Endothelin-1 binding to human brain microvascular and capillary endothelium: membranes vs. intact cells.
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Brain↗
Biomedical subjects
S Uematsu
Publications and source records attributed to S Uematsu.
Functional significance of the mu rhythm of human cortex: an electrophysiologic study with subdural electrodes.
The existence of the mu rhythm and its general anatomical and physiological relationships are well known. There are few data, however, regarding the details of its anatomical and physiological specificity. We implanted fronto-temporal subdural electrode grids in 9 patients with intractable epilepsy to facilitate their surgical management. A 7-11 Hz cortical mu rhythm was observed in 5-16 electrodes located over the sensorimotor cortex as mapped by electrical stimulation. The mu rhythm was blocked by contralateral face and arm movements, passive movements of contralateral arm, and by ipsilateral arm movements. There was correspondence between the body area movement of which blocked the mu at a given site and the body region that was affected by stimulation at the same site. Power spectral analysis showed an overall decrease in power in all frequency bands. This was less prominent in the 14-100 Hz band resulting in a relative increase in high frequency power in association with movement. We conclude that both the presence and blocking of mu rhythm are specific to the somatic representation of the cortex from which it is recorded. Its functional significance may be similar to other sensory rhythms like the occipital alpha rhythm.
Adolescent↗
Profile of prostaglandins induced by endothelin-1 in human brain capillary endothelium.
The vasoactive peptide, endothelin-1 (ET-1) has been implicated in the pathophysiology of various diseases. Recently, we have shown that human brain endothelial cells both secrete and express immunoreactive ET-1 high-affinity ETA receptors coupled to activation of phospholipase C (PLC). The present study demonstrates concentration-dependent stimulation of prostanoids [thromboxane B2 (TxB2), prostaglandin F2 alpha (PGF2 alpha), 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) prostaglandin E2 (PGE2), and prostaglandin D2 (PGD2)] production by ET-1 in capillary endothelial cells derived from human brain (HBCEC). The increase in the vasoconstrictive prostanoids TxA2 and PGF2 alpha temporally preceded that of the vasodilatory PGI2, PGE2 and PGD2, and was seen after 15 min of incubation with ET-1 (10 nM). Increased production of vasodilatory prostanoids was observed between 4-8 h of incubation, whereas normalization of both vasoconstrictive and vasodilatory prostaglandins occurred 24 h after addition of ET-1. Both ET-1-stimulated prostanoid and IP3 production were inhibited by BQ123, a specific antagonist of ETA receptors. ET-1-induced prostanoid secretion by HBCEC was also inhibited by dexamethasone (50 microM) and diminished by neomycin (50 microM) and verapamil (10 microM) but not by nifedipine. Phorbol myristate ester potentiated ET-1-stimulated prostanoid secretion, whereas it inhibited IP3 production. Data indicate that ET-1 activates phospholipase A2 (PLA2) and PLC in HBCEC by different intracellular mechanisms. The subsequently induced secretion of vasoactive prostanoids by HBCEC may contribute both qualitatively and temporally to the vasoactive actions of ET-1.
Analysis of Variance↗
Prostaglandin D2 and endothelin-1 induce the production of prostaglandin F2 alpha, 9 alpha, 11 beta-prostaglandin F2, prostaglandin E2, and thromboxane in capillary endothelium of human brain.
Endothelial cells derived from human brain capillaries (HBCEC) synthesize prostaglandin D2 (PGD2) which can be stimulated, among other prostanoids, by endothelin 1 (ET-1). Both the PGD2 induced by ET-1 and the exogenously added PGD2 to HBCEC are converted to 9 alpha, 11 beta-prostaglandin F2 (9 alpha, 11 beta-PGF2), a known potent vasoconstrictor. Exogenous PGD2 also dose-dependently enhanced the production of vasoconstrictive PGF2 alpha, thromboxane B2 (TXB2), and the vasodilatory PGE2 as well as cAMP by HBCEC. The PGD2-induced formation of PGF2 alpha, PGE2, and TXB2 was reduced by the cyclooxygenase inhibitors acetylsalicylic acid (ASA) or indomethacin (Indo), indicating for the first time that PGD2 may contribute to the formation of prostanoids in HBCEC. These results strongly suggest that PGD2 may play an important role in the regulation of cerebral capillary function under physiologic and pathologic conditions.
1-Methyl-3-isobutylxanthine↗
Mirth, laughter and gelastic seizures.
