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Biomedical subjects

J E Olson

Publications and source records attributed to J E Olson.

At least 55 records · Page 3Linked to original sources
PubMed1996

Relation of taurine transport and brain edema in rats with simple hyperammonemia or liver failure.

Taurine (Tau), an amino acid that abounds in brain, has been implicated in inhibitory neuromodulation and osmoregulation, the latter function being manifested by Tau release along with osmotically obligated water in response to brain tissue edema. A previous study (Hilgier and Olson: J. Neurochem. 62:197-204, 1994) had shown that simple hyperammonemia (HA) induced in rats by daily administration of ammonium acetate resulted in a decrease of both tissue specific gravity indicative of edema and Tau content, in basal ganglia (BG) but not in cerebral cortex (CC). By contrast, rats with hepatic encephalopathy (HE) following administration of a hepatotoxin, thioacetamide, were characterized by CC edema and an increased Tau content in both BG and CC. In the present study, we tested the following parameters that may potentially have affected Tau distribution in the two models: a) spontaneous, and stimulated (hypoosmolarity-induced) release of loaded [3H] Tau in vitro from CC and BG slices; b) blood Tau content; and c) uptake of [14C] Tau in vivo from blood to brain corrected for [3H] water passage-the so-called brain uptake index (BUI). The two edema-affected structures: BG in the HA model and CC in the HE model, showed increased spontaneous Tau release. Edema-associated spontaneous release of Tau may favor inhibitory neurotransmission contributing to the pathomechanism of HA or HE. Stimulated release, reflecting the ability of the tissue to reduce water content, was decreased in the BG from HA rats, in agreement with the postulated role of Tau in osmoregulation. Stimulated release was unchanged in CC of HE rats. Neither spontaneous nor stimulated release of Tau were affected in CC of HA rats or in BG of HE rats. HE, but not HA, was associated with elevated blood content and increased BUI for TAU, which in combination, contributed to the increase of Tau content in CC. The latter phenomenon adds to the list of metabolic changes distinguishing simple HA from toxic liver damage, reemphasizing the crucial role of factors other than ammonia in the pathomechanism of HE.

Ammonia↗
PubMed1996

Hyperosmotic exposure alters total taurine quantity and cellular transport in rat astrocyte cultures.

Taurine content and cellular taurine transport were characterized in astrocytes from rat cerebral cortex after growth in isoosmotic or hyperosmotic culture conditions to investigate mechanisms of taurine accumulation during conditions of increased osmolality. Total taurine content of the culture dishes was significantly (P < 0.05) elevated after 8, 24, and 48 h of hyperosmotic exposure compared to cultures grown for the same period in isoosmotic (300 mOsm, control) conditions. Hyperosmotic medium elevated intracellular taurine (nmol/mg protein) levels by 29-108% over control cultures. Significant (P < 0.02) increases in carrier-mediated taurine uptake rates were observed in astrocytes exposed to 350, 400, and 450 mOsm culture medium for 24 h compared to control cultures at the same time point. The increase in uptake rate decreased to control values by 48 h in 450 mOsm treated cultures. The carrier-mediated transport binding constant for taurine uptake, Km, was not altered at any time after hyperosmotic treatment. Maximal velocity of uptake, V(max), increased by 70% and 36% after 24 h growth in 400 and 450 mOsm culture medium, respectively, compared to control cells at the same time. After 48 h of hyperosmotic exposure, V(max) returned to control values. The diffusional transport rate for taurine efflux, Kdiff, was not affected by hyperosmotic exposure at any time point. Taurine release rates were increased by over two-fold during the first 8 h of exposure to 450 mOsm medium compared with cells grown in control conditions. After 24 and 48 h hyperosmotic exposure, release rates decreased to 44-72% of the release from control cultures. These data indicate at least three mechanisms contribute to taurine accumulation in cultured cerebral astrocytes exposed to hyperosmotic conditions. These mechanisms are (i) an increased rate of taurine uptake from the extracellular space within 24 h, (ii) a decrease in net taurine efflux by 48 h, and (iii) an enhanced rate of taurine synthesis.

