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Biomedical subjects

S Fitzgerald

Publications and source records attributed to S Fitzgerald.

At least 55 records · Page 3Linked to original sources
PubMed1990

Alpha 1-adrenergic receptor mediates arachidonic acid release in spinal cord neurons independent of inositol phospholipid turnover.

The alpha 1-adrenergic receptor has been shown to mediate the release of arachidonic acid in FRTL5 thyroid cells and MDCK kidney cells. In primary cultures of spinal cord cells, norepinephrine stimulated release of arachidonic acid (from neurons only) and turnover of inositol phospholipids (from neurons and glia) via alpha 1-adrenergic receptors. These two responses were dissociated by treatment with phorbol ester and pertussis toxin, which inhibited production of inositol phosphates with no appreciable effect on release of arachidonic acid. Extracellular calcium was required for release of arachidonic acid, but not for production of inositol phosphates. The calcium channel blockers nifedipine and verapamil inhibited release of arachidonic acid only. However, 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8), a compound that blocks intracellular calcium release, diminished production of inositol phosphates, but had little effect on release of arachidonic acid. These results suggest that alpha 1-adrenergic receptors couple to release of arachidonic acid in primary cultures of spinal cord cells by a mechanism independent of activation of phospholipase C, possibly via the activation of phospholipase A2.

Animals↗
PubMed1990

Elevated blood cholesterol. A risk factor for coronary heart disease.

1. The Report of the Adult Treatment Panel on the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults is designed to provide guidance to healthcare professionals in the detection, evaluation, and treatment of adult hypercholesterolemic patients. 2. Dietary intervention, an essential part of every treatment plan, is highlighted followed by the introduction of drug treatment if the dietary intervention fails to achieve the desired results. 3. Guidelines for intervention at the worksite, including those using community resources, are discussed.

Coronary Disease↗
PubMed1989

Relaxin in paired samples of serum and milk from women after term and preterm delivery.

In a study to determine if relaxin could be measured in milk and if so to correlate concentrations in milk and serum, paired samples of milk and serum were collected from 12 women 3 days after term delivery (term group), from 16 women 3 days after preterm delivery (preterm group), and from some of these patients 6 weeks after delivery (eight term and six preterm). Relaxin was measured by specific human relaxin radioimmunoassay. Relaxin from milk and sera behaved similarly in the relaxin radioimmunoassay and reverse-phase high-performance liquid chromatography. Concentrations of relaxin in sera and milk collected 3 days after delivery did not differ significantly within the term or preterm groups. Neither were there differences in relaxin levels in sera and milk between the term and preterm groups. At 6 weeks postpartum, relaxin was not measured in any sera but was measured in milk from six of eight patients in the term group and five of six patients in the preterm group. Relaxin concentrations in milk were higher in the preterm group. The presence of relaxin in milk at 6 weeks postpartum suggests a nonluteal site of synthesis.

Chromatography, High Pressure Liquid↗
PubMed1987

Functional evidence of persistent airway obstruction in rats following a two-hour inhalation exposure to methyl isocyanate.

Pulmonary function was assessed in male, F344 rats 1,2,4,7, and 13 weeks after a single 2-hr exposure to 0, 3, 10, or 30 ppm methyl isocyanate. No significant changes were observed in the rats exposed to 3 ppm through 13 weeks. Diffusing capacity (DLco), quasistatic lung compliance, and homogeneity of ventilation, as determined by multibreath nitrogen washout, were depressed in the rats exposed to 10 and 30 ppm by 1 week after exposure. None of the rats exposed to 30 ppm survived beyond 1 week. By 13 weeks, dramatic increases in lung volumes were observed in the rats exposed to 10 ppm, while DLco and lung compliance were only mildly affected. However, volume-specific DLco and compliance were depressed in the rats exposed to 10 ppm, suggesting that lung hyperinflation or other compensatory means of increasing lung size occurred in response to the methyl isocyanate-induced lung lesion. This group also exhibited increased expiratory times during tidal breathing and severely impaired distribution of ventilated air. Collectively, these results suggest the development and likely progression of a severe, obstructive airway lesion with associated gas trapping, and the existence of a pronounced concentration-response relationship between 3 and 10 ppm methyl isocyanate exposures.

Airway Obstruction↗
PubMed1987

Hospital nurse counseling of patients who smoke.

Smoking-related diseases comprise a large portion of hospital admissions. This paper reports the attitudes and behaviors of a group of hospital-based nurses toward counseling patients on smoking cessation. The majority of nurses do not counsel patients who smoke. Counseling practices vary with the smoking status of the nurse. Barriers to increased nursing participation in counseling efforts include the lack of counseling training and physician failure to utilize nurses in this role.

Attitude of Health Personnel↗
PubMed1986

Induction of malignant transformation of cocultivated hematopoietic stem cells by X-irradiation of murine bone marrow stromal cells in vitro.

