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Biomedical subjects

S A Moore

Publications and source records attributed to S A Moore.

At least 127 records · Page 7Linked to original sources
PubMed1988

Eicosanoid metabolism in cerebromicrovascular endothelium.

Cultured murine cerebral microvessel endothelia produce predominantly prostacyclin and prostaglandin (PG) E2 when exposed to trace amounts of arachidonic acid. At higher concentrations of arachidonate or with ionophore A23187, they produce more PGE2 than prostacyclin and additionally make PGF2 alpha and small amounts of eicosanoids comigrating with hydroxylated derivatives of arachidonate. Endothelia grown on micropore filters release prostaglandins from both apical and basal surfaces; however, the ratio of basal to apical release is as high as 4:1. This polarity suggests that cerebral endothelial prostaglandins can interact with neighboring cells of the vessel wall and brain parenchyma, where they may play important roles in the control of cerebrovascular tone and neuroglial function. These eicosanoids also are produced by mouse brain microvessels, but the major microvessel product is 12-hydroxyeicosatetraenoic acid. This suggests that 12-hydroxyeicosatetraenoic acid may be abundant in brain injuries after arachidonate release. Cultured cerebral endothelia rapidly convert 12-hydroxyeicosatetraenoic to more polar metabolites and thus may prevent the accumulation of this potentially deleterious hydroxyacid.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1987

Brain microvascular smooth muscle expresses class II antigens.

Mouse (BALB/c) splenic lymphocytes co-cultured in vitro with syngeneic brain-derived microvascular smooth muscle (SM) proliferate and become activated. After subsequent transfer of the activated lymphocytes to a syngeneic host, a vasculitis develops in the host. Investigation of the possible antigen-presenting properties of the cultured SM has resulted in the demonstration of class II (Ia) antigens on the SM. Fluorescence-activated cell sorter analysis has shown that an average of 31% of unstimulated SM cells in culture were positive when stained with an anti-IE of the appropriate haplotype (H2d), and an average of 20% were positive with an anti-IA of the H2d haplotype. Controls consisting of irrelevant antibodies of the same isotype, as well as an anti-IA of the H2s haplotype, were negative. In contrast, BALB/c-derived brain microvascular endothelial cells showed considerably less class II antigen expression (7% for both IA and IE).

Animals↗
PubMed1987

Shift in subfractions of rat alveolar macrophages in vivo during endotoxin-induced alveolitis.

To elucidate changes in alveolar macrophages that accompany sepsis-induced lung injury, this study analyzed the subfractions of alveolar macrophages (AM) recovered by lung lavage during the onset of endotoxin-induced acute neutrophilic alveolar inflammation in the rat model. Centrifugation on continuous self-generated density gradients of Percoll was used to fractionate AM into subpopulations between density limits 1.012 and 1.130. Two-thirds of AM recovered from pathogen-free control rats (group C) were in a fraction with a density range of 1.058-1.078 ["normal" density fraction, (ND)]. Only 6% were located in a very low density (VLD) fraction 1.037-1.048. Neutrophils accounted for less than 1% of recovered cells and usually were found in the fraction with density range of 1.079-1.130. By contrast, if rats underwent lung lavage 15 hours after the administration of endotoxin (group E), only 38% of macrophages were recovered in the "normal" density fraction, whereas 26% of the AM recovered were in the VLD fraction. This shift in the relative sizes of the density based subpopulations coincided with the onset of acute bronchoalveolar inflammation as indicated by the recovery of neutrophils by bronchoalveolar lavage (PMN = 7 X 10(4) in C, vs. 9.4 X 10(5) in E, p less than .001). The macrophages on the low density subfractions showed functional impairment: they were less viable in culture and migrated poorly in response to endotoxin-activated serum compared to macrophages in the "normal" density fraction from the endotoxin-treated animals. The rapid emergence of the low density population after endotoxin could represent an influx of new cells, but more likely indicates that injury to or previous activation of resident macrophages has caused their density to decrease. We speculate that the emergence of a population of AM in airspaces with low density and impaired function could weaken pulmonary host defence following endotoxemia.