Animals↗
PubMed1996

Optimal positioning for cervical immobilization.

STUDY OBJECTIVE: We hypothesized that optimal positioning of the head and neck to protect the spinal cord during cervical spine immobilization can be determined with reference to external landmarks. In this study we sought to determine the optimal position for cervical spine immobilization using magnetic resonance imaging (MRI) and to define this optimal position in a clinically reproducible fashion. METHODS: Our subjects were 19 healthy adult volunteers (11 women, 8 men). In each, we positioned the head to produce various degrees of neck flexion and extension. This positioning was followed by quantitative MRI of the cervical spine. RESULTS: The mean ratio of spinal canal and spinal cord cross-sectional areas was smallest at C6 but exceeded 2.0 at all levels from C2 to T1 (P < .05). At the C5 and C6 levels, the maximal area ratio was most consistently obtained with slight flexion (cervical-thoracic angle of 14 degrees) (P < .05). For a patient lying flat on a backboard, this corresponds to raising the occiput 2 cm. More extreme flexion or extension produced variable results. CONCLUSION: In healthy adults, a slight degree of flexion equivalent to 2 cm of occiput elevation produces a favorable increase in spinal canal/spinal cord ration at levels C5 and C6, a region of frequent unstable spine injuries.

Adult↗
PubMed1996

Antimalarial effects of vinyl sulfone cysteine proteinase inhibitors.

We evaluated the antimalarial effects of vinyl sulfone cysteine proteinase inhibitors. A number of vinyl sulfones strongly inhibited falcipain, a Plasmodium falciparum cysteine proteinase that is a critical hemoglobinase. In studies of cultured parasites, nanomolar concentrations of three vinyl sulfones inhibited parasite hemoglobin degradation, metabolic activity, and development. The antimalarial effects correlated with the inhibition of falcipain. Our results suggest that vinyl sulfones or related cysteine proteinase inhibitors may have promise as antimalarial agents.

Animals↗
PubMed1995

Hypoosmotic volume regulation and osmolyte transport in astrocytes is blocked by an anion transport inhibitor, L-644,711.

Cell volume, potassium content, and potassium influx were measured in rat cerebral astrocytes grown in primary culture following exposure to hypoosmotic medium containing either 3.2 mM or 50 mM potassium. Some solutions also contained 1 mM L-644,711, an anion transport inhibitor. L-644,711 inhibited volume regulation and taurine efflux induced by hypoosmotic exposure in medium containing either potassium concentration. L-644,711 also inhibited potassium uptake associated and not associated with the sodium/potassium pump. The correlation of reduced taurine efflux and volume decrease produced by L-644,711 exposure indicates the important role for this amino acid in hypoosmotic astrocyte volume regulation. However, the effects of L-644,711 on potassium transport indicate that multiple actions of this drug may be important factors in its effect on astrocyte volume regulatory mechanisms.

Amino Acids↗
PubMed1995

Hypoosmotic volume regulation of astrocytes in elevated extracellular potassium.