X-irradiation of purified primary cultures of mouse bone marrow stroma or permanent cloned marrow stromal cell lines in plateau phase decreases production of macrophage progenitor cell-specific colony-stimulating factor to a plateau minimum of 40% of control levels after doses of 50 to 500 Gy delivered at 2 Gy/min. After 50 Gy there is increased bioavailability of another growth factor(s) that is distinct from macrophage progenitor cell-specific colony-stimulating factor, granulocyte-macrophage progenitor cell colony-stimulating factor, or colony-stimulating factor for multipotential hematopoietic stem cells (interleukin 3). Liquid-phase cocultivation of irradiated stromal cells with either nonadherent cells from continuous marrow cultures or cloned dual granulocyte-macrophage progenitor cell colony-stimulating factor/interleukin 3-dependent hematopoietic progenitor cell lines induces evolution over 5 weeks of factor-independent colony-forming cells. Subcultured factor-independent colonies generated clonal malignant cell lines with multiple distinct karyotypic alterations. Inoculation of 10(6) cells s.c. from factor-independent clones into syngeneic mice produces local granulocytic monomyeloid tumors with spread to spleen, lymph nodes, and bone marrow. These data provide the first demonstration in vitro of indirect X-irradiation leukemogenesis through cells of the marrow stroma.

Animals↗
PubMed1985

Functional and morphologic changes in the lungs of guinea pigs exposed to freshly generated ultrafine zinc oxide.

Guinea pigs were exposed by nose only for 3 hr/day for 6 days to freshly formed zinc oxide (ZnO) particles (projected area diameter = 0.05 micron, sigma g = 2.0) at 5 mg/m3, the currently recommended threshold limit value (TLV). Ventilation, lung mechanics, lung volumes, and diffusing capacity for carbon monoxide (DLCO) in anesthetized, tracheostomized animals at 1, 24, 48, or 72 hr after the end of the last exposure were evaluated. At the same time intervals lung weight, lung fluid content, respiratory epithelial permeability to horseradish peroxidase, gross and microscopic appearance, and [3H]thymidine labeling of nuclei of bronchial and bronchiolar epithelial cells in other groups of animals were measured. Vital capacity, functional residual capacity, alveolar volume, and DLCO were all decreased following the last exposure and did not return to normal values by 72 hr. Increases in flow resistance and decreases in compliance and total lung capacity returned to normal by 72 hr. Lung weights were elevated due to inflammation involving the proximal portion of the alveolar ducts and adjacent alveoli. These changes were still present at 72 hr. [3H]Thymidine labeling of bronchiolar epithelial cell nuclei was increased for 48 hr. Respiratory epithelial permeability to horseradish peroxidase was not affected by the exposures. These results suggest that the current TLV for ZnO may not be adequate.

Animals↗
PubMed1985

Lung injury in guinea pigs caused by multiple exposures to submicron zinc oxide mixed with sulfur dioxide in a humidified furnace.

Sulfur dioxide, water vapor, and ultrafine particles rich in oxides of zinc and other surface-deposited trace elements are important products of coal combustion. In order to study the toxicity of zinc oxide generated under conditions simulating combustion, guinea pigs were exposed in a nose-only apparatus for 3 h on 6 consecutive days to 6 mg/m3 of submicron zinc oxide particles (count median diameter of 0.05 micron, sigma g 2.0), which were generated in a humid furnace and mixed with 1 ppm sulfur dioxide. The exposures caused increases in lung weight and [3H] thymidine labeling index of terminal bronchiolar cell nuclei and inflammation of the proximal portion of the alveolar duct. The lung weights and labeling index had returned to normal and inflammatory changes had nearly resolved by 72 h after the last exposure. Total lung capacity, vital capacity, functional residual volume, alveolar volume, and diffusing capacity for carbon monoxide were decreased following exposure and had not returned to normal by 72 h after the last exposure. Large airways were not affected by the repeated exposures, as indicated by normal morphology of trachea and bronchi, unchanged secretory cell concentration, and unaltered epithelial permeability to horseradish peroxidase. These results are essentially identical to changes we reported in guinea pigs exposed to zinc oxide alone, suggesting that surface-deposited sulfur compounds, which are important determinants of the response to a single exposure to these ultrafine particles, become less important as exposure progresses.

Animals↗
PubMed1985

Neuronal survival during electrical blockade is increased by 8-bromo cyclic adenosine 3',5' monophosphate.

Dissociated cultures from spinal cord-dorsal root ganglion were used as a model system to study the interaction between electrical activity and cyclic nucleotides on neuronal survival. Neuronal death produced by electrical blockade with tetrodotoxin (TTX) was attenuated by the addition of 8-Bromo cyclic AMP (8-Br cAMP). [125I]Tetanus toxin fixation, choline acetyltransferase activity and neuronal cell counts were used to quantitate the effects of 8-Br cAMP on the cultures. A dose-dependent increase in both tetanus toxin fixation (neuronal surface marker) and choline acetyltransferase activity was observed with 8-Br cAMP application to TTX-treated cultures as compared to those treated with TTX alone. The rate of choline acetyltransferase induction by 8-Br cAMP was decreased in the presence of TTX. Supplementation of the cultures with 8-bromo cyclic GMP, under the same conditions, had no protective or inductive effects. These data suggest that cholinergic neurons are among those cells affected by electrical blockade and by increased culture cAMP levels. Electrical blockade with TTX produced significant decreases in cAMP levels during a critical period in development. The onset of the critical period was found to be between day 5 and day 8 in vitro and the vulnerability to TTX-mediated decreases in cAMP were not evident in cultures which were older than 1 month. Conditioned medium obtained from spinal cord-dorsal root ganglion cultures before the critical period were tested on TTX-treated cultures that were within the critical period. No decrease in cAMP levels from that of controls was observed after 50% conditioned medium plus TTX treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1984

Interaction between trophic action and electrical activity in spinal cord cultures.

