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J E Olson

Publications and source records attributed to J E Olson.

At least 19 recordsLinked to original sources
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↗
PubMed1990

Transmodulation of epidermal growth factor binding by platelet-derived growth factor and 12-O-tetradecanoylphorbol-13-acetate is not sodium-dependent in Balb/c/3T3 cells.

The addition of platelet-derived growth factor (PDGF) to many types of cells causes a rapid decrease in high affinity binding of 125I-epidermal growth factor (EGF), a process which has been termed transmodulation. Treatment with the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA) also results in the transmodulation of the EGF receptor in many cell types. PDGF can transmodulate EGF binding through a mechanism that is not dependent on protein kinase C activity. A recent report (Wattenberg, E. V., McNeil, P. L., Fujiki, H., and Rosner, M. R. (1989) J. Biol. Chem. 264, 213-219) described the requirement for a sodium ion influx in the down-modulation of the EGF receptor stimulated by a non-TPA-type tumor promoter, palytoxin, in Swiss 3T3 cells. We tested for a similar sodium requirement in Balb/c/3T3 and Swiss 3T3 cells stimulated by PDGF or TPA in Balb cells treated with TPA for prolonged periods to down-regulate protein kinase C activity. Our results clearly show that the PDGF- and TPA-stimulated transmodulation of the EGF receptor does not require external sodium nor is the process affected by amiloride. In each of these experiments, the loss of 125I-EGF binding occurred to a similar extent and at a similar rate in the presence or absence of sodium. Intracellular pH also did not appear to have a role in the response. The sodium ionophore, monensin, was previously shown to bring about the down-modulation of 125I-EGF binding in Swiss cells. However, our results indicate that monensin-induced transmodulation of the EGF receptor occurs with or without external sodium, suggesting that the loss of binding is not the result of a sodium ion influx. These findings demonstrate that an increase in intracellular sodium does not cause nor is it required for PDGF- or TPA-stimulated EGF receptor transmodulation.

Animals↗
PubMed1990

Intracellular lipid droplets in functioning transitional parathyroid oxyphil adenomas. A caveat.

Histochemical demonstration of intracellular lipid droplets on frozen section has been used to distinguish normal parathyroid tissue from that of adenoma and chief cell hyperplasia. Differentiation is based on the observation that the cells of adenoma and chief-cell hyperplasia largely lack intracellular lipid, which is present in the suppressed chief cells of normal glands in patients with adenoma. We present two functional transitional oxyphil adenomas that contained abundant intracellular lipid. Failure to recognize that transitional oxyphilic adenomas may contain focal accumulation of intracellular lipid droplets could lead to confusion in histologic interpretation.

Adenoma↗
PubMed1990

Control of astrocyte volume by intracellular and extracellular Ca2+.

Astrocytes from primary culture were exposed to conditions that affect intracellular and extracellular Ca2+ concentrations. Astrocyte cell volume was increased approximately 16% after a 30 min exposure to isoosmotic phosphate-buffered saline (PBS) containing the Ca2+ buffer EDTA. Cell volume returned to control values within 30 min of resuspension in normal PBS. Cellular calcium content was not affected by these treatments; however, the recovery of normal cell volume following EDTA exposure was inhibited by 0.1-1.0 mM quinine HCl in a dose-dependent fashion suggesting that a potassium channel controlled by the intracellular Ca2+ concentration is important in this volume response. Intracellular accumulation of an exogenous Ca2+ buffer, BAPTA, also produced cell swelling that persisted following resuspension in normal PBS. Lowering the extracellular Ca2+ concentration with EDTA enhanced the swelling of BAPTA-loaded cells. These data suggest that conditions leading to a decrease in free intracellular Ca2+ concentration may influence astrocyte volume by a mechanism similar to that described in other cell types.

Animals↗
PubMed1990

Amino acid content of rat cerebral astrocytes adapted to hyperosmotic medium in vitro.