Cellular volume and potassium contents were determined in rat astrocytes from primary culture following suspension in isoosmotic (269 mOsm) and hypoosmotic (136 mOsm) phosphate-buffered saline (PBS) containing various potassium concentrations. Within 1 min of suspension in hypoosmotic PBS, cells swelled to 135% of their volume in isoosmotic PBS. This initial swelling was not altered by varying the potassium concentration of the hypoosmotic PBS. After suspension in hypoosmotic PBS containing 3.2 mM potassium, a regulatory volume decrease (RVD) was observed. Higher concentrations of potassium in hypoosmotic PBS inhibited RVD following osmotic swelling. Cells swollen in hypoosmotic PBS containing 50 mM potassium continued to swell for 7 min, reaching a volume of 141% of their initial isoosmotic volume. After 7 min, these cells demonstrated a subsequent decrease in volume. The swelling observed between 1-7 min after suspension in hypoosmotic PBS containing 50 mM potassium was not affected by 10 microM gadolinium, 1 mM quinine, 1 mM DIDS (4,4'-diisothiocyanato-2,2'-stilbenedisulfonic acid), 1 mM SITS (4-acetamido-4'-isothiocyanato-2,2'-stilbenedisulfonic acid), 1 mM furosemide, or 100 microM bumetanide. Normal RVD was obtained in hypoosmotic PBS containing 50 mM potassium, if chloride was replaced with gluconate (but not nitrate) to reduce the extracellular K.Cl product to that of hypoosmotic PBS containing 3.2 mM potassium. The volume decrease seen between 7-30 min after exposure to hypoosmotic PBS containing 50 mM potassium was blocked by 1 mM DIDS, 1 mM SITS, or 1 mM furosemide. Cellular potassium content was elevated by approximately 60% after 7 min exposure to isoosmotic or hypoosmotic PBS containing 50 mM potassium. In hypoosmotic PBS, this increase in cellular potassium was reduced with replacement of chloride by gluconate, but not by nitrate. The results indicate that astrocytes swollen in PBS containing elevated potassium concentrations continue to swell, in part, by accumulation of potassium plus chloride mediated by an approach to Donnan equilibrium. Cotransport carriers or stretch-activated channels do not play a role in the enhanced swelling observed in hypoosmotic PBS containing 50 mM potassium. We suggest that a voltage-sensitive chloride channel mediates this continuation of cell swelling. This mechanism may be important in the persistent swelling of astrocytes observed in pathologic conditions such as trauma and seizures where extracellular potassium is elevated, or when other factors are present which may cause astroglial depolarization.

Animals↗
PubMed1995

Eleven years' experience with pericardial-peritoneal window in the management of malignant and benign pericardial effusions.

BACKGROUND: Before 1983 we routinely used subxiphoid drainage for the management of pericardial effusions. Pericardial-pleural window through a left anterior thoracotomy was used in selected patients. Due to frustration over the rate of recurrent pericardial effusions with subxiphoid drainage alone and concern over the higher morbidity with thoracotomy, the creation of a 3-cm pericardial-peritoneal window in the fused portion of the pericardium and diaphragm overlying the left lobe of the liver was added to subxiphoid drainage in 1983. METHODS: This study is a retrospective chart review of the 33 patients undergoing pericardial-peritoneal window from 1983 through 1993. Eighteen patients had malignancies, mainly lung and breast, and 15 had benign pericardial effusions. RESULTS: The procedure was well tolerated, with a 30-day mortality of 9%; however, no deaths were directly related to the pericardial effusion or the procedure. No patient developed peritoneal carcinomatosis or diaphragmatic hernia. One patient developed recurrent pericardial effusion during follow-up, and two required pericardiectomy for constrictive disease. Among those with malignancies, patients with breast cancer had the longest survival after pericardial-peritoneal window. CONCLUSIONS: Pericardial-peritoneal window is a simple, safe, and effective procedure and applicable to most patients with malignant and noninfectious benign pericardial effusion, including those with tamponade.

Adult↗
PubMed1994

Brain osmolyte content and blood-brain barrier water permeability surface area product in osmotic edema.

Brain edema was induced in adult rats by intraperitoneal injection of distilled water equivalent to 15% of the animal's body weight. Mean +/- SEM serum osmolality fell from 291 +/- 3 mOsm to 253 +/- 4 mOsm during the next hour while cerebral gray matter water content increased from 79.5 +/- 0.2% to 80.9 +/- 0.2%. Gray matter content of sodium, potassium, taurine, glycine, glutamine, and glutamate were unchanged. However, the blood-brain barrier permeability/surface area product for water decreased by 40%. This alteration in water permeability may represent a response to limit water influx during the first hour of hypoosmotic brain edema.

Animals↗
PubMed1994

Brain ion and amino acid contents during edema development in hepatic encephalopathy.