Little is known about what pathways subserve mirth and its expression laughter. We present three patients with gelastic seizures and laughter elicited by electrical stimulation of the cortex who provide some insight into the mechanisms of laughter and its emotional concomitants. The first patient had seizures manifested by laughter without a subjective feeling of mirth. Magnetic resonance imaging showed a cavernous haemangioma in the left superior mesial frontal region. Ictal subdural electrode recording showed the seizure onset to be in the left anterior cingulate gyrus. Removal of the lesion and of the seizure focus rendered the patient virtually seizure free over 16 months of follow-up. The other two patients had complex partial seizures of temporal lobe origin. Electrical stimulation of the fusiform gyrus and parahippocampal gyrus produced bursts of laughter accompanied by a feeling of mirth. These cases reveal a high likelihood of cingulate and basal temporal cortex contribution to laughter and mirth in humans, and suggest the possibility that the anterior cingulate region is involved in the motor act of laughter, while the basal temporal cortex is involved in processing of laughter's emotional content in man.
Adult↗
Secretion of immunoreactive endothelin-1 by capillary and microvascular endothelium of human brain.
Modulation of immunoreactive endothelin-1 (IR-ET-1) production by vasoactive substances was investigated in cultured endothelial cells (EC) derived from capillaries and microvessels of human brain. Peptides, catecholamines, thrombin, protein kinase C-activating phorbol ester, and calcium ionophore enhanced the secretion of IR-ET-1. The known vasoconstrictive peptides, angiotensin II (Ang II) and arginine-vasopressin (AVP) dose-dependently stimulated the endothelial secretion of IR-ET-1. The angiotensin and vasopressin-inducible production of IR-ET-1 was completely inhibited by their respective receptor antagonists [Sar1, Ala8]-angiotensin II and [1-6 (beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-O-methyl-tyrosine]. The results indicate that the peptide-stimulated secretion of IR-ET-1 is receptor-mediated in EC which have specific angiotensin II and arginine-vasopressin receptors. These findings represent the first demonstration of IR-ET-1 production by capillary and microvascular endothelium of human brain.
Angiotensin II↗
Adrenergic receptors coupled to adenylate cyclase in human cerebromicrovascular endothelium.
Cultured endothelium derived from three microvascular fractions of human brain was used to characterize adrenergic receptors coupled to adenylate cyclase activity. Catecholamines (norepinephrine, epinephrine) and their analogs (isoproterenol, phenylephrine, 6-fluoronorepinephrine) dose-dependently stimulated endothelial production of cAMP. Antagonists for beta 1 and beta 2 receptors (propranolol, atenolol, and butoxamine) and for alpha 1-receptors (prazosin) dose-dependently blocked cAMP formation induced by the tested adrenergic agonists. Clonidine, an alpha 2 > alpha 1-agonist, also inhibited isoproterenol-stimulated production of cAMP while yohimbine (alpha 2 > alpha 1 antagonist) augmented the norepinephrine or epinephrine-induced accumulation of cAMP. Cholera toxin-induced ADP ribosylation of the stimulatory guanine nucleotide binding protein (Gs) abolished the stimulatory effect of norepinephrine, epinephrine, phenylephrine or 6-fluoronorepinephrine on cAMP formation. ADP ribosylation of the inhibitory guanine nucleotide binding protein (Gi) by pertussis toxin had no effect on either phenylephrine- or 6-fluoronorepinephrine-induced production of cAMP while it increased the norepinephrine and epinephrine-induced accumulation of cAMP. These findings represent the first documentation of beta 1-, beta 2-, alpha 1 and alpha 2-adrenergic receptors linked to adenylate cyclase in endothelium derived from human brain microvasculature. These data also indicate that activation of endothelial alpha 1 -adrenergic receptors is mediated by a signal transduction mechanism associated with Gs protein. The results strongly support the presence of various receptor-controlled adrenergic regulatory mechanisms on human cerebromicrovascular endothelium.
Adenylyl Cyclases↗
Comparison of Indium-111-labeled leukocyte scintigraphy and Technetium-99m joint scintigraphy in rheumatoid arthritis and osteoarthritis.
This study was undertaken to evaluate the use of Indium-111-labeled leukocyte (111In-WBC) imaging compared with Technetium-99m pertechnetate (99mTcO4-) imaging in 19 patients with rheumatoid arthritis (RA) and 8 with osteoarthritis. Knee and wrist joints were evaluated for both radionuclides. The results indicated a good correlation of the clinical assessment of pain and swelling with joint uptake ratio (JUR) between 111In-WBC and 99mTcO4- in RA and osteoarthritis patients. We observed a discrepancy in both imagings in "burned out" cases. It was concluded that a JUR of 111In-WBC could distinguish active RA from inactive RA or osteoarthritis at a value of 1.15 and that the use of 111In-WBC was a more reliable procedure than 99mTcO4-.
Adult↗
Prostaglandin D2 in cultured capillary and microvascular endothelium of human brain.
