Search PubMed⌕ Search

Biomedical subjects

M W Miller

Publications and source records attributed to M W Miller.

At least 127 records · Page 7Linked to original sources

Hemolysis of albunex-supplemented, 40% hematocrit human erythrocytes in vitro by 1-MHz pulsed ultrasound: acoustic pressure and pulse length dependence.

The tested hypothesis was that ultrasound-induced hemolysis in blood supplemented with a microbubble contrast agent varies with ultrasound intensity and pulse duration. Human erythrocytes in autologous plasma containing 3.6% v:v Albunex microspheres were exposed to 1.07-MHz ultrasound pulses of 5 to 1000 mus at SPTP intensities of 0 to 1100 W/cm2. The dependence of hemolysis on the mechanical index (MI) value of the exposures was also examined. Ultrasound-induced hemolysis: (1) was evident at all pulse/intensity combinations; (2) increased generally with increasing pulse duration at constant intensity; and (3) increased with increasing MI at constant pulse duration. For pulses of 10 to 30 mus, ultrasound-induced hemolysis remained low (< or = 2%) at MI values < approximately 2 and increased sharply with further increase in MI; for 5-mus pulses, this abrupt increase in hemolysis was associated with a larger MI (approximately 3).

Adult↗

A review of in vitro bioeffects of inertial ultrasonic cavitation from a mechanistic perspective.

This selective review of the biological effects of ultrasound presents a synopsis of our current understanding of how cells insonated in vitro are affected by inertial cavitation from the standpoint of physical and chemical mechanisms. The focus of this review is on the physical and chemical mechanisms of action of inertial cavitation which appear to be effective in causing biological effects. There are several fundamental conditions which must be satisfied before cavitation-related bioeffects may arise. First, bubbles must be created and then brought into proximity to cells. Exposure methods are critical in this regard, and simple procedures such as rotation of a vessel containing the cells during exposure can drastically alter the results. Second, once association is achieved between bubbles and cells, the former must interact with the latter to produce a bioeffect. It is not certain that the inertial event is the prime mechanism by which cells are lysed; there is evidence that the turbulence associated with bubble translation may cause lysis. Additionally, there appear to be chemical and other physical mechanisms by which inertial cavitation may affect cells; these include the generation of biologically effective sonochemicals and the apparent emission of ultraviolet (UV) and soft X-rays. The evidence for inertial cavitation occurring within cells is critically reviewed.

Animals↗

Ethanol inhibits basic fibroblast growth factor-mediated proliferation of C6 astrocytoma cells.

Early ethanol exposure alters the proliferative activity of glial and neuronal precursors in the developing CNS. The present study tests the hypothesis that ethanol-induced alterations in cell proliferation result from interference with growth factors. An in vitro model of astroglia (C6 astrocytoma cells) was used to study the effects of ethanol on proliferation mediated by basic fibroblast growth factor (bFGF). bFGF stimulated the proliferation of C6 cells. This bFGF-enhanced proliferation was evident by increases in total cell number, DNA synthesis (as measured by [3H]thymidine incorporation), and the number of cells that took up bromodeoxyuridine. A synthetic peptide that specifically blocked the binding of bFGF to its high-affinity receptor completely abolished the proliferation-promoting effect of bFGF. The action of another mitogen for C6 cells, insulin-like growth factor-1, was not affected by this peptide. Therefore, the bFGF-stimulated proliferation was mediated through a specific bFGF receptor. Ethanol inhibited bFGF-mediated proliferation in a concentration-dependent manner. Ethanol concentrations of 100 and 200 mg/dl partially inhibited bFGF-mediated proliferation (by 58 and 74%, respectively), whereas concentrations of > or = 400 mg/dl completely abolished the growth-stimulating effect of bFGF. Our data show that ethanol alters proliferative activity of C6 cells by disrupting the action of bFGF. The target of ethanol neurotoxicity is a receptor-mediated activity. bFGF can affect cell proliferation by a non-receptor-mediated intracellular pathway, but ethanol does not have an impact on this pathway.

Analysis of Variance↗

Development of trigeminal nucleus principalis in the rat: effects of target removal at birth.