Brain edema in hepatic encephalopathy has been associated with circulating ammonia that is metabolized to glutamine. We measured alterations in blood chemistry and brain regional specific gravity and ion and amino acid contents in models of simple hyperammonemia and liver failure induced by daily administrations of ammonium acetate (AAc) or thioacetamide (TAA), respectively. Serum and brain ammonia increased to similar levels (200 and 170% of control, respectively) in both experimental groups. Serum transaminase activities increased 10-fold in animals injected with TAA but were unchanged in animals given AAc injections. In both experimental groups glutamine was elevated in cerebral white matter, cerebral gray matter, and basal ganglia, whereas brain tissue specific gravity decreased in all brain regions, indicating edema formation. In the AAc group, we observed a decrease in glutamate and taurine contents concomitant with the development of brain edema. In these animals, cerebral gray matter specific gravity and taurine contents returned to control levels 24 h after the third AAc injection. TAA-injected animals demonstrated similar decreases in brain tissue specific gravity, whereas glutamine, glutamate, and taurine contents were all elevated. During hepatic encephalopathy, ammonia-induced changes in brain amino acid content may contribute to brain edema development.

Acetates↗
PubMed1993

Taurine transport in rat astrocytes adapted to hyperosmotic conditions.

[3H]Taurine uptake and release was characterized in astrocytes from rat cerebral cortex grown in normal and hyperosmotic culture conditions to investigate mechanisms of cell volume regulation and adaptation to states of altered osmolality. In high concentrations of taurine (1 mM), uptake was linear in both osmotic conditions for at least 30 min. The uptake rate in 1 mM taurine was not affected by exposure to hyperosmotic conditions. The mean +/- S.E.M. apparent binding constant for carrier-mediated taurine transport, Km, was not altered by hyperosmotic conditions (22.8 +/- 5.1 microM in iso-osmotic media, 21.3 +/- 11.9 microM in hyperosmotic media). However, maximal velocity of uptake, Vmax (mean +/- S.E.M.), of taurine was significantly lower in hyperosmotically treated astrocytes (0.175 +/- 0.035 nmol/mg protein.min) compared with the Vmax of iso-osmotically treated astrocytes (0.299 +/- 0.026 nmol/mg protein.min). The diffusional transport rate, Kdiff, was not affected by growth in hyperosmotic conditions (0.221 +/- 0.033 microliter/mg protein.min in iso-osmotic media, 0.295 +/- 0.043 microliter/mg protein.min in hyperosmotic media). Taurine release rate, expressed as a percent of the total cell content, was not affected by hyperosmotic exposure. However, astrocytes grown in hyperosmotic conditions contain nearly 60% more taurine than control cells. Thus, the absolute rate of taurine release (mean +/- S.E.M.) was significantly larger (P < 0.05) in hyperosmotic cells (0.1592 +/- 0.0082 nmol/mg protein.min) compared with control cells (0.0943 +/- 0.0096 nmol/mg protein.min). Quantitative analysis of these data indicate that maintenance of elevated taurine contents by cultured cerebral astrocytes exposed to hyperosmotic conditions is not due to alterations in rates of transport.

Adaptation, Physiological↗
PubMed1993

Cell cycle-dependent gene expression in V point-arrested BALB/c-3T3 cells.

Density-arrested BALB/c-3T3 cells stimulated to proliferate in an amino acid-deficient medium arrest in mid-G1 at a point termed the V point. Cells released from V point arrest require 6 hr to traverse late G1 and enter S phase. As data presented here show that mRNA synthesis is needed for 2-3 hr after release of cells from the V point, after which inhibition of mRNA synthesis does not prevent entry into S phase, we used this mid-G1 arrest protocol to analyze gene expression in late G1. We found that although stimulation of cells in amino acid-deficient medium did not inhibit the induction of genes expressed in early G1, genes normally expressed in late G1 were expressed only after release from the V point. The expression of late G1 genes in cells released from the V point was temporally similar, in respect to G1 location, as was seen in stimulation of quiescent G0 cells. As this protocol effectively divides gene expression into early (pre-V point) and late (post-V point) categories, it should be useful in studies of growth factor-modulated events that regulate traverse of late G1 and commitment to DNA synthesis. In addition, we used c-myb antisense oligonucleotides to show that c-myb expression, which occurs in late G1, is required for BALB/c-3T3 fibroblasts to traverse late G1 and initiate DNA synthesis.