Production of prostaglandin D2 (PGD2) was investigated in cultured endothelial cells derived from capillaries and microvessels (small and large) of human brain using radioimmunoassays. Peptides, catecholamines, thrombin, protein kinase C-activating phorbol ester and calcium ionophore greatly stimulated the secretion of endothelial PGD2. Secretion of PGD2 induced by vasoconstricting peptides, angiotensin II and arginine-vasopressin, was almost completely abolished by their respective specific receptor antagonists [Sar1, Ala8]-Ang II and [1-6(beta-mercapto-beta,beta-cyclopentamethylene propionic acid) 2-O-methyltyrosine]. Thus, the augmented production of PGD2 by angiotensin II and arginine-vasopressin is a receptor-mediated event. It also indicates that the EC have specific angiotensin II and arginine-vasopressin (V1) receptors. This study represents the first demonstration of vasoactive agents modulating PGD2 production in capillary and microvascular endothelium of human brain.
Brain Chemistry↗
High-frequency EEG activity at the start of seizures.
Frequencies above 35-40 Hz are poorly visualized on conventional EEG scalp recordings. We investigated frequency components up to 150 Hz in digitally recorded EEGs of seizures in five patients with implanted subdural grids, as part of their evaluation for epilepsy surgery. Amplifier bandpass was set from 0.1 to 300 Hz, and EEG was digitized at 2,000 samples per second. Seizures with electrodecremental patterns at the start showed a significant increase in spectral power above 35 Hz, with a twofold increase in the 40-50-Hz range, and up to a fivefold increase in the 80-120-Hz portion of the spectrum. Activity above 40 Hz could represent summed action potentials, harmonics of synaptic potentials or transient sharp components of synaptic potentials. High-frequency increases were largely localized to the region of the seizure focus. Grid sites remote from the focus did not show significant energy in the EEG band above 40 Hz at baseline, nor at time of seizure onset. Our findings suggest that high-frequency recordings may be of use in localizing seizure foci.
Adolescent↗
Simple partial seizures: clinicofunctional correlation--a case report.
A 12-year-old girl developed simple partial motor and sensory seizures due to a right perirolandic astrocytoma. Subdural EEG recording and functional stimulation disclosed close correlation between EEG-clinical manifestations of focal seizures and functional responses to cortical stimulation. This case supports the idea that responses in the perirolandic area to endogenous epileptogenic activity and to cortical stimulation reflect common underlying physiologic mechanisms.
Brain↗
Localization of sensorimotor cortex: the influence of Sherrington and Cushing on the modern concept.
According to Penfield, the work of Charles Sherrington's laboratory forced a change from the long-held concept of a broad, overlapping sensorimotor cortex to the concept of a narrow, discrete pre-Rolandic motor cortex separate from the post-Rolandic sensory strip. Harvey Cushing, one of the founders of modern neurosurgery, coined the term narrow motor strip. Cushing also appears to have been the first to color the precentral gyrus in a mosaic pattern and to use red coloring for the motor cortex and blue for the sensory cortex. Cushing's red and blue color coding is still used in textbooks, nearly 100 years later. In this article, we review the historical evolution of and the evidence for the concept of narrow and discrete motor and sensory strips anterior and posterior to the Rolandic cortex. A review of the historical development of the concept and recent physiological studies reaffirms the proposition that the motor and sensory areas are much broader and more complex than they were thought to be in the classic teaching that originated with Sherrington and Cushing.
Animals↗
Motor and sensory cortex in humans: topography studied with chronic subdural stimulation.
Classic neurosurgical teaching holds that once the Rolandic fissure (Rf) has been located, there are distinct differentiated primary motor and sensory functional units confined within a narrow cortical strip: Brodmann's Areas 4 and 6 for primary motor units in front of the Rf and 3, 1, and 2 for sensory units behind the Rf. To test this assumption, we examined in detail the records of cortical mapping done by electrical stimulation of the cerebral cortex via implanted subdural electrode grids in 35 patients with seizure disorders. Of 1381 stimulations of the electrode sites, 346 (25.1%) produced primary motor or motor-arrest and sensory responses in contralateral body parts: 56.8% were primary motor responses; 16.2% were motor-arrest; 22.5% were sensory; and the remaining 4.5% were mixed motor and sensory responses. Two-thirds (65.9%) of the primary motor responses were located within 10 mm of the Rf, and the remaining one-third (34.1%) were more than 10 mm anterior to the Rf or were posterior to the Rf. Furthermore, in the patient group with brain lesions, fewer than one-third (28.1%) of the responses were within the 10-mm narrow anterior strip. Our study reconfirmed that a significant number--at least one-third--of motor responses are distributed outside the classic narrow cortical strip. In patients with brain lesions, the motor representation is further displaced outside the narrow strip. This finding indicates that primary motor cortex may extend beyond the gyrus immediately anterior to the Rf.