Rat cerebral astrocytes from confluent primary cultures were grown for two weeks in medium made hyperosmotic with additional NaCl. At the time the cells were harvested (four weeks in culture), the medium osmolality of experimental cultures was approximately 600 mOsm. Amino acid, protein, and potassium contents and the cell volume were measured. Compared to cells maintained in control medium (approximately 300 mOsm), cells grown in hyperosmotic conditions had over two times the content of taurine and five times the content of glutamine. Alanine, aspartate, glutamate, glycine, and tyrosine contents also were elevated in these hyperosmotic-treated cells, while asparagine contents were unchanged relative to control cells. Cell volume and potassium content were decreased to approximately 50% of control levels by the hyperosmotic treatment while total protein content per cell was unchanged relative to cells from control cultures. Seven min after hyperosmotic-exposed cells were rapidly diluted into PBS with osmolality equal to about 330 mOsm, cell contents of alanine, asparagine, glutamine, glutamate, glycine, taurine, and tyrosine fell toward control levels. The data indicate that significant alterations in intracellular osmolytes occur in astrocytes adapted to hyperosmotic conditions. We suggest that a loss of intracellular potassium is at least partially compensated by accumulation of taurine, glutamine, and perhaps other amino acids acting as intracellular osmolytes.

Amino Acids↗
PubMed1990

Brain water content, brain blood volume, blood chemistry, and pathology in a model of cerebral edema.

STUDY OBJECTIVES: The objective was to correlate regional changes during brain water content with alterations in blood chemistry and cerebral pathology during hypo-osmotic edema. PARTICIPANTS: Sprague-Dawley male adult rats were used in these studies. DESIGN: Animals were block-randomized to receive either an intraperitoneal distilled water injection equivalent to 5% or 15% of their body weight or no injection (controls). Rats were sacrificed 15 or 60 minutes after water injection or at an equivalent time for controls. INTERVENTIONS: No interventions were performed. MEASUREMENTS AND MAIN RESULTS: Water content of cerebral cortical gray and white matter was calculated from measurements of tissue specific gravity. Blood plasma osmolality and sodium and potassium concentrations were determined at various times after water injection. An index of blood-brain barrier permeability was obtained by measuring brain red blood cell and plasma volumes. A qualitative assessment of edema was made from light and electron micrographs of the cerebral cortex. We found that water injection produced a dose-dependent decrease in plasma osmolality and sodium concentration within 15 minutes. Cortical water content was unchanged after this period. An influx of water into cerebral gray, and, less readily, into cerebral white matter occurred during the next 15 minutes. Whole blood specific gravity and brain blood content were unchanged and thus did not confound the measurement of cerebral water content. Hematocrit was increased 60 minutes after a 15% water injection. The blood-brain barrier remained intact throughout this period. Microscopy revealed astrocytic swelling with slight extracellular fluid accumulation 60 minutes after the water injection. CONCLUSIONS: Homeostatic mechanisms in the cerebral cortex can maintain constant water content for at least 15 minutes during maintained intravascular hypo-osmolality. Fluid that subsequently moves into the tissue primarily enters an intracellular compartment. This model will be useful in investigating physiological mechanisms of brain water regulation and the pathogenesis of brain edema, a common clinical entity in emergency conditions.

Animals↗
PubMed1990

The effect of tamoxifen on cervical squamous maturation in Papanicolaou stained cervical smears of post-menopausal women.

Using cervical smears obtained as part of routine gynaecological examinations, a retrospective study of the effects of the drug tamoxifen on squamous epithelial maturation of the cervix of post-menopausal women being treated for advanced breast cancer was made. The degree of squamous epithelial maturation was quantitated by using the Maturation Index and the Maturation Value. Although tamoxifen is a synthetic, non-steroidal compound classified as anti-oestrogenic, the findings indicate that this drug commonly produces a level of squamous maturation indicative of oestrogenic stimulation in Papanicolaou stained cervical smears from post-menopausal patients receiving this drug. Knowledge of the oestrogenic effect of tamoxifen in the cervix can obviate clinical concern about endometrial carcinoma.

Adenocarcinoma↗
PubMed1989

Octanoic acid inhibits astrocyte volume control: implications for cerebral edema in Reye's syndrome.

Octanoic acid has been implicated in the pathogenesis of cytotoxic cerebral edema in Reye's syndrome. Using astrocytes from primary culture, we studied the dose-dependent effects of octanoate on cellular volume regulation and metabolism. Astrocyte volume recovery following hypoosmotic swelling was stimulated by 1.0 mM octanoate and inhibited by 3.0 mM octanoate. Parallel effects were obtained at these concentrations on the activity of the Na+,K+-dependent ATPase. Cellular ATP concentrations also were reduced 36% with the higher octanoate concentration. These effects of octanoate may contribute to the severe astrocyte swelling observed in the brains of Reye's syndrome patients.

Adenosine Triphosphate↗
PubMed1989

Cerebral oxygenation and blood flow in infant and young adult rats.