3T3 Cells↗
PubMed1992

Rapid induction of competence formation is PDGF-isoform specific.

Platelet-derived growth factor (PDGF) stimulates the expression of a number of genes associated with entry of quiescent Balb/c-3T3 fibroblasts into the cell cycle. We determined that two of these genes, c-myc and c-fos, are induced equivalently in medium supplemented with platelet-poor plasma (PPP) and either PDGF-BB or PDGF-AA. The rate at which fibroblasts entered S phase was also similar in PDGF-BB- and AA-treated cells as was the expression of the late G1 gene, thymidine kinase (TK). However, PDGF-AA must be present for a period of 16 h to stimulate the proliferation of 90% of the cells, whereas PDGF-BB was required for only 4 h. Exposure of cells to PDGF-AA for 4 h, a time during which maximum expression of c-fos and c-myc occurred, only induced 20% of the cells in a quiescent population to enter the cell cycle. Therefore, PDGF-AA-mediated expression of the immediate early genes c-fos and c-myc may be necessary but is not sufficient to rapidly stimulate density-arrested Balb/c-3T3 fibroblasts into the competent state. Thus, these data suggest that PDGF-AA and PDGF-BB initiate traverse of the cell cycle by distinct mechanisms.

3T3 Cells↗
PubMed1992

Evaluation of acute brain edema using quantitative magnetic resonance imaging: effects of pretreatment with dexamethasone.

We developed a quantitative magnetic resonance imaging method to permit a rapid assessment of brain water content during osmotic brain edema produced by intraperitoneal (ip) injection of distilled water. Fifteen minutes after water injection, the normalized mean image intensity (MIn) from a spin-echo pulse sequence (TE = 80 ms, TR = 1085 ms) was the same as that measured from control animals not injected with water. Sixty minutes after the water injection, the mean +/- SEM brain image MIn had increased by 10.8 +/- 2.4% compared to 3.4 +/- 0.7% in control animals (P less than 0.05). Blood plasma osmolality decreased by 6-10% during this time interval. A subsequent ip injection of hypertonic NaCl solution (100 gm/liter) caused the blood plasma osmolality and brain image MIn to return toward their initial values. MIn of cerebral gray matter correlated with tissue water content measured in parallel studies. Animals pretreated with 0.25 mg/(kg day) dexamethasone had cerebral gray matter MIn values during osmotic edema which were lower than those of untreated animals.

Acute Disease↗
PubMed1992

Astrocyte volume regulation and ATP and phosphocreatine concentrations after exposure to salicylate, ammonium, and fatty acids.

Cellular volume regulation following swelling in hypo-osmotic phosphate-buffered saline (PBS) and ATP and phosphocreatine concentrations of cells incubated in iso-osmotic or hypo-osmotic PBS were measured in primary cultured rat cerebral astrocytes exposed for 30 min to NH4Cl, salicylate, hexanoate, octanoate, and/or dodecanoate. These compounds have been implicated in the pathogenesis of cerebral edema in Reye's Syndrome. NH4Cl (0.10 - 10 mM) had no effect on astrocyte volume regulation or ATP concentration. Salicylate significantly reduced ATP concentrations at 3.0 mM and 10 mM but had no effect on volume regulation. Hexanoate (10 mM and 30 mM) decreased astrocyte ATP content by over 80% while octanoate (10 mM) reduced ATP content by more than 50%. Concentrations of these fatty acids at or below 3.0 mM had no effect on ATP content. Volume regulation was inhibited by 3.0 mM hexanoate and 3.0 mM octanoate but not lower concentrations. Dodecanoate (0.1-3.0 mM) decreased cellular ATP content by 33-51% in iso-osmotic PBS solutions. Phosphocreatine content was reduced by exposure to salicylate or octanoate at concentrations which had no effect on ATP content. These results indicate that astrocyte energy metabolism and volume regulation may be compromised by agents associated with cerebral edema in Reye's Syndrome. Analysis of the dose-dependence of these effects suggests that inhibition of astrocyte energy metabolism is not sufficient to affect volume regulation.