Adolescent↗
Assessment of surgical outcome.
Evaluation of outcome of epilepsy surgery is complex because of several factors. Epilepsy is itself a heterogeneous disorder. Different epilepsy centers encounter different referral mixes of patients. Institutions employ various methods for pre-operative evaluation and widely varying surgical techniques. Clear definitions of surgical success and reliable scales for its measurement are lacking. Few data are acquired prospectively and maintained in a format allowing inter-institutional collation of results. A better representation of surgical outcome could in the future be served by adherence to 4 principles: collection of common data in standard formats; comparison of like, rather than disparate, populations; maintenance of quantitative data in raw form; and measurement of outcome along several dimensions or scales. Psychosocial issues have been underemphasized in most prior analyses of outcome.
Cerebral Cortex↗
Stereotactic brain biopsy in the diagnosis of malignant lymphoma.
Fifteen patients with cerebral involvement by malignant non-Hodgkin's lymphoma were identified, among more than 200 patients who underwent stereotactic biopsy at The Johns Hopkins Hospital. All but one of these cases were diagnosed accurately by the stereotactic biopsy procedure. In 12 of 14 patients, the material was adequate to classify the lymphoma according to the Working Formulation. Because all but one of the lesions were intermediate or high-grade neoplasms, a diagnosis of lymphoma was often possible by conventional light microscopic examination alone. Monotypic light chain expression was demonstrated by immunohistochemical techniques in six patients, and positivity for B-cell markers was observed in an additional case. In one instance, two stereotactic biopsy specimens were interpreted as being suggestive of lymphoma, but necrosis and inflammation prevented a definitive diagnosis. Nine patients had no known risk factors for cerebral lymphoma, and the diagnosis often was unsuspected clinically.
Adolescent↗
Dopaminergic receptors linked to adenylate cyclase in human cerebromicrovascular endothelium.
Cultured endothelium derived from three fractions of human cerebral microvessels was used to characterize dopamine (DA) receptors linked to adenylate cyclase activity. DA or D1 agonist, (+/-)-SKF-82958 hydrobromide, stimulated endothelial cyclic AMP formation in a dose-dependent manner. The selective D1 antagonist, (+/-)SCH-23390, inhibited in a dose-dependent manner the production of cyclic AMP induced by DA. The affinity for the D1 receptor appeared to be greater in endothelium derived from large and small microvessels than from capillaries. Cholera toxin ADP-ribosylation of Gs proteins abolished the DA stimulatory effect on endothelial adenylate cyclase, whereas pertussis toxin ADP-ribosylation enhanced the DA-inducible formation, indicating the presence of both D1 and D2 receptors. Agonists of alpha 1-adrenergic receptors (phenylephrine, 6-fluoronorepinephrine) or serotonin (5-HT), which stimulated the production of cyclic AMP, had no additive effect on DA-stimulated cyclic AMP formation. Incubation of these agents with DA produced the same or lower levels of cyclic AMP as compared to that formed by DA alone. The effect of alpha 1-adrenergic agonists or 5-HT on DA production of cyclic AMP was partially prevented by the D2 antagonist, S(-)-sulpiride, or ketanserin (5-HT2 greater than alpha 1 greater than H1 antagonists), respectively. These findings represent the first demonstration of D1- (stimulatory) and D2- (inhibitory) receptors linked to adenylate cyclase in microvascular endothelium derived from human brain. The data also indicate that dopaminergic receptors can interact with either alpha 1-adrenergic or or 5-HT receptors in endothelium on the adenylate cyclase level.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenylate Cyclase Toxin↗
Application of gadolinium-DTPA magnetic resonance imaging for detection of a filum terminale myxopapillary ependymoma allowing successful surgical resection.
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Adult↗
Multifocal independent epileptiform discharges in children: ictal correlates and surgical therapy.
We obtained continuous EEG/video recordings on four children who had the interictal EEG pattern of multifocal independent epileptiform discharges (MIED). The prominent feature of their evaluation was the evidence that their clinical seizures appeared to be of focal origin; 42/44 seizures were manifested by "fencing postures." Three patients subsequently underwent epilepsy surgery: one focal resection of superior frontal-parietal cortex and two hemidecorticectomies. Seizure control improved in all three patients, and one patient is now seizure-free. Our patients differ from those previously reported in that they had a predominance of tonic seizures and had no history of infantile spasms or Lennox-Gastaut syndrome. Some patients, such as ours, with MIED may have clinical seizures of more focal origin than might be expected from their interictal EEG and, therefore, may benefit from resective epilepsy surgery.
Adolescent↗