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Biomedical subjects

R E Anderson

Publications and source records attributed to R E Anderson.

At least 289 records · Page 16Linked to original sources
PubMed1987

Some characteristics of academic departments of pathology in the United States. Implications for training of academic pathologists.

Data concerning the activities of faculty and various characteristics of academic departments of pathology were obtained from questionnaires returned by 94 chairmen and 1571 faculty members. Data concerning manpower that was the subject of a previous report indicated that the projected supply of MD pathologists for faculty positions was significantly less than the anticipated demand. This article describes the characteristics of academic departments, particularly the activities of faculty that have bearing on the training and expectations of pathologists who are seeking faculty positions.

Academic Medical Centers↗
PubMed1986

Inhibition of electrically induced seizures by a dihydropyridine calcium channel blocker.

Nimodipine, a calcium channel blocker with high affinity for central dihydropyridine Ca2+ channels, produced a dose-dependent suppression of electrically induced seizures in the rabbit. Verapamil, a diphenylalkylamine which acts at peripheral Ca2+ channels, was ineffective. Phenytoin was less effective than nimodipine. These results suggest that calcium flux into neurons may be a biochemical precipitant for seizure genesis. Centrally acting calcium channel blockers may prove to be a new class of anticonvulsants.

Animals↗
PubMed1986

In vivo incorporation of [2-3H]-myo-inositol into frog opsin.

The in vivo incorporation of [2-3H]-myo-inositol into frog retinal rod outer segment membranes was examined. About 25% of the recovered radioactivity was found to be protein-associated. Following acid hydrolysis of this material and extraction with hexane, all the radioactivity remained in the aqueous phase, indicating that the label was not in fatty acids. Following ion exchange column chromatography of the hydrolysate, the major radioactive compound comigrated on TLC with an internal standard of [U-14C]-myo-inositol. SDS polyacrylamide gel electrophoresis of unextracted membranes indicated that the majority of the label was associated with opsin. These results indicate that [2-3H]-myo-inositol was incorporated in vivo into opsin, presumably with retention of its chemical identity.

Animals↗
PubMed1986

Effect in cat of locus coeruleus lesions on the response of cerebral blood flow and cardiac output to altered paCO2.

In pentobarbital-anesthetized cats, over arterial paCO2 values of 20-60 mm Hg, cerebral blood flow (CBF, Xenon) and cardiac output (CO, thermal dilution) show positively inflicted curves with slopes significantly greater than zero. To examine the role of the locus coeruleus (LC) in these responses, bilateral stereotactic thermo-coagulation lesions of the LC were made. The effect of lesions confirmed to involve the LC bilaterally (n = 10), were compared with the effects of misdirected lesions placed in the cerebellum and lateral to the LC (n = 10) and sham lesions (n = 10). Ten days after the lesioning procedure, the animals were re-anesthetized with pentobarbital and paCO2 response curves were determined for CBF and CO prior to and following intravenous administration of propranolol (1 mg/kg, i.v.). The results obtained with the sham-operated animals and the animals with lesions outside of the LC were indistinguishable. Bilateral LC lesions had no significant effect on normocapnic CBF as compared to control animals. They did, however, significantly reduce the slope of the CBF paCO2 response curve. Propranolol produced a significant reduction in CBF in lesioned and non-lesioned animals measured at all levels of pCO2 and did not alter the slope of the pCO2 response curve for any group as compared to predrug values. Bilateral lesions of the LC did not significantly alter either normocapnic CO or the slope of the CO-paCO2 relationship, but did reduce the elevation in mean arterial blood pressure otherwise observed during hypercarbia. Measurement of norepinephrine levels in cortex indicate a close correlation between the ability of the lesion to reduce norepinephrine content and produce the observed physiological effects. The results of these experiments suggest that the hypercapnic response of CBF, but not CO to arterial paCO2 is modulated by systems which traverse the dorsal brainstem. The role of the locus coeruleus-catecholamine cell bodies in this effect, however, must be considered speculative until further transmitter-selective interventions are carried out.

Animals↗
PubMed1986

Humoral and ionic regulation of osteoclast acidity.

