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Biomedical subjects

R H Simon

Publications and source records attributed to R H Simon.

At least 73 records · Page 4Linked to original sources
PubMed1986

Neutrophil-induced injury of rat pulmonary alveolar epithelial cells.

The damage to pulmonary alveolar epithelial cells that occurs in many inflammatory conditions is thought to be caused in part by phagocytic neutrophils. To investigate this process, we exposed monolayers of purified rat alveolar epithelial cells to stimulated human neutrophils and measured cytotoxicity using a 51Cr-release assay. We found that stimulated neutrophils killed epithelial cells by a process that did not require neutrophil-generated reactive oxygen metabolites. Pretreatment of neutrophils with an antibody (anti-Mo1) that reduced neutrophil adherence to epithelial cells limited killing. Although a variety of serine protease inhibitors partially inhibited cytotoxicity, we found that neutrophil cytoplasts, neutrophil lysates, neutrophil-conditioned medium, purified azurophilic or specific granule contents, and purified human neutrophil elastase did not duplicate the injury. We conclude that stimulated neutrophils can kill alveolar epithelial cells in an oxygen metabolite-independent manner. Tight adherence of stimulated neutrophils to epithelial cell monolayers appears to promote epithelial cell killing.

Animals↗
PubMed1985

Attenuation by 2,3-dihydroxybenzoic acid of acute lung injury induced by cobra venom factor in the rat.

Neutrophil-derived oxygen metabolites are thought to play an important role in the genesis of acute lung injury in a variety of diseases. In an effort to find an agent that might limit the injury, we evaluated the beneficial effects of 2,3-dihydroxybenzoic acid (DHB), a drug that has been safely administered to humans as an iron-chelating agent. Because experimental evidence has demonstrated that DHB can act as an inhibitor of free radical-induced reactions, we tested its protective effect against the neutrophil-dependent lung injury that occurs in rats after the intravenous infusion of cobra venom factor (CVF). Using a permeability index that measures the amount of intravenously administered 125I-albumin that accumulates in lung tissue, we found that pretreatment with DHB reduced (p less than 0.05) the lung injury in CVF-treated rats in a dose-dependent manner. Morphometric analysis of lung tissue indicated that the protection by DHB was not caused by inhibition of CVF-induced neutrophil sequestration within the lung vasculature. Because iron-saturated DHB did not attenuate lung injury, and because in vitro experiments demonstrated that DHB inhibited iron-hydrogen peroxide-induced peroxidation of phospholipid liposomes, we suspect that DHB may be protecting the lung via chelation of iron. We conclude that dihydroxybenzoic acid protects the rat lung from the neutrophil-dependent lung injury that occurs after cobra venom factor infusion. Because this drug has been safely administered to humans, it may have potential as an agent to prevent acute lung injury.

Animals↗
PubMed1985

Evidence for adenosine triphosphate degradation in critically-ill patients.

Alterations of cellular energy metabolism may provide important markers during the clinical course of critically ill patients. To determine whether adenosine triphosphate (ATP) degradation occurs in critically ill patients, we measured levels of adenosine, inosine, hypoxanthine, and xanthine in 18 patients and seven control subjects. The mean concentration of hypoxanthine (3.8 microM) in the critically ill patients was elevated (p less than 0.01) compared to that of our control population (0.1 microM). A subgroup of seven critically ill patients had levels of hypoxanthine, xanthine, or inosine higher than those of any member of the control group. This subgroup was characterized by a lower systolic blood pressure, an increased requirement for vasopressors, and a markedly decreased survival rate when compared to the other critically ill patients. Arterial and mixed venous blood gas values were not helpful in predicting survival and did not correlate with levels of ATP degradation products. In two patients who showed subsequent clinical improvement, the initially elevated levels of hypoxanthine and xanthine returned to normal. This study indicates that critically ill patients have elevated levels of ATP degradation products. These increased levels may indicate cellular hypoxia.

Adenosine↗
PubMed1984

Model referenced method of evoked potential analysis.

We have described a method for identifying component wave forms of evoked potentials by reference to a model of the dynamic behavior of neuronal systems. The method parsimoniously reproduces measured data and provides a means for utilizing a priori information from sets of experimental data to discriminate between experimental variables. The method appears successful in quantifying the physiologic variability in the amplitude, shape and latency of EP component wave forms.

Adolescent↗
PubMed1984

Beta-endorphin injected into the nucleus of the raphe magnus facilitates metastatic tumor growth.

Electrical stimulation of the periaqueductal gray of the rat's midbrain analgesia leads to an increase in the number of artificial pulmonary metastases from the Walker 256 tumor. In an effort to investigate the influence of the pain suppression system and its associated peptides on this phenomenon, we activated the pain suppression system directly from the Nucleus of the Raphe Magnus, a non-opioid subsystem. After inducing analgesia by direct injection of beta-endorphin on the Nucleus of the Raphe Magnus, we noted an increase in the number of artificial pulmonary metastases. This result could be blocked by pretreatment with naloxone. If the Nucleus of the Raphe Magnus was activated by electrical stimulation sufficient to induce analgesia, the metastatic effect was still present but markedly attenuated.

Animals↗
PubMed1984

A comparison of pressure-volume models in hydrocephalus.