Animals↗
PubMed1987

Isolation and culture of cells derived from human cerebral microvessels.

Microvessels were isolated from non-neoplastic human cerebral cortical fragments resected for treatment of intractable seizure disorder. The microvessels were incubated in modified Lewis medium with 20 or 30% fetal bovine serum. Within 1-2 weeks, two cell populations emerged from the isolates. One type of cells had polygonal morphology, showed density-dependent contact inhibition at confluence in vitro, showed lectin-binding characteristics of endothelium (but only moderate positivity for factor VIII antigen), demonstrated induction of gamma-glutamyl transpeptidase when exposed to astrocyte-conditioned media, and responded to insulin by a pronounced increase in DNA synthesis. The other variety of cells grew in vitro more slowly in irregular strands separated by clear zones, showed ultrastructural features of smooth muscle, and isoelectric focusing of cell proteins revealed the presence of smooth-muscle-specific alpha-isoactin. Both types of cells could be serially subcultured. The ability to isolate and grow the two cell types, tentatively identified as human cerebral microvascular endothelium and smooth muscle, may facilitate studies of human blood-brain barrier function as well as the pathogenesis of cerebral microangiopathies unique to the human brain.

Adolescent↗
PubMed1987

Alpha-factor inhibition of the rate of cell passage through the "start" step of cell division in Saccharomyces cerevisiae yeast: estimation of the division delay per alpha-factor.receptor complex.

A highly sensitive, kinetically unambiguous assay for alpha-factor-induced delay of cell passage through the "start" step of cell division in yeast is presented. The assay employs perfusion with periodic microscopy to monitor the bud emergence kinetics on the 20% of cells within an exponentially growing population which exist prior to the alpha-factor execution point of start. The t1/2 for cell passage through start by this population of cells is 31 min in the absence of alpha-factor. The inhibition constant, KI, represents the alpha-factor concentration which produces a 50% inhibition of this rate and is equal to 2 X 10(-10) M. A second assay for maximal cell division arrest by alpha-factor on whole populations of cells is presented. This assay shows a maximum cell division arrest time of 125 +/- 5 h at saturating alpha-factor, and a K50 (that is, an alpha-factor concentration which produces a half-maximal response) of 2.5 X 10(-8) M. Both assays were performed in the effective absence of alpha-factor inactivation. Values of the dissociation constant KD and total number of receptors per cell which specifically mediate cell division arrest or delay were estimated to be 2.5 X 10(-8) M and 10(4), respectively. These estimates, along with the quantitative dose-response data for division arrest which are presented here, are consistent with each receptor.alpha-factor complex which is present on the cell at equilibrium producing a 43 +/- 10 s delay of cell passage through start. Surprisingly, this number is constant within twofold over the entire range of cellular division arrest responses to alpha-factor, that is, from a 1.9-fold inhibition of the rate of cell passage through start at 0.17 nM alpha-factor to a 125 +/- 5 h maximum arrest at saturating alpha-factor concentrations of greater than 170 nM. The possible significance of this observation toward the mechanism of alpha-factor-induced cell division arrest is discussed.

Cell Division↗
PubMed1987

Differential opening of the brain endothelial barrier following neutralization of the endothelial luminal anionic charge in vitro.

This study was undertaken to determine the effect of neutralization of brain endothelial cell luminal membrane anionic charge on endothelial permeability properties. Mouse brain microvessel endothelial cells were grown to confluence on a nitrocellulose filter. The permeability of the endothelium to Evan's blue dye (EBD) (molecular weight 960) and fluoresceinated dextran (FITC-D) (molecular weight 20,000), both polar molecules, was assessed before and after the exposure of the endothelium to cationic ferritin (CF) or native ferritin (NF). The use of CF resulted in a significant increase in permeability of the endothelium to EBD compared to NF. This result indicates that ablation of endothelial surface anionic charge enhances endothelial transport of a small, polar-charged molecule. Cationic ferritin did not increase the permeability of FITC-D compared to NF. This negative result is not surprising because FITC-D differs from EBD in terms of charge and solubility as well as in size. The electrical resistance of the endothelial cell layer after the application of CF was unchanged from baseline values suggesting a transcellular rather than a paracellular route of the EBD leakage.

