-associated reduction in serotonergic functions in the hippocampus.
Aging↗
Muscarinic receptors mediating depression and long-term potentiation in rat hippocampus.
1. Two concentration-dependent effects of the muscarinic agonist carbachol (CCh) were characterized in submerged slices of rat hippocampus using extracellular recordings of excitatory postsynaptic potentials (EPSPs): muscarinic long-term potentiation (LTP(m)) and depression. 2. LTP(m) of the EPSP slope was seen following long exposure (20 min) of the slice to low concentrations of CCh (0.2-0.5 microM). This LTP(m) was not accompanied by a change in the size of the afferent fibre volley or by a change in paired-pulse potentiation, consistent with a postsynaptic locus of CCh action. 3. Intracellular recordings from voltage-clamped neurons of inward current evoked by iontophoretically applied alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and N-methyl-D-aspartate (NMDA) revealed that, while cellular responses to NMDA rose transiently upon superfusion with 0.5 microM CCh, responses to AMPA increased gradually and remained potentiated after washout of CCh. 4. LTP(m) is mediated by an M2 muscarinic receptor. Two M2 muscarinic receptor antagonists, methoctramine and AFDX-116, blocked LTP(m). The M2 agonist oxotremorine induced LTP(m) at low agonist concentrations. None of the M1 and M3 receptor agonists and antagonists tested affected LTP(m). 5. Muscarinic fast onset depression of the EPSP was seen in response to higher concentrations of CCh (2-5 mu M). This depression was accompanied by an increase in paired-pulse potentiation, indicating a possible presynaptic locus of action. The M3 muscarinic receptor antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) blocked the muscarinic depression of the EPSP slope. M1, M2 and M4 muscarinic antagonists did not block this response. 6. Blockade of the muscarinic depression by 4-DAMP did not uncover a suppressed LTP(m). However, addition of picrotoxin facilitated the expression of LTP(m) induced by high concentrations of CCh, indicating an involvement of interneurons in regulation of LTP(m). 7. Cholinergic denervation produced by fimbria-fornix transection resulted in supersensitivity of both M2- and M3-mediated effects, indicating that the receptors mediating these effects are not located on presynaptic cholinergic fibres. In the presence of 4-DAMP and picrotoxin the dose-response curve for CCh-induced effects in slices from lesioned animals was shifted to the left relative to that of normal animals, indicating a supersensitivity of both receptor types.
Animals↗
Placental-site trophoblastic tumor following metastatic gestational trophoblastic neoplasia.
Placental site trophoblastic tumor generally follows term pregnancy or nonmolar abortion. Thus far, 10 cases of placental site trophoblastic tumor have been described which were preceded by a hydatidiform mole. This is the first reported case where placental site trophoblastic tumor has been preceded by metastatic gestational trophoblastic neoplasia treated by chemotherapy.
Adult↗
Morphological plasticity in dendritic spines of cultured hippocampal neurons.
Rat hippocampal neurons, grown in dissociated culture for about 18 days, were exposed for 6 h to three days to stimuli which cause either an increase (GABAA antagonists, bicuculline or picrotoxin), or decrease (tetrodotoxin) in spontaneous neuronal activity. Individual neurons were stained with 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate and visualized with a confocal laser scanning microscope. GABA antagonists caused a marked, up to 60%, increase in spine density on secondary dendrites of cultured hippocampal neurons. This was associated with a small decrease in spine length. The rise in spine density was partially prevented by treatment with the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetra-acetate, or by blockade of protein synthesis with cycloheximide. Tetrodotoxin caused a marked elongation of dendritic spines (but did not cause a decrease in spine density comparable to the increase caused by picrotoxin). This effect was seen primarily but not exclusively in spines with no distinct head. Both treatments were most effective within 24 h of exposure. There were no other systematic effects of the drugs on the morphology of the dendritic spines. These results indicate that dendritic spines in cultured neurons depend on ongoing synaptic activity to maintain their shape, and that neurons respond to an increase in synaptic demand by an increase in spine density. Thus, dendritic spines are likely to have a role in short-term synaptic interaction rather than to constitute a long-term memory storage device.
Action Potentials↗