5,550 research outputs found
Lead activates calmodulin sensitive processes
The effect of lead on two calcium sensitive processes was determined. Micromolar concentrations of lead successfully replaced calcium in the activation of calmodulin-sensitive phosphodiesterase and in the promotion of potassium loss from erythrocytes. Both actions of lead were blocked by trifluoperazine--an inhibitor of calmodulin function. We propose that some of the toxic effects of lead may be explained by its interaction with calmodulin.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25113/1/0000546.pd
Use of an in vitro system to study the effects of lead on astrocyte-endothelial cell interactions: A model for studying toxic injury to the blood-brain barrier
We investigated the effect of inorganic lead on the interaction of immature rat astrocytes and bovine adrenal endothelial cells. The two cell types were cultured alone and in coculture in the presence or absence of lead acetate for up to 1 week. A battery of cell specific markers was used for cell identification. Newborn Sprague-Dawley rat brain astrocytes were more sensitive than bovine adrenal endothelial cells to the cytotoxic effects of 10-50 [mu] lead acetate, as demonstrated by a decrease in cell number and by the presence of intracellular vacuoles and detached cells. The number of astrocytes decreased to 50% of control after 4 days in culture at a concentration of 10 [mu] lead. In contrast, a mitogenic effect of lead was observed on the endothelial cells at this concentration, with an increase in cell number to 110% of control. In coculture, the two cell types demonstrated a distinctive cellular organization and the astrocytes were less sensitive to the cytotoxic effects of lead than when they were cultured alone. A lead-enhanced induction of a neural capillary enzyme activity, [gamma]-GTP, was detected histochemically in the coculture system. These results are consistent with a maturing of differentiating effect of the endothelial cells on the astrocytes, making them less susceptible to lead and mature enough to induce [gamma]-GTP activity in the endothelial cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27260/1/0000269.pd
A Group-Based Yule Model for Bipartite Author-Paper Networks
This paper presents a novel model for author-paper networks, which is based
on the assumption that authors are organized into groups and that, for each
research topic, the number of papers published by a group is based on a
success-breeds-success model. Collaboration between groups is modeled as random
invitations from a group to an outside member. To analyze the model, a number
of different metrics that can be obtained in author-paper networks were
extracted. A simulation example shows that this model can effectively mimic the
behavior of a real-world author-paper network, extracted from a collection of
900 journal papers in the field of complex networks.Comment: 13 pages (preprint format), 7 figure
PHENOBARBITONE AND NEONATAL INTRAVENTRICULAR HAEMORRHAGE
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23977/1/0000226.pd
PREVENTION OF INTRAVENTRICULAR HAEMORRHAGE IN PRETERM INFANTS BY PHENOBARBITONE : A Controlled Trial
Sixty infants with birth-weights less than 1500 g and who were less than 6 h old were randomly assigned to a group given phenobarbitone or a control group. Intravenous phenobarbitone was given in doses sufficient to achieve anticonvulsant serum levels within 12-18 h. Maintenance therapy was continued for one week. Periventricular/intraventricular haemorrhage (IVH) occurred in 133% (4/30) of the phenobarbitone group and in 46.7% (14/30) of the control group. The occurrence of risk factors related to IVH was similar in the two groups. Phenobarbitone may reduce the incidence of IVH in small preterm infants.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24291/1/0000557.pd
Phosphoinositide metabolism and prostacyclin formation in retinal microvascular endothelium: Stimulation by adenine nucleotides
Phosphoinositide lipid metabolism and prostacyclin production are implicated in endothelium dependent vascular relaxation in large blood vessels. To determine if these biochemical pathways might be involved in the regulation of microvascular tone in the retina, we measured the formation of 6-keto-prostaglandin-F1[alpha], the stable end product of prostacyclin, and inositol phosphates from 3H-labeled phosphoinositide lipids, in endothelial cells prepared from bovine retinal microvessels and maintained in long-term culture. We found that adenosine 5'-triphosphate and adenosine 5'-diphosphate both stimulated a dose-dependent accumulation of inositol phosphates and of 6-keto-prostaglandin-F1[alpha] in these cells. The agonist specificity of the responses, with stimulation by adenosine 5'-triphosphate and adenosine 5'-diphosphate, and inactivity of adenosine 5'-monophosphate and adenosine, suggest that they are mediated through P2 purinergic receptors. The similar early time courses of 6-keto-prostaglandin-F1[alpha] and inositol triphosphate production support the hypothesis that prostacyclin formation could result from the mobilization of intracellular calcium by inositol triphosphate, which activates phospholipase A, and thereby releases arachidonic acid to form prostacyclin. These findings point to a role for these cells in the regulation of normal retinal vascular tone. Because phosphoinositide lipid metabolism is altered in diabetes, dysfunction of these biochemical pathways in retinal endothelium could underlie the pathophysiology of diabetic retinopathy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28775/1/0000607.pd
EEG abnormalities aid diagnosis of Rett syndrome
