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Biomedical subjects

M Spatz

Publications and source records attributed to M Spatz.

At least 109 records · Page 6Linked to original sources

The presence of catechol-o-methyltransferase activity in separately cultured cerebromicrovascular endothelial and smooth muscle cells.

The activity of catechol-o-methyltransferase (COMT) was investigated in cultured and propagated cerebromicrovascular endothelial and smooth muscle cells using high performance liquid chromatography and immunocytochemistry. The existence of COMT was detected in both cell types. The demonstration of this enzyme activity in the cerebromicrovascular smooth muscle cells, in addition to the endothelium, indicates that the enzymatic barrier to catecholamine is not limited to capillaries, the main constituents of the blood-brain barrier.

Animals↗

Modulation of glycogen metabolism in cerebromicrovascular smooth muscle and endothelial cultures.

The separately cultured smooth muscle and endothelial cells derived from dissociated cerebral microvessels are characterized by high content of glycogen. Norepinephrine induces glycogenolysis while 5-hydroxytryptamine stimulates glycogenesis in both cell types. The endogenous glucose of the endothelium but not that of the smooth muscle serves as a direct source for the 5-HT enhancement of glycogen formation. Indomethacin, the known inhibitor of cyclooxygenase modulates the glycogen content in the smooth muscle only. These findings strongly suggest that the carbohydrate metabolism of each cell has a distinct control mechanism compatible with the underlying integral microvascular function.

Adenosine Triphosphate↗

Cell volume regulation of cerebrovascular endothelium in vitro.

Regulation of cell volume as a fundamental cellular function of high biological priority was studied in cultured cerebrovascular endothelium. The use of a multiparameter flow cytometric system allowed simultaneous measurements of cell volume, viability, and membrane potential or intracellular pH. Endothelium, the cellular constituent of the blood-brain barrier (BBB), swells immediately on exposure to low osmolality. This is associated with membrane depolarization and a fall of intracellular pH. Within 30-60 min, cell volume and membrane potential recover completely, although the extracellular osmolality is kept low. Intracellular pH does not normalize fully. Measurements of intracellular K+ and Na+ concentrations reveal their involvement in the regulatory process. The findings strongly suggest that the cerebrovascular endothelium has a highly effective built-in capacity for homeostatic control essential for normal BBB function.

Animals↗

Composite technique for regional neurochemical studies: measurement of energy and neurotransmitter metabolites in single tissue sample.

A combined method is described for the determination of various metabolites from a single tissue sample of the brain. It comprises a quick inactivation of cerebral enzymes by microwave irradiation, easy separation of the desired brain regions, and perchloric acid extraction of tissue substances, which are assayed either by specific enzymatic techniques or by HPLC with electrochemical detection. The obtained values of most energy and neurotransmitter metabolites in the brain are in agreement with those reported using other methods. However, this technique, in contrast to the brain freezing in vitro or freeze-blowing, provides a more efficient procedure for rapid arrest of cerebral metabolism even in the deep brain structures and is therefore suitable for detection of early changes particularly those occurring in experimental pathological conditions such as ischemia.

Adenosine Triphosphate↗

Efficacy of routine annual studies in the care of elderly patients.

The authors reviewed the results of annual laboratory screening (SMA 20, T3, T4, UA, EKG, chest x-ray) performed on a population of 500 institutionalized and ambulatory patients retrospectively followed from 1 to 19 years. With 30 laboratory values recorded for each annual exam, there were an average of 1.56 new abnormal laboratory findings per year per patient. A sample of 100 patients was further reviewed to determine the incidence of new diagnoses and treatment initiated by the appearance of new abnormal laboratory findings; 756 new abnormalities were recorded out of a possible 15,000, and 66 medical work-ups were initiated, which lead to new diagnoses in 21 cases and a treatment plan in 12 cases. The authors suggest that, in view of the rapid increase in the number of elderly persons and the consequent need to conserve limited health care resources, "standard" laboratory screening may not be warranted on a yearly basis in the elderly population.

Aged↗

Presentation of myelin basic protein by murine cerebral vascular endothelial cells.

Guinea pig basic protein (GPBP)-sensitized murine lymph node cell cultures depleted of macrophages-monocytes (MO) are no longer able to proliferate in response to specific antigen in vitro. The addition of MO reconstitutes the response that can be blocked by the addition of syngeneic anti-I-A antisera. Freshly isolated murine central nervous system endothelial cells (CNS-EC) cannot replace MO for the presentation of GPBP antigen to specifically sensitized lymph node lymphocytes. The pretreatment of CNS-EC with concanavalin A-conditioned media resulted in the expression of Ia molecules and the consequent ability to present GPBP. Antigen presentation by CNS-EC could be blocked by anti-I-A antisera for the CNS-EC donor haplotype.

Animals↗

Cerebrovascular smooth muscle culture. II. Characterization of adrenergic receptors linked to adenylate cyclase.