Regulation of the acidity of osteoclasts was determined in situ on the endocranial surfaces of mouse calvaria using acridine orange, a fluorescent weak base. Osteoclasts could be identified by large size, multiple nuclei, relatively small numbers of cells, and the way and the extent to which they took up the dye. Nonosteoclastic cells were stained mainly in their nuclei and occasionally in a few lysosomes surrounding their nuclei, which were uniformly single in nonosteoclasts. Nuclei in osteoclasts were also stained, but the staining of the nuclei was partially masked by the intensity and completeness of the staining of the cytoplasm. In some cells the cytoplasmic staining appeared to be in discrete granules, giving the cytoplasm a bright, frothy appearance. This fluorescence was present in both treated and untreated cells and aided in identifying the osteoclasts. Acridine orange fluorescence at 624 nm intensity, and hence, osteoclast acidity, was increased by parathyroid hormone and prostaglandin E2. Parathyroid hormone-induced increases in acidity were inhibited by calcitonin, cortisol, sodium fluoride, and prostaglandin E2. Furthermore, osteoclast acidity was dependent largely or partially on maintenance of K+ and Na+ gradients, patent Na+ channels, chloride-bicarbonate exchange, and H+, K+-ATPase. These findings demonstrate that osteoclasts become acidified by mechanisms similar to those occurring in gastric parietal cells.

Acridine Orange↗
PubMed1986

Oil droplets of the retinal epithelium of the rat.

Oil droplets are observed in the retinal pigment epithelium (RPE) of both light- and dark-adapted rats. The accumulation of these droplets is strongly correlated with the clearance of large phagosomes that are found on a circadian basis in the RPE. Although strongly correlated with phagosomes in this way, the composition of the oil droplets does not resemble the lipid composition of rod outer segments (ROS). The important differences are that most of the 18:0 fatty acid (stearic) and virtually all of the polyunsaturated ones (principally docosahexaenoic, 22:6) are absent from the droplets. The major (greater than 95%) constituents of the droplets are triglycerides admixed with small amounts of vitamin A esters (less than 5%). This result suggests that certain of the ROS lipids, especially the polyunsaturated fatty acids, are cleared quickly from the RPE and are, perhaps, recycled to the neural retina. Such a process would account for the known ability of the retina to conserve the polyunsaturates despite dietary deficiencies.

Adaptation, Ocular↗
PubMed1986

Selective central nervous system calcium channel blockers--a new class of anticonvulsant agents.

Current research suggests that Ca2+ flux into the neuron may be a critical factor in the genesis of seizures. We report herein the influence of nimodipine, a selective central nervous system calcium channel blocker, in 60 rabbits with seizures that had been induced through ischemia, postischemia reperfusion, pentylenetetrazol, and bicuculline. In 30 animals subjected to 4 hours of ischemia, 9 of the 15 control animals had seizures in comparison with 1 of the 15 treated animals (P less than 0.005). Five animals with reperfusion seizures demonstrated similar results. In 10 animals in which a convulsant was applied topically to both cerebral hemispheres, unilateral intracarotid injection of nimodipine arrested seizures in that hemisphere alone, whereas the control contralateral hemisphere continued to have electrical seizure activity (P less than 0.001). Both placebo and verapamil were ineffective. These results suggest that Ca2+ influx is a common biochemical precipitant for various types of experimental seizures. Selective central nervous system calcium channel blockers may prove to be a new class of anticonvulsant agents.

Animals↗
PubMed1986

Effect of preischemia cyclooxygenase inhibition by zomepirac sodium on reflow, cerebral autoregulation, and EEG recovery in the cat after global ischemia.

Zomepirac sodium (ZS) (5 mg/kg i.v.) was used to evaluate the effects of preischemia cyclooxygenase inhibition on CBF (as assessed by 133Xe clearance), CBF-PaCO2 responsiveness, and electrophysiologic (EEG) parameters before and after a 15-min period of complete global ischemia produced by four-vessel occlusion and mild hypotension. During the 15-min period of ischemia, CBF was essentially zero. Following reflow all groups displayed an initial hyperemia as compared with control (92 +/- 11 vs. 141-146 ml/100 g/min). Saline-treated animals during reflow displayed a delayed hypoperfusion (26 +/- 3 ml/100 g/min), which showed no improvement during the 2-h reflow period prior to death. In contrast, ZS-treated animals during reflow displayed significantly higher flows during the hypoperfusion phase (72 +/- 9 ml/100 g/min). The CBF-PaCO2 response displayed an approximately sevenfold reduction in slope at 2 h after reflow in saline-treated animals. This decrease in PaCO2 reactivity was not observed in the ZS-pretreated animals. With regard to EEG, all animals showed a total flattening during the 15 min of ischemia. In saline-treated animals only one of seven showed any sign of even marginal recovery. In ZS-treated animals EEG activity showed prominent recovery in seven of seven. Brainstem auditory evoked potentials were monitored and showed prominent recovery of amplitude and latency in ZS but not saline-treated animals during reflow.