Little is known about how neurons develop in the trigeminal nucleus principalis (PrV) despite their acknowledged role in establishing whisker-related patterns in the thalamus and cortex. Golgi-impregnated PrV cells were studied in newborn, 4-day-old and adult rats. Adult neurons typically had short dendrites that were confined to a hemisphere around the soma. In contrast, at birth PrV neurons had radial trees and more primary dendrites than did adults, but adult-like numbers of dendritic spines. By day 4, most neurons had eccentric dendritic trees and the numbers of primary dendrites per neuron were adult-like, yet spines were more prevalent than in adults and newborns. Thus, it appears that there is a pruning of the dendritic tree during the first postnatal week. To assess the role of retrograde signals from the thalamus on PrV development, the right thalamus was destroyed at birth. By postnatal day 6, the number of neurons in the left PrV was 59% of that in the right PrV, PrV transverse area was reduced by 21%, cell density was reduced by 48%, and somatic diameter was increased by 36%, relative to the intact right PrV. By contrast, in the left V subnucleus interpolaris, which has only a weak thalamic projection, these measures were unaffected. Thus, neonatal thalamic lesions selectively depopulated the PrV. The morphology of PrV neurons was affected by the thalamic lesions: e.g. the total dendritic length, the number of dendritic branch points and the total number of spines were increased. The number of primary dendrites and the tree's eccentricity, area, and volume of influence were unaffected by the lesion. The structure of neurons in subnucleus interpolaris was unaffected by the lesion. Thus, normal afferent patterning is insufficient for normal development of PrV cells. Interactions among dendrites and retrograde signals from a target are also important.

Animals↗

Limited ethanol exposure selectively alters the proliferation of precursor cells in the cerebral cortex.

The present in vivo study tests the hypothesis that limited (4-day) exposure to ethanol differentially affects the proliferation of cortical precursors in the two cortical germinal zones [the ventricular zone (VZ) and the subventricular zone (SZ)] and their descendants in the mature brain. The offspring of pregnant rats fed a liquid diet containing 6.7% (v/v) ethanol when prosencephalic stem cells [gestation day (G) 6-69], VZ cells (G12-G15), and SZ cells were proliferating (G18- G21) throughout much of gestation (G6-G21). In addition, the offspring of rats pair-fed a liquid control diet or fed chow were examined. The pregnant dams were administered with bromodeoxyuridine (BrdU) on either G15 or G21. The ratio of the number of cells that incorporated BrdU to the total number (the labeling index) was determined 1-hr postinjection (i.e., on G15 or G21) or on postnatal day 60, Ethanol treatment between G6 and G21 reduced the ratio of cells labeled by an injection of BrdU on G15 in the fetus and in the adult, and increased the ratio of cells labeled on G21. Regardless of when the injection was placed, ethanol treatment between G6 and G9 had no effect upon the ratio of BrdU-labeled cells in the fetus or mature cortex. Exposure from G12 to G15 decreased the number of VZ cells in the fetus and the number of immunolabeled cells in the adult cortex labeled by an injection on G15. This exposure had no effect on the incorporation by SZ cells. In contrast, ethanol exposure from G18 to G21 increased the labeling indices for fetal SZ cells and for cells in the adult, but it had no effect on the ratio of labeled VZ cells. Although ethanol had no apparent effect on the proliferation of stem cells, it did alter the proliferation of cells in the VZ and SZ. These effects are time-dependent and underlie the ethanol-induced changes in the number of cells in the adult.

Animals↗

Effect of static pressure on acoustic transmittance of Albunex microbubble suspensions.

Albunex (ALX), an albumin-stabilized microbubble echo contrast agent, is sensitive to pressures similar to those produced by the heart. The tested hypothesis was that the acoustic transmittance of ALX suspensions will increase with increasing hydrostatic pressure (Ps). The test involved an acoustic setup analogous to a spectrophotometer. The acoustic transmittance of microbubble suspensions was strongly Ps dependent. Transmittance at 1 MHz was essentially zero at ambient pressure, increasing to approximately 50%, approximately 63%, and nearly 100% at Ps of 80, 120, and 400 mm Hg, respectively. The ultrasound pulses used to interrogate samples were without measurable effect on the acoustic transmittance of suspensions maintained at ambient pressure during experimental measurements. The data indicate that many of the microbubbles are destroyed at Ps comparable to those produced by the heart.

Acoustics↗

Effect of metacycloprodigiosin, an inhibitor of killer T cells on murine skin and heart transplants.

Metacycloprodigiosin is an antibiotic that has been shown to suppress T-cell proliferation induced by concanavalin A in vitro. We examined the effect of metacycloprodigiosin on murine allogenic skin and heart transplantation models, and compared graft rejection with donor-specific cytotoxic T-cells and antibody activity. The antibiotic slightly prolonged the survival of C57Bl/6 heart and skin grafts in BALB/c mice, although the effect was less that that of cyclosporin A. The effect was more evident in Bm1 (H-2D mutant) skin grafts on C57B1/6 hosts or in a minor histocompatibility antigen-mismatched model. In contrast, metacycloprodigiosin suppressed anti-graft cytotoxic T-cell activity of BALB/c spleen grafted with C57B1/6 skin as comparable to cyclosporin A, but had only partial effect on antibody production. Thus, metacycloprodigiosin is more effective in reducing splenic cytotoxic T-cell activity than in prolonging murine skin or cardiac allografts.

