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Biomedical subjects

S Uematsu

Publications and source records attributed to S Uematsu.

At least 19 recordsLinked to original sources

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

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

A cellist with arm pain: thermal asymmetry in scalenus anticus syndrome.

We report on a cellist with pain and coldness of the upper extremity. Abnormal thermographic studies were instrumental in uncovering intermittent compression of the subclavian artery, and this prompted us to study the effects of cello playing on skin temperature asymmetry. Temperature asymmetry was defined as the temperature difference (delta-T) from one hand to the other. In 57 controls, mean delta-T at rest was .309 +/- .254C. Exercising the upper extremities by prolonged elbow flexion or by movements mimicking cello playing in controls did not significantly affect delta-T. In our patient, delta-T was ten times control (3.6C). Angiography showed extrinsic compression of the subclavian artery occurring only after cello playing; sympathetic ganglion block relieved the pain. Our patient's abnormal skin temperature may have reflected sympathetic vasomotor hyperactivity. Intermittent neurovascular compression and sympathetic hyperactivity appear to be factors in scalenus anticus syndrome.

Adult

The role of arachidonic acid and oxygen radicals on cerebromicrovascular endothelial permeability.

Arachidonic acid release from tissue membranes and/or formation of free radical species have been considered to affect blood-brain barrier permeability and formation of brain oedema. To determine whether exogenous arachidonic acid or H2O2 may alter blood-brain barrier permeability, we examined their effect on cultured endothelium derived from cerebral microvessels of human and animals. Release of 51Cr from labeled endothelium exposed to these substance was used as a main marker for the assessment of endothelial injury. The results of these studies indicate that endothelial cells (EC) are susceptible to exogenous arachidonic acid or H2O2 insult irrespective of their origin. However human endothelial cells are less affected than animal EC by H2O2-generated systems. The findings suggest that a disturbance of the existing balance between the endogenous antioxidant properties of EC and exogenous oxidant leads to EC injury.

Animals

Parameters for direct cortical electrical stimulation in the human: histopathologic confirmation.

Safe parameters for electrical cortical stimulation in humans are difficult to estimate from the animal experimental literature. We therefore examined the light microscopic histology at a total of 11 sites of direct subdural electrical stimulation, taken as part of anterior temporal lobectomies in 3 patients. Stimulations had been done through 3.175 mm diameter electrodes, with 0.3 msec square wave pulses of alternating polarity at 50 pulses/sec. In 2 patients, one site each had been used as a common reference for stimulation, receiving over 251 stimulation trials, most of 2-5 sec duration, at currents of 12.5-15.0 mA, 1 day prior to resection. The maximum charge per phase was 4.0-4.4 microC; the maximum charge density was 52-57 microC per geometric cm2 per pulse at the electrode surfaces. Comparison of hematoxylin and eosin, periodic acid-Schiff, and cresyl violet-stained material from the electrode sites with that from other regions did not show any histologic abnormalities attributable to the electrical stimulation. The relatively brief and intermittent periods utilized for human stimulation testing do not appear to cause structural damage at the light microscopic level at charge densities that exceed the threshold for damage established in animal studies with more continuous, chronic stimulation schedules.

Electric Stimulation