In vitro cerebral oxidative metabolism undergoes dramatic increases in infant rats between 10 and 20 days of age. To determine this was also the case in vivo, comparisons were made of cerebral blood flow (CBF) and oxygenation in rats at 10, 20, and 60-90 days of age, under pentobarbital sodium anesthesia. Measurements were made of CBF, arterial and venous O2 content, cerebral PO2 distributions, and the oxidation state of cytochrome-c oxidase (cytochrome aa3). CBF, O2 delivery, and O2 consumption all increased progressively with maturation. In contrast, cerebral PO2, cytochrome aa3 oxidation state, and O2 extraction fraction were higher in 20-day-old rats than in either 10-day-old or adult rats. We attribute this difference primarily to the high density of cerebral capillaries in the 20-day-old rat. We conclude that cerebral tissue PO2 and the oxidation state of cytochrome aa3 are determined by the density of perfused capillaries in addition to the more commonly accepted factors of cerebral O2 delivery and consumption.

Animals↗
PubMed1989

Six-year results of the Eastern Cooperative Oncology Group trial of observation versus CMFP versus CMFPT in postmenopausal patients with node-positive breast cancer.

The Eastern Cooperative Oncology Group (ECOG) trial of adjuvant cyclophosphamide, methotrexate, fluorouracil, and prednisone (CMFP) or CMFP plus tamoxifen (CMFPT) for 1 year compared with observation alone in 265 postmenopausal patients with node-positive breast cancer is reported with 74 months median follow-up. Overall relapse-free survival tended to favor CMFPT (P = .08), but no survival differences existed between any treatment group. The addition of tamoxifen to CMFP led to slightly (but not significantly) better relapse-free status in all subgroups analyzed. Subgroup analysis based on stratification variables showed significant benefit from CMFP (+/- T) only in estrogen receptor (ER)-negative patients with respect to disease-free status (P = .0003), but not survival (P = .54). Relapse-free status was actually worse for CMFP-treated patients with ER-positive tumors, but not significantly so (P = .15). By multivariate analysis other significant risk factors for relapse-free status were primary tumor size, number of nodes pathologically involved, and the number of nodes examined. ER status was prognostic only for the observation group with the benefit from chemotherapy on ER-negative patients obliterating this difference in treated patients. Survival was affected by the number of involved nodes, tumor size, presence of tumor necrosis, and patient obesity. Analysis of toxicity showed elevation of liver enzymes during the first year to be more common in the observation group compared with those patients receiving adjuvant treatment and to be associated with early recurrence. Toxicity from adjuvant treatment persisted beyond termination of therapy in 53% of patients, but was usually mild and self-limited. We conclude CMFPT offers relapse-free survival benefit in ER-negative patients, but the value of chemotherapy in ER-positive postmenopausal, node-positive patients must be questioned.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Plasma free thyroxine concentrations in patients receiving levothyroxine for thyroid suppression.

The usual recommendation is to follow total triiodothyronine (T3) concentration during levothyroxine (L-thyroxine) therapy because 65% of clinically euthyroid patients receiving L-thyroxine have normal T3 but elevated total thyroxine (T4) levels. Because free thyroxine (FT4) is the metabolically active form of T4, our study was designed to determine whether FT4 by analog radioimmunoassay method is normal or increased in euthyroid patients receiving L-thyroxine. Twenty-seven clinically euthyroid patients, 5 males and 22 females, receiving L-thyroxine for thyroid suppression, were studied in a prospective protocol. Twenty-one euthyroid patients not receiving L-thyroxine served as controls. Samples were analyzed for T4, T3, T3 (RU), TSH, and FT4 by three analog methods. Mean FT4 levels were greater than control for all three assays. The percentage of patients with FT4 in the hyperthyroid range was 63% for assay I, 41% for assay II, and 52% for assay III. When patients were grouped by dose of L-thyroxine, FT4 levels were not significantly increased. Sixty-two percent of patients receiving L-thyroxine had T4 levels in the hyperthyroid range. T3 concentrations were not significantly greater in the L-thyroxine group when compared with control. In the L-thyroxine group, thyrotropin was significantly less than in the control group. FT4 concentration by analog method is in the hyperthyroid range in as many as 63% of clinically euthyroid patients receiving L-thyroxine. The use of FT4 to assess thyroid status may cause inappropriate adjustment of L-thyroxine dose. T3 level continues to parallel closely the physician's clinical impression and best represents peripheral metabolic status.

Adenocarcinoma↗