Animals↗

Effects of embedded tungsten-bismuth-tin shot and steel shot on mallards (Anas platyrhynchos).

We assessed the potential for embedded steel and tungsten-bismuth-tin (TBT) shot to adversely affect health of mallards (Anas platyrhynchos). Ducks were implanted with three number four steel (n = 19) or TBT (n = 20) shot pellets in their pectoral muscles. None of seven hematology parameters measured differed in response to treatment (P > or = 0.17). At necropsy 1, 2, 4, and 8 wk posttreatment, we observed only localized tissue reactions to embedded steel or TBT shot. Reactions differed grossly: after wk 1, embedded steel shot were enveloped in 0.5 to 2 mm grayish capsules, whereas TBT shot were surrounded by thinner (< 0.5 mm), translucent capsules. Corrosion of steel shot was apparent. Microscopic lesions associated with steel shot were characterized by moderate to severe histiocytic and lymphocytic inflammation and considerable particle deposition, whereas histiocytic inflammation was mild and particle deposition minimal in TBT lesions. Overall scores of inflammation at steel shot implant sites were greater (P < or = 0.043) than at TBT sites during wk 1 and 8. Inflammation at steel implant sites was relatively consistent over the 8-wk period, but decreased (P = 0.0017) at TBT sites by wk 8. Weights of steel shot recovered from muscle tissue declined logarithmically (R2 = 0.978, P = 0.0014) over 8 wk, but TBT shot weights remained unchanged (P = 0.255). Embedded TBT shot, as compared to steel, resisted corrosion and induced comparatively mild inflammatory responses in mallard muscle tissue. However, inflammatory reactions to both embedded steel and TBT shot were localized and had no detectable systemic effects on mallard health under experimental conditions.

Animals↗

Efficacy and safety of naltrexone hydrochloride for antagonizing carfentanil citrate immobilization in captive Rocky Mountain elk (Cervus elaphus nelsoni).

We evaluated efficacy and safety of naltrexone for antagonizing carfentanil immobilization in 12 captive Rocky Mountain elk (Cervus elaphus nelsoni) using a randomized incomplete block experiment. In three replicate trials, elk were hand-injected with 10 micrograms carfentanil citrate/kg body weight intramuscularly. Fifteen min after each elk became recumbent, we administered naltrexone HCl (25% of dose intravenously, 75% subcutaneously) dosed at 0 (control), 25, 50, or 100 mg/mg carfentanil; after an additional 15 min of immobilization, controls received 500 mg naltrexone HCl/mg carfentanil. Elk were immobilized in 34 of 36 attempts; the mean (+/-SE) induction time was 3.1 +/- 0.2 min. Regardless of dose, all elk stood < 9 min after receiving naltrexone; controls remained immobilized until they received antagonist. Mean recovery times did not differ with increasing naltrexone dose (P = 0.31) or among individuals (P = 0.16). None of the elk receiving 100 or 500 mg naltrexone/mg carfentanil renarcotized, but three of eight and seven of nine elk receiving 50 and 25 mg naltrexone/mg carfentanil, respectively, showed signs of mild renarcotization 8 to 24 hr later (P = 0.0002). We observed no adverse clinical effects in elk receiving < or = 500 mg naltrexone/mg carfentanil. Based on these data, we recommend 100 mg/mg carfentanil as a minimum effective dose for rapidly antagonizing immobilization and preventing renarcotization.

Analgesics, Opioid↗

A test of the hypothesis that a 60-Hz magnetic field affects ornithine decarboxylase activity in mouse L929 cells in vitro.

Four replicate experiments were performed to test the hypothesis that a 4-hr exposure of L929 cells in vitro to a 60 Hz, 10 microT magnetic field results in a large increase in ornithine decarboxylase (ODC) enzyme activity (1-2). A positive control yielded a highly statistically significant increase in ODC activity. However, magnetic field exposure had no statistically significant effect on extractable ODC activity of L929 cells relative to that of sham-exposed cells.

Analysis of Variance↗

Long-term consequences of prenatal cocaine exposure on biogenic amines in the brains of mice: the role of sex.

Prenatal cocaine exposure leads to multiple abnormalities in the mature offspring. We explored the effects of gestational exposure to cocaine on neurotransmitter systems of adult mice. The subjects were the mature offspring of mice (a) prenatally fed cocaine between gestational day (G) 8 and G19, (b) pair-fed chow and water, or fed chow and water ad libitum. The forebrains of the mature offspring were assayed for monoamines and amino acids. Cocaine exposure particularly affected the dopaminergic system and in a sex-specific manner. In males dopamine concentrations were decreased and dopamine turnover was increased, whereas in females dopamine concentrations were increased and turnover was decreased. Neither norepinephrine, the serotonergic system, nor neuroactive amino acids (or their precursors) were affected by cocaine. Thus, in utero exposure to cocaine produces long-lasting, specific defects in the dopaminergic system.