Nine girls with Rett syndrome had 22 electroencephalographic studies performed over 5 years. Nineteen waking tracings demonstrated moderate background slowing. Focal epileptiform activity was observed in 13 studies, 10 of which had bilateral independent foci. Spikes were invariably maximal in central regions, diphasic or triphasic, and of very short duration. In 3 patients, epileptiform activity preceded clinical seizures by up to 2 years. Two children had spontaneous hyperpnea preceding apnea during wakefulness with further background slowing. Video monitoring of 2 children revealed that episodic behavioral changes were not seizures. Ten of 12 sleep recordings had abnormal background activity with absent or rudimentary spindles. Normal activity occurred only in girls younger than years of age. Epileptiform activity was markedly increased during sleep in 8 tracings in which both wakefulness and sleep were obtained. It was characterized by bilaterally independent and bisynchronous spike-and-wave activity, maximal in parasagittal areas. One patient had bursts of high-voltage slow-wave activity followed by attenuation. No apneic episodes were recorded during sleep. In Rett syndrome, electroencephalographic abnormalities include background slowing, centrally located short-duration spikes, and increased epileptiform activity during sleep. This activity commonly preceded clinical seizures in patients studied at initial presentation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27084/1/0000075.pd
Cell proliferation after ischemic injury in gerbil brain
Tritiated thymidine autoradiography was used to measure cellular proliferation after ischemic injury in gerbil brain. Gerbils were subjected to bilateral occlusion of the common carotid arteries which resulted in areas of necrosis, or infarcts, in the posterior thalamus or midbrain. From 12 h to 10 days following the ischemia, gerbils were injected with 3 H thymidine, sacrificed 4 h later, and the brains sectioned. In order to identify astrocytes and monocytes/macrophages, immunocytochemistry was performed prior to autoradiography, using antisera against glial fibrillary acidic protein and endothelial-monocyte reticuloendothelial antigen, respectively. Immunocytochemistry was also used to visualize microvessel laminin, myelin, and leakage of serum albumin. Lastly, a histochemical procedure for acid phosphatase activity was employed to verify cellular phagocytic activity in the wound. A reproducible sequence of reactions took place during the first 10 days after ischemia. Early changes included leakage of albumin and myelin breakdown, followed by arrival of monocytes at 2 days and their differentiation into macrophages by 5 days. These cells exhibited intense proliferation from 2 to 6 days post-ischemia. Microvessel endothelial cells were maximally labeled at 4 days post-ischemia. Hypertrophied astrocytes were apparent at 2 days and proliferated from 3 to 7 days post-ischemia, and by 10 days the wound was replaced by a “glial scar”.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47681/1/441_2004_Article_BF00225558.pd
Isolated rat brain capillarie spossess intact, structurally complex, interendothelial tight junctions; freeze-fracture verification of tight junction integrity
Populations of isolated brai capillaries have been proposed as useful models for in vitro studies of the blood-brain barrier. Preliminary investigations of barrier properties using such preparations of brain microvessels have suggested that the tight interendothelial junctions (zonulae occludentes) are intact and retain the impermeability to the protein tracer horseradish peroxidase, exhibited by them in vivo. The endothelial junctions of isolated capillaries are therefore assumed to be functionally `tight' in vitro. In order to determine the precise structural organization of these occluding junctions, including an estimate of their tightness (complexity), and to demonstrate a method for simple but precise assessment of junctional integrity, pellets of isolated rat brain capillaries were freeze-fractured and then replicated with platinum and carbon. The freeze-fracture images of interendothelial zonulae occludentes revealed complex arrays of intramembrane ridges and grooves characteristics of tight junctions. Longitudinal fractures of the cellular lining of capillaries exposed vast expanses of interendothelial plasma membrane interfaces and the junctional complexes situated between the cells. From such arrays, the elaborate and complex architecture of the zonulae occludentes could bre readily appreciated. Situated on the PF fracture faces are 6-8 parallel ridges which display a high degree of anastomosing between adjacent strands. The EF facture face contains grooves complementary to the PF face ridges. The zonulae occludentes of these capillary endothelial cells are similar in complexity to those reported in the literature for reptilian brain capillaries and therefore can be presumed `very tight'. This study demonstrate that freeze-fracture of pellets of brain capillaries alleviates problems inherent in whole tissue preparations and, in addition, demonstrates the usefulness of freeze-fracture as a tool to monitor junction structure during in vitro investigation of the blood-brain barrier.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24599/1/0000007.pd
Inhibition by steroids of the uptake of potassium by capillaries isolated from rat brain
The effect of steroids on the uptake and release of K+ by capillaries isolated from rat brain was investigated. 86Rb+ uptake was used as a transport analog of K+. The uptake of 86Rb+ by the capillaries was markedly inhibited by ouabain. The ouabain sensitive fraction of 86Rb+ uptake was inhibited by corticosterone with an I50 of 8 x 10-4 M. Inhibition was immediate in onset and rapidly reversible after removal of the steroid. Corticosterone did not alter the affinity of the transport carrier for K+ or the passive efflux of 86Rb+ from the capillaries. Other steroids inhibited ouabain sensitive 86Rb+ uptake in relation to their lipid solubility. These features suggest a direct membrane action for high dose steroid therapy, possibly on Na+,K+ATPase, rather than a nuclear mediated change in cell function.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24467/1/0000742.pd
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