Animals↗
PubMed1987

Chorea-amyotrophy with chronic hemolytic anemia: a variant of chorea-amyotrophy with acanthocytosis.

We studied two siblings with chorea and amyotrophy of adult onset and spherocytic hemolytic anemia. Autopsy revealed an atrophic striatum with iron deposition and spheroid bodies. Degeneration of the substantia nigra and spinal cord anterior horns was seen without iron deposition. The disorder seems to be a variant of the chorea-amyotrophy-acanthocytosis syndrome, and the pathology may account for evidence of parkinsonism and amyotrophy in that syndrome. Acanthocytosis may not be the only hematologic abnormality in this disorder.

Acanthocytes↗
PubMed1986

A case of stenotic obstruction of the jejunum secondary to slow-release potassium.

This case report describes the clinical, radiographic, and pathological findings in an adult male presenting with small bowel obstruction caused by an annular, fibromuscular abnormality of the jejunal muscularis mucosa. No clinical or pathological evidence of trauma or neoplasm was found. The patient had, however, been taking a wax matrix potassium chloride preparation. The nature of the annular lesion strongly suggests that it arose as a repair phenomenon after focal, potassium-induced ulceration of the jejunum.

Delayed-Action Preparations↗
PubMed1985

Effects of water restriction on nitrogen metabolism and urea recycling in the macropodid marsupials Macropus eugenii (tammar wallaby) and Thylogale thetis (red-necked pademelon).

The effects of water restriction on nitrogen metabolism were compared in the semi-arid adapted tammar wallaby (Macropus eugenii) and a wallaby from a moist forest environment, the red-necked pademelon (Thylogale thetis). On a medium (9 to 13%) protein diet water restriction depressed dry matter and nitrogen intakes in both species. Nitrogen balance remained positive, but fell further in the pademelons. Urea excretion decreased in the tammars, but increased in the pademelons. Urea recycling as a proportion of urea entry rate tended to increase in the tammars but not in the pademelons. These findings suggest that T. thetis is not as well adapted as M. eugenii to coping with water shortages. In a second experiment water restriction depressed nitrogen balance in tammars on both high (15%) and low (5%) protein diets, but only on the latter diet did nitrogen balance become negative. Urea recycling was greater on the low than on the high protein diet, but was unaffected by water restriction. Although better able to withstand water stress, M. eugenii was unable to cope with both water stress and a low protein diet together. The reported ability of M. eugenii to maintain water intake by drinking sea water during the dry season when fresh water is unavailable and vegetation is of low protein content is thus of great ecological significance.

Animals↗
PubMed1985

Cellular and vessel wall morphology of cerebral cortical arterioles after short-term diabetes in adult rats.

Microvascular pathology is one of the major problems associated with prolonged diabetes mellitus. The purpose of the present study was to determine if anatomical cellular pathology of the cerebral cortical microvessels could be detected very early after the onset of a streptozotocin-induced model of diabetes. Male rats at age 14-16 weeks were hyperglycemic (greater than 250 mg/dl) for 4 weeks prior to scanning and transmission electron microscopic analysis of the external and internal cell and vessel wall morphology of the arterioles. Scanning electron microscopic studies indicated that many processes of vascular smooth muscle cells changed their normal spindle shape to a branched or stellate configuration. The internal cellular changes included swollen mitochondria and cisternae of the endoplasmic reticulum and reduced cytoplasmic staining. Necrosis of arteriolar endothelial cells was evident in virtually every vessel section studied. These data indicate that vascular smooth muscle and endothelial cellular degeneration of cerebral cortical arterioles begins in the very early stages of the streptozotocin model of diabetes.