Animals↗
PubMed1986

Effects of clonidine on cerebral blood flow and the response to arterial CO2.

CBF, as measured by the clearance of 133Xe or 85Kr in the pentobarbital-anesthetized cat, displays a monotonic increase as the PaCO2 is elevated over a range of 20-60 mm Hg (slope Xe, 1.65 +/- 0.14 ml/100g/min/mm Hg; slope Kr, 1.40 +/- 0.11 ml/100 g/min/mm Hg). Clonidine (20 micrograms/kg i.v.), a centrally acting, alpha 2-preferring agonist, reduced the slope of the PaCO2-CBF response functions for Xe and Kr by 70 and 64%, respectively. Clonidine reduced normocarbic CBF-Xe by 36%, but had no effect on normocarbic CBF-Kr. ST-91, a polar structural analog of clonidine that does not cross the blood-brain barrier, did not reproduce the effects of clonidine when administered at an equivalent dose. This indicates that the effects of clonidine observed were secondary to its action on central rather than peripheral sites. In addition to the effects on the clearance of CBF markers, clonidine reduced the increased MABP otherwise evoked by elevated PaCO2. Reduction in the MABP response to PaCO2 did not account for the lowering of CBF during hypercarbia. In separate experiments where MABP was elevated to correspond with the PaCO2-MABP response observed in the absence of clonidine, a comparable reduction in the slope of the PaCO2 response was also observed. In addition, the pressure autoregulatory response was unaltered after clonidine treatment. These observations suggest that the central action of alpha 2-receptors on the CBF-CO2 response cannot be attributed to an altered perfusion pressure.

Animals↗
PubMed1986

Intracellular brain pH, indicator tissue perfusion, electroencephalography, and histology in severe and moderate focal cortical ischemia in the rabbit.

Intracellular brain pH and indicator tissue perfusion were measured with a lipid-soluble, pH-sensitive fluorescent indicator in 10 rabbits who had either severe or moderate focal ischemia depending on whether the middle cerebral artery was occluded at its main trunk or bifurcation. Preocclusion tissue indicator perfusion was 50.1 ml/100 g/min and intracellular brain pH was 7.03. In severe focal ischemia, immediate postocclusion tissue perfusion was 12.7 ml/100 g/min and intracellular brain pH was 6.64. Four hours after occlusion, the perfusion was 5.2 ml/100 g/min and intracellular brain pH was 6.08. There was EEG and histological confirmation of infarction. In the moderate focal ischemia group, immediate postocclusion flow was 20.0 ml/100 g/min and intracellular brain pH was 6.92. At 3 h, postocclusion tissue perfusion was 22.6 ml/100 g/min and intracellular brain pH was 6.86. Therefore, for the first 3 h, this ischemic penumbra was stable. At the fourth hour, both cerebral tissue perfusion and intracellular brain pH worsened. This suggests that the ischemic penumbra is a dynamic state. The rabbit is a good experimental model for the production of both severe and moderate focal ischemia.

Animals↗
PubMed1986

Adrenal steroid responses to continuous intravenous adrenocorticotropin infusion compared to bolus injection in normal volunteers.

We compared the adrenal steroid responses after synthetic ACTH-(1-24) (Cosyntropin) administration given by either continuous iv infusion or bolus injection in 11 normal women and 6 normal men. Each subject received 250 micrograms Cosyntropin as a bolus iv injection on 1 occasion and as a continuous 2-h iv infusion on another occasion, in random order. There was a 1-week interval between the studies. We measured the plasma levels of cortisol, 11-deoxycortisol, 17-hydroxyprogesterone, progesterone, pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, delta 5-androstenediol, androstenedione, and testosterone by RIA 15 and 0 min before and 30, 45, 60, and 120 min after administering ACTH. The steroid concentrations and their increments, ratios, or areas above baseline did not differ significantly between the bolus injection and the continuous infusion. Thus, at the dose of 250 micrograms, a bolus ACTH injection stimulates adrenal steroid secretion as effectively as a 2-h continuous ACTH infusion.

Adrenal Cortex Hormones↗
PubMed1986

Hematoporphyrin derivative photocytotoxicity of human glioblastoma in cell culture.