Traditional descriptions of the pressure-volume properties of the craniospinal axis have expressed pressure as a function of volume. This study develops a theoretical and practical rationale for expressing volume as a function of pressure. We tested the rationale by comparing the two functions using pressure and volume data collected from 37 hydrocephalic patients during ventricular fluid removal. Two equivalent expressions were evaluated, one expressing pressure as an exponential function of volume and one relating volume as an exponential function of pressure. Each expression had three parameters, adjustable to the specific case. We used a nonlinear curve-fitting algorithm to determine the best estimate of the parameters. We could fit three-parameter exponential functions of either type to the data in all cases. We found a superior goodness-of-fit to aggregated data when expressing volume as a three-parameter exponential function of pressure changes. This finding is discussed in the context of the preferable number of parameters in a model and the interpretation of the terms in the models. This "reversed" volume-pressure relationship has importance in the development of more complicated models involving these same relationships.

Computers↗
PubMed1983

Effect of midbrain stimulation on amphetamine-induced stereotypy in rats.

Behavioral changes were induced in rats by administration of high doses of amphetamine (5 mg/kg): among these was the development of rapid sniffing. The effect of electrical stimulation of the midbrain periaqueductal gray was then examined. This stimulation is known to release an enkephalin-like substance into the ventricular spinal fluid and to induce analgesia. Stimulation blocked amphetamine-induced sniffing. This effect was blocked in turn by pretreatment with naloxone, a specific opiate antagonist. We discuss this finding in the context of opiate-catecholamine antagonism in the CNS.

Amphetamines↗
PubMed1983

A model referenced method for the identification of evoked potential component wave forms.

Visual evoked potentials from rat visual cortex are described as the sum of components. Each component wave form is based on a mathematical model of neural activity. The model referenced approach yields an accurate description of the evoked potential wave forms before and after administration of an anesthetic known to alter neural activity. Thus, the method is efficient, is based in neurophysiology and is sensitive to drug effect on brain activity.

Animals↗
PubMed1983

Wound geometry and the kinetics of wound contraction.

Contraction of an excisional wound can be described by a decaying exponential with a non-zero asymptote between days 6 and 39 after wounding. Regardless of size or shape, the contraction-rate constant is invariant within age- and species-matched animals. Differently shaped wounds of the same size contract at the same rate during the exponential period. Shape exerts its effect prior to the onset of contraction by defining the size of the wound entering the exponential period. Perimeter is the factor by which shape determines size.

Animals↗
PubMed1982

Spectral analysis of photic stimulation in migraine.

In seeking an electrophysiologic discriminator of migraine, we applied computer technology to power spectral analysis of the EEG with photic stimulation. In 11 normal volunteers and 11 migraineurs (both classic and common) we were able to classify all migraineurs and misclassified only one normal based on the spectral analysis. The discriminator contained 5 elements: the increased driving power of migraineurs with photic stimulation at 24 flashes/sec, 34 flashes/sec, and 38 flashes/sec; and the increased power in the alpha band in both parietal and occipital leads at 20 flashes/sec. Power spectral analysis in conjunction with photic stimulation may provide the necessary data for effective discrimination of migraine from non-migraine states.

Adult↗
PubMed1982

Elevation of serum prostaglandin E levels following electrical stimulation of the midbrain.

Serum prostaglandin E (PGE) levels were measured in rats immediately following electrical stimulation of the mesencephalic periaqueductal gray (PAG) region and the nucleus raphe magnus (NRM) and compared to controls. An additional group received aspirin prior to PAG stimulation. A significant increase in serum PGE levels was found after stimulation of the PAG, but not the NRM. Aspirin inhibited the stimulation-induced increases in PGE.

Animals↗
PubMed1981

Hydrogen peroxide causes the fatal injury to human fibroblasts exposed to oxygen radicals.

Oxygen radicals are suspected as being a cause of the cellular damage that occurs at sites of inflammation. The phagocytic cells that accumulate in areas of inflammation produce superoxide, hydrogen peroxide, hydroxyl radical, and probably singlet oxygen in the extracellular fluid. The mechanism by which these oxygen molecules kill cells is unknown. To determine which of the oxygen species is responsible for the cellular killing, we exposed human fibroblasts in culture to oxygen radicals generated by the enzymatic action of xanthine oxidase upon acetaldehyde. Using the amount of chromium-51 released from labeled fibroblasts as an index of cellular death, we found that cells were protected only by interventions that reduce hydrogen peroxide concentration. Agents that inactivate superoxide, hydroxyl radical, and singlet oxygen were ineffective in limiting oxygen radical-induced cellular death.

Cell Survival↗
PubMed1981

Neuroleptic drug effects on average evoked response augmentation-reduction in rats.

The hypothesis that one of the effects of neuroleptic medication is the induction of a reducing response in the average evoked response (AER) was explored in rats. Periodic AER recordings were made in rats receiving either haloperidol or chlorpromazine, and following the drugs discontinuance. When compared to a group of rats which received no drugs, the drug groups showed a significant trend toward increased AER reducing. This effect was delayed from the beginning of drug administration, and reached a maximum following drug discontinuation. Suggestions are made regarding the significance of these findings for further investigations into mechanisms of neuroleptic effect and mechanisms of the augmentation-reduction phenomenon of the AER.

Animals↗
PubMed1980

Electrical stimulation of the midbrain mediates metastatic tumor growth.

Pulmonary metastases were counted 10 days after female rats received tail-vein injections of Walker-256 carcinosarcoma cells. Previous observations that halothane anesthesia plus hind-limb amputation increases the number of metastases were confirmed. Amputation under the analgesia of electrical stimulation of the midbrain was found to increase metastatic activity. However, the stimulus-produced analgesia alone also increased the number of metastases. Systemically administered naloxone blocked the analgesic effect of midbrain stimulation but did not block the increase in the number of pulmonary metastases.

Anesthesia↗