The effect of conditioned medium (CM) on tetrodotoxin (TTX)-mediated neuronal cell death was investigated in dissociated spinal cord-dorsal root ganglion (SC-DRG) cultures. Nutrient medium was collected from donor SC-DRG cultures at 3--4-day intervals throughout development. The presence of survival-promoting neurotrophic material (NTM) in the conditioned medium was tested on TTX-treated cultures which were within the critical period of vulnerability to electrical blockade (days 7-21 in culture). Cultures were assayed by neuronal cell counts, choline acetyltransferase (ChAT) activity or fixation of [125I]tetanus toxin, a neuronal surface marker. Evidence of NTM was found in CM collected prior to day 8 and after day 21 in culture. Increasing the percentage of CM in fresh nutrient medium resulted in a dose-dependent increase in [125I]tetanus toxin fixation and ChAT activity in TTX-treated cultures. In addition, CM plus TTX treatment produced a 25% increase in neuronal cell counts as compared to controls. TTX treatment alone resulted in 20-25% decrease in neuronal number from that of control cultures. Cultures treated with CM alone had neuronal counts that were similar to controls. When electrical activity was blocked with TTX, NTM was not detectable in CM collected from donor cells during days 1-5. CM obtained from control cultures during the same interval had NTM activity. The existence of the critical period for electrical blockade-associated neuron death is associated with a decrease in the availability of NTM. Furthermore, the release of NTM from donor cells and the survival response of target neurons to NTM are apparently dependent on ongoing electrical activity.

Animals↗
PubMed1983

Effects of proton release from adenine nucleotide degradation during ischemic necrosis of myocardium in vitro.

The effects of the progressive production of hydrogen ions and inorganic phosphate from adenine nucleotides on the lowering of pH in heart muscle has been investigated in dog myocardium maintained under anoxic conditions in vitro at 37 degrees C. Tissue samples were taken at 15-min intervals for up to 105 min and the following biochemical parameters determined: pH, lactate, Pi, ATP, ADP, AMP, G6P, and PC in selected instances. From these data the net proton changes during prolonged anoxia were calculated, assuming homogeneity of the tissue milieu. Net proton change was negative after 15 min and became increasingly more so throughout the remainder of the experimental period, indicating that adenine nucleotide catabolism in fact has a protective effect against fall in pH. When tissue pH falls to ca. 6.2 (45-60 min anoxia), proton production due to lactic acid is reduced by approximately 16% because of absorption of protons by phosphate and ammonia liberated from the nucleotides.

Adenine Nucleotides↗
PubMed1982

Electrical development in spinal cord cell culture.

Parallel electrophysiological and neurochemical studies of development are reported for mouse spinal cord cell cultures. The time course of electrical activity and the stage-dependent effects of tetrodotoxin on levels of the neuronal enzyme choline acetyltransferase were compared to establish the presence of spontaneous electrical activity at a time when tetrodotoxin adversely affects development. The extracellular patch electrode makes it possible to examine the ongoing electrical activity of the small cells present in young cultures. A rapid increase in spontaneous electrical activity during the first 2 weeks in culture was found to correlate closely with the onset of tetrodotoxin-induced depression of choline acetyltransferase activity, supporting the idea that ongoing electrical activity plays a role in neuronal development. The development of inhibitory synaptic activity occurs gradually throughout the period of culture, whereas excitatory synaptic activity and action potentials develop in unison, reaching maximal levels during the 2nd week in culture. For all cultures tested, ranging in age from 9 to 45 days old, acute bath application of gamma-aminobutyric acid (GABA) abolished spontaneous electrical activity. Glycine is relatively ineffective in abolishing spontaneous activity in young cultures which have few inhibitory postsynaptic potentials (IPSPs), but glycine becomes as effective as GABA at a later stage of development. This suggests rather different timetables of development for GABA and glycine receptors, with glycine receptors developing in parallel with IPSPs.

Animals↗
PubMed1981

Adverse effects of phenobarbital on morphological and biochemical development of fetal mouse spinal cord neurons in culture.

The effects of chronic phenobarbital treatment on neuronal development were assessed in cell cultures of fetal rodent spinal cord. The activity of the principal enzyme involved in acetylcholine synthesis, choline acetyltransferase (CAT), and counts of large spinal cord neurons were used as indicators of neuronal development Phenobarbital (30 to 120 micrograms/ml) added to cultures for two- or six-week periods produced dose-dependent decreases in both CAT activity and neurons counts. Barbituric acid at doses equimolar to those at which phenobarbital produced these decreases had no effect.

Acetylcholine↗