The parameters of hematoporphyrin-derivative (HpD) photocytotoxicity of human glioma cells in cell culture were studied to determine the optimum wavelength and power density of light, to investigate the influence of tissue oxygenation, and to evaluate the role of singlet oxygen and free radicals in producing cell death. Cell survival curves demonstrated a relative killing efficiency of 12:1 for violet compared to red light. Eighty joules of red light were required to produce 100% cell kill at an HpD concentration of 10 micrograms/ml, a level of HpD that has been quantitated in biopsies from patients receiving HpD photoradiation therapy. No difference in cellular killing efficiency was observed for power densities of red light varying from 10 to 100 mW/cm2. Cytotoxicity was directly related to O2 tension from 12 to 490 torr with a slight but consistent increase in cell kill at O2 tensions from 7 to 12 torr. Cytotoxicity was effectively quenched by beta-carotene, whereas mannitol had no effect, indicating that cytotoxicity is probably mediated via a mechanism involving singlet oxygen. This information may serve as a basis for more effective application of HpD photoradiation therapy and for designing protocols to study the efficacy of such therapy.

Cell Line↗
PubMed1986

Effect of nimodipine on intracellular brain pH, cortical blood flow, and EEG in experimental focal cerebral ischemia.

Intracellular brain pH, cortical blood flow, and electroencephalograms (EEG's) were recorded in severely and moderately ischemic regions in 10 control and 10 nimodipine-treated rabbits prior to and following major branch occlusion of the middle cerebral artery (MCA). Preocclusion cortical blood flow was 51 ml/100 gm/min and intracellular brain pH was 7.01 in both the control and the treated animals. After MCA occlusion, the severely ischemic regions in the control group showed initial and 4-hour postocclusion flows of 12.7 and 5.2 ml/100 gm/min with a brain pH of 6.64 and 6.08, respectively. In animals given nimodipine after MCA occlusion, blood flow increased from 10.5 to 18.8 ml/100 gm/min, with an associated elevation in intracellular brain pH from 6.57 to 6.91. Comparable findings were observed in areas of moderate ischemia. Improvements in cortical blood flow, intracellular brain pH, and EEG attenuations produced by nimodipine were all statistically significant. Inspection of the cortex revealed reversal of cortical pallor and small-vessel spasm following treatment with nimodipine. It is hypothesized that nimodipine exerts its effects through reversal of ischemia-induced secondary vasoconstriction, and that this drug may be an important adjunctive treatment for patients with focal cerebral ischemia.

Animals↗
PubMed1986

Effect of hyperglycemia on brain pH levels in areas of focal incomplete cerebral ischemia in monkeys.

The adverse effect of a minimal cerebral blood flow (CBF) in models of global ischemia has been noted by many investigators. One factor believed important in this situation is the level of blood glucose, since a continued supply of this metabolite results in increased tissue lactate, decreased brain pH, and increased cell damage. The authors have extended these observations to a model of focal incomplete ischemia. Brain pH was measured in fasted squirrel monkeys in regions of focal incomplete ischemia after transorbital occlusion of the middle cerebral artery (MCA). In both control and hyperglycemic animals, CBF was reduced to less than 30% of baseline. At 3 hours after MCA occlusion, brain pH in the control group was 6.66 +/- 0.68 as compared to 6.27 +/- 0.26 in the glucose-treated group. This difference was statistically significant by Student's unpaired t-test (p less than 0.05). Thus, hyperglycemia results in decreased tissue pH in regions of focal incomplete cerebral ischemia in monkeys.

Animals↗
PubMed1986

Polyunsaturated fatty acids and vitamin E in rat rod outer segments during light damage.

Previous evidence suggests that lipid peroxidation may initiate photoreceptor damage induced by constant light exposure. In order to investigate the role of the antioxidant vitamin E in light damage, Long-Evans (pigmented) rats were atropinized and exposed to constant fluorescent light (Vita-Lite) of 10-20 foot candles for intervals up to 5 days. Following light exposure, retinal rod outer segments (ROS) were prepared and their lipids extracted. Retinas processed in parallel for morphological examination showed progressive ROS deterioration and selective loss of photoreceptor cells at 3 and 5 days of constant light. Similar to previous observations in undilated albino rats, constant illumination resulted in the specific loss of docosahexaenoic acid (22:6 omega 3) in the ROS. A novel finding in this study was an increase in the content of vitamin E relative to lipid phosphorus, stearic acid, and docosahexaenoic acid in the ROS of constant light-exposed animals.

Animals↗