Adenosine Triphosphate↗
PubMed1992

Correlations between energy metabolism, ion transport, and water content in astrocytes.

Energy metabolism, ion transport, and water content are interrelated in mechanisms of homeostasis of the brain intracellular and extracellular environment. The simplest model of cell homeostasis, the pump-leak hypothesis, incorporates basic relationships between these variables. Although this model accurately calculates steady-state cell volumes, ion concentrations, and metabolic rates, it fails to predict dynamic changes in these properties during elevated extracellular potassium, metabolic inhibition, and osmotic swelling. We have investigated relationships between ions, energy metabolism, and water content in cerebral astrocytes cultured from the neonatal rat. These cells swell more in hypoosmotic phosphate-buffered saline (PBS) containing NaCl than in hypoosmotic PBS with all NaCl replaced equiosmotically by sucrose. Unidirectional Na+ influx also is greater in cells suspended in hypoosmotic, compared with isoosmotic PBS. These data suggest that astrocytes possess a cell volume dependent mechanism of Na+ accumulation. The influx of Na+ during swelling may be coupled to metabolism via Na-K ATPase and may contribute to the sustained swelling of astrocytes observed in hypoosmotic swelling of the brain in situ.

Animals↗
PubMed1992

Family members of patients with sporadic medullary thyroid carcinoma must be screened for hereditary disease.

BACKGROUND: Medullary thyroid carcinoma (MTC), a tumor arising from calcitonin-secreting C cells, appears in either a sporadic nonfamilial or a hereditary form as a component of a multiple endocrine neoplasia syndrome or familial non-multiple endocrine neoplasia MTC. Screening kindred of a patient with familial MTC to detect MTC in the early curable state is standard practice. Opinions conflict about whether it is necessary to screen relatives of patients with apparently nonfamilial MTC to exclude hereditary disease or whether the clinicopathologic features can differentiate between the two forms. METHODS: Clinically well kindred of a patient with MTC that was histopathologically characteristic of the sporadic type were screened for hereditary disease by measurement of plasma levels of basal and stimulated calcitonin. RESULTS: Three of four immediate relatives tested positive for excessive calcitonin secretion and underwent thyroidectomy. All had C-cell hyperplasia, the premalignant phase of MTC. CONCLUSIONS: The patient with apparently sporadic (nonfamilial) MTC was clearly an index case of familial disease. We conclude that clinical presentation and histopathologic examination are not adequate to reliably exclude hereditary MTC. Until genetic markers are readily available to distinguish between sporadic and familial forms, biochemical screening should be done in primary relatives of all patients with newly detected MTC.

Adult↗
PubMed1991

The effects of fructose-1,6-diphosphate on myocardial damage in acute coronary artery occlusion.

Acute myocardial infarction can result from thrombosis of a coronary artery. The purpose of this study was to evaluate the ability of fructose-1,6-diphosphate (FDP; Esafosfina) to reduce myocardial necrosis during acute thrombosis of a coronary artery. A canine model of acute myocardial infarction was used to produce intraluminal thrombosis by placement of a coil of wire in a coronary artery. After developing a coronary thrombosis of the left anterior descending artery, dogs were injected intravenously with 90 mg/kg, 175 mg/kg, or 350 mg/kg of FDP or normal saline (controls). Hemodynamic, biochemical and electrocardiographic parameters were evaluated before, and 30 min and 4 h after occlusion. Four hours after acute coronary occlusion, the animals were sacrificed, and the weights of ischemic and necrotic myocardial tissue were quantified using a histologic-staining method. There were no significant differences between control and treated animals in biochemical or hemodynamic parameters. All animal groups treated with FDP demonstrated significant reductions in the amount of necrotic and ischemic tissue compared to controls (P less than 0.05). However, only the 175 mg/kg group had a significant reduction compared to controls in necrotic tissue weight as a percentage of ischemic myocardium (24 +/- 15% vs. 72 +/- 22%, respectively, P less than 0.01). These data suggest that FDP may have a role in limiting the amount of myocardial damage after an acute coronary artery occlusion.

Animals↗