Animals↗
PubMed1985

Modification by hyperoxia in vivo of endotoxin-induced neutrophil alveolitis in rats. Production of chemotactic factors by alveolar macrophages and ultrastructure.

We have previously shown that prior exposure to hyperoxia intensifies the influx of polymorphonuclear leukocytes into bronchoalveolar spaces after endotoxemia (E), but the mechanism is unknown. Because pulmonary alveolar macrophages (PAM) regulate the migration of polymorphonuclear leukocytes into the lung in several types of acute and chronic alveolitis, we studied the effect of pretreatment with hyperoxia in vivo on production of chemotactic factors by PAM after E. In this study, we cultured PAM recovered by lung lavage from oxygen- and air-pretreated rats 4, 15, and 48 h after E to determine whether a direct effect of hyperoxia on the release of chemotactic factors by PAM in response to E in vivo could contribute to the previous observations. We found that the chemotactic activity of the culture media supernatants from PAM recovered from oxygen-pretreated rats given E was 80% higher than that of media from PAM recovered from air-exposed rats given E. Neither PAM from air-exposed rats nor those from oxygen-exposed rats spontaneously released chemotaxins selective for other PAM. In contrast, when PAM were stimulated with zymosan in vitro, those from the oxygen-breathing group produced 50% more chemotactic activity for other PAM than did those from the air-breathing group. These differences in secretion of chemotactic factors were not associated with decreased viability of PAM either in vivo or in tissue culture, or with impaired adherence by PAM in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Autoimmune vasculitis resulting from in vitro immunization of lymphocytes to smooth muscle.

Lymphocytes sensitized in vitro to syngenic microvascular smooth muscle and transferred to syngeneic recipients produced in vivo microvessel vasculitis characterized by mononuclear cells which adhered to endothelium, infiltrated the vessel wall, and formed a perivascular cuff. A granulomatous type of vascular inflammation was seen in 20% of the affected recipients in which the vessel smooth muscle appeared to be preferentially attacked. These lesions bear a striking resemblance to certain human vasculitides, and the model provides an important means of studying vasculitis as well as general cellular autoimmune disease mechanisms.

Animals↗
PubMed1984

Yeast cells recover from mating pheromone alpha factor-induced division arrest by desensitization in the absence of alpha factor destruction.

Saccharomyces cerevisiae MATa cells arrest cell division in response to the mating pheromone, alpha factor. After some interval of time the cells resume division. It is demonstrated here that cells recover from division arrest by becoming insensitive to the alpha factor under conditions of low cell density (10(2) cells/ml) where no alpha factor destruction occurs. The time of desensitization occurs later at higher alpha factor concentrations. Using the technique of perfusion photomicroscopy developed in this study, it was found that 95% of the desensitized cells remain insensitive to the alpha factor for greater than or equal to 3 generations at the alpha factor concentration where recovery occurred. Upon recovery, cells have generation times which are similar or identical to the calculated time from the cdc28 "start" step of cell division to cell separation. Therefore, the abnormally large recovered cells behave as if they have no growth time requirement for cell division for several generations. Desensitization was found to occur asymmetrically for parent and daughter cells. While parents (cells which have budded) are insensitive to alpha factor, their daughters (cells which have never budded and which were formed from desensitized parents during continuous perfusion with alpha factor) show 54% with a delayed generation time compared to control daughter cells.

Cell Division↗
PubMed1984

Cerebral microvascular smooth muscle in tissue culture.