Cultured and propagated smooth muscle cells contain adenylate cyclase (AC) responsive to catecholamines and their analogues. Isoproterenol and zinterol were the most effective stimulants of AC activity with EC50 = 8.5 X 10(-8)M. They were followed by epinephrine, phenylephrine and norepinephrine (EC50 = 7.5 X 10(-7)M, 6.5 X 10(-6)M and 4 X 10(-6)M, respectively). When the selective antagonists for beta 1 and beta 2 receptors (beta 1-type practolol and atenolol, beta 1/beta 2-type propranolol and beta 2-type butoxamine) were tested against isoproterenol, epinephrine and norepinephrine stimulation of AC activity, the beta 1 in contrast to beta 2 antagonists were found ineffective. The alpha-blockers (phentolamine alpha 1/alpha 2-type antagonists) and yohimbine (alpha 2-type antagonist) alone or in the presence of propranolol did not significantly inhibit the catecholamine-induced enhancement of cAMP formation. On the other hand, prazosine (alpha 1-type antagonist) blocked the stimulatory effect of epinephrine and norepinephrine on AC system. Similarly, the alpha 2-agonist, clonidine, did not affect the catecholamines' stimulated AC activity while alpha 1 agonist, phenylephrine, induced an additive enhancement of norepinephrine production of cAMP. The findings of beta-2- and alpha-1-type adrenergic receptors in the cultured cerebrovascular smooth muscle provide additional support for the implicated involvement of adrenergic innervation in the regulation of cerebral blood flow and/or systemic blood pressure.

Adenylyl Cyclases↗

Cerebrovascular endothelial cell culture: metabolism and synthesis of 5-hydroxytryptamine.

The presence of 5-hydroxytryptamine was investigated in cultured and propagated cerebrovascular endothelium using immunohistochemistry and high pressure liquid chromatography. These studies demonstrate that the endothelium has the ability to take up and metabolize 5-hydroxytryptamine as well as to synthesize this amine from its precursor L-tryptophan, thus providing evidence for extraneural synthesis of 5-hydroxytryptamine in the central nervous system.

Animals↗

Cerebrovascular muscle cultures. I. Isolation, growth and morphological characterization.

This study describes the development and establishment of pure cerebrovascular smooth muscle cells derived from dissociated cells of microvessels obtained from brains of rats. The cultured and propagated vascular smooth muscle cells display histochemical and ultrastructural characteristics of smooth muscle cells consistent with those reported in cultures of peripheral vessels. Thus, the cerebrovascular smooth muscle cultures provide a new model system for the investigation of their function, particularly in relation to the regulation of cerebral blood flow and blood pressure.

Animals↗

Cerebral endothelial cell culture. II. Adenylate cyclase response to prostaglandins and their interaction with the adrenergic system.

The response of endothelial adenylate cyclase (AC) to prostaglandins (PGE1, PGE2, PGF1 alpha, PGF2 alpha, PGD2 and PGI2) and the relationship of PGE2 to adrenergic systems were investigated in cerebrovascular endothelial cultures. E-type prostaglandins and PGI2 were more effective in stimulating endothelial AC (EC50 = 3 x 10(-7)M, and 3 x 10(-6)M, respectively) than prostaglandins of the F-series and PGD2 which activated AC at high doses only. A modulation of endothelial AC response to either PGE2 or norepinephrine (NE) was observed in the presence of both agents in the system. It was manifested by a dose-dependent NE inhibition of the PGE2-stimulated formation of cAMP, which was partially restored by phentolamine. Alpha and beta-adrenergic agonists (alpha, clonidine and 6-fluoronorepinephrine; beta, isoproterenol) also partly blocked while forskolin and PGE2 synergistically stimulated the production of cAMP in the endothelial cultures. These findings strongly suggest that the interaction of prostaglandins and alpha- and beta-adrenergic agonists with the AC system in cerebrovascular endothelium may play a role in the regulation of the cerebral microcirculation and/or blood pressure.

Adenylyl Cyclases↗

Cerebral endothelial cell culture. I. The presence of beta 2 and alpha 2-adrenergic receptors linked to adenylate cyclase activity.

Cultured endothelial cells derived from cerebral microvessels separated from 2-day-old rat brain contain a specific beta 2 and alpha 2-adrenergic sensitive adenylate cyclase (AC). Among the various tested hormones, PGE1 and PGE2 were found to be the most potent activators, while adenosine, angiotensin I and II, gamma-aminobutyric acid and vasoactive intestinal peptide inhibited the enzyme activity. However, acetylcholine, histamine, serotonin, glycine, glutamine, bradykinin, neurotensin and vasopressin (Lysine and Arginine) had no effect on the adenylate cyclase activity in this model. The susceptibility of the cerebrovascular endothelial AC system to the vasoactive substances as well as presence of beta 2 and alpha 2-type adrenergic receptors in the cultured endothelium provides additional support for the proposed endothelial involvement in the regulation of cerebrovascular permeability and blood flow.

Adenylyl Cyclases↗

Evaluation of the dye-protein tracers in pathophysiology of the blood-brain barrier.

1. Sodium fluorescein and Evans Blue, commonly used tracers in the study of blood-brain barrier disturbances, revealed considerable differences in their respective protein binding capacity in the plasma, passage through the barrier and in the rate of their elimination from the brain parenchyma. 2. In the plasma a considerable portion of the sodium fluorescein remains free and behaves like a micromolecular barrier tracer. On the other hand, almost complete binding of the Evans Blue to albumin confers to it properties of a protein tracer. 3. Following the extravasation of the tracers, the sodium fluorescein is relatively soon eliminated, whereas Evans Blue remains in the cellular elements of the brain parenchyma for a considerable time, although the protein moiety of the tracer is removed much sooner from the cytoplasm of glial cells, presumably by the lysosomal digestion.

Animals↗