Amino Acids↗

Relationship of the time of origin and death of neurons in rat somatosensory cortex: barrel versus septal cortex and projection versus local circuit neurons.

The birth of a neuron initiates a series of ontogenetic events, e.g., neuronal migration and differentiation. The outcomes of these events are neurons that successfully integrate into the cortical circuitry and neurons that are unsuccessful and ultimately die. The present study determined whether there is a relationship between the generation and death of cortical neurons. The decrease in the density of postmigratory neurons (heavily labeled by a single injection of [3H]thymidine) during normal development was used as an index of neuronal death. The survival indices of neurons varied with their times of origin. Neurons born from gestational day (G) 15 to G18 had the highest rates of survival. In contrast, the earliest and latest generated neurons (i.e., those born on G12-G13 and those born on G19-G21, respectively) had the lowest survival rates. The role of neuronal death in the formation of cortical patterns was determined by assessing the survival of neurons in the barrels and septa of somatosensory cortex. No differences in the survival index were determined for neurons in the C-row barrels and adjacent septa with a particular time of origin. The survival rate of projection and local circuit neurons was determined with a double-labeling technique. One label, [3H]thymidine, was used to determine the time of origin of the neurons. The second label was used to identify the chemical or hodological characteristics of a neuron; projection neurons were labeled either by retrograde transport of horseradish peroxidase or by glutamate immunohistochemistry, and local circuit neurons were immunohistochemically identified with an antibody directed against gamma-aminobutyric acid (GABA) antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Behavior patterns of the aplysiid gastropod Bursatella leachii in its natural habitat and in the laboratory.

The behavior of the ragged sea hare, Bursatella leachii pleii Rang, was observed in its natural habitat and in captivity. An indication of the seasonal availability of Bursatella in Puerto Rico was obtained by making multiple observations at a single site. The behavior patterns of Bursatella in the field were indicative of a daily rhythm. They tended to be found in groups at sunrise and as isolated individuals in the afternoon. They were observed to assemble following sunset and to disperse in the morning. Certain aspects of this rhythmic pattern of behavior persisted in animals held in the laboratory, where copulation was the most common behavior in the morning and feeding-related activities became more prevalent in the afternoon. Specific behaviors related to autonomic function (respiration and digestion) were also observed and quantified. It is proposed that the rich behavioral repertoire exhibited by B. leachii, and the ease with which these animals are observed in their native habitat, provide favorable systems for studying neuronal mechanisms involved in the organization and evolution of complex behavior.

Animals↗

Chlorinated contaminants in chorio-allantoic membranes from great blue heron eggs at Whidbey Island Naval Air Station.

Chorio-allantoic membranes (CAMs) were collected and analyzed for chlorinated hydrocarbons as part of a wildlife toxicology demonstration project at Naval Air Station (NAS) Whidbey Island, Washington, USA. Concentrations of DDT, DDE, DDD, Aroclor 1254, and Aroclor 1260 were found at concentrations below 0.4 ppm for 13 of 14 samples. The low correlations among DDT and its metabolites in CAMs suggest herons are not being exposed to a consistent source of these compounds. Comparison of chlorinated hydrocarbon data for CAMs from three Puget Sound heron colonies, NAS Whidbey, Samish Island and Dumas Bay, indicates contaminant burdens in herons from NAS Whidbey and Samish Island are significantly lower than burdens in herons from Dumas Bay.

Allantois↗

Iron regulation in the developing rat brain: effect of in utero ethanol exposure.

Fetal alcohol syndrome produces defects that parallel abnormalities associated with early iron deficiency. Hence, we examined the effects of prenatal exposure to ethanol on iron, transferrin, and ferritin concentrations. The subjects were the offspring of pregnant rats fed an ethanol-containing diet (Et), pair-fed an isocaloric control diet (Ct), or fed chow and water. The amounts of iron, transferrin, and ferritin were assessed in three CNS regions (cerebral cortex, subcortical forebrain, and brainstem). In all three segments of the control rats, iron, transferrin, and ferritin levels decreased during the first 2 postnatal weeks, reached a minimum during week 3, and then rose to adult levels. This pattern was delayed by ethanol treatment, e.g., the minimal concentrations in iron, transferrin, and ferritin in the Et-treated rats were achieved later (3 days, 7 days, and 2 weeks, respectively) than they were in the Ct-treated rats. Ethanol-induced alterations in iron homeostasis persisted into adulthood; iron concentration was reduced, transferrin concentration was unaffected, and ferritin concentration was increased. The net result was that the timely delivery and bioavailability of iron were compromised by ethanol exposure. The defects in iron regulation are permanent and may underlie ethanol-induced abnormalities in iron-dependent growth processes such as myelination.

Aging↗