Cerebral endothelium is being studied rather extensively in tissue culture, but no reports are available describing the tissue culture of cerebral microvascular smooth muscle. The present paper describes for the first time the isolation and culture of non-neoplastic mouse cerebral vascular smooth muscle. Microvessels from a dounce homogenate of mouse brain are plated onto plastic culture dishes in Dulbecco's modified Eagle media plus 20% fetal bovine serum and treated briefly with collagenase. Cells migrate from vessels and proliferate sufficiently to be transferred out of primary culture in 2 to 3 wk. Light microscopy reveals generally broad, polygonal cells that grow collectively in a "hill and valley" pattern. By transmission electron microscopy the cells possess many characteristics of smooth muscle: basal laminas, clusters of pinocytotic vesicles, and bundles of thin filaments. Several ill-defined cell-to-cell junctions are also present. Isoelectric focusing and sodium dodecyl sulfate-electrophoresis of cellular proteins on polyacrylamide gels after pulse labeling cultures with [S-35]methionine demonstrate that these cells actively synthesize a smooth-muscle-specific isoactin, alpha-actin. The identity of alpha-actin is confirmed by analysis of NH2-terminal peptides after actin digestion with trypsin and subsequent peptide cleavage with thermolysin. Both their morphology and active synthesis of alpha-actin strongly suggest that these cells are of smooth-muscle origin. Future studies of their metabolism and interactions with endothelium and astrocytes should provide a better understanding of the cerebral microcirculation.

Actins↗
PubMed1984

Synchronous cell growth occurs upon synchronizing the two regulatory steps of the Saccharomyces cerevisiae cell cycle.

There are two known asynchronous steps in the budding yeast Saccharomyces cerevisiae cell cycle, where an asynchronous step is one which is completed in different lengths of time by different cells in an isogenic population. It is shown here that elimination of the asynchrony due to cell size by preincubation of cells with the mating pheromone alpha-factor, and decreasing the asynchrony in the cdc28 'start' step by lowering the pH, yields highly synchronous cell growth measured as the time period between the emergence of buds. In one experiment, cell budding for 92% of cells occurred within a 12-min period for at least two generations. Under identical conditions, cell number increase is not as synchronous as bud emergence indicating that there is a third asynchronous step, which is concluded to be at cell separation. These results are consistent with there being two--and only two--asynchronous steps in the cell cycle, measured from bud emergence to bud emergence. Surprisingly, these two steps are also the two major regulatory steps of the cell cycle. It is concluded that asynchrony may be a general feature of cell cycle regulatory steps. The asynchrony in the completion of the cdc28 'start' step which occurs in the first cell cycle after alpha-factor washout is shown here to be almost or entirely eliminated for the second passage through this step after alpha-factor washout. The 'true' time between the onset of budding and the point where 50% of cells have budded (called t50BE) is 17 and less than or equal to 2 min for the first and second budding, respectively, after alpha-factor washout. The cell cycle models requiring a transition probability, or asynchrony, at 'start' for every cell cycle are therefore incorrect.

Animals↗
PubMed1983

Comparison of dose-response curves for alpha factor-induced cell division arrest, agglutination, and projection formation of yeast cells. Implication for the mechanism of alpha factor action.

MAT alpha cells of the yeast Saccharomyces cerevisiae produce a polypeptide mating pheromone, alpha factor. MATa cells respond to the pheromone by undergoing several inducible responses: the arrest of cell division, the production of a cell surface agglutinin, and the formation of one or more projections on the cell surface commonly termed the "shmoo" morphology. Dose-response curves were determined for each of these inducible responses as a function of alpha factor concentration. It is shown that under conditions commonly employed in previous studies, the dose-response for cell division arrest is determined by the rate at which cells inactivate the alpha factor. In order to achieve conditions where inactivation would not be the dominant parameter, the cell division response to alpha factor was monitored at low cell densities. Under conditions of essentially no alpha factor destruction, the dose of alpha factor at which cells exhibit a half-maximal response for cell division arrest (2.5 X 10(-10) M) is nearly the same as that at which cells exhibit a half-maximal response for agglutination induction (1.0 X 10(-10) M). On the contrary, the half-maximal response for projection formation was obtained at doses of alpha factor 2 orders of magnitude higher (1.4 X 10(-8) M). These results are consistent with the same high affinity alpha factor receptor mediating both cell division arrest and agglutination induction. A different system of lower affinity must mediate projection formation. Alternatively, if the same system and receptor are used, then a much higher occupancy is required for the induction of projections compared to division arrest and agglutination induction.